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Sample records for neurobiological mechanism underlying

  1. Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms.

    Science.gov (United States)

    Zilverstand, Anna; Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z

    2016-01-01

    Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain's reward circuitry, and the recruitment and strengthening of the brain's inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. © 2016 Elsevier B.V. All rights reserved.

  2. Weaving a Net of Neurobiological Mechanisms in Schizophrenia and Unraveling the Underlying Pathophysiology.

    Science.gov (United States)

    Bitanihirwe, Byron K Y; Mauney, Sarah A; Woo, Tsung-Ung W

    2016-10-15

    Perineuronal nets (PNNs) are enigmatic structures composed of extracellular matrix molecules that encapsulate the soma, dendrites, and axon segments of neurons in a lattice-like fashion. Although most PNNs condense around parvalbumin-expressing gamma-aminobutyric acidergic interneurons, some glutamatergic pyramidal cells in the brain are also surrounded by PNNs. Experimental findings suggest pivotal roles of PNNs in the regulation of synaptic formation and function. Also, an increasing body of evidence links PNN abnormalities to schizophrenia. The number of PNNs progressively increases during postnatal development until plateauing around the period of late adolescence and early adulthood, which temporally coincides with the age of onset of schizophrenia. Given the established role of PNNs in modulating developmental plasticity, the PNN represents a possible candidate for altering the onset and progression of schizophrenia. Similarly, the reported function of PNNs in regulating the trafficking of glutamate receptors places them in a critical position to modulate synaptic pathology, considered a cardinal feature of schizophrenia. We discuss the physiologic role of PNNs in neural function, synaptic assembly, and plasticity as well as how they interface with circuit/system mechanisms of cognition. An integrated understanding of these neurobiological processes should provide a better basis to elucidate how PNN abnormalities influence brain function and contribute to the pathogenesis of neurodevelopmental disorders such as schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Neurobiology Underlying Fibromyalgia Symptoms

    Directory of Open Access Journals (Sweden)

    Marta Ceko

    2012-01-01

    Full Text Available Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that include cognitive and sleep disturbances, and other abnormalities such as increased sensitivity to painful stimuli, increased sensitivity to multiple sensory modalities, and altered pain modulatory mechanisms. Here we relate experimental findings of fibromyalgia symptoms to anatomical and functional brain changes. Neuroimaging studies show augmented sensory processing in pain-related areas, which, together with gray matter decreases and neurochemical abnormalities in areas related to pain modulation, supports the psychophysical evidence of altered pain perception and inhibition. Gray matter decreases in areas related to emotional decision making and working memory suggest that cognitive disturbances could be related to brain alterations. Altered levels of neurotransmitters involved in sleep regulation link disordered sleep to neurochemical abnormalities. Thus, current evidence supports the view that at least some fibromyalgia symptoms are associated with brain dysfunctions or alterations, giving the long-held “it is all in your head” view of the disorder a new meaning.

  4. Formation and adaptation of memory : Neurobiological mechanisms underlying learning and reversal learning

    NARCIS (Netherlands)

    Havekes, Robbert

    2008-01-01

    The hippocampus is a brain region that plays a critical role in memory formation. In addition, it has been suggested that this brain region is important for ‘updating’ information that is incorrect or outdated. The main goal of this thesis project was to investigate which neurobiological processes

  5. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  6. Translational clinical neuroscience perspectives on the cognitive and neurobiological mechanisms underlying alcohol-related aggression.

    Science.gov (United States)

    Beck, Anne; Heinz, Adrienne J; Heinz, Andreas

    2014-01-01

    Alcohol-related violence, a longstanding, serious, and pervasive social problem, has provided researchers from diverse disciplines with a model to study individual differences in aggressive and violent behavior. Of course, not all alcohol consumers will become aggressive after drinking and similarly, not all individuals with alcohol use disorders will exhibit such untoward behavior. Rather, the relationship is best conceptualized as complex and indirect and is influenced by a constellation of social, cognitive, and biological factors that differ greatly from one person to the next. Animal experiments and human studies have elucidated how these mechanisms and processes explain (i.e., mediate) the relation between acute and chronic alcohol consumption and aggressive behavior. Further, the rich body of literature on alcohol-related aggression has allowed for identification of several potential high-yield targets for clinical intervention, e.g., cognitive training for executive dysfunction; psychopharmacology targeting affect and threat perception, which may also generalize to other psychiatric conditions characterized by aggressive behavior. Here we aim to integrate pertinent findings, derived from different methodological approaches and theoretical models, which explain heterogeneity in aggressive responses to alcohol. A translational platform is provided, highlighting common factors linking alcohol and aggression that warrant further, interdisciplinary study in order to reduce the devastating social impact of this phenomenon.

  7. [Recent progress in neurobiological mechanisms of depression].

    Science.gov (United States)

    Gao, Yu-Bo; Li, Liang-Ping; Zhu, Xin-Hong; Gao, Tian-Ming

    2012-08-25

    Revealing the neurobiological mechanism of depression has always been a big challenge in the field of neuroscience. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but also some symptoms are impossible to reproduce in animal models. Nevertheless, great progress has been made on the understanding and treatment of depression in recent years. In this review, we focus on key leading hypotheses in the neurobiological mechanism of depression, examine their strengths and weaknesses critically, and also highlight new insights that promise to extend the understanding of depression and its treatment.

  8. Neurobiological Mechanisms of Pelvic Pain

    Science.gov (United States)

    Leone Roberti Maggiore, Umberto; Candiani, Massimo

    2014-01-01

    Pelvic pain is a common condition which significantly deteriorates health-related quality of life. The most commonly identified causes of pain in the pelvic region are gynaecologic, urologic, gastrointestinal, neurological, and musculoskeletal. However, in up to 33% of patients the source of this symptom is not identified, frustrating both patients and health-care professionals. Pelvic pain may involve both the somatic and visceral systems, making the differential diagnosing challenging. This paper aimed to review the mechanisms involved in pelvic pain perception by analyzing the neural plasticity and molecules which are involved in these complex circuits. PMID:25110704

  9. Neurobiological mechanisms of state-dependent learning.

    Science.gov (United States)

    Radulovic, Jelena; Jovasevic, Vladimir; Meyer, Mariah Aa

    2017-08-01

    State-dependent learning (SDL) is a phenomenon relating to information storage and retrieval restricted to discrete states. While extensively studied using psychopharmacological approaches, SDL has not been subjected to rigorous neuroscientific study. Here we present an overview of approaches historically used to induce SDL, and highlight some of the known neurobiological mechanisms, in particular those related to inhibitory neurotransmission and its regulation by microRNAs (miR). We also propose novel cellular and circuit mechanisms as contributing factors. Lastly, we discuss the implications of advancing our knowledge on SDL, both for most fundamental processes of learning and memory as well as for development and maintenance of psychopathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Untangling the neurobiology of coping styles in rodents: Towards neural mechanisms underlying individual differences in disease susceptibility.

    Science.gov (United States)

    de Boer, Sietse F; Buwalda, Bauke; Koolhaas, Jaap M

    2017-03-01

    Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding of coping style variation is fundamental for biobehavioral neurosciences in probing individual disease susceptibility. This review outlines individual differences in trait-aggressiveness as an adaptive component of the natural sociobiology of rats and mice, and highlights that these reflect the general style of coping that varies from proactive (aggressive) to reactive (docile). We propose that this qualitative coping style can be disentangled into multiple quantitative behavioral domains, e.g., flexibility/impulse control, emotional reactivity and harm avoidance/reward processing, that each are encoded into selective neural circuitries. Since functioning of all these brain circuitries rely on fine-tuned serotonin signaling, autoinhibitory control mechanisms of serotonergic neuron (re)activity are crucial in orchestrating general coping style. Untangling the precise neuromolecular mechanisms of different coping styles will provide a roadmap for developing better therapeutic strategies of stress-related diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Neurobiological mechanisms of treatment resistant depression: Functional, structural and molecular imaging studies

    NARCIS (Netherlands)

    de Kwaasteniet, B.P.

    2015-01-01

    This thesis investigated the neurobiological mechanisms of TRD using functional, structural and molecular imaging studies. First the neurobiological mechanisms of MDD were investigated and revealed decreased functional connectivity between the ventral and dorsal network. Thereafter, structural

  12. Child abuse: underlying mechanisms

    OpenAIRE

    Martínez, Gladys S.

    2009-01-01

    Exposure to traumatic stress during childhood, in the form of abuse or neglect, is related to an increased vulnerability resulting in the development of several pathologies, this relation has been confi rmed by epidemiological studies; however, the neural mechanisms underlying such abnormalities are still unknown. Most of the research done has focused on the effects in the infant, and only recently it has begun to focus on the neurobiological changes in the abusive parents. In this article, I...

  13. Freeze for action: neurobiological mechanisms in animal and human freezing

    Science.gov (United States)

    2017-01-01

    Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in freezing and the shift to fight-or-flight action. Freezing is not a passive state but rather a parasympathetic brake on the motor system, relevant to perception and action preparation. Study of these defensive responses in humans may advance insights into human stress-related psychopathologies characterized by rigidity in behavioural stress reactions. The paper therefore concludes with a research agenda to stimulate translational animal–human research in this emerging field of human defensive stress responses. This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’. PMID:28242739

  14. Neurobiological mechanisms supporting experience-dependent resistance to social stress.

    Science.gov (United States)

    Cooper, M A; Clinard, C T; Morrison, K E

    2015-04-16

    Humans and other animals show a remarkable capacity for resilience following traumatic, stressful events. Resilience is thought to be an active process related to coping with stress, although the cellular and molecular mechanisms that support active coping and stress resistance remain poorly understood. In this review, we focus on the neurobiological mechanisms by which environmental and social experiences promote stress resistance. In male Syrian hamsters, exposure to a brief social defeat stressor leads to increased avoidance of novel opponents, which we call conditioned defeat. Also, hamsters that have achieved dominant social status show reduced conditioned defeat as well as cellular and molecular changes in the neural circuits controlling the conditioned defeat response. We propose that experience-dependent neural plasticity occurs in the prelimbic (PL) cortex, infralimbic (IL) cortex, and ventral medial amygdala (vMeA) during the maintenance of dominance relationships, and that adaptations in these neural circuits support stress resistance in dominant individuals. Overall, behavioral treatments that promote success in competitive interactions may represent valuable interventions for instilling resilience. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Freeze for action: neurobiological mechanisms in animal and human freezing.

    Science.gov (United States)

    Roelofs, Karin

    2017-04-19

    Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in freezing and the shift to fight-or-flight action. Freezing is not a passive state but rather a parasympathetic brake on the motor system, relevant to perception and action preparation. Study of these defensive responses in humans may advance insights into human stress-related psychopathologies characterized by rigidity in behavioural stress reactions. The paper therefore concludes with a research agenda to stimulate translational animal-human research in this emerging field of human defensive stress responses.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'. © 2017 The Authors.

  16. Stress and Memory: Behavioral Effects and Neurobiological Mechanisms

    Science.gov (United States)

    Sandi, Carmen; Pinelo-Nava, M. Teresa

    2007-01-01

    Stress is a potent modulator of learning and memory processes. Although there have been a few attempts in the literature to explain the diversity of effects (including facilitating, impairing, and lack of effects) described for the impact of stress on memory function according to single classification criterion, they have proved insufficient to explain the whole complexity of effects. Here, we review the literature in the field of stress and memory interactions according to five selected classifying factors (source of stress, stressor duration, stressor intensity, stressor timing with regard to memory phase, and learning type) in an attempt to develop an integrative model to understand how stress affects memory function. Summarizing on those conditions in which there was enough information, we conclude that high stress levels, whether intrinsic (triggered by the cognitive challenge) or extrinsic (induced by conditions completely unrelated to the cognitive task), tend to facilitate Pavlovian conditioning (in a linear-asymptotic manner), while being deleterious for spatial/explicit information processing (which with regard to intrinsic stress levels follows an inverted U-shape effect). Moreover, after reviewing the literature, we conclude that all selected factors are essential to develop an integrative model that defines the outcome of stress effects in memory processes. In parallel, we provide a brief review of the main neurobiological mechanisms proposed to account for the different effects of stress in memory function. Glucocorticoids were found as a common mediating mechanism for both the facilitating and impairing actions of stress in different memory processes and phases. Among the brain regions implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as critical for the mediation of stress effects. PMID:18060012

  17. Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

    Science.gov (United States)

    Fowler, Christie D.; Kenny, Paul J.

    2013-01-01

    Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action is considered critical in establishing and maintaining the tobacco smoking habit. Compounds that attenuate nicotine reward are considered promising therapeutic candidates for tobacco dependence, but many of these agents have other actions that limit their potential utility. Nicotine is also highly noxious, particularly at higher doses, and aversive reactions to nicotine after initial exposure can decrease the likelihood of developing a tobacco habit in many first time smokers. Nevertheless, relatively little is known about the mechanisms of nicotine aversion. The purpose of this review is to present recent new insights into the neurobiological mechanisms that regulate avoidance of nicotine. First, the role of the mesocorticolimbic system, so often associated with nicotine reward, in regulating nicotine aversion is highlighted. Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed. Third, the role of the habenular complex in nicotine aversion, primarily medial habenular projections to the interpeduncular nucleus (IPN) but also lateral habenular projections to rostromedial tegmental nucleus (RMTg) and ventral tegmental area (VTA) are reviewed. Forth, brain circuits that are enriched in nAChRs, but whose role in nicotine avoidance has not yet been assessed, will be proposed. Finally, the feasibility of developing novel therapeutic agents for tobacco dependence that act not by blocking nicotine reward but by enhancing nicotine avoidance will be considered. PMID:24055497

  18. Stress and Memory: Behavioral Effects and Neurobiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Carmen Sandi

    2007-01-01

    Full Text Available Stress is a potent modulator of learning and memory processes. Although there have been a few attempts in the literature to explain the diversity of effects (including facilitating, impairing, and lack of effects described for the impact of stress on memory function according to single classification criterion, they have proved insufficient to explain the whole complexity of effects. Here, we review the literature in the field of stress and memory interactions according to five selected classifying factors (source of stress, stressor duration, stressor intensity, stressor timing with regard to memory phase, and learning type in an attempt to develop an integrative model to understand how stress affects memory function. Summarizing on those conditions in which there was enough information, we conclude that high stress levels, whether intrinsic (triggered by the cognitive challenge or extrinsic (induced by conditions completely unrelated to the cognitive task, tend to facilitate Pavlovian conditioning (in a linear-asymptotic manner, while being deleterious for spatial/explicit information processing (which with regard to intrinsic stress levels follows an inverted U-shape effect. Moreover, after reviewing the literature, we conclude that all selected factors are essential to develop an integrative model that defines the outcome of stress effects in memory processes. In parallel, we provide a brief review of the main neurobiological mechanisms proposed to account for the different effects of stress in memory function. Glucocorticoids were found as a common mediating mechanism for both the facilitating and impairing actions of stress in different memory processes and phases. Among the brain regions implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as critical for the mediation of stress effects.

  19. Neurobiology of song learning

    Science.gov (United States)

    Mooney, Richard

    2016-01-01

    Birdsong is a culturally transmitted behavior that depends on a juvenile songbird’s ability to imitate the song of an adult tutor. Neurobiological studies of birdsong can reveal how a complex form of imitative learning, which bears strong parallels to human speech learning, can be understood at the level of underlying circuit, cellular, and synaptic mechanisms. This review focuses on recent studies that illuminate the neurobiological mechanisms for singing and song learning. PMID:19892546

  20. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics

    Science.gov (United States)

    Kreek, Mary Jeanne; Levran, Orna; Reed, Brian; Schlussman, Stefan D.; Zhou, Yan; Butelman, Eduardo R.

    2012-01-01

    Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction. PMID:23023708

  1. Neurobiological mechanisms behind the spatiotemporal illusions of awareness that are used for advocating prediction or postdiction

    Directory of Open Access Journals (Sweden)

    Talis eBachmann

    2013-01-01

    Full Text Available The fact that it takes time for the brain to process information from the changing environment underlies many experimental phenomena of awareness of spatiotemporal events, including a number of astonishing illusions. These phenomena have been explained from the predictive and postdictive theoretical perspectives. Here I describe the most extensively studied phenomena in order to see how well the two perspectives can explain them. Next, the neurobiological perceptual retouch mechanism of producing stimulation awareness is characterized and its work in causing the listed illusions is described. A perspective on how brain mechanisms of conscious perception produce the phenomena supportive of the postdictive view is presented in this article. At the same time, some of the phenomena cannot be explained by the traditional postdictive account, but can be interpreted from the perceptual retouch theory perspective.

  2. New approach to the neurobiological mechanisms of addiction.

    Science.gov (United States)

    Fürst, Zsuzsanna; Riba, Pál; Al-Khrasani, Mahmoud

    2013-12-01

    Much progress has been made in the last decade in the understanding the neural substrates of drug addiction, transmitters involved, epigenetic background and their relation to learning and memory but much remains to be elucidated and strong effort is necessary to integrate the rich information at the molecular, cellular systems, and behavioral levels to further clarify the mechanisms and therapy of this complex disease. The aim of this review is to collect and interpret the latest opinions in the development, the underlying mechanisms and therapy of addiction as a disease of central nervous system. The neurocircuitry, the transmitters and the epigenetics of addiction are discussed.

  3. Consciousness, Neurobiology and Quantum Mechanics: The Case for a Connection

    Science.gov (United States)

    Hameroff, Stuart

    Consciousness is generally considered to emerge from synaptic computation among brain neurons, but this approach cannot account for its critical features. The Penrose-Hameroff "Orch OR" model suggests that consciousness is a sequence of quantum computations in microtubules within brain neurons, shielded from decoherence to reach threshold for objective reduction (OR), the Penrose quantum gravity solution to the measurement problem. The quantum computations are "orchestrated" by neuronal/synaptic inputs (hence "Orch OR"), and extend throughout cortex by tunneling through gap junctions. Each Orch OR is proposed as a conscious event, akin to Whitehead's philosophical "occasion of experience", occurring in concert with brain electrophysiology. This chapter discusses the need for such an approach and its neurobiological requirements.

  4. E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

    Directory of Open Access Journals (Sweden)

    Arun Upadhyay

    2017-05-01

    Full Text Available Cells regularly synthesize new proteins to replace old or damaged proteins. Deposition of various aberrant proteins in specific brain regions leads to neurodegeneration and aging. The cellular protein quality control system develop various defense mechanisms against the accumulation of misfolded and aggregated proteins. The mechanisms underlying the selective recognition of specific crucial protein or misfolded proteins are majorly governed by quality control E3 ubiquitin ligases mediated through ubiquitin-proteasome system. Few known E3 ubiquitin ligases have shown prominent neurodevelopmental functions, but their interactions with different developmental proteins play critical roles in neurodevelopmental disorders. Several questions are yet to be understood properly. How E3 ubiquitin ligases determine the specificity and regulate degradation of a particular substrate involved in neuronal proliferation and differentiation is certainly the one, which needs detailed investigations. Another important question is how neurodevelopmental E3 ubiquitin ligases specifically differentiate between their versatile range of substrates and timing of their functional modulations during different phases of development. The premise of this article is to understand how few E3 ubiquitin ligases sense major molecular events, which are crucial for human brain development from its early embryonic stages to throughout adolescence period. A better understanding of these few E3 ubiquitin ligases and their interactions with other potential proteins will provide invaluable insight into disease mechanisms to approach toward therapeutic interventions.

  5. Expert financial advice neurobiologically "Offloads" financial decision-making under risk.

    Science.gov (United States)

    Engelmann, Jan B; Capra, C Monica; Noussair, Charles; Berns, Gregory S

    2009-01-01

    Financial advice from experts is commonly sought during times of uncertainty. While the field of neuroeconomics has made considerable progress in understanding the neurobiological basis of risky decision-making, the neural mechanisms through which external information, such as advice, is integrated during decision-making are poorly understood. In the current experiment, we investigated the neurobiological basis of the influence of expert advice on financial decisions under risk. While undergoing fMRI scanning, participants made a series of financial choices between a certain payment and a lottery. Choices were made in two conditions: 1) advice from a financial expert about which choice to make was displayed (MES condition); and 2) no advice was displayed (NOM condition). Behavioral results showed a significant effect of expert advice. Specifically, probability weighting functions changed in the direction of the expert's advice. This was paralleled by neural activation patterns. Brain activations showing significant correlations with valuation (parametric modulation by value of lottery/sure win) were obtained in the absence of the expert's advice (NOM) in intraparietal sulcus, posterior cingulate cortex, cuneus, precuneus, inferior frontal gyrus and middle temporal gyrus. Notably, no significant correlations with value were obtained in the presence of advice (MES). These findings were corroborated by region of interest analyses. Neural equivalents of probability weighting functions showed significant flattening in the MES compared to the NOM condition in regions associated with probability weighting, including anterior cingulate cortex, dorsolateral PFC, thalamus, medial occipital gyrus and anterior insula. Finally, during the MES condition, significant activations in temporoparietal junction and medial PFC were obtained. These results support the hypothesis that one effect of expert advice is to "offload" the calculation of value of decision options from the

  6. Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications

    Science.gov (United States)

    Felger, Jennifer C.; Lotrich, Francis E.

    2013-01-01

    Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, e.g. brain derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression’s development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. PMID:23644052

  7. Stress, depression, and cardiovascular dysregulation: A review of neurobiological mechanisms and the integration of research from preclinical disease models

    Science.gov (United States)

    Grippo, Angela J.; Johnson, Alan Kim

    2008-01-01

    A bidirectional association between mood disorders such as depression, and cardiovascular diseases such as myocardial infarction and congestive heart failure, has been described; however, the precise neurobiological mechanisms that underlie these associations have not been fully elucidated. This review is focused on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders, with an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction including dopamine, norepinephrine and serotonin, and (e) behavioral changes including fatigue and physical inactivity. We also focus specifically on experimental investigations with preclinical disease models, conducted to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with the extensive literature describing findings from human research, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and can promote the development of better treatments and interventions for individuals with these co

  8. Neurobiological mechanisms of exercise and psychotherapy in depression: The SPeED study-Rationale, design, and methodological issues.

    Science.gov (United States)

    Heinzel, Stephan; Rapp, Michael A; Fydrich, Thomas; Ströhle, Andreas; Terán, Christina; Kallies, Gunnar; Schwefel, Melanie; Heissel, Andreas

    2018-02-01

    Even though cognitive behavioral therapy has become a relatively effective treatment for major depressive disorder and cognitive behavioral therapy-related changes of dysfunctional neural activations were shown in recent studies, remission rates still remain at an insufficient level. Therefore, the implementation of effective augmentation strategies is needed. In recent meta-analyses, exercise therapy (especially endurance exercise) was reported to be an effective intervention in major depressive disorder. Despite these findings, underlying mechanisms of the antidepressant effect of exercise especially in combination with cognitive behavioral therapy have rarely been studied to date and an investigation of its neural underpinnings is lacking. A better understanding of the psychological and neural mechanisms of exercise and cognitive behavioral therapy would be important for developing optimal treatment strategies in depression. The SPeED study (Sport/Exercise Therapy and Psychotherapy-evaluating treatment Effects in Depressive patients) is a randomized controlled trial to investigate underlying physiological, neurobiological, and psychological mechanisms of the augmentation of cognitive behavioral therapy with endurance exercise. It is investigated if a preceding endurance exercise program will enhance the effect of a subsequent cognitive behavioral therapy. This study will include 105 patients diagnosed with a mild or moderate depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.). The participants are randomized into one of three groups: a high-intensive or a low-intensive endurance exercise group or a waiting list control group. After the exercise program/waiting period, all patients receive an outpatient cognitive behavioral therapy treatment according to a standardized therapy manual. At four measurement points, major depressive disorder symptoms (Beck Depression Inventory, Hamilton Rating Scale for Depression

  9. The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review.

    Science.gov (United States)

    Kamal, Rama M; van Noorden, Martijn S; Franzek, Ernst; Dijkstra, Boukje A G; Loonen, Anton J M; De Jong, Cornelius A J

    2016-01-01

    x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices. In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB. Chronic abuse of GHB exerts multifarious neurotransmitter and neuromodulator effects on x03B3;-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine and cholinergic systems. Moreover, important effects on neurosteroidogenesis and oxytocin release are wielded. GHB acts mainly via a bidirectional effect on GABAB receptors (GABABR; subunits GABAB1 and GABAB2), depending on the subunit of the GIRK (G-protein-dependent ion inwardly rectifying potassium) channel involved, and an indirect effect of the cortical and limbic inputs outside the nucleus accumbens. GHB also activates a specific GHB receptor and β1-subunits of α4-GABAAR. Reversing this complex interaction of neurobiological mechanisms by the abrupt cessation of GHB use results in a withdrawal syndrome with a diversity of symptoms of different intensity, depending on the pattern of GHB abuse. The GHB withdrawal symptoms cannot be related to a single mechanism or neurological pathway, which implies that different medication combinations are needed for treatment. A single drug class, such as benzodiazepines, gabapentin or antipsychotics, is unlikely to be sufficient to avoid life-threatening complications. Detoxification by means of titration and tapering of pharmaceutical GHB can be considered as a promising treatment that could make polypharmacy redundant. © 2016 S. Karger AG, Basel.

  10. Adolescent angst or true intent? Suicidal behavior, risk, and neurobiological mechanisms in depressed children and teenagers taking antidepressants.

    Science.gov (United States)

    Morrison, Julia; Schwartz, Thomas L

    2014-01-01

    Suicide is one of the major causes of morbidity and mortality amongst children and adolescents. In 2004 the Food and Drug Administration (FDA) issued a "black-box" warning for antidepressants in children and adolescents, stating that these drugs may increase suicidality, a term encompassing both suicidal thoughts and behavior, especially in the first few weeks of treatment. The warning was extended in 2007 to antidepressants prescribed to adults aged 25 and under. The evidence behind this decision stemmed from meta-analyses of antidepressant clinical trials that demonstrated a slight increase in suicidality in those receiving antidepressants versus those treated with a placebo. Due to methods of this pooled data compilation, the relationship between antidepressants and suicidality remains controversial. This report investigates a case where a 14 year old with major depressive disorder (MDD) developed suicidal ideation shortly after being prescribed a selective serotonin reuptake inhibitor (SSRI). Investigating the role antidepressants may play in suicidality suggests the need to explore the neurobiological mechanisms within the serotonin system. This case and its theoretical explanations attempt to bridge the gap between neurobiology and pharmacology in order to better delineate the etiology of this adverse effect.

  11. Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use

    Science.gov (United States)

    Barson, Jessica R.; Morganstern, Irene; Leibowitz, Sarah F.

    2013-01-01

    Consummatory behavior is driven not just by caloric need but also by emotional need. In the last several decades, a wide variety of models have been used to study the systems that drive food and drug intake. These include selective breeding for a specific trait, manipulation of gene expression, forced or voluntary exposure to a substance, and identification of biomarkers that predict which animals are prone to overconsuming specific substances. From this research, numerous brain areas and neurochemicals have been identified that drive consummatory behavior. While energy homeostasis is primarily mediated by the hypothalamus, reinforcement is more strongly mediated by nuclei outside of the hypothalamus, in mesocorticolimbic regions. Orexigenic neurochemicals that control food intake can provide a general signal for promoting caloric intake or a more specific signal for stimulating consumption of a particular macronutrient, fat, carbohydrate or protein. Those involved in controlling fat ingestion, including galanin, enkephalin, orexin, melanin-concentrating hormone and the endocannabinoids, show positive feedback with this macronutrient, with these peptides both increasing fat intake and being further stimulated by its intake. This positive relationship offers some explanation for why foods high in fat are so often overconsumed. Consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by these neurochemical systems involved in fat intake, consistent with evidence closely relating fat and ethanol consumption. Further understanding of these systems involved in consummatory behavior will allow researchers to develop effective therapies for the treatment of overeating as well as drug abuse. PMID:23520598

  12. Neurobiology of pair bonding in fishes; convergence of neural mechanisms across distant vertebrate lineages

    KAUST Repository

    Nowicki, Jessica

    2017-11-14

    Pair bonding has independently evolved numerous times among vertebrates. The governing neural mechanisms of pair bonding have only been studied in depth in the mammalian model species, the prairie vole, Microtus ochrogaster. In this species, oxytocin (OT), arginine vasopressin (AVP), dopamine (DA), and opioid (OP) systems play key roles in signaling in the formation and maintenance of pair bonding by targeting specific social and reward-mediating brain regions. By contrast, the neural basis of pair bonding is poorly studied in other vertebrates, and especially those of early origins, limiting our understanding of the evolutionary history of pair bonding regulatory mechanisms. We compared receptor gene expression between pair bonded and solitary individuals across eight socio-functional brain regions. We found that in females, ITR and V1aR receptor expression varied in the lateral septum-like region (the Vv/Vl), while in both sexes D1R, D2R, and MOR expression varied within the mesolimbic reward system, including a striatum-like region (the Vc); mirroring sites of action in M. ochrogaster. This study provides novel insights into the neurobiology of teleost pair bonding. It also reveals high convergence in the neurochemical mechanisms governing pair bonding across actinopterygians and sarcopterygians, by repeatedly co-opting and similarly assembling deep neurochemical and neuroanatomical homologies that originated in ancestral osteithes.

  13. Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

    Science.gov (United States)

    Goldstein, Rita Z.; Volkow, Nora D.

    2005-01-01

    Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

  14. Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging

    Science.gov (United States)

    O’Donovan, Aoife; Slavich, George M; Epel, Elissa S.; Neylan, Thomas C

    2015-01-01

    Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals. PMID:23127296

  15. How we remember the stuff that dreams are made of: neurobiological approaches to the brain mechanisms of dream recall.

    Science.gov (United States)

    De Gennaro, Luigi; Marzano, Cristina; Cipolli, Carlo; Ferrara, Michele

    2012-01-15

    Intrinsic and historical weaknesses delayed the spread of a sound neurobiological investigation on dreaming. Nevertheless, recent independent findings confirm the hypothesis that the neurophysiological mechanisms of encoding and recall of episodic memories are largely comparable across wakefulness and sleep. Brain lesion and neuroimaging studies converge in indicating that temporo-parieto-occipital junction and ventromesial prefrontal cortex play a crucial role in dream recall. Morphoanatomical measurements disclose some direct relations between volumetric and ultrastructural measures of the hippocampus-amygdala on the one hand, and some specific qualitative features of dreaming on the other. Intracranial recordings of epileptic patients also provide support for the notion that hippocampal nuclei mediate memory formation during sleep as well as in wakefulness. Finally, surface EEG studies showed that sleep cortical oscillations associated to a successful dream recall are the same involved in encoding and recall of episodic memories during wakefulness. Although preliminary, these converging pieces of evidence strengthen the general view that the neurophysiological mechanisms underlying episodic/declarative memory formation may be the same across different states of consciousness. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Behavioral and Neurobiological Mechanisms of Extinction in Pavlovian and Instrumental Learning

    Science.gov (United States)

    Todd, Travis P.; Vurbic, Drina; Bouton, Mark E.

    2013-01-01

    This article reviews research on the behavioral and neural mechanisms of extinction as it is represented in both Pavlovian and instrumental learning. In Pavlovian extinction, repeated presentation of a signal without its reinforcer weakens behavior evoked by the signal; in instrumental extinction, repeated occurrence of a voluntary action without its reinforcer weakens the strength of the action. In either case, contemporary research at both the behavioral and neural levels of analysis has been guided by a set of extinction principles that were first generated by research conducted at the behavioral level. The review discusses these principles and illustrates how they have informed the study of both Pavlovian and instrumental extinction. It shows that behavioral and neurobiological research efforts have been tightly linked and that their results are readily integrated. Pavlovian and instrumental extinction are also controlled by compatible behavioral and neural processes. Since many behavioral effects observed in extinction can be multiply determined, we suggest that the current close connection between behavioral-level and neural-level analyses will need to continue. PMID:23999219

  17. Incision and stress regulation in borderline personality disorder: neurobiological mechanisms of self-injurious behaviour.

    Science.gov (United States)

    Reitz, Sarah; Kluetsch, Rosemarie; Niedtfeld, Inga; Knorz, Teresa; Lis, Stefanie; Paret, Christian; Kirsch, Peter; Meyer-Lindenberg, Andreas; Treede, Rolf-Detlef; Baumgärtner, Ulf; Bohus, Martin; Schmahl, Christian

    2015-08-01

    Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress. Investigation of neurobiological mechanisms of NSSI in borderline personality disorder. In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed. We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group. Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension. © The Royal College of Psychiatrists 2015.

  18. Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities

    Science.gov (United States)

    Sippel, Lauren M.; Allington, Casey E.; Pietrzak, Robert H.; Harpaz-Rotem, Ilan; Mayes, Linda C.; Olff, Miranda

    2017-01-01

    Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social–emotional brain. In this review, we present an overview of evidence supporting OT’s utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e.g., the salience network and hypothalamic–pituitary–adrenal axis). Third, we present the sparse but promising findings from clinical populations, followed by discussion of critical moderating variables to consider in the service of maximizing the therapeutic potential of OT (e.g., patient sex and child maltreatment). We also identify heterogeneous findings and limitations of existing research, including reliance on single-dose studies in psychiatrically healthy samples and unanswered questions regarding the effectiveness of IN drug delivery and dosing schedules. Well-controlled multidose studies including women and measures of potentially moderating variables are sorely needed and would inform our understanding of the utility of OT for preventing and treating stress-related psychiatric disorders. PMID:28649672

  19. 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.

  20. Getting Better. Neurobiological mechanisms of recovery from combat-related PTSD

    NARCIS (Netherlands)

    Rooij, S.J.H. van

    2015-01-01

    Military personnel often experience traumatic events during deployment. In the aftermath of a traumatic event, a subgroup of trauma survivors develops posttraumatic stress disorder (PTSD).Most (neurobiological) studies aim at understanding why some trauma survivors develop PTSD whereas others do

  1. The underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review.

    Science.gov (United States)

    Iorfino, Frank; Hickie, Ian B; Lee, Rico S C; Lagopoulos, Jim; Hermens, Daniel F

    2016-05-23

    Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence. We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders. Of the one hundred and thirty-four studies selected, 7.6 % investigated social and economic participation, 2.1 % physical health, 15.3 % suicide and self-harm behaviours, 6.9 % alcohol and substance use, whereas the majority (68.1 %) focussed on clinical syndrome. Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories.

  2. Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

    Directory of Open Access Journals (Sweden)

    Jillian Vinall

    2016-12-01

    Full Text Available Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and behavioral factors that lead to the development and/or maintenance of both conditions. Particularly within the pediatric chronic pain population, these factors are embedded within the broader context of the parent–child relationship. In this review, we will explore the epidemiology of, and current working models explaining, these comorbidities. Particular emphasis will be made on shared neurobiological mechanisms, given that the majority of previous research to date has centered on cognitive, affective, and behavioral mechanisms. Parental contributions to co-occurring chronic pain and psychopathology in childhood and adolescence will be discussed. Moreover, we will review current treatment recommendations and future directions for both research and practice. We argue that the integration of biological and behavioral approaches will be critical to sufficiently address why these comorbidities exist and how they can best be targeted in treatment.

  3. Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment.

    Science.gov (United States)

    Vinall, Jillian; Pavlova, Maria; Asmundson, Gordon J G; Rasic, Nivez; Noel, Melanie

    2016-12-02

    Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and behavioral factors that lead to the development and/or maintenance of both conditions. Particularly within the pediatric chronic pain population, these factors are embedded within the broader context of the parent-child relationship. In this review, we will explore the epidemiology of, and current working models explaining, these comorbidities. Particular emphasis will be made on shared neurobiological mechanisms, given that the majority of previous research to date has centered on cognitive, affective, and behavioral mechanisms. Parental contributions to co-occurring chronic pain and psychopathology in childhood and adolescence will be discussed. Moreover, we will review current treatment recommendations and future directions for both research and practice. We argue that the integration of biological and behavioral approaches will be critical to sufficiently address why these comorbidities exist and how they can best be targeted in treatment.

  4. Self-Awareness, Self-Regulation, and Self-Transcendence (S-ART: A Framework for Understanding the Neurobiological Mechanisms of Mindfulness

    Directory of Open Access Journals (Sweden)

    David R. Vago

    2012-10-01

    Full Text Available Mindfulness - as a state, trait, process, type of meditation, and intervention has proven to be beneficial across a diverse group of psychological disorders as well as for general stress reduction. Yet, there remains a lack of clarity in the operationalization of this construct, and underlying mechanisms. Here, we provide an integrative theoretical framework and systems-based neurobiological model that explains the mechanisms by which mindfulness reduces biases related to self-processing and creates a sustainable healthy mind. Mindfulness is described through systematic mental training that develops meta-awareness (self-awareness, an ability to effectively modulate one’s behavior (self-regulation, and the development of a positive relationship between self and other that transcends self-focused needs and increases prosocial characteristics (self-transcendence. This framework of self-awareness, regulation, and transcendence (S-ART illustrates a method for becoming aware of the conditions that cause (and remove distortions or biases. The development of S-ART through meditation is proposed to modulate self-specifying and narrative self-networks through an integrative fronto-parietal control network. Relevant perceptual, cognitive, emotional, and behavioral neuropsychological processes are highlighted, including intention and motivation, attention regulation, emotion regulation, extinction and reconsolidation, prosociality, non-attachment and decentering. The S-ART framework and neurobiological model is based on our growing understanding of the mechanisms for neurocognition, empirical literature, and through dismantling the specific meditation practices thought to cultivate mindfulness. The proposed framework will inform future research in the contemplative sciences and target specific areas for development in the treatment of psychological disorders.

  5. Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder.

    Science.gov (United States)

    Robinson, Emma S J

    2018-03-19

    Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'. © 2018 The Authors.

  6. Characterizing ingestive behavior through licking microstructure: Underlying neurobiology and its use in the study of obesity in animal models.

    Science.gov (United States)

    Johnson, Alexander W

    2017-07-03

    Ingestive behavior is controlled by multiple distinct peripheral and central physiological mechanisms that ultimately determine whether a particular food should be accepted or avoided. As rodents consume a fluid they display stereotyped rhythmic tongue movements, and by analyzing the temporal distribution of pauses of licking, it is possible through analyses of licking microstructure to uncover dissociable evaluative and motivational variables that contribute to ingestive behavior. The mean number of licks occurring within each burst of licking (burst and cluster size) reflects the palatability of the consumed solution, whereas the frequency of initiating novel bouts of licking behavior (burst and cluster number) is dependent upon the degree of gastrointestinal inhibition that accrues through continued fluid ingestion. This review describes the analysis of these measures within a context of the behavioral variables that come to influence the acceptance or avoidance of a fluid, and the neurobiological mechanisms that underlie alterations in the temporal distribution of pauses of licks. The application of these studies to models of obesity in animals is also described. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. Recent Insights into the Neurobiology of Impulsivity

    OpenAIRE

    Mitchell, Marci R.; Marc N Potenza

    2014-01-01

    Impulsivity is associated with various psychopathologies, and elevated impulsivity is typically disadvantageous. This manuscript reviews recent investigations into the neurobiology of impulsivity using human imaging techniques and animal models. Both human imaging and preclinical pharmacological manipulations have yielded important insights into the neurobiological underpinnings of impulsivity. A more thorough understanding of the complex neurobiology underlying aspects of impulsivity may pro...

  8. The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

    Science.gov (United States)

    Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2017-10-01

    After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Acute stress and episodic memory retrieval: neurobiological mechanisms and behavioral consequences.

    Science.gov (United States)

    Gagnon, Stephanie A; Wagner, Anthony D

    2016-04-01

    Episodic retrieval allows people to access memories from the past to guide current thoughts and decisions. In many real-world situations, retrieval occurs under conditions of acute stress, either elicited by the retrieval task or driven by other, unrelated concerns. Memory under such conditions may be hindered, as acute stress initiates a cascade of neuromodulatory changes that can impair episodic retrieval. Here, we review emerging evidence showing that dissociable stress systems interact over time, influencing neural function. In addition to the adverse effects of stress on hippocampal-dependent retrieval, we consider how stress biases attention and prefrontal cortical function, which could further affect controlled retrieval processes. Finally, we consider recent data indicating that stress at retrieval increases activity in a network of brain regions that enable reflexive, rapid responding to upcoming threats, while transiently taking offline regions supporting flexible, goal-directed thinking. Given the ubiquity of episodic memory retrieval in everyday life, it is critical to understand the theoretical and applied implications of acute stress. The present review highlights the progress that has been made, along with important open questions. © 2016 New York Academy of Sciences.

  10. Fundamental interfacial mechanisms underlying electrofreezing.

    Science.gov (United States)

    Acharya, Palash V; Bahadur, Vaibhav

    2017-12-08

    This article reviews the fundamental interfacial mechanisms underlying electrofreezing (promotion of ice nucleation via the application of an electric field). Electrofreezing has been an active research topic for many decades, with applications in food preservation, cryopreservation, cryogenics and ice formation. There is substantial literature detailing experimental and simulations-based studies, which aim to understand the complex mechanisms underlying accelerated ice nucleation in the presence of electric fields and electrical charge. This work provides a critical review of all such studies. It is noted that application-focused studies of electrofreezing are excluded from this review; such studies have been previously reviewed in literature. This review focuses only on fundamental studies, which analyze the physical mechanisms underlying electrofreezing. Topics reviewed include experimental studies on electrofreezing (DC and AC electric fields), pyroelectricity-based control of freezing, molecular dynamics simulations of electrofreezing, and thermodynamics-based explanations of electrofreezing. Overall, it is seen that electrofreezing can enable disruptive advancements in the control of liquid-to-solid phase change, and that our current understanding of the underlying mechanisms can be significantly improved through further studies of various interfacial effects coming into play. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Neurobiological mechanisms for nonverbal IQ tests: implications for instruction of nonverbal children with autism

    Directory of Open Access Journals (Sweden)

    Andrey Vyshedskiy

    2017-04-01

    Full Text Available Traditionally, the neurological correlates of IQ test questions are characterized qualitatively in terms of ‘control of attention’ and ‘working memory.’ In this report we attempt to characterize each IQ test question quantitatively by two factors: a the number of disparate objects that have to be imagined in concert in order to solve the problem and, b the amount of recruited posterior cortex territory. With such a classification, an IQ test can be understood on a neuronal level and a subject’s IQ score could be interpreted in terms of specific neurological mechanisms available to the subject. Here we present the results of an analysis of the three most popular nonverbal IQ tests: Test of Nonverbal Intelligence (TONI-4, Standard Raven's Progressive Matrices, and Wechsler Intelligence Scale for Children (WISC-V. Our analysis shows that approximately half of all questions (52±0.02% are limited to mental computations involving only a single object; these easier questions are found towards the beginning of each test. More difficult questions located towards the end of each test rely on mental synthesis of several disparate objects and the number of objects involved in computations gradually increases with question difficulty. These more challenging questions require the organization of wider posterior cortex networks by the lateral prefrontal cortex (PFC. This conclusion is in line with neuroimaging studies showing that activation level of the lateral PFC and the posterior cortex positively correlates with task difficulty. This analysis has direct implications for brain pathophysiology and, specifically, for therapeutic interventions for children with language impairment, most notably for children with Autism Spectrum Disorder (ASD and other developmental disorders.

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

    Science.gov (United States)

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

    2013-06-01

    Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse. 2013 APA, all rights reserved

  13. [Neurobiological basis of depressive disorders].

    Science.gov (United States)

    Stoppel, C; Bielau, H; Bogerts, B; Northoff, G

    2006-12-01

    Depressive disorders belong to the most frequent diseases worldwide showing a lifetime prevalence of up to 20%. Moreover they are one of the leading causes for the amount of years lived with disability. Increasing knowledge about the pathological mechanisms underlying depressive syndromes is obtained by using modern neurobiological research-techniques. Thereby some older theories that have been the basis of emotion-research for decades--like the monoamine hypothesis--have been strengthened. In addition new aspects of the pathological processes underlying depressive disturbances have been unraveled. In this review established models and recent findings will be discussed, to bridge various research-fields, ranging from genetics, epigenetics and morphological changes to the functional consequences of depression. Finally therapeutic implications that could be derived from these results will be presented, showing up putative possibilities for diagnosis and treatment of depressive syndromes.

  14. The Neurobiological Mechanism of Chemical Aversion (Emetic) Therapy for Alcohol Use Disorder: An fMRI Study

    Science.gov (United States)

    Elkins, Ralph L.; Richards, Todd L.; Nielsen, Robert; Repass, Richard; Stahlbrandt, Henriettae; Hoffman, Hunter G.

    2017-01-01

    A recent NIH epidemiology study found the lifetime prevalence of alcohol use disorder in the United States to be 29%. Alcohol drinking behavior is strongly “learned” via pleasure center activation/reinforcement. Alcohol craving is a powerful desire to drink alcoholic beverages. Craving was added as one of the defining criteria for alcohol use disorder in DSM5, and craving reduction is becoming an increasingly important treatment goal. In the current study, patients with alcohol use disorder received 10 days of inpatient multi-modal treatments at Schick Shadel Hospital (SSH) of Seattle. The treatments included five chemical aversion conditioning sessions that associated alcohol cues (and alcohol) with nausea and emesis. All patients met DSM4 criteria for alcohol use disorder, were heavy drinkers, and reported craving alcohol pre-treatment. Craving reduction was one of the primary treatment goals. This is the first fMRI study to measure the effects of chemical aversion therapy on alcohol craving-related brain activity. Patients were recruited as subjects for the University of Washington (UW) brain scan study following SSH admission but before treatment onset. Prior to treatment, patients reported craving/desire for alcohol. After treatment (after four SSH chemical aversion treatments, again after five SSH chemical treatments, 30 and 90-days post-discharge), these same patients reported avoidance/aversion to alcohol. Most of the participants (69%) reported being still sober 12 months post-treatment. Consistent with a craving reduction mechanism of how chemical aversion therapy facilitates sobriety, results of the UW fMRI brain scans showed significant pre- to post-treatment reductions in craving-related brain activity in the occipital cortex. Additional fMRI brain scan studies are needed to further explore the neurobiological mechanism of chemical aversion therapy treatment for alcohol use disorder, and other substance use disorders for which chemical aversion

  15. The neurobiology of successful abstinence.

    Science.gov (United States)

    Garavan, H; Brennan, K L; Hester, R; Whelan, R

    2013-08-01

    This review focuses on the neurobiological processes involved in achieving successful abstinence from drugs of abuse. While there is clinical and public health value in knowing if the deficits associated with drug use correct with abstinence, studying the neurobiology that underlies successful abstinence can also illuminate the processes that enable drug-dependent individuals to successfully quit. Here, we review studies on human addicts that assess the neurobiological changes that arise with abstinence and the neurobiological predictors of successfully avoiding relapse. The literature, while modest in size, suggests that abstinence is associated with improvement in prefrontal structure and function, which may underscore the importance of prefrontally mediated cognitive control processes in avoiding relapse. Given the implication that the prefrontal cortex may be an important target for therapeutic interventions, we also review evidence indicating the efficacy of cognitive control training for abstinence. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Molecular mechanisms underlying bacterial persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn

    2014-01-01

    All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent...... technological advances in microfluidics and reporter genes have improved this scenario. Here, we summarize recent progress in the field, revealing the ubiquitous bacterial stress alarmone ppGpp as an emerging central regulator of multidrug tolerance and persistence, both in stochastically and environmentally...... induced persistence. In several different organisms, toxin-antitoxin modules function as effectors of ppGpp-induced persistence....

  17. Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

    OpenAIRE

    Jillian Vinall; Maria Pavlova; Asmundson, Gordon J.G.; Nivez Rasic; Melanie Noel

    2016-01-01

    Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and be...

  18. Recent Insights into the Neurobiology of Impulsivity

    Science.gov (United States)

    Mitchell, Marci R.; Potenza, Marc N.

    2014-01-01

    Impulsivity is associated with various psychopathologies, and elevated impulsivity is typically disadvantageous. This manuscript reviews recent investigations into the neurobiology of impulsivity using human imaging techniques and animal models. Both human imaging and preclinical pharmacological manipulations have yielded important insights into the neurobiological underpinnings of impulsivity. A more thorough understanding of the complex neurobiology underlying aspects of impulsivity may provide insight into new treatment options that target elevated impulsivity and psychopathologies such as addictions. PMID:25431750

  19. HAE Pathophysiology and Underlying Mechanisms.

    Science.gov (United States)

    Zuraw, Bruce L; Christiansen, Sandra C

    2016-10-01

    Remarkable progress in understanding the pathophysiology and underlying mechanisms of hereditary angioedema has led to the development of effective treatment for this disorder. Progress in three separate areas has catalyzed our understanding of hereditary angioedema. The first is the recognition that HAE type I and type II result from a deficiency in the plasma level of functional C1 inhibitor. This observation has led to a detailed understanding of the SERPING1 mutations responsible for this deficiency as well as the molecular regulation of C1 inhibitor expression and function. The second is that the fundamental cause of swelling is enhanced contact system activation leading to increased generation of bradykinin. Substantial progress has been made in defining the parameters regulating bradykinin generation and catabolism as well as the receptors that transduce the biologic effects of kinins. The third is the understanding that tissue swelling in hereditary angioedema primarily involves the function of endothelial cell adherens junctions. This knowledge is driving increased attention to the role of endothelial biology in determining disease activity in hereditary angioedema. While there has been considerable progress made, large gaps still remain in our knowledge. Important areas that remain poorly understood include the factors that lead to very low plasma functional C1 inhibitor levels, the triggers of contact system activation in hereditary angioedema, and the role of the bradykinin B1 receptor. The phenotypic variability of hereditary angioedema has been extensively documented but never understood. The mechanisms discussed in this chapter likely contribute to this variability. Future progress in understanding these mechanisms should provide new means to improve the diagnosis and treatment of hereditary angioedema.

  20. The neurobiological causes and effects of alloparenting.

    Science.gov (United States)

    Kenkel, William M; Perkeybile, Allison M; Carter, C Sue

    2017-02-01

    Alloparenting, defined as care provided by individuals other than parents, is a universal behavior among humans that has shaped our evolutionary history and remains important in contemporary society. Dysfunctions in alloparenting can have serious and sometimes fatal consequences for vulnerable infants and children. In spite of the importance of alloparenting, they still have much to learn regarding the underlying neurobiological systems governing its expression. Here, they review how a lack of alloparental behavior among traditional laboratory species has led to a blind spot in our understanding of this critical facet of human social behavior and the relevant neurobiology. Based on what is known, they draw from model systems ranging from voles to meerkats to primates to describe a conserved set of neuroendocrine mechanisms supporting the expression of alloparental care. In this review we describe the neurobiological and behavioral prerequisites, ontogeny, and consequences of alloparental care. Lastly, they identified several outstanding topics in the area of alloparental care that deserve further research efforts to better advance human health and wellbeing. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 214-232, 2017. © 2016 Wiley Periodicals, Inc.

  1. Fundamentals of neurobiology.

    Science.gov (United States)

    Greg Hall, D

    2011-01-01

    Session 1 of the 2010 STP/IFSTP Joint Symposium on Toxicologic Neuropathology, titled "Fundamentals of Neurobiology," was organized to provide a foundation for subsequent sessions by presenting essential elements of neuroanatomy and nervous system function. A brief introduction to the session titled "Introduction to Correlative Neurobiology" was provided by Dr. Greg Hall (Eli Lilly and Company, Indianapolis, IN). Correlative neurobiology refers to considerations of the relationships between the highly organized and compartmentalized structure of nervous tissues and the functioning within this system.

  2. Tetanus toxin as a neurobiological tool to study mechanisms of neuronal cell death in the mammalian brain.

    Science.gov (United States)

    Bagetta, G; Nisticò, G

    1994-01-01

    Tetanus toxin is a potent clostridial neurotoxin responsible for causing spastic paralysis in humans, often accompanied by seizures and death. The tetanic syndrome is believed to originate from a disinhibitory action of the toxin in the CNS. To produce its effects, tetanus toxin undergoes retrograde, intra-axonal transport to the CNS, where it blocks preferentially the release of gamma-aminobutyric acid and glycine, two inhibitory neurotransmitters. These effects stem from the cleavage of synaptobrevin, a constitutive small-vesicle protein, by tetanus toxin, whose zinc-dependent metalloprotease characteristics recently have been recognized. Blockade of inhibitory transmission produces a predominance of excitatory amino acid neurotransmission, which is responsible for the neurodegenerative effect caused by tetanus toxin after intrahippocampal injection in rats. In fact, hippocampal damage can effectively be prevented by reduction of glutamate-mediated excitatory transmission, thus suggesting that unopposed excitation may be the underlying mechanism for neuronal cell death.

  3. Toward a Neurobiology of Delusions

    Science.gov (United States)

    Corlett, P.R.; Taylor, J.R.; Wang, X.-J.; Fletcher, P.C.; Krystal, J.H.

    2013-01-01

    Delusions are the false and often incorrigible beliefs that can cause severe suffering in mental illness. We cannot yet explain them in terms of underlying neurobiological abnormalities. However, by drawing on recent advances in the biological, computational and psychological processes of reinforcement learning, memory, and perception it may be feasible to account for delusions in terms of cognition and brain function. The account focuses on a particular parameter, prediction error – the mismatch between expectation and experience – that provides a computational mechanism common to cortical hierarchies, frontostriatal circuits and the amygdala as well as parietal cortices. We suggest that delusions result from aberrations in how brain circuits specify hierarchical predictions, and how they compute and respond to prediction errors. Defects in these fundamental brain mechanisms can vitiate perception, memory, bodily agency and social learning such that individuals with delusions experience an internal and external world that healthy individuals would find difficult to comprehend. The present model attempts to provide a framework through which we can build a mechanistic and translational understanding of these puzzling symptoms. PMID:20558235

  4. Stress: Neurobiology, consequences and management

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2013-01-01

    Full Text Available Stress, both physical and psychological, is attracting increasing attention among neuroresearchers. In the last 20 decades, there has been a surge of interest in the research of stress-induced manifestations and this approach has resulted in the development of more appropriate animal models for stress-associated pathologies and its therapeutic management. These stress models are an easy and convenient method for inducing both psychological and physical stress. To understand the behavioral changes underlying major depression, molecular and cellular studies are required. Dysregulation of the stress system may lead to disturbances in growth and development, and may this may further lead to the development of various other psychiatric disorders. This article reviews the different types of stress and their neurobiology, including the different neurotransmitters affected. There are various complications associated with stress and their management through various pharmacological and non-pharmacological techniques. The use of herbs in the treatment of stress-related problems is practiced in both Indian and Western societies, and it has a vast market in terms of anti-stress medications and treatments. Non-pharmacological techniques such as meditation and yoga are nowadays becoming very popular as a stress-relieving therapy because of their greater effectiveness and no associated side effects. Therefore, this review highlights the changes under stress and stressor and their impact on different animal models in understanding the mechanisms of stress along with their effective and safe management.

  5. Molecular Mechanisms Underlying Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Christian Trepo

    2009-11-01

    Full Text Available Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis.

  6. Metacognitive mechanisms underlying lucid dreaming.

    Science.gov (United States)

    Filevich, Elisa; Dresler, Martin; Brick, Timothy R; Kühn, Simone

    2015-01-21

    Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring. Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group. Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams. Copyright © 2015 the authors 0270-6474/15/351082-07$15.00/0.

  7. Neurobiology of the incubation of drug craving.

    Science.gov (United States)

    Pickens, Charles L; Airavaara, Mikko; Theberge, Florence; Fanous, Sanya; Hope, Bruce T; Shaham, Yavin

    2011-08-01

    It was suggested in 1986 that cue-induced drug craving in cocaine addicts progressively increases over the first several weeks of abstinence and remains high for extended periods. During the past decade, investigators have identified an analogous incubation phenomenon in rodents, in which time-dependent increases in cue-induced drug seeking are observed after withdrawal from intravenous cocaine self-administration. Such an incubation of drug craving is not specific to cocaine, as similar findings have been observed after self-administration of heroin, nicotine, methamphetamine and alcohol in rats. In this review, we discuss recent results that have identified important brain regions involved in the incubation of drug craving, as well as evidence for the underlying cellular mechanisms. Understanding the neurobiology of the incubation of drug craving in rodents is likely to have significant implications for furthering understanding of brain mechanisms and circuits that underlie craving and relapse in human addicts. Published by Elsevier Ltd.

  8. Deciphering the Cognitive and Neural Mechanisms Underlying ...

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

    Deciphering the Cognitive and Neural Mechanisms Underlying Auditory Learning. This project seeks to understand the brain mechanisms necessary for people to learn to perceive sounds. Neural circuits and learning. The research team will test people with and without musical training to evaluate their capacity to learn ...

  9. Mechanisms Underlying Sexual Violence Exposure and Psychosocial Sequelae: A Theoretical and Empirical Review

    Science.gov (United States)

    Walsh, Kate; Galea, Sandro; Koenen, Karestan C.

    2015-01-01

    Sexual violence is associated with a range of negative mental health and behavioral sequelae, including posttraumatic stress disorder (PTSD), depression, substance abuse/dependence, risky sexual behavior, and interpersonal relationship problems. However, mechanisms underlying these associations are not well understood. Identifying mechanisms that explain linkages between sexual violence and poor outcomes is of paramount importance in determining when and how to intervene to prevent or reduce the magnitude of these outcomes. This review focuses on theories that have been proposed to explain risk of negative outcomes among sexual violence victims, including the development of traumagenic dynamics and emotion dysregulation. We also review promising biological mechanisms that may explain the risk of negative outcomes among sexual violence victims, including studies concerned with epigenetic and neurobiological mechanisms. PMID:25762853

  10. Re-Training 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

    2013-01-01

    Addiction has generally been characterized as a chronic relapsing condition. 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 to 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. Importantly, 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. PMID:22775773

  11. Neurobiology of inflammation-associated anorexia

    Directory of Open Access Journals (Sweden)

    Laurent Gautron

    2010-01-01

    Full Text Available Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients.

  12. An investigation into the mechanism underlying enhanced ...

    African Journals Online (AJOL)

    An investigation into the mechanism underlying enhanced hydrolysis of complex carbon in a biosulphidogenic recycling sludge bed reactor (RSBR) ... By using toluene as an inhibitor of bacterial uptake of soluble carbohydrates, it was possible to determine the rate of production of various key products of the hydrolytic step.

  13. The neurobiology of decision: consensus and controversy.

    Science.gov (United States)

    Kable, Joseph W; Glimcher, Paul W

    2009-09-24

    We review and synthesize recent neurophysiological studies of decision making in humans and nonhuman primates. From these studies, the basic outline of the neurobiological mechanism for primate choice is beginning to emerge. The identified mechanism is now known to include a multicomponent valuation stage, implemented in ventromedial prefrontal cortex and associated parts of striatum, and a choice stage, implemented in lateral prefrontal and parietal areas. Neurobiological studies of decision making are beginning to enhance our understanding of economic and social behavior as well as our understanding of significant health disorders where people's behavior plays a key role.

  14. Neurobiology of Gambling Behaviors

    Science.gov (United States)

    Potenza, Marc N.

    2013-01-01

    For many, gambling is a recreational activity that is performed periodically without ill effects, but for some, gambling may interfere with life functioning. A diagnostic entity, pathological gambling, is currently used to define a condition marked by excessive and problematic gambling. In this review, the current status of understanding of the neurobiologies of gambling and pathological gambling is described. Multiple neurotransmitter systems (norepinephrine, serotonin, dopamine, opioid and glutamate) and brain regions (ventral striatum, ventromedial prefrontal cortex, insula, among others) have been implicated in gambling and pathological gambling. Considerations for future directions in gambling research, with a view towards translating neurobiological advances into more effective prevention and treatment strategies, are discussed. PMID:23541597

  15. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

    Directory of Open Access Journals (Sweden)

    Tim eKroon

    2013-10-01

    Full Text Available Brain function and behaviour undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability neurodevelopmental disorders (NDDs and their corresponding genetic mouse models, impairments in many neuronal and behavioural phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioural development (referred to also as ‘neurotypical’ development and timing of NDD impairments are not fully investigated.This perspective highlights temporal patterns of synaptic and neuronal impairment, with a restricted focus on autism and intellectual disability types of NDDs. Given the varying known genetic and environmental causes for NDDs, this perspective proposes two strategies for investigation: (1 a focus on neurobiological mechanisms underlying known critical periods in the (typically normal-developing brain (2 investigation of spatio-temporal expression profiles of genes implicated in monogenic syndromes throughout affected brain regions.This approach may help explain why many NDDs with differing genetic causes can result in overlapping phenotypes at similar developmental stages and better predict vulnerable periods within these disorders, with implications for both therapeutic rescue and ultimately, prevention.

  16. Mechanisms underlying the portion-size effect.

    Science.gov (United States)

    Peter Herman, C; Polivy, Janet; Pliner, Patricia; Vartanian, Lenny R

    2015-05-15

    The portion-size effect (PSE) refers to the fact that people eat more when served larger portions. This effect is neither obvious nor artifactual. We examine the prevailing explanations (or underlying mechanisms) that have been offered for the PSE. The dominant candidate mechanism is "appropriateness"; that is, people accept the portion that they are served as being of an appropriate size and eat accordingly. Because people do not necessarily finish the portion that they are served, variations on the basic appropriateness mechanism have been suggested. We also consider some evidence that is inconsistent with an appropriateness explanation, including the appearance of the PSE in children as young as two years of age. We also examine other mechanisms that do not rely on appropriateness norms. Visual food cues may assist in assessing appropriateness but may also drive food intake in a more mindless fashion. Larger portions induce larger bites, which may increase intake by reducing oral exposure time and sensory-specific satiety. We consider further research questions that could help to clarify the mechanisms underlying the PSE. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Neurobiology Research Findings: How the Brain Works during Reading

    Science.gov (United States)

    Kweldju, Siusana

    2015-01-01

    In the past, neurobiology for reading was identical with neuropathology. Today, however, the advancement of modern neuroimaging techniques has contributed to the understanding of the reading processes of normal individuals. Neurobiology findings today have uncovered and illuminated the fundamental neural mechanism of reading. The findings have…

  18. DNA under Force: Mechanics, Electrostatics, and Hydration

    Directory of Open Access Journals (Sweden)

    Jingqiang Li

    2015-02-01

    Full Text Available Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

  19. Multimodal nociceptive mechanisms underlying chronic pelvic pain.

    Science.gov (United States)

    Hellman, Kevin M; Patanwala, Insiyyah Y; Pozolo, Kristen E; Tu, Frank F

    2015-12-01

    We sought to evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain (CPP) and/or painful bladder syndrome (PBS)/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds (PPTs), between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of postexam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver operator characteristic curves adjusted for prevalence. A total of 23 women with CPP, 23 women with PBS, and 42 pain-free controls completed the study. Women with CPP or PBS exhibited enhanced pain sensitivity with lower PPTs (1.18 [interquartile range, 0.87-1.41] kg/cm(2)) than pain-free participants (1.48 [1.11-1.76] kg/cm(2); P pain aftersensation (3.5 [0-9] vs 0 [0-1] minutes; P pelvic floor anatomy, muscle tone, or strength. The combination of PPTs and aftersensation duration correlated with severity of pelvic floor tenderness (R(2), 41-51; P pain-free controls from women with CPP or PBS (area under the curve, 0.87). Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain phenotypes. These findings suggest systematic clinical assessment of the time course of provoked pain symptoms, which occurs over seconds for mechanical pain thresholds vs minutes for aftersensation pain, would be helpful in identifying the fundamental mechanisms of pelvic floor pain. Longitudinal studies of therapies differentially targeting these discrete mechanisms are needed to confirm their

  20. Gas Bubble Dynamics under Mechanical Vibrations

    Science.gov (United States)

    Mohagheghian, Shahrouz; Elbing, Brian

    2017-11-01

    The scientific community has a limited understanding of the bubble dynamics under mechanical oscillations due to over simplification of Navier-Stockes equation by neglecting the shear stress tensor and not accounting for body forces when calculating the acoustic radiation force. The current work experimental investigates bubble dynamics under mechanical vibration and resulting acoustic field by measuring the bubble size and velocity using high-speed imaging. The experimental setup consists of a custom-designed shaker table, cast acrylic bubble column, compressed air injection manifold and an optical imaging system. The mechanical vibrations resulted in accelerations between 0.25 to 10 times gravitational acceleration corresponding to frequency and amplitude range of 8 - 22Hz and 1 - 10mm respectively. Throughout testing the void fraction was limited to bubble size is larger than resonance size and smaller than acoustic wavelength. The amplitude of acoustic pressure wave was estimated using the definition of Bjerknes force in combination with Rayleigh-Plesset equation. Physical behavior of the system was capture and classified. Bubble size, velocity as well as size and spatial distribution will be presented.

  1. Marijuana Neurobiology and Treatment

    OpenAIRE

    Elkashef, Ahmed; Vocci, Frank; Huestis, Marilyn; Haney, Margaret; Budney, Alan; Gruber, Amanda; el-Guebaly, Nady

    2008-01-01

    Marijuana is the number one illicit drug of abuse worldwide and a major public health problem, especially in the younger population. The objective of this article is to update and review the state of the science and treatments available for marijuana dependence based on a pre-meeting workshop that was presented at ISAM 2006. At the workshop, several papers were presented addressing the neurobiology and pharmacology of marijuana and treatment approaches, both psychotherapy and medications, for...

  2. [Neurobiology of Tourette Syndrome].

    Science.gov (United States)

    Ünal, Dilek; Akdemir, Devrim

    2016-01-01

    Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Although it is a common disorder in childhood, the etiology of Tourette Syndrome has not been fully elucidated yet. Studies, -conducted so far- have revealed differences in neurobiological structures of individuals who suffer from Tourette Syndrome. The objective of this review is to assess etiological and pathophysiological studies in the Tourette Syndrome literature. An electronical search was conducted in PubMed database using the keywords tic disorders, Tourette Syndrome, neurobiology, genetics, neuroimaging and animal models. Research and review studies published between 1985 and 2015, with a selection preference towards recent publications, were reviewed. According to the studies, genetic predisposition hypothesis is considered as a priority. However, a precise genetic disorder associated with Tourette Syndrome has not been found. The evidence from postmortem and neuroimaging studies in heterogenous patient groups and animal studies supports the pathological involvement of cortico-striato-thalamo-cortical (CSTC) circuits in Tourette Syndrome. Consequently, the most emphasized hypothesis in the pathophysiology is the dopaminergic dysfunction in these circuits. Furthermore, these findings of the animal, postmortem and neuroimaging studies have confirmed the neurodevelopmental hypothesis of Tourette Syndrome. In conclusion, more studies are needed to understand the etiology of the disorder. The data obtained from neurobiological studies of the disorder will not only shed light on the way of Tourette Syndrome, but also guide studies on its treatment options.

  3. Multimodal nociceptive mechanisms underlying chronic pelvic pain

    Science.gov (United States)

    HELLMAN, Kevin M.; PATANWALA, Insiyyah Y.; POZOLO, Kristen E.; TU, Frank F.

    2015-01-01

    Objective To evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain and/or painful bladder syndrome/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. Study Design As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds, between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of post-exam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver-operator characteristic curves adjusted for prevalence. Results A total of 23 women with chronic pelvic pain, 23 painful bladder syndrome, and 42 pain-free controls completed the study. Women with chronic pelvic pain or painful bladder syndrome exhibited enhanced pain sensitivity with lower pressure pain thresholds (1.18 [interquartile range: 0.87–1.41] kg/cm2) than pain-free participants (1.48 [1.11–1.76] kg/cm2; ppelvic pain there were no consistently observed group differences in pelvic floor anatomy, muscle tone or strength. The combination of pressure pain thresholds and aftersensation duration correlated with severity of pelvic floor tenderness (R2 =41–51, p’spelvic pain or painful bladder syndrome (area under the curve=0.87). Conclusion Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain phenotypes. These findings suggest systematic clinical assessment of the time course of provoked pain symptoms, which occurs over seconds for mechanical pain thresholds vs. minutes for aftersensation pain, would be helpful in identifying the fundamental mechanisms of pelvic

  4. Neurobiological and psychosocial processes associated with depressive and substance-related disorders in adolescents.

    Science.gov (United States)

    Rao, Uma; Chen, Li-Ann

    2008-01-01

    Adolescents are at heightened risk for the development of both depressive and substance-related disorders. These two disorders frequently co-occur in adolescents and are associated with significant morbidity and mortality. Given the substantial economic and psychosocial burden associated with the comorbid condition, the identification of causal mechanisms associated with their co-occurrence is of great public health importance. Although there is significant understanding of the environmental and neurobiological factors involved in depression and addictive disorders considered separately, the mechanisms underlying the comorbid illness have not been investigated carefully. The purpose of this review is to summarize the extant literature on genetic, environmental and neurobiological processes involved in the etiology of depressive and substance-related disorders in adolescents and adults. It is important to note that the data on common neurobiological systems that link addictive and depressive disorders are primarily from research with adult animals and humans. Given the ongoing maturation of these systems throughout adolescence and early adult life, it is not clear how these neurobiological processes influence the development and progression of both disorders. A better understanding of the pathophysiological mechanisms leading to the onset and course of these disorders during adolescence will be helpful in developing more effective preventive and treatment strategies not only for this population but also for adult patients with early-onset illness.

  5. Atypical Neurotransmitters and the Neurobiology of Depression.

    Science.gov (United States)

    Joca, Samia Regiane; Moreira, Fabricio Araujo; Wegener, Gregers

    2015-01-01

    Since the first report that the mechanism of action of antidepressants involves the facilitation of monoaminergic neurotransmission in the brain in the 1960s, the leading hypothesis about the neurobiology of depression has been the so called "monoaminergic hypothesis". However, a growing body of evidence from the last two decades also supports important involvement of non-monoaminergic mechanisms in the neurobiology of depression and antidepressant action. The discovery of nitric oxide (NO) and endocannabinoid signaling in the brain during the 1990s challenged the wellestablished criteria of classical neurotransmission. These transmitters are synthesized and released on demand by the postsynaptic neurons, and may act as a retrograde messenger on the presynaptic terminal, modulating neurotransmitter release. These unconventional signaling mechanisms and the important role as neural messengers have classified NO and endocannabinoids as atypical neurotransmitters. They are able to modulate neural signaling mediated by the main conventional neurotransmitters systems in the brain, including the monoaminergic, glutamatergic and GABAergic signaling systems. This review aims at discussing the fundamental aspects of NO- and endocannabinoid-mediated signaling in the brain, and how they can be related to the neurobiology of depression. Both preclinical and clinical evidence supporting the involvement of these atypical neurotransmitters in the neurobiology of depression, and in the antidepressant effects are presented here. The evidence is discussed on basis of their ability to modulate different neurotransmitter systems in the brain, including monoaminergic and glutamatergic ones. A better comprehension of NO and endocannabinoid signaling mechanisms in the neurobiology depression could provide new avenues for the development of novel non-monoamine based antidepressants.

  6. An Underlying Geometrical Manifold for Hamiltonian Mechanics

    CERN Document Server

    Horwitz, L P; Levitan, J; Lewkowicz, M

    2015-01-01

    We show that there exists an underlying manifold with a conformal metric and compatible connection form, and a metric type Hamiltonian (which we call the geometrical picture) that can be put into correspondence with the usual Hamilton-Lagrange mechanics. The requirement of dynamical equivalence of the two types of Hamiltonians, that the momenta generated by the two pictures be equal for all times, is sufficient to determine an expansion of the conformal factor, defined on the geometrical coordinate representation, in its domain of analyticity with coefficients to all orders determined by functions of the potential of the Hamilton-Lagrange picture, defined on the Hamilton-Lagrange coordinate representation, and its derivatives. Conversely, if the conformal function is known, the potential of a Hamilton-Lagrange picture can be determined in a similar way. We show that arbitrary local variations of the orbits in the Hamilton-Lagrange picture can be generated by variations along geodesics in the geometrical pictu...

  7. Mechanisms underlying methamphetamine-related dental disease.

    Science.gov (United States)

    Clague, Jason; Belin, Thomas R; Shetty, Vivek

    2017-06-01

    The authors clarified the causal mechanisms underlying the high prevalence of dental disease encountered in people who habitually use methamphetamine (meth). Using a stratified sampling approach, the authors conducted comprehensive oral examinations and psychosocial assessments for 571 study participants who used meth. Three calibrated dentists, who used National Health and Nutrition Examination Survey (NHANES) protocols, characterized the study participants' dental disease. The authors also collected data related to study participants' history of meth use and other attributes linked to dental disease. Study participants who used meth manifested higher rates of xerostomia and caries experience compared with NHANES control participants. Participants who used meth had a higher level of daily consumption of sugary beverages compared with NHANES control participants. Smoking meth did not increase caries experience over other modes of intake. Dental hygiene was a significant determinant of dental health outcomes. Mode of intake and frequency of meth use have a minimal impact on dental health outcomes. Behaviors, such as sugary beverage consumption and poor oral hygiene, better explain dental health outcomes. Having a better understanding of the causal mechanisms of "meth mouth" sets the stage for clinicians to provide more personalized interventions and management of dental disease in people who use meth. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

  8. Enteric Neurobiology: Discoveries and Directions.

    Science.gov (United States)

    Wood, Jackie D

    Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus.

  9. [Recent neurobiological data on cannabis].

    Science.gov (United States)

    Costentin, Jean

    2002-01-01

    The alarming increase in cannabis abuse has triggered a renewed interest in the neurobiological mechanisms which underlie its effects, particularly as regards its addictive properties either intrinsic or when crossed with other narcotics as well as its subsequent damage. We here report an evaluation of experimental data which reveal in animals a psychological dependence, common to all addictive drugs; a physical dependence, which is considered up to now as the characteristic of "hard addictive drugs"; the incentive effect that cannabis should exert on the inclination to abuse other addictive drugs, especially heroin; and finally the close relationships which seem to exist between cannabis and schizophrenia. Most of these recent data are far from reassuring as regards cannabis psychotoxicity. Furthermore they underline its potential danger and prompt increased caution.

  10. Neurobiology of Dyslexia

    Science.gov (United States)

    Norton, Elizabeth S.; Beach, Sara D.; Gabrieli, John D. E.

    2014-01-01

    Dyslexia is one of the most common learning disabilities, yet its brain basis and core causes are not yet fully understood. Neuroimaging methods, including structural and functional magnetic resonance imaging, diffusion tensor imaging, and electrophysiology, have significantly contributed to knowledge about the neurobiology of dyslexia. Recent studies have discovered brain differences prior to formal instruction that likely encourage or discourage learning to read effectively, distinguished between brain differences that likely reflect the etiology of dyslexia versus brain differences that are the consequences of variation in reading experience, and identified distinct neural networks associated with specific psychological factors that are associated with dyslexia. PMID:25290881

  11. Neurobiology of dyslexia.

    Science.gov (United States)

    Norton, Elizabeth S; Beach, Sara D; Gabrieli, John D E

    2015-02-01

    Dyslexia is one of the most common learning disabilities, yet its brain basis and core causes are not yet fully understood. Neuroimaging methods, including structural and functional magnetic resonance imaging, diffusion tensor imaging, and electrophysiology, have significantly contributed to knowledge about the neurobiology of dyslexia. Recent studies have discovered brain differences before formal instruction that likely encourage or discourage learning to read effectively, distinguished between brain differences that likely reflect the etiology of dyslexia versus brain differences that are the consequences of variation in reading experience, and identified distinct neural networks associated with specific psychological factors that are associated with dyslexia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Neurobiology of fibromyalgia and chronic widespread pain.

    Science.gov (United States)

    Sluka, Kathleen A; Clauw, Daniel J

    2016-12-03

    Fibromyalgia is the current term for chronic widespread musculoskeletal pain for which no alternative cause can be identified. The underlying mechanisms, in both human and animal studies, for the continued pain in individuals with fibromyalgia will be explored in this review. There is a substantial amount of support for alterations of central nervous system nociceptive processing in people with fibromyalgia, and that psychological factors such as stress can enhance the pain experience. Emerging evidence has begun exploring other potential mechanisms including a peripheral nervous system component to the generation of pain and the role of systemic inflammation. We will explore the data and neurobiology related to the role of the CNS in nociceptive processing, followed by a short review of studies examining potential peripheral nervous system changes and cytokine involvement. We will not only explore the data from human subjects with fibromyalgia but will relate this to findings from animal models of fibromyalgia. We conclude that fibromyalgia and related disorders are heterogenous conditions with a complicated pathobiology with patients falling along a continuum with one end a purely peripherally driven painful condition and the other end of the continuum is when pain is purely centrally driven. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Social Context Effects on Decision-Making: A Neurobiological Approach

    NARCIS (Netherlands)

    M. Stallen (Mirre)

    2013-01-01

    textabstractThis thesis explores how social context influences the neurobiological processes underlying decision-making. To this end, this research takes an interdisciplinary approach, combining methods and insights from Psychology, Marketing, Economics, and Neuroscience. In particular, behavioural

  14. Neurobiology of functional (psychogenic) movement disorders.

    Science.gov (United States)

    Edwards, Mark J; Fotopoulou, Aikaterini; Pareés, Isabel

    2013-08-01

    This review explores recent developments in understanding the neurobiological mechanism of functional (psychogenic) movement disorders (FMDs). This is particularly relevant given the resurgence of academic and clinical interest in patients with functional neurological symptoms and the clear shift in diagnostic and treatment approaches away from a pure psychological model of functional symptoms. Recent research findings implicate three key processes in the neurobiology of FMD (and by extension other functional neurological symptoms): abnormal attentional focus, abnormal beliefs and expectations, and abnormalities in sense of agency. These three processes have been combined in recent neurobiological models of FMD in which abnormal predictions related to movement are triggered by self-focused attention, and the resulting movement is generated without the normal sense of agency that accompanies voluntary movement. New understanding of the neurobiology of FMD forms an important part of reappraising the way that patients with FMD (and other functional disorders) are characterized and treated. It also provides a testable framework for further exploring the pathophysiology of these common causes of ill health.

  15. Dissociable cognitive mechanisms underlying human path integration.

    Science.gov (United States)

    Wiener, Jan M; Berthoz, Alain; Wolbers, Thomas

    2011-01-01

    Path integration is a fundamental mechanism of spatial navigation. In non-human species, it is assumed to be an online process in which a homing vector is updated continuously during an outward journey. In contrast, human path integration has been conceptualized as a configural process in which travelers store working memory representations of path segments, with the computation of a homing vector only occurring when required. To resolve this apparent discrepancy, we tested whether humans can employ different path integration strategies in the same task. Using a triangle completion paradigm, participants were instructed either to continuously update the start position during locomotion (continuous strategy) or to remember the shape of the outbound path and to calculate home vectors on basis of this representation (configural strategy). While overall homing accuracy was superior in the configural condition, participants were quicker to respond during continuous updating, strongly suggesting that homing vectors were computed online. Corroborating these findings, we observed reliable differences in head orientation during the outbound path: when participants applied the continuous updating strategy, the head deviated significantly from straight ahead in direction of the start place, which can be interpreted as a continuous motor expression of the homing vector. Head orientation-a novel online measure for path integration-can thus inform about the underlying updating mechanism already during locomotion. In addition to demonstrating that humans can employ different cognitive strategies during path integration, our two-systems view helps to resolve recent controversies regarding the role of the medial temporal lobe in human path integration.

  16. Neurobiological studies of fatigue

    Science.gov (United States)

    Harrington, Mary E.

    2012-01-01

    Fatigue is a symptom associated with many disorders, is especially common in women and in older adults, and can have a huge negative influence on quality of life. Although most past research on fatigue uses human subjects instead of animal models, the use of appropriate animal models has recently begun to advance our understanding of the neurobiology of fatigue. In this review, results from animal models using immunological, developmental, or physical approaches to study fatigue are described and compared. Common across these animal models is that fatigue arises when a stimulus induces activation of microglia and/or increased cytokines and chemokines in the brain. Neurobiological studies implicate structures in the ascending arousal system, sleep executive control areas, and areas important in reward. In addition, the suprachiasmatic nucleus clearly plays an important role in homeostatic regulation of the neural network mediating fatigue. This nucleus responds to cytokines, shows decreased amplitude firing rate output in models of fatigue, and responds to exercise, one of our few treatments for fatigue. This is a young field but very important as the symptom of fatigue is common across many disorders and we do not have effective treatments. PMID:22841649

  17. The neurobiology of individuality

    Science.gov (United States)

    de Bivort, Benjamin

    2015-03-01

    Individuals often display conspicuously different patterns of behavior, even when they are very closely related genetically. These differences give rise to our sense of individuality, but what is their molecular and neurobiological basis? Individuals that are nominally genetically identical differ at various molecular and neurobiological levels: cell-to-cell variation in somatic genomes, cell-to-cell variation in expression patterns, individual-to-individual variation in neuronal morphology and physiology, and individual-to-individual variation in patterns of brain activity. It is unknown which of these levels is fundamentally causal of behavioral differences. To investigate this problem, we use the fruit fly Drosophila melanogaster, whose genetic toolkit allows the manipulation of each of these mechanistic levels, and whose rapid lifecycle and small size allows for high-throughput automation of behavioral assays. This latter point is crucial; identifying inter-individual behavioral differences requires high sample sizes both within and across individual animals. Automated behavioral characterization is at the heart of our research strategy. In every behavior examined, individual flies have individual behavioral preferences, and we have begun to identify both neural genes and circuits that control the degree of behavioral variability between individuals.

  18. Untangling the neurobiology of coping styles in rodents : Towards neural mechanisms underlying individual differences in disease susceptibility

    NARCIS (Netherlands)

    de Boer, Sietse F; Buwalda, Bauke; Koolhaas, Jaap M.

    Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding

  19. The neurobiology of syntax: beyond string sets

    Science.gov (United States)

    Petersson, Karl Magnus; Hagoort, Peter

    2012-01-01

    The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty. PMID:22688633

  20. The neurobiology of syntax: beyond string sets.

    Science.gov (United States)

    Petersson, Karl Magnus; Hagoort, Peter

    2012-07-19

    The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty.

  1. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  2. Neurobiological Alterations Induced by Exercise and Their Impact on Depressive Disorders

    OpenAIRE

    Helmich, Ingo; Latini, Alexandra; Sigwalt, Andre; Carta, Mauro Giovanni; Machado,Sergio; Velasques, Bruna; Ribeiro, Pedro; Budde, Henning

    2010-01-01

    Background: The impact of physical activity on brain metabolic functions has been investigated in different studies and there is growing evidence that exercise can be used as a preventive and rehabilitative intervention in the treatment of depressive disorders. However, the exact neuronal mechanisms underlying the latter phenomenon have not been clearly elucidated. The present article summarises key results derived from studies that focussed on the neurobiological impact of exercise on brain ...

  3. Aspects of psychodynamic neuropsychiatry III: magic spells, the placebo effect, and neurobiology.

    Science.gov (United States)

    Brockman, Richard

    2011-01-01

    Through a case study, the importance of supporting the positive transference is stressed-from both a psychological and neurobiological perspective. The article argues that the neurobiology of expectation underlies transference. This neurobiology has been investigated particularly over the past several decades in work concerning the placebo effect. By understanding the neurobiology of expectation, one gains a better understanding of the neurobiology of the transference. This enables clinical predictions-and decisions-that are informed not just by the teachings of psychology but also by the science of biology.

  4. Stalking: a neurobiological perspective.

    Science.gov (United States)

    Marazziti, Donatella; Falaschi, Valentina; Lombardi, Amedeo; Mungai, Francesco; Dell'Osso, Liliana

    2015-01-01

    Nowadays stalking is becoming a real social emergency, as it may often fuel severe aggressive behaviours. No exhaustive aetiological hypothesis is still available regarding this complex phenomenon. However, the detailed descriptions of some of its peculiar features allow to draw with cautions some general suggestions. Probably stalking may arise from the derangement of those neural networks subserving the so-called social brain and the pair bonding formation, in particular the processes of attachment/separation, attraction/romantic love/reward. In addition, it seems to be modulated by excessive functioning of the dopamine system coupled with decreased serotonin tone. It is believed that the investigation and deepening of its possible neurobiological substrates may be helpful in the prevention of the severe consequences of stalking.

  5. Integrating ecology, psychology and neurobiology within a food-hoarding paradigm.

    Science.gov (United States)

    Pravosudov, Vladimir V; Smulders, Tom V

    2010-03-27

    Many animals regularly hoard food for future use, which appears to be an important adaptation to a seasonally and/or unpredictably changing environment. This food-hoarding paradigm is an excellent example of a natural system that has broadly influenced both theoretical and empirical work in the field of biology. The food-hoarding paradigm has played a major role in the conceptual framework of numerous fields from ecology (e.g. plant-animal interactions) and evolution (e.g. the coevolution of caching, spatial memory and the hippocampus) to psychology (e.g. memory and cognition) and neurobiology (e.g. neurogenesis and the neurobiology of learning and memory). Many food-hoarding animals retrieve caches by using spatial memory. This memory-based behavioural system has the inherent advantage of being tractable for study in both the field and laboratory and has been shaped by natural selection, which produces variation with strong fitness consequences in a variety of taxa. Thus, food hoarding is an excellent model for a highly integrative approach to understanding numerous questions across a variety of disciplines. Recently, there has been a surge of interest in the complexity of animal cognition such as future planning and episodic-like-memory as well as in the relationship between memory, the environment and the brain. In addition, new breakthroughs in neurobiology have enhanced our ability to address the mechanisms underlying these behaviours. Consequently, the field is necessarily becoming more integrative by assessing behavioural questions in the context of natural ecological systems and by addressing mechanisms through neurobiology and psychology, but, importantly, within an evolutionary and ecological framework. In this issue, we aim to bring together a series of papers providing a modern synthesis of ecology, psychology, physiology and neurobiology and identifying new directions and developments in the use of food-hoarding animals as a model system.

  6. Successful and unsuccessful psychopaths: a neurobiological model.

    Science.gov (United States)

    Gao, Yu; Raine, Adrian

    2010-01-01

    Despite increasing interest in psychopathy research, surprisingly little is known about the etiology of non-incarcerated, successful psychopaths. This review provides an analysis of current knowledge on the similarities and differences between successful and unsuccessful psychopaths derived from five population sources: community samples, individuals from employment agencies, college students, industrial psychopaths, and serial killers. An initial neurobiological model of successful and unsuccessful psychopathy is outlined. It is hypothesized that successful psychopaths have intact or enhanced neurobiological functioning that underlies their normal or even superior cognitive functioning, which in turn helps them to achieve their goals using more covert and nonviolent methods. In contrast, in unsuccessful, caught psychopaths, brain structural and functional impairments together with autonomic nervous system dysfunction are hypothesized to underlie cognitive and emotional deficits and more overt violent offending.

  7. Neurobiological consequences of childhood trauma.

    Science.gov (United States)

    Nemeroff, Charles B

    2004-01-01

    There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.

  8. Gravitational Neurobiology of Fish

    Science.gov (United States)

    Rahmann, H.; Anken, R. H.

    In vertebrates (including man), altered gravitational environments such as weightlessness can induce malfunctions of the inner ears, based on irregular movements of the semicircular cristae or on dislocations of the inner ear otoliths from the corresponding sensory epithelia. This will lead to illusionary tilts, since the vestibular inputs are not confirmed by the other sensory organs, which results in an intersensory conflict. Vertebrates in orbit therefore face severe orientation problems. In humans, the intersensory conflict may additionally lead to a malaise, commonly referred to as space motion sickness (SMS), a kinetosis. During the first days at weightlessness, the orientation problems (and SMS) disappear, since the brain develops a new compensatory interpretation of the available sensory data. The present review reports on the neurobiological responses - particularly of fish - observed at altered gravitational states, concerning behaviour and neuroplastic reactivities. Recent investigations employing microgravity (spaceflight, parabolic aircraft flights, clinostat) and hyper-gravity (laboratory centrifuges as ground based research tools) yielded clues and insights into the understanding of the respective basic phenomena

  9. Adenosine receptor neurobiology: overview.

    Science.gov (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases. © 2014 Elsevier Inc. All rights reserved.

  10. Ameliorative Effect and Underlying Mechanisms of Total ...

    African Journals Online (AJOL)

    0.05 or p < 0.01) by TTPGL in sciatic nerve. Mechanism analysis indicated that the ameliorative effect of TTPGL, in part, is through suppression of the expression of pro - inflammatory cytokines by NF - κB pathway mediation. Conclusion: TTPGL offers a potential therapeutic approach for the treatment of diabetic peripheral.

  11. Epigenetic mechanisms underlying nervous system diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2018-01-01

    Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are intimately involved in executing fundamental genomic programs, including gene transcription, posttranscriptional RNA processing and transport, translation, X-chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA replication, and DNA repair and the maintenance of genomic stability. For the nervous system, epigenetics offers a novel and robust framework for explaining how brain development and aging occur, neural cellular diversity is generated, synaptic and neural network connectivity and plasticity are mediated, and complex cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic factors and processes are, not surprisingly, implicated in nervous system disease pathophysiology through several emerging paradigms - mutations and genetic variation in genes encoding epigenetic factors; impairments in epigenetic factor expression, localization, and function; epigenetic mechanisms modulating disease-associated factors and pathways; and the presence of deregulated epigenetic profiles in central and peripheral tissues. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. The Mechanism Underlying Inhibition of Saccadic Return

    Science.gov (United States)

    Ludwig, Casimir J. H.; Farrell, Simon; Ellis, Lucy A.; Gilchrist, Iain D.

    2009-01-01

    Human observers take longer to re-direct gaze to a previously fixated location. Although there has been some exploration of the characteristics of inhibition of saccadic return (ISR), the exact mechanisms by which ISR operates are currently unknown. In the framework of accumulation models of response times, in which evidence is integrated over…

  13. Neurobiology of migraine.

    Science.gov (United States)

    Goadsby, P J; Charbit, A R; Andreou, A P; Akerman, S; Holland, P R

    2009-06-30

    Migraine is a complex disorder of the brain whose mechanisms are only now being unraveled. It is common, disabling and economically costly. The pain suggests an important role of the nociceptive activation, or the perception of activation, of trigeminal cranial, particularly intracranial afferents. Moreover, the involvement of a multi-sensory disturbance that includes light, sound and smells, as well as nausea, suggests the problem may involve central modulation of afferent traffic more broadly. Brain imaging studies in migraine point to the importance of sub-cortical structures in the underlying pathophysiology of the disorder. Migraine may thus be considered an inherited dysfunction of sensory modulatory networks with the dominant disturbance affecting abnormal processing of essentially normal neural traffic.

  14. Optical highlighter molecules in neurobiology.

    Science.gov (United States)

    Datta, Sandeep Robert; Patterson, George H

    2012-02-01

    The development of advanced optical methods has played a key role in propelling progress in neurobiology. Genetically-encoded fluorescent molecules found in nature have enabled labeling of individual neurons to study their physiology and anatomy. Here we discuss the recent use of both native and synthetic optical highlighter proteins to address key problems in neurobiology, including questions relevant to synaptic function, neuroanatomy, and the organization of neural circuits. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. What can medical education learn from the neurobiology of learning?

    Science.gov (United States)

    Friedlander, Michael J; Andrews, Linda; Armstrong, Elizabeth G; Aschenbrenner, Carol; Kass, Joseph S; Ogden, Paul; Schwartzstein, Richard; Viggiano, Thomas R

    2011-04-01

    The last several decades have seen a large increase in knowledge of the underlying biological mechanisms that serve learning and memory. The insights gleaned from neurobiological and cognitive neuroscientific experimentation in humans and in animal models have identified many of the processes at the molecular, cellular, and systems levels that occur during learning and the formation, storage, and recall of memories. Moreover, with the advent of noninvasive technologies to monitor patterns of neural activity during various forms of human cognition, the efficacy of different strategies for effective teaching can be compared. Considerable insight has also been developed as to how to most effectively engage these processes to facilitate learning, retention, recall, and effective use and application of the learned information. However, this knowledge has not systematically found its way into the medical education process. Thus, there are considerable opportunities for the integration of current knowledge about the biology of learning with educational strategies and curricular design. By teaching medical students in ways that use this knowledge, there is an opportunity to make medical education easier and more effective. The authors present 10 key aspects of learning that they believe can be incorporated into effective teaching paradigms in multiple ways. They also present recommendations for applying the current knowledge of the neurobiology of learning throughout the medical education continuum. © by the Association of American Medical Colleges.

  16. Aggression and anxiety: social context and neurobiological links

    Directory of Open Access Journals (Sweden)

    Inga D Neumann

    2010-03-01

    Full Text Available Psychopathologies such as anxiety- and depression-related disorders are often characterized by impaired social behaviours including excessive aggression and violence. Excessive aggression and violence likely develop as a consequence of generally disturbed emotional regulation, such as abnormally high or low levels of anxiety. This suggests an overlap between brain circuitries and neurochemical systems regulating aggression and anxiety. In this review, we will discuss different forms of male aggression, rodent models of excessive aggression, and neurobiological mechanisms underlying male aggression in the context of anxiety. We will summarize our attempts to establish an animal model of high and abnormal aggression using rats selected for high (HAB versus low (LAB anxiety-related behaviour. Briefly, male LAB rats and, to a lesser extent, male HAB rats show high and abnormal forms of aggression compared with non-selected (NAB rats, making them a suitable animal model for studying excessive aggression in the context of extremes in innate anxiety. In addition, we will discuss differences in the activity of the hypothalamic-pituitary-adrenal axis, brain arginine vasopressin, and the serotonin systems, among others, which contribute to the distinct behavioural phenotypes related to aggression and anxiety. Further investigation of the neurobiological systems in animals with distinct anxiety phenotypes might provide valuable information about the link between excessive aggression and disturbed emotional regulation, which is essential for understanding the social and emotional deficits that are characteristic of many human psychiatric disorders.

  17. Investigation of Mechanisms Underlying Odor Recognition.

    Science.gov (United States)

    1984-02-01

    olfactory epithelium of the rat using a procedure similar to that used in .amphibian forms (e.g., Kubie & Moulton, 1979). The detailed description of most...distinct differences in responsiveness of the underlying receptor sheet depending upon the region stimulated (e.g., Kauer & Moulton, 1979; Kubie M...patterns of olfactory bulb neurons using odor stimulation of small nasal areas in the salamander. J. Physiol. (London), 1974, 243, 717-737. Kubie , J.S

  18. Polymers under mechanical stress- an NMR investigation

    Energy Technology Data Exchange (ETDEWEB)

    Boehme, Ute; Scheler, Ulrich [Leibniz Institute of Polymer Research Dresden (Germany); Xu, Bo; Leisen, Johannes; Beckham, Haskell W. [Georgia Institute of Technology, Atlanta, Georgia (United States)

    2010-07-01

    Low-field NMR using permanent magnets in Halbach arrangements permit NMR investigation without the limits present in high-field NMR. The lower field in conjunction with confined stray field permit the application of NMR, in particular relaxation NMR in a stretching apparatus and a rheometer. Crystalline and amorphous fraction of semi-crystalline polymers are distinguished by their transverse relaxation times. Upon mechanical load the relaxation times of the amorphous fraction changes as seen in in-situ measurements on polypropylene rods. During the formation of a neck the crystalline fraction becomes more prominent.

  19. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    National Research Council Canada - National Science Library

    Nguyen Quoc Vuong Tran; Kunio Miyake

    2017-01-01

    .... Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis...

  20. Synaptic mechanisms underlying persistent cocaine craving

    Science.gov (United States)

    Wolf, Marina E.

    2017-01-01

    Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

  1. Environmental genotoxicity: Probing the underlying mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L. [Oak Ridge National Lab., TN (United States); Theodorakis, C. [Tennessee Univ., Knoxville, TN (United States)

    1993-12-31

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.

  2. Epigenetic mechanisms underlying extinction of memory and drug-seeking behavior

    Science.gov (United States)

    Malvaez, Melissa; Barrett, Ruth M.

    2011-01-01

    An increasing body of evidence shows that structural modifications of chromatin, the DNA–protein complex that packages genomic DNA, do not only participate in maintaining cellular memory (e.g., cell fate), but they may also underlie the strengthening and maintenance of synaptic connections required for long-term changes in behavior. Accordingly, epigenetics has become a central topic in several neurobiology fields such as memory, drug addiction, and several psychiatric and mental disorders. This interest is justified as dynamic chromatin modifications may provide not only transient but also stable (or even potentially permanent) epigenetic marks to facilitate, maintain, or block transcriptional processes, which in turn may participate in the molecular neural adaptations underlying behavioral changes. Through epigenetic mechanisms the genome may be indexed in response to environmental signals, resulting in specific neural modifications that largely determine the future behavior of an organism. In this review we discuss recent advances in our understanding of how epigenetic mechanisms contribute to the formation of long-term memory and drug-seeking behavior and potentially how to apply that knowledge to the extinction of memory and drug-seeking behavior. PMID:19789849

  3. Mechanisms underlying adverse reactions to vaccines.

    Science.gov (United States)

    Siegrist, C-A

    2007-07-01

    A broad spectrum of adverse events is reported following human vaccination but such reactions are considered to be relatively rare. A variety of mechanisms has been proposed to account for such adverse events. These most commonly relate to the actual process of vaccination and range from the vagal reaction associated with anxiety about needle injection, to use of an inappropriate site of administration, or infection of the healthcare worker by accidental injection during needle-capping. Other adverse events directly associated with the vaccine include reversion to virulence of attenuated vaccine strains of organisms, or contamination of the vaccine product. Adverse events may involve immune-mediated phenomena triggered by exposure to the microbial or other components of vaccines. These include: classical IgE-mediated type I hypersensitivity reactions, and immune-complex type III hypersensitivity (Arthus) reactions. Such reactions may be localized or systemic in nature. A variety of autoimmune reactions has been suggested to be triggered by vaccination, but in general the evidence for such associations remains largely anecdotal. Finally, many reported adverse events are simply chance instances of infection or disease onset around the time of vaccination and are not causally associated with administration of vaccine.

  4. Epigenetic mechanisms underlying genomic imprinting in plants.

    Science.gov (United States)

    Köhler, Claudia; Wolff, Philip; Spillane, Charles

    2012-01-01

    Genomic imprinting, the differential expression of an autosomal gene that is dependent on its parent of origin, has independently evolved in flowering plants and mammals. In both of these organism classes, imprinting occurs in embryo-nourishing tissues-the placenta and the endosperm, respectively. It has been proposed that some imprinted genes control nutrient flow from the mother to the offspring. Genome-wide analyses of imprinted genes in plants have revealed that many imprinted genes are located in the vicinity of transposon or repeat sequences, implying that transposon insertions are associated with the evolution of imprinted loci. Imprinted expression of a number of genes is conserved between monocots and dicots, suggesting that long-term selection can maintain imprinted expression at some loci. In terms of epigenetic mechanisms, imprinted expression is largely controlled by an antagonistic action of DNA methylation and Polycomb group-mediated histone methylation in the vicinity of imprinted genes, whereby the position of such epigenetic modifications can determine whether a gene will be expressed mainly from either the maternally or paternally inherited alleles.

  5. MECHANISMS UNDERLYING MATERNAL VENOUS ADAPTATION IN PREGNANCY

    Science.gov (United States)

    Jones, Cresta Wedel; Mandala, Maurizio; Barron, Carolyn; Bernstein, Ira; Osol, George

    2009-01-01

    To define the effects of pregnancy on mechanical properties and reactivity, mesenteric veins from late pregnant (LP) and virgin control (NP) rats were pressurized to determine gestational changes in size and distensibility. Reactivity studies used an adrenergic constrictor (norepinephrine, NE) and an endothelium-mediated vasodilator (acetylcholine, ACh). The contribution of nitric oxide (NO) to endothelial function was evaluated with pharmacologic inhibition of NO synthase. Roles of NO and cGMP in smooth muscle vasodilation were determined by using an NO donor with and without cGMP inhibition using ODQ, a selective inhibitor of guanylyl cyclase. In pregnancy, endothelium-dependent vasodilation markedly increased (largely due to endogenous NO), smooth muscle response to NO decreased (primarily related to cGMP production), and NE sensitivity decreased considerably, with no changes in vessel size or distensibility. Our results identify a pro-vasodilatory state in the systemic venous system which would serve to facilitate the accommodation to plasma volume expansion requisite for normal pregnancy. PMID:19318688

  6. Changes of trabecular bone under control of biologically mechanical mechanism

    Science.gov (United States)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

  7. Neurobiology of dysregulated motivational systems in drug addiction

    Science.gov (United States)

    Edwards, Scott; Koob, George F

    2010-01-01

    The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312

  8. [Neurological diseases and suicide: from neurobiology to hopelessness].

    Science.gov (United States)

    Costanza, A; Baertschi, M; Weber, K; Canuto, A

    2015-02-11

    Neurologic diseases expose at a high risk of suicidal behaviors and they constitute a privileged domain for exploring the heterogeneity of underlying mechanisms. They are in fact characterized by strictly biological injuries that may be involved in cerebral systems considered at the basis of neurobiological vulnerability for suicide. At the same time, they oblige a numberof existential topics to emerge, as the hopelessness in respect of several particularly severe conditions without an etiologic treatment. A clinical approach reserving an unconditional listening can prevent a suicidal attempt. Furthermore, it can illustrate the role of the liaison's psychiatrist, who tries to transform a hopelessness situation into a patient's personal questioning and try to be present when therapeutic action is not longer possible.

  9. Integrating neuroimmune systems in the neurobiology of depression.

    Science.gov (United States)

    Wohleb, Eric S; Franklin, Tina; Iwata, Masaaki; Duman, Ronald S

    2016-08-01

    Data from clinical and preclinical studies indicate that immune dysregulation, specifically of inflammatory processes, is associated with symptoms of major depressive disorder (MDD). In particular, increased levels of circulating pro-inflammatory cytokines and concomitant activation of brain-resident microglia can lead to depressive behavioural symptoms. Repeated exposure to psychological stress has a profound impact on peripheral immune responses and perturbs the function of brain microglia, which may contribute to neurobiological changes underlying MDD. Here, we review these findings and discuss ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity. Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation.

  10. Neurobiology of Everyday Communication: What Have We Learned From Music?

    Science.gov (United States)

    Kraus, Nina; White-Schwoch, Travis

    2016-06-09

    Sound is an invisible but powerful force that is central to everyday life. Studies in the neurobiology of everyday communication seek to elucidate the neural mechanisms underlying sound processing, their stability, their plasticity, and their links to language abilities and disabilities. This sound processing lies at the nexus of cognitive, sensorimotor, and reward networks. Music provides a powerful experimental model to understand these biological foundations of communication, especially with regard to auditory learning. We review studies of music training that employ a biological approach to reveal the integrity of sound processing in the brain, the bearing these mechanisms have on everyday communication, and how these processes are shaped by experience. Together, these experiments illustrate that music works in synergistic partnerships with language skills and the ability to make sense of speech in complex, everyday listening environments. The active, repeated engagement with sound demanded by music making augments the neural processing of speech, eventually cascading to listening and language. This generalization from music to everyday communications illustrates both that these auditory brain mechanisms have a profound potential for plasticity and that sound processing is biologically intertwined with listening and language skills. A new wave of studies has pushed neuroscience beyond the traditional laboratory by revealing the effects of community music training in underserved populations. These community-based studies reinforce laboratory work highlight how the auditory system achieves a remarkable balance between stability and flexibility in processing speech. Moreover, these community studies have the potential to inform health care, education, and social policy by lending a neurobiological perspective to their efficacy. © The Author(s) 2016.

  11. Neurodynamics: nonlinear dynamics and neurobiology.

    Science.gov (United States)

    Abarbanel, H D; Rabinovich, M I

    2001-08-01

    The use of methods from contemporary nonlinear dynamics in studying neurobiology has been rather limited.Yet, nonlinear dynamics has become a practical tool for analyzing data and verifying models. This has led to productive coupling of nonlinear dynamics with experiments in neurobiology in which the neural circuits are forced with constant stimuli, with slowly varying stimuli, with periodic stimuli, and with more complex information-bearing stimuli. Analysis of these more complex stimuli of neural circuits goes to the heart of how one is to understand the encoding and transmission of information by nervous systems.

  12. Do horizontal saccadic eye movements increase interhemispheric coherence? Investigation of a hypothesized neural mechanism underlying EMDR

    Directory of Open Access Journals (Sweden)

    Zoe eSamara

    2011-03-01

    Full Text Available Series of horizontal saccadic eye movements (EMs are known to improve episodic memory retrieval in healthy adults and to facilitate the processing of traumatic memories in eye-movement desensitization and reprocessing (EMDR therapy. Several authors have proposed that EMs achieve these effects by increasing the functional connectivity of the two brain hemispheres, but direct evidence for this proposal is lacking. The aim of this study was to investigate whether memory enhancement following bilateral EMs is associated with increased interhemispheric coherence in the electroencephalogram (EEG. Fourteen healthy young adults were asked to freely recall lists of studied neutral and emotional words after a series of bilateral EMs and a control procedure. Baseline EEG activity was recorded before and after the EM and control procedures. Phase and amplitude coherence between bilaterally homologous brain areas were calculated for six frequency bands and electrode pairs across the entire scalp. Behavioral analyses showed that participants recalled more emotional (but not neutral words following the EM procedure than following the control procedure. However, the EEG analyses indicated no evidence that the EMs altered participants’ interhemispheric coherence or that improvements in recall were correlated with such changes in coherence. These findings cast doubt on the interhemispheric interaction hypothesis, and therefore may have important implications for future research on the neurobiological mechanism underlying EMDR.

  13. The neurobiology of uncertainty: implications for statistical learning.

    Science.gov (United States)

    Hasson, Uri

    2017-01-05

    The capacity for assessing the degree of uncertainty in the environment relies on estimating statistics of temporally unfolding inputs. This, in turn, allows calibration of predictive and bottom-up processing, and signalling changes in temporally unfolding environmental features. In the last decade, several studies have examined how the brain codes for and responds to input uncertainty. Initial neurobiological experiments implicated frontoparietal and hippocampal systems, based largely on paradigms that manipulated distributional features of visual stimuli. However, later work in the auditory domain pointed to different systems, whose activation profiles have interesting implications for computational and neurobiological models of statistical learning (SL). This review begins by briefly recapping the historical development of ideas pertaining to the sensitivity to uncertainty in temporally unfolding inputs. It then discusses several issues at the interface of studies of uncertainty and SL. Following, it presents several current treatments of the neurobiology of uncertainty and reviews recent findings that point to principles that serve as important constraints on future neurobiological theories of uncertainty, and relatedly, SL. This review suggests it may be useful to establish closer links between neurobiological research on uncertainty and SL, considering particularly mechanisms sensitive to local and global structure in inputs, the degree of input uncertainty, the complexity of the system generating the input, learning mechanisms that operate on different temporal scales and the use of learnt information for online prediction.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

  14. Functional chronic pain syndromes and naturopathic treatments: neurobiological foundations.

    Science.gov (United States)

    Musial, Frauke; Michalsen, Andreas; Dobos, Gustav

    2008-04-01

    There is increasing clinical evidence that reflex therapies such as massage, Gua Sha, cupping, wet packs, acupuncture etc. are helpful in reducing symptoms of chronic pain. However, the neurobiological basis of these effects has rarely been investigated even though the increasing knowledge of the pathophysiology of chronic pain syndromes allows for specific hypotheses. Reflex therapies are likely able to influence chronic pain at the level of the nociceptor and the spinal cord. Moreover, it can be speculated that these therapies have a strong impact on relaxation and maybe understood as a social, comforting interaction. Since it is well accepted that the positive effect of grooming has a neurobiological basis in non-human primates, its biosocial impact on wellbeing and pain processing in humans may be underestimated. A synopsis of the neurobiological foundations of pain perception, from the nociceptor up the spinal cord to brain mechanisms provides the basis for the investigation of the 'way of action' of reflex therapies. Specific hypotheses on their neurobiological bases and methods suitable for their investigation are outlined. Further clarification of the mechanisms of action of reflex therapies will support their clinical evidence and add to our understanding of the neurobiology of complementary medicine. Copyright 2008 S. Karger AG, Basel.

  15. Co-morbidity of complex genetic disorders and hypersomnias of central origin: lessons from the underlying neurobiology of wake and sleep.

    Science.gov (United States)

    Weselake, S V; Wevrick, R

    2012-10-01

    Appropriate wake and sleep cycles are important to physical well-being, and are modulated by neuronal networks in the brain. A variety of medical conditions can disrupt sleep or cause excessive daytime sleepiness. Clinical diagnostic classification schemes have historically lumped genetic disorders together into a category that considers the sleep dysfunction to be secondary to a medical condition. The unique nature of sleep endophenotypes that occur more frequently in particular genetic disorders has been underappreciated. Increased understanding of the pathophysiology of wake/sleep dysfunction in rare genetic disorders could inform studies of the neurological mechanisms that underlie more common forms of wake and sleep dysfunction. In this review, we highlight genetic developmental disorders in which sleep endophenotypes have been described, and then consider genetic neurodegenerative disorders with sleep characteristics that set them apart from the disruptions to sleep that are typically associated with aging and dementia. © 2012 John Wiley & Sons A/S.

  16. The neurobiology of circadian rhythms

    NARCIS (Netherlands)

    Van der Zee, Eddy A.; Boersma, Gretha J.; Hut, Roelof A.

    2009-01-01

    Purpose of review There is growing awareness of the importance of circadian rhythmicity in various research fields. Exciting developments are ongoing in the field of circadian neurobiology linked to sleep, food intake, and memory. With the current knowledge of critical clock genes' (genes found to

  17. Neurobiological Substrates of Tourette's Disorder

    NARCIS (Netherlands)

    Leckman, James F.; Bloch, Michael H.; Smith, Megan E.; Larabi, Daouia; Hampson, Michelle

    Objective: This article reviews the available scientific literature concerning the neurobiological substrates of Tourette's disorder (TD). Methods: The electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for relevant studies using relevant search terms. Results:

  18. Mental health: More than neurobiology

    NARCIS (Netherlands)

    Fried, E.; Tuerlinckx, F.; Borsboom, D.

    2014-01-01

    The decision by the US National Institute of Mental Health (NIMH) to fund only research into the neurobiological roots of mental disorders (Nature 507, 288; 2014) presumes that these all result from brain abnormalities. But this is not the case for many people with mental-health issues and we fear

  19. Neural Mechanisms Underlying Compensatory and Noncompensatory Strategies in Risky Choice

    NARCIS (Netherlands)

    van Duijvenvoorde, A.C.K.; Figner, B.; Weeda, W.D.; van der Molen, M.W.; Jansen, B.R.J.; Huizenga, H.M.

    Individuals may differ systematically in their applied decision strategies, which has critical implications for decision neuroscience but is yet scarcely studied. Our study's main focus was therefore to investigate the neural mechanisms underlying compensatory versus noncompensatory strategies in

  20. Neural mechanisms underlying compensatory and noncompensatory strategies in risky choice

    NARCIS (Netherlands)

    Duijvenvoorde, A.C.K. van; Figner, B.; Weeda, W.D.; Molen, M.W. van der; Jansen, B.R.J.; Huizenga, H.M.

    2016-01-01

    Individuals may differ systematically in their applied decision strategies, which has critical implications for decision neuroscience but is yet scarcely studied. Our study's main focus was therefore to investigate the neural mechanisms underlying compensatory versus noncompensatory strategies in

  1. Underlying Mechanisms of Improving Physical Activity Behavior after Rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, Hidde P.; Streppel, Kitty R.M.; van der Beek, Allard J.; Woude, Luc H.V.; van Harten, Willem H.; Vollenbroek-Hutten, Miriam Marie Rosé; van Mechelen, Willem

    2008-01-01

    Background: Regular physical activity is beneficial for the health and functioning of people with a disability. Effective components of successful physical activity promotion interventions should be identified and disseminated. Purpose: To study the underlying mechanisms of the combined sport

  2. Underlying mechanisms of improving physical activity behavior after rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, H.P.; Streppel, K.R.; van der Beek, A.J.; van der Woude, L.H.V.; van Harten, W.H.; van Mechelen, W.

    2008-01-01

    Background: Regular physical activity is beneficial for the health and functioning of people with a disability. Effective components of successful physical activity promotion interventions should be identified and disseminated. Purpose: To study the underlying mechanisms of the combined sport

  3. Mechanisms underlying action of Xinmailong injection, a traditional ...

    African Journals Online (AJOL)

    Mechanisms underlying action of Xinmailong injection, a traditional Chinese medicine in cardiac function improvement. Zhengtao Li, Sujuan Li, Lin Hu, Fang Li, Alex Chun Cheung, Weizai Shao, Yuling Que, George Pek-heng Leung, Cui Yang ...

  4. Molecular neurobiology of addiction.

    Science.gov (United States)

    Nestler, E J

    2001-01-01

    Addiction can be viewed as a form of drug-induced neural plasticity. One of the best established molecular mechanisms of addiction is the upregulation of the cAMP second messenger pathway, which occurs in many neuronal cell types in response to chronic administration of opiates or other drugs of abuse. This upregulation and the resulting activation of the transcription factor CREB appear to mediate aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed delta FosB, exerts the opposite effect and may contribute to sensitized responses to drug exposure. Knowledge of these mechanisms could lead to more effective treatments for addictive disorders.

  5. Stress analysis in a functionally graded disc under mechanical loads ...

    Indian Academy of Sciences (India)

    Stress analysis in a functionally graded disc under mechanical loads and a steady state temperature distribution. HASAN ÇALLIO ˘GLU. Department of Mechanical Engineering, Pamukkale University, 20070,. Denizli, Turkey e-mail: hcallioglu@pau.edu.tr. MS received 25 November 2009; revised 12 August 2010; accepted.

  6. Neurobiological effects of exercise on major depressive disorder: A systematic review.

    Science.gov (United States)

    Schuch, Felipe Barreto; Deslandes, Andrea Camaz; Stubbs, Brendon; Gosmann, Natan Pereira; Silva, Cristiano Tschiedel Belem da; Fleck, Marcelo Pio de Almeida

    2016-02-01

    Exercise displays promise as an efficacious treatment for people with depression. However, no systematic review has evaluated the neurobiological effects of exercise among people with major depressive disorder (MDD). The aim of this article was to systematically review the acute and chronic biological responses to exercise in people with MDD. Two authors conducted searches using Medline (PubMed), EMBASE and PsycINFO. From the searches, twenty studies were included within the review, representing 1353 people with MDD. The results demonstrate that a single bout of exercise increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), copepetin and growth hormone among people with MDD. Exercise also potentially promotes long-term adaptations of copeptin, thiobarbituric acid reactive species (TBARS) and total mean frequency (TMF). However, there is limited evidence that exercise promotes adaptations on neurogenesis, inflammation biomarkers and brain structure. Associations between depressive symptoms improvement and hippocampus volume and IL-1β were found. Nevertheless, the paucity of studies and limitations presented within, precludes a more definitive conclusion of the underlying neurobiological explanation for the antidepressant effect of exercise in people with MDD. Further trials should utilize appropriate assessments of neurobiological markers in order to build upon the results of our review and further clarify the potential mechanisms associated with the antidepressant effects of exercise. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The neurobiology of pain.

    Science.gov (United States)

    Besson, J M

    1999-05-08

    Understanding the plasticity of pain and analgesia exhibited in different pain states may improve therapies for the two major types of pain, neuropathic and inflammatory pain, in which nerve and tissue damage leads to alterations at both peripheral and central levels. At the level of the peripheral nerve, drugs that act on particular sodium channels may target only pain-related activity. Agents that act on some of the peripheral mediators of pain may control peripheral nerve activity. A new generation of non-steroidal anti-inflammatory drugs, cyclo-oxygenase 2 inhibitors, that lack gastric actions are becoming available. In the spinal cord, the release of peptides and glutamate causes activation of multiple receptors, particularly, the N-methyl-D-aspartate receptor for glutamate, which, in concert with other spinal systems, generates spinal hypersensitivity. Blocking the generation of excitability is one approach, but increasing inhibitions may also provide analgesia. Opioid actions are via presynaptic and post-synaptic inhibitory effects on central and peripheral C fibre terminals, spinal neurones, and supraspinal mechanisms. Our knowledge of brain mechanisms of pain is still, however, limited. Other new targets have been revealed by molecular biology and animal models of clinical pain, but the possibility of a "magic bullet" is doubtful. Thus, another approach could be single molecules with dual drug actions, that encompass targets where additive or synergistic effects of different mechanisms may enable pain relief without major adverse effects.

  8. Neurobiological basis of frustration

    Directory of Open Access Journals (Sweden)

    Justel, Nadia

    2010-12-01

    Full Text Available The main feature shared by the phenomena involving unexpected changes of reinforcement is that there is a discrepancy between expected and received reward. Consequently, the behavior is modified according to this difference; the animals have an emotional response to the surprising reward change, called frustration. Some of the paradigms that are commonly used to study these problems are: consummatory Successive Negative Contrast and consummatory Extinction. This review describes the major works that investigate the neuroanatomical and neurophysiological mechanisms involved in these studies, and the main tasks related with the administration of drugs that modulate the memory of the surprising reward changes.

  9. “Love” Phenomenon and Neurobiology of Love Relations

    Directory of Open Access Journals (Sweden)

    Ali Evren Tufan

    2010-01-01

    Full Text Available The biology; especially the neurobiological features of the “love” phenomenon has recently started to attract attention. Love relations and attachment, which is closely related with them, are known to be important in health and disease. Love and love relations are found to be complex neurobiological phenomena based on activation of the limbic system of the brain. Those processes involve oxytocin, vasopressin, dopamine and serotonergic functions. Additionally, endorphine and endogenous opiate systems as well as nitrous oxide play role in those processes. The stages of love and love relations may demonstrate different neurochemical and neurophysiological features and may partially overlap with m aternal, romantic and sexual love and attachments. The aim of this article is to evaluate the common neurobiological pathways underlying the “love” phenomenon as well as their importance in medicine and health.

  10. The neurobiology of social phobia.

    Science.gov (United States)

    Potts, N L; Book, S; Davidson, J R

    1996-06-01

    Studies in the neurobiology of social phobia have used neuroendocrine, naturalistic and chemical challenges, pharmacological probes, neurotransmitter system measures, peripheral receptor binding and magnetic resonance measures. Studies of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes have been largely unrevealing; adrenaline, carbon dioxide, caffeine and yohimbine tests have provided mixed results; probe studies using L-dopa, clonidine and fenfluramine have provided some evidence of post-synaptic serotonergic abnormality; studies on platelet and lymphocyte binding have failed to distinguish social phobia from other groups; magnetic resonance imaging and magnetic resonance spectroscopy studies suggest possible differences between patients with social phobia and healthy controls in respect of dopamine, serotonin and second-messenger function. In aggregate, these studies have provided some neurobiological basis for separating social phobia from panic disorder and non-psychiatric healthy controls.

  11. [What brings neurobiology to addictions?

    Science.gov (United States)

    Lenoir, Magalie; Noble, Florence

    2016-12-01

    Addictions are multifactorial, and there are no experimental models replicating all aspects of this pathology. The development of animal models reproducing the clinical symptoms of addictions allows significant advances in the knowledge of the neurobiological processes involved in addiction. Preclinical data highlight different neuroadaptations according to the routes of administration, speeds of injection and frequencies of exposure to drugs of abuse. The neuroadaptations induced by an exposure to drugs of abuse follow dynamic processes in time. Despite significant progresses in the knowledge of neurobiology of addictions allowing to propose new therapeutic targets, the passage of new drugs in clinical is often disappointing. The lack of treatment efficacy reported in clinical trials is probably due to a very important heterogeneity of patients with distinct biological and genetic factors, but also with different patterns of consumption that can lead to different neuroadaptations, as clearly observed in preclinical studies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Neurobiology of Intimate Relationships

    Directory of Open Access Journals (Sweden)

    Ozge Saracli

    2012-12-01

    Full Text Available The limbic brain appears to be the source of basic emotions and urges. In contrast the neocortex gives humans the ability to think in abstract and symbolic terms and to use language. Emotions by neural projections from the limbic system to neocortex influence all aspect of cognition, from perception to rational decision making. Although the cases whose intellectual and motor abilities appeared fully functional, decision making ability and emotional processing impaired together after a damage to the ventromedial prefrontal lobes suggest that the emotions had priority in the brain processing. The effectiveness of the psychotherapy is thought to be related to the left prefrontal cortex activity. The rational decisions are changing easily under the stressful moments and experiencing the same problems over and over again. This concept may explain why the couples under the stressful conditions may easily fall into radicalism, and decide that they are right but the others wrong. The specific kinds of conflict behaviors between couples like the criticism, contempt, defensiveness and stonewalling are correlated with the physical signs of the amygdala activation. For this reason, before the people to engage new forms of thought and behavior must notice and change the emotional processes. In the light of these concepts in addition the cognitive and behavioral approach, it would not be wrong to think that the therapy working with the emotional techniques will be more successful.

  13. Neurobiology of Resilience

    Science.gov (United States)

    Russo, Scott J.; Murrough, James W.; Han, Ming–Hu; Charney, Dennis S.; Nestler, Eric J.

    2013-01-01

    Humans exhibit a remarkable degree of resilience in the face of extreme stress, with most resisting the development of neuropsychiatric disorders. Over the past 5 years, there has been increasing interest in the active, adaptive coping mechanisms of resilience; however, in humans, the majority of published work focuses on correlative neuroendocrine markers that are associated with a resilient phenotype. In this review, we highlight a growing literature in rodents that is starting to complement the human work by identifying the active behavioral, neural, molecular, and hormonal basis of resilience. The therapeutic implications of these findings are important and can pave the way for an innovative new approach to drug development for a range of stress–related syndromes. PMID:23064380

  14. The Neurobiology of Anesthetic Emergence.

    Science.gov (United States)

    Tarnal, Vijay; Vlisides, Phillip E; Mashour, George A

    2016-07-01

    Achieving a smooth and rapid emergence from general anesthesia is of particular importance for neurosurgical patients and is a clinical goal for neuroanesthesiologists. Recent data suggest that the process of emergence is not simply the mirror image of induction, but rather controlled by distinct neural circuits. In this narrative review, we discuss (1) hysteresis, (2) the concept of neural inertia, (3) the asymmetry between the neurobiology of induction and emergence, and (4) recent attempts at actively inducing emergence.

  15. Applications of carbon nanotubes in neurobiology.

    Science.gov (United States)

    Malarkey, Erik B; Parpura, Vladimir

    2007-01-01

    Carbon nanotubes are one of the most promising materials for the electronics, computer and aerospace industries. There are numerous properties of carbon nanotubes that make them attractive for applications in neurobiology: small size, flexibility, strength, inertness, electrical conductivity and ease of modification with biological compounds. Here, we discuss the current applications of carbon nanotubes in neuroscience. Carbon nanotubes and their derivatives can be used as substrates/scaffolds for neural cell growth. The chemical properties of carbon nanotubes can be systematically varied by attaching different functional groups; manipulation of the charge carried by functionalized carbon nanotubes can be used to control the outgrowth and branching pattern of neuronal processes. The ease with which carbon nanotubes can be patterned makes them attractive for studying the organization of neural networks and the electrical conductivity of nanotubes can provide a mechanism to monitor or stimulate neurons through the substrate itself. However, it is important to recognize that carbon nanotubes themselves can affect neuronal function, most likely by interaction with ion channels. The use of carbon nanotubes in neurobiology is a promising application that has the potential to develop new methods and techniques to advance the study of neuroscience.

  16. Apolipoprotein E: from lipid transport to neurobiology

    Science.gov (United States)

    Hauser, Paul S.; Narayanaswami, Vasanthy; Ryan, Robert O.

    2010-01-01

    Apolipoprotein (apo) E has a storied history as a lipid transport protein. The integral association between cholesterol homeostasis and lipoprotein clearance from circulation are intimately related to apoE's function as a ligand for cell surface receptors of the low density lipoprotein receptor family. The receptor binding properties of apoE are strongly influenced by isoform specific amino acid differences as well as the lipidation state of the protein. As understanding of apoE as a structural component of circulating plasma lipoproteins has evolved, exciting developments in neurobiology have revitalized interest in apoE. The strong and enduring correlation between the apoE4 isoform and age of onset and increased risk of Alzheimer's disease has catapulted apoE to the forefront of neurobiology. Using genetic tools generated for study of apoE lipoprotein metabolism, transgenic “knock-in” and gene-disrupted mice are now favored models for study of its role in a variety of neurodegenerative diseases. Key structural knowledge of apoE and isoform specific differences is driving research activity designed to elucidate how a single amino acid change can manifest such profoundly significant pathological consequences. This review describes apoE through a lens of structure-based knowledge that leads to hypotheses that attempt to explain the functions of apoE and isoform specific effects relating to disease mechanism. PMID:20854843

  17. [Neurobiology of imprinting].

    Science.gov (United States)

    Ohki-Hamazaki, Hiroko

    2012-06-01

    Imprinting is an example of learning and memory acquisition in infancy. In the case of precocial birds, such as geese, ducks, and chickens, the baby birds learn the characteristics of the first moving object that they see within a critical period, and they imprint on it and follow it around. We analyzed the neural basis of this behavior in order to understand the neural mechanism of learning and memory in infancy. Information pertaining to a visual imprinting stimulus is recognized and processed in the visual Wulst, a region that corresponds to the mammalian visual cortex. It is then transmitted to the posterior region of the telencephalon, followed by the core region of the hyperpallium densocellulare (HDCo), periventricular region of the hyperpallium densocellulare (HDPe), and finally, the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. Memory is stored in the IMM. After imprint training, plastic changes are observed in the visual Wulst as well as in the neurons of this circuit. HDCo cells, located at the center of this circuit, express N-methyl-D-aspartate (NMDA) receptors containing the NMDA receptor (NR) 2B subunit; the expression of this receptor increased after the imprint training. Inhibition of this receptor in the cells of the HDCo region leads to failure of imprinting and inactivation of this circuit. Thus, NMDA receptors bearing the NR2B subunit play a critical role in plastic changes in this circuit and in induction of imprinting.

  18. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Karine Thibault

    Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  19. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Science.gov (United States)

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  20. Depression and Chronic Liver Diseases: Are There Shared Underlying Mechanisms?

    Directory of Open Access Journals (Sweden)

    Xiaoqin Huang

    2017-05-01

    Full Text Available The occurrence of depression is higher in patients with chronic liver disease (CLD than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD may provide more information to understand both diseases.

  1. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    Science.gov (United States)

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  2. Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations.

    Science.gov (United States)

    King, Joseph A; Frank, Guido K W; Thompson, Paul M; Ehrlich, Stefan

    2018-02-01

    Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and extreme weight loss. Pseudoatrophic brain changes are often readily visible in individual brain scans, and AN may be a valuable model disorder to study structural neuroplasticity. Structural magnetic resonance imaging studies have found reduced gray matter volume and cortical thinning in acutely underweight patients to normalize following successful treatment. However, some well-controlled studies have found regionally greater gray matter and persistence of structural alterations following long-term recovery. Findings from diffusion tensor imaging studies of white matter integrity and connectivity are also inconsistent. Furthermore, despite the severity of AN, the number of existing structural neuroimaging studies is still relatively low, and our knowledge of the underlying cellular and molecular mechanisms for macrostructural brain changes is rudimentary. We critically review the current state of structural neuroimaging in AN and discuss the potential neurobiological basis of structural brain alterations in the disorder, highlighting impediments to progress, recent developments, and promising future directions. In particular, we argue for the utility of more standardized data collection, adopting a connectomics approach to understanding brain network architecture, employing advanced magnetic resonance imaging methods that quantify biomarkers of brain tissue microstructure, integrating data from multiple imaging modalities, strategic longitudinal observation during weight restoration, and large-scale data pooling. Our overarching objective is to motivate carefully controlled research of brain structure in eating disorders, which will ultimately help predict therapeutic response and improve treatment. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Phytochemicals: Potential in Management of Climacteric Neurobiology.

    Science.gov (United States)

    Chopra, Kanwaljit; Bansal, Seema; Sachdeva, Anand Kamal

    2016-01-01

    Menopause jeopardizes the integrity of brain and makes it vulnerable to various diseases, both of psychiatric and degenerative nature. Exogenous estrogen supplementation confers neuroprotection but the results of Women's Health Initiative (WHI), Million Women Study (MWS) and incidence of endometrial cancer, breast cancer and venous thromboembolism reported with estrogen use have engendered doubts over its clinical translation for postmenopausal neurological disorders. Scientific community and general public have started recognizing the protective potential of phytochemicals in climacteric medicine. These phytochemicals are plant-derived, non-steroidal bioactive estrogenic compounds. Emerging preclinical studies have suggested that these phytochemicals display potential benefits in mitigating postmenopausal depression, anxiety, cerebral ischemia and cognitive dysfunction. Thus, the aim of present review is: a) to give an overview of neuroprotective action of estrogen, b) to address the chemical and pharmacological features of various classes of phytoestrogens, and c) to present preclinical and clinical evidence of effect of phytoestrogens on climacteric neurobiology with their possible mechanisms of action.

  4. Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

    Science.gov (United States)

    Cross, Sarah J; Lotfipour, Shahrdad; Leslie, Frances M

    2017-03-01

    Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

  5. The neurobiology of climate change

    Science.gov (United States)

    O'Donnell, Sean

    2018-02-01

    Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

  6. Neurobiology of aggression and violence

    OpenAIRE

    Ortega-Escobar, Joaquín; Alcázar-Córcoles, Miguel Ángel

    2016-01-01

    La neurobiología de la agresión y la violencia es de interés para la psicología jurídica porque buenaparte de la conducta delictiva tiene componentes violentos. En esta revisión se definen en primer lugarambos conceptos, para diferenciar a continuación los tipos de agresión (impulsiva vs. instrumental) queaparecen en la literatura científica y finalmente analizar las estructuras nerviosas que según los estudiossobre lesiones cerebrales o de neuroimagen están asociadas con la agresión. Esta re...

  7. Biodiversity and ecosystem stability: a synthesis of underlying mechanisms.

    Science.gov (United States)

    Loreau, Michel; de Mazancourt, Claire

    2013-05-01

    There is mounting evidence that biodiversity increases the stability of ecosystem processes in changing environments, but the mechanisms that underlie this effect are still controversial and poorly understood. Here, we extend mechanistic theory of ecosystem stability in competitive communities to clarify the mechanisms underlying diversity-stability relationships. We first explain why, contrary to a widely held belief, interspecific competition should generally play a destabilising role. We then explore the stabilising effect of differences in species' intrinsic rates of natural increase and provide a synthesis of various potentially stabilising mechanisms. Three main mechanisms are likely to operate in the stabilising effects of biodiversity on ecosystem properties: (1) asynchrony of species' intrinsic responses to environmental fluctuations, (2) differences in the speed at which species respond to perturbations, (3) reduction in the strength of competition. The first two mechanisms involve temporal complementarity between species, while the third results from functional complementarity. Additional potential mechanisms include selection effects, behavioural changes resulting from species interactions and mechanisms arising from trophic or non-trophic interactions and spatial heterogeneity. We conclude that mechanistic trait-based approaches are key to predicting the effects of diversity on ecosystem stability and to bringing the old diversity-stability debate to a final resolution. © 2013 John Wiley & Sons Ltd/CNRS.

  8. Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development.

    Science.gov (United States)

    Hostinar, Camelia E; Sullivan, Regina M; Gunnar, Megan R

    2014-01-01

    Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  9. Insights into the mechanisms underlying colonic motor patterns

    Science.gov (United States)

    Dinning, Phil G.; Brookes, Simon J.; Costa, Marcello

    2016-01-01

    Abstract In recent years there have been significant technical and methodological advances in our ability to record the movements of the gastrointestinal tract. This has led to significant changes in our understanding of the different types of motor patterns that exist in the gastrointestinal tract (particularly the large intestine) and in our understanding of the mechanisms underlying their generation. Compared with other tubular smooth muscle organs, a rich variety of motor patterns occurs in the large intestine. This reflects a relatively autonomous nervous system in the gut wall, which has its own unique population of sensory neurons. Although the enteric nervous system can function independently of central neural inputs, under physiological conditions bowel motility is influenced by the CNS: if spinal pathways are disrupted, deficits in motility occur. The combination of high resolution manometry and video imaging has improved our knowledge of the range of motor patterns and provided some insight into the neural and mechanical factors underlying propulsion of contents. The neural circuits responsible for the generation of peristalsis and colonic migrating motor complexes have now been identified to lie within the myenteric plexus and do not require inputs from the mucosa or submucosal ganglia for their generation, but can be modified by their activity. This review will discuss the recent advances in our understanding of the different patterns of propagating motor activity in the large intestine of mammals and how latest technologies have led to major changes in our understanding of the mechanisms underlying their generation. PMID:26990133

  10. Neurobiology of value integration: when value impacts valuation.

    Science.gov (United States)

    Park, Soyoung Q; Kahnt, Thorsten; Rieskamp, Jörg; Heekeren, Hauke R

    2011-06-22

    Everyday choice options have advantages (positive values) and disadvantages (negative values) that need to be integrated into an overall subjective value. For decades, economic models have assumed that when a person evaluates a choice option, different values contribute independently to the overall subjective value of the option. However, human choice behavior often violates this assumption, suggesting interactions between values. To investigate how qualitatively different advantages and disadvantages are integrated into an overall subjective value, we measured the brain activity of human subjects using fMRI while they were accepting or rejecting choice options that were combinations of monetary reward and physical pain. We compared different subjective value models on behavioral and neural data. These models all made similar predictions of choice behavior, suggesting that behavioral data alone are not sufficient to uncover the underlying integration mechanism. Strikingly, a direct model comparison on brain data decisively demonstrated that interactive value integration (where values interact and affect overall valuation) predicts neural activity in value-sensitive brain regions significantly better than the independent mechanism. Furthermore, effective connectivity analyses revealed that value-dependent changes in valuation are associated with modulations in subgenual anterior cingulate cortex-amygdala coupling. These results provide novel insights into the neurobiological underpinnings of human decision making involving the integration of different values.

  11. The Neurobiology of Orofacial Pain and Sleep and Their Interactions.

    Science.gov (United States)

    Lavigne, G J; Sessle, B J

    2016-09-01

    This article provides an overview of the neurobiology of orofacial pain as well as the neural processes underlying sleep, with a particular focus on the mechanisms that underlie pain and sleep interactions including sleep disorders. Acute pain is part of a hypervigilance system that alerts the individual to injury or potential injury of tissues. It can also disturb sleep. Disrupted sleep is often associated with chronic pain states, including those that occur in the orofacial region. The article presents many insights that have been gained in the last few decades into the peripheral and central mechanisms involved in orofacial pain and its modulation, as well as the circuits and processes in the central nervous system that underlie sleep. Although it has become clear that sleep is essential to preserve and maintain health, it has also been found that pain, particularly chronic pain, is commonly associated with disturbed sleep. In the presence of chronic pain, a circular relationship may prevail, with mutual deleterious influences causing an increase in pain and a disruption of sleep. This article also reviews findings that indicate that reducing orofacial pain and improving sleep need to be targeted together in the management of acute to chronic orofacial pain states in order to improve an orofacial pain patient's quality of life, to prevent mood alterations or exacerbation of sleep disorder (e.g., insomnia, sleep-disordered breathing) that can negatively affect their pain, and to promote healing and optimize their health. © International & American Associations for Dental Research 2016.

  12. Molecular Neurobiology and Promising New Treatment in Depression

    Directory of Open Access Journals (Sweden)

    Sang Won Jeon

    2016-03-01

    Full Text Available The limited effects of currently available antidepressants are becoming an urgent issue in depression research. It takes a long time to determine treatment effects, and the overall remission rate is low. Although we expect the development of non-monoamine antidepressants in the near future, efforts in this regard over the past several decades have not yet been compensated. Thus, researchers and clinicians should clarify the neurobiological mechanisms of integrated modulators that regulate changes in genes, cells, the brain, and behaviors associated with depression. In this study, we review molecular neurobiological theories and new treatments for depression. Beyond neuroanatomy and monoamine theory, we discuss cells and molecules, neural plasticity, neurotrophisms, endocrine mechanisms, immunological mechanisms, genetics, circadian rhythms, and metabolic regulation in depression. In addition, we introduce the possibility of new antidepressant drug development using protein translation signaling (mTOR pathways.

  13. Biological sex affects the neurobiology of autism

    Science.gov (United States)

    Lombardo, Michael V.; Suckling, John; Ruigrok, Amber N. V.; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C. L.; Craig, Michael C.; Murphy, Declan G. M.; Bullmore, Edward T.; Baron-Cohen, Simon

    2013-01-01

    In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the ‘extreme male brain’ theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P females with autism remains to be understood. Future research should stratify by biological sex to reduce heterogeneity and to provide greater insight into the neurobiology of autism. PMID:23935125

  14. Biological sex affects the neurobiology of autism.

    Science.gov (United States)

    Lai, Meng-Chuan; Lombardo, Michael V; Suckling, John; Ruigrok, Amber N V; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C L; Craig, Michael C; Murphy, Declan G M; Bullmore, Edward T; Baron-Cohen, Simon

    2013-09-01

    In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the 'extreme male brain' theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P neurobiology of autism.

  15. Nanomaterial-modulated autophagy: underlying mechanisms and functional consequences.

    Science.gov (United States)

    Zheng, Wei; Wei, Min; Li, Song; Le, Weidong

    2016-06-01

    Autophagy is an essential lysosome-dependent process that controls the quality of the cytoplasm and maintains cellular homeostasis, and dysfunction of this protein degradation system is correlated with various disorders. A growing body of evidence suggests that nanomaterials (NMs) have autophagy-modulating effects, thus predicting a valuable and promising application potential of NMs in the diagnosis and treatment of autophagy-related diseases. NMs exhibit unique physical, chemical and biofunctional properties, which may endow NMs with capabilities to modulate autophagy via various mechanisms. The present review highlights the impacts of various NMs on autophagy and their functional consequences. The possible underlying mechanisms for NM-modulated autophagy are also discussed.

  16. Application of fracture mechanics to graphite under complex stress conditions

    Science.gov (United States)

    Yahr, G. T.; Valachovic, R. S.

    1974-01-01

    The purpose of this study was to examine the applicability of linear-elastic fracture mechanics to graphite under multiaxial stress conditions. The specimens were thick-walled graphite cylinders with flat heads which were internally pressurized. Two series of specimens were used. The first series had complete circumferential notches machined diagonally into the head-cylinder juncture region, while the second series was unnotched. The methods of linear-elastic fracture mechanics and a finite-element analysis were used to predict pressures to cause fracture for both notched and unnotched specimens.

  17. The neurobiology of addictive disorders.

    Science.gov (United States)

    Ross, Stephen; Peselow, Eric

    2009-01-01

    Addiction is increasingly understood as a neurobiological illness where repetitive substance abuse corrupts the normal circuitry of rewarding and adaptive behaviors causing drug-induced neuroplastic changes. The addictive process can be examined by looking at the biological basis of substance initiation to the progression of substance abuse to dependence to the enduring risk of relapse. Critical neurotransmitters and neurocircuits underlie the pathological changes at each of these stages. Enhanced dopamine transmission in the nucleus accumbens is part of the common pathway for the positively rewarding aspects of drugs of abuse and for initiation of the addictive process. F-Aminobutyric acid,opioid peptides, serotonin, acetylcholine, the endocannabinoids, and glutamate systems also play a role in the initial addictive process. Dopamine also plays a key role in conditioned responses to drugs of abuse, and addiction is now recognized as a disease of pathological learning and memory. In the path from substance abuse to addiction, the neurochemistry shifts from a dopamine-based behavioral system to a predominantly glutamate-based one marked by dysregulated glutamate transmission from the prefrontal cortex to the nucleus accumbens in relation to drug versus biologically oriented stimuli. This is a core part of the executive dysfunction now understood as one of the hallmark features of addiction that also includes impaired decision making and impulse dysregulation.Understanding the neurobiology of the addictive process allows for a theoretical psychopharmacological approach to treating addictive disorders,one that takes into account biological interventions aimed at particular stages of the illness.

  18. Mechanical Property Analysis of Circular Polymer Membrane under Uniform Pressure

    Directory of Open Access Journals (Sweden)

    Sang Jianbing

    2017-01-01

    Full Text Available Mechanical property analysis of circular hyperelastic polymer membrane under uniform pressure has been researched in this work. The polymer membrane material is assumed to be homogeneous and isotropic and incompressibility of materials has been considered. Based on the modified stain energy function from Gao and nonmomental theory of axial symmetry thin shell, finite deformation analysis of polymer membrane under uniform pressure has been proposed in current configuration and governing equations of polymer membrane have been achieved. By utilizing the boundary condition, theoretical results of governing equations have been obtained and vertical displacement distribution and stress distribution have been achieved. The results show that the constitutive parameter n has a strengthening effect on the polymer material and the constitutive parameter α plays a controlling role for the second strain invariant I2, which also has a strengthening effect on the polymer material. This research has revealed the deformational mechanism of polymer membrane and provided reference for the design of polymer membrane.

  19. Mechanism Underlying Levofloxacin Uptake by Human Polymorphonuclear Neutrophils

    OpenAIRE

    Vazifeh, Doina; Bryskier, André; Labro, Marie-Thérèse

    1999-01-01

    The mechanism of radiolabeled levofloxacin ([3H]levofloxacin) uptake by human polymorphonuclear neutrophils (PMNs) was investigated by a classical velocity centrifugation technique. PMNs were incubated with levofloxacin for 5 to 180 min under various conditions before centrifugation through an oil cushion. Radioactivity was measured in the cell pellet to determine the amount of cell-associated drug. The uptake of levofloxacin was moderate with a cellular concentration/extracellular concentrat...

  20. Control of a perturbed under-actuated mechanical system

    KAUST Repository

    Zayane, Chadia

    2015-11-05

    In this work, the trajectory tracking problem for an under-actuated mechanical system in presence of unknown input disturbances is addressed. The studied inertia wheel inverted pendulum falls in the class of non minimum phase systems. The proposed high order sliding mode control architecture including a controller and differentiator allows to track accurately the predefined trajectory and to stabilize the internal dynamics. The robustness of the proposed approach is illustrated through different perturbation and output noise configurations.

  1. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  2. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  3. Contactins in the neurobiology of autism.

    Science.gov (United States)

    Zuko, Amila; Kleijer, Kristel T E; Oguro-Ando, Asami; Kas, Martien J H; van Daalen, Emma; van der Zwaag, Bert; Burbach, J Peter H

    2013-11-05

    Autism is a disease of brain plasticity. Inspiring work of Willem Hendrik Gispen on neuronal plasticity has stimulated us to investigate gene defects in autism and the consequences for brain development. The central process in the pathogenesis of autism is local dendritic mRNA translation which is dependent on axodendritic communication. Hence, most autism-related gene products (i) are part of the protein synthesis machinery itself, (ii) are components of the mTOR signal transduction pathway, or (iii) shape synaptic activity and plasticity. Accordingly, prototype drugs have been recognized that interfere with these pathways. The contactin (CNTN) family of Ig cell adhesion molecules (IgCAMs) harbours at least three members that have genetically been implicated in autism: CNTN4, CNTN5, and CNTN6. In this chapter we review the genetic and neurobiological data underpinning their role in normal and abnormal development of brain systems, and the consequences for behavior. Although data on each of these CNTNs are far from complete, we tentatively conclude that these three contactins play roles in brain development in a critical phase of establishing brain systems and their plasticity. They modulate neuronal activities, such as neurite outgrowth, synaptogenesis, survival, guidance of projections and terminal branching of axons in forming neural circuits. Current research on these CNTNs concentrate on the neurobiological mechanism of their developmental functions. A future task will be to establish if proposed pharmacological strategies to counteract ASD-related symptomes can also be applied to reversal of phenotypes caused by genetic defects in these CNTN genes. © 2013 Elsevier B.V. All rights reserved.

  4. Mechanical properties of graphene nanoribbons under uniaxial tensile strain

    Science.gov (United States)

    Yoneyama, Kazufumi; Yamanaka, Ayaka; Okada, Susumu

    2018-03-01

    Based on the density functional theory with the generalized gradient approximation, we investigated the mechanical properties of graphene nanoribbons in terms of their edge shape under a uniaxial tensile strain. The nanoribbons with armchair and zigzag edges retain their structure under a large tensile strain, while the nanoribbons with chiral edges are fragile against the tensile strain compared with those with armchair and zigzag edges. The fracture started at the cove region, which corresponds to the border between the zigzag and armchair edges for the nanoribbons with chiral edges. For the nanoribbons with armchair edges, the fracture started at one of the cove regions at the edges. In contrast, the fracture started at the inner region of the nanoribbons with zigzag edges. The bond elongation under the tensile strain depends on the mutual arrangement of covalent bonds with respect to the strain direction.

  5. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  6. Evolutionary themes in the neurobiology of social cognition.

    Science.gov (United States)

    Weitekamp, Chelsea A; Hofmann, Hans A

    2014-10-01

    Remarkable examples of social cognition have been described across a diverse range of species, yet surprisingly little is known about the neurobiological underpinnings of these behaviors. Recent studies suggest that the molecular pathways and neural networks that mediate social behavior have been relatively conserved across vertebrate evolution, suggesting that shared mechanisms may drive adaptive behavioral responses to social stimuli. Here, we review recent advances in the neurobiology of flexible and context-dependent social behaviors across vertebrate taxa, focusing on female mate choice, pair-bonding, and aggressive behavior. Furthermore, we highlight the outstanding opportunities for uncovering the mechanisms mediating cooperative behavior, an exemplar of social cognition. We suggest a framework for investigating context-dependent neural organization and the evoked neural response to social stimuli. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The Neurobiology of Impulsive Aggression.

    Science.gov (United States)

    Blair, Robert J R

    2016-02-01

    This selective review provides a model of the neurobiology of impulsive aggression from a cognitive neuroscience perspective. It is argued that prototypical cases of impulsive aggression, those associated with anger, involve the recruitment of the acute threat response system structures; that is, the amygdala, hypothalamus, and periaqueductal gray. It is argued that whether the recruitment of these structures results in impulsive aggression or not reflects the functional roles of ventromedial frontal cortex and dorsomedial frontal and anterior insula cortex in response selection. It is also argued that impulsive aggression may occur because of impaired decision making. The aggression may not be accompanied by anger, but it will reflect disrupted evaluation of the rewards/benefits of the action.

  8. Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

    Science.gov (United States)

    Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

    2017-03-01

    The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Physical mechanisms underlying the strain-rate-dependent mechanical behavior of kangaroo shoulder cartilage

    Science.gov (United States)

    Thibbotuwawa, Namal; Oloyede, Adekunle; Li, Tong; Singh, Sanjleena; Senadeera, Wijitha; Gu, YuanTong

    2015-09-01

    Due to anatomical and biomechanical similarities to human shoulder, kangaroo was chosen as a model to study shoulder cartilage. Comprehensive enzymatic degradation and indentation tests were applied on kangaroo shoulder cartilage to study mechanisms underlying its strain-rate-dependent mechanical behavior. We report that superficial collagen plays a more significant role than proteoglycans in facilitating strain-rate-dependent behavior of the kangaroo shoulder cartilage. By comparing the mechanical properties of degraded and normal cartilages, it was noted that proteoglycan and collagen degradation significantly compromised strain-rate-dependent mechanical behavior of the cartilage. Superficial collagen contributed equally to the tissue behavior at all strain-rates. This is different to the studies reported on knee cartilage and confirms the importance of superficial collagen on shoulder cartilage mechanical behavior. A porohyperelastic numerical model also indicated that collagen disruption would lead to faster damage of the shoulder cartilage than when proteoglycans are depleted.

  10. Results of airway clearance techniques in respiratory mechanics of preterm neonates under mechanical ventilation.

    Science.gov (United States)

    Santos, Mara Lisiane de Moraes Dos; Souza, Lais Alves de; Batiston, Adriane Pires; Palhares, Durval Batista

    2009-06-01

    This research aimed to evaluate the repercussions of specific chest physiotherapy procedures in mean airway resistance and in dynamic compliance in preterm infants in mechanical ventilation. Eighteen preterm infants in conventional mechanical ventilation were submitted to one session of chest physiotherapy (manual chest compression during expiration + intermittent aspiration of intratracheal cannula). Mean airway resistance and dynamic compliance measurements were taken prior to, 10, 40 and 70 minutes after intervention using a pneumotachograph with graphic display (Newport Navigator GM-250®), coupled to a flow transducer (Varfley-Bicore®). For analysis of results the infants were divided into 2 groups; less than 5 days (group mechanical ventilation 5) on mechanical ventilation. Values were analyzed by Friedman Test, with Dunn's Multiple Comparisons Test (p5 mean airway resistance had a significant reduction at the 10th (ptechniques used in preterm neonates under conventional mechanical ventilation >5 improved mean airway resistance and dynamic compliance, with best results for the mean airway resistance.

  11. Neurobiological alterations induced by exercise and their impact on depressive disorders [corrected].

    Science.gov (United States)

    Helmich, Ingo; Latini, Alexandra; Sigwalt, Andre; Carta, Mauro Giovanni; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Budde, Henning

    2010-11-30

    The impact of physical activity on brain metabolic functions has been investigated in different studies and there is growing evidence that exercise can be used as a preventive and rehabilitative intervention in the treatment of depressive disorders. However, the exact neuronal mechanisms underlying the latter phenomenon have not been clearly elucidated. The present article summarises key results derived from studies that focussed on the neurobiological impact of exercise on brain metabolic functions associated with depressive disorders. Since major depressive disorder (MDD) is a life threatening disease it is of great significance to find reliable strategies to prevent or to cure this illness. Therefore, the aim of this paper is to review (1) the physiological relationship between physical activity and depressive disorders and (2) the potential neurobiological alterations induced by exercise that might lead to the relief of mental disorders like depression. We searched electronic databases for literature concerning the relationship between exercise and depression from 1963 until 2009. The data suggests an association between physical inactivity and higher levels of depressive symptoms. Properly designed studies could show that exercise training can be as effective as antidepressive medications. The exact mechanisms how exercise affects the brain are not fully understood and the literature lacks of well designed studies concerning the effects of exercise training on depressive disorders. But the observed antidepressant actions of exercise are strong enough that it already can be used as an alternative to current medications in the treatment of depressive disorders.

  12. Neurobiological Alterations Induced by Exercise and Their Impact on Depressive Disorders

    Science.gov (United States)

    Helmich, Ingo; Latini, Alexandra; Sigwalt, Andre; Carta, Mauro Giovanni; Machado, Sergio; Velasques, Bruna; Ribeiro, Pedro; Budde, Henning

    2010-01-01

    Background: The impact of physical activity on brain metabolic functions has been investigated in different studies and there is growing evidence that exercise can be used as a preventive and rehabilitative intervention in the treatment of depressive disorders. However, the exact neuronal mechanisms underlying the latter phenomenon have not been clearly elucidated. The present article summarises key results derived from studies that focussed on the neurobiological impact of exercise on brain metabolic functions associated with depressive disorders. Since major depressive disorder (MDD) is a life threatening disease it is of great significance to find reliable strategies to prevent or to cure this illness. Therefore, the aim of this paper is to review (1) the physiological relationship between physical activity and depressive disorders and (2) the potential neurobiological alterations induced by exercise that might lead to the relief of mental disorders like depression. Methods: We searched electronic databases for literature concerning the relationship between exercise and depression from 1963 until 2009. Results: The data suggests an association between physical inactivity and higher levels of depressive symptoms. Properly designed studies could show that exercise training can be as effective as antidepressive medications. Conclusion: The exact mechanisms how exercise affects the brain are not fully understood and the literature lacks of well designed studies concerning the effects of exercise training on depressive disorders. But the observed antidepressant actions of exercise are strong enough that it already can be used as an alternative to current medications in the treatment of depressive disorders. PMID:21283646

  13. Mechanisms underlying astringency: introduction to an oral tribology approach

    Science.gov (United States)

    Upadhyay, Rutuja; Brossard, Natalia; Chen, Jianshe

    2016-03-01

    Astringency is one of the predominant factors in the sensory experience of many foods and beverages ranging from wine to nuts. The scientific community is discussing mechanisms that explain this complex phenomenon, since there are no conclusive results which correlate well with sensory astringency. Therefore, the mechanisms and perceptual characteristics of astringency warrant further discussion and investigation. This paper gives a brief introduction of the fundamentals of oral tribology forming a basis of the astringency mechanism. It discusses the current state of the literature on mechanisms underlying astringency describing the existing astringency models. The review discusses the crucial role of saliva and its physiology which contributes significantly in astringency perception in the mouth. It also provides an overview of research concerned with the physiological and psychophysical factors that mediate the perception of this sensation, establishing the ground for future research. Thus, the overall aim of the review is to establish the critical roles of oral friction (thin-film lubrication) in the sensation of astringency and possibly of some other specific sensory features.

  14. The neurobiology of speech perception decline in aging.

    Science.gov (United States)

    Bilodeau-Mercure, Mylène; Lortie, Catherine L; Sato, Marc; Guitton, Matthieu J; Tremblay, Pascale

    2015-03-01

    Speech perception difficulties are common among elderlies; yet the underlying neural mechanisms are still poorly understood. New empirical evidence suggesting that brain senescence may be an important contributor to these difficulties has challenged the traditional view that peripheral hearing loss was the main factor in the etiology of these difficulties. Here, we investigated the relationship between structural and functional brain senescence and speech perception skills in aging. Following audiometric evaluations, participants underwent MRI while performing a speech perception task at different intelligibility levels. As expected, with age speech perception declined, even after controlling for hearing sensitivity using an audiological measure (pure tone averages), and a bioacoustical measure (DPOAEs recordings). Our results reveal that the core speech network, centered on the supratemporal cortex and ventral motor areas bilaterally, decreased in spatial extent in older adults. Importantly, our results also show that speech skills in aging are affected by changes in cortical thickness and in brain functioning. Age-independent intelligibility effects were found in several motor and premotor areas, including the left ventral premotor cortex and the right supplementary motor area (SMA). Age-dependent intelligibility effects were also found, mainly in sensorimotor cortical areas, and in the left dorsal anterior insula. In this region, changes in BOLD signal modulated the relationship between age and speech perception skills suggesting a role for this region in maintaining speech perception in older ages. These results provide important new insights into the neurobiology of speech perception in aging.

  15. The Neurobiological Grounding of Persistent Stuttering: from Structure to Function.

    Science.gov (United States)

    Neef, Nicole E; Anwander, Alfred; Friederici, Angela D

    2015-09-01

    Neuroimaging and transcranial magnetic stimulation provide insights into the neuronal mechanisms underlying speech disfluencies in chronic persistent stuttering. In the present paper, the goal is not to provide an exhaustive review of existing literature, but rather to highlight robust findings. We, therefore, conducted a meta-analysis of diffusion tensor imaging studies which have recently implicated disrupted white matter connectivity in stuttering. A reduction of fractional anisotropy in persistent stuttering has been reported at several different loci. Our meta-analysis revealed consistent deficits in the left dorsal stream and in the interhemispheric connections between the sensorimotor cortices. In addition, recent fMRI meta-analyses link stuttering to reduced left fronto-parieto-temporal activation while greater fluency is associated with boosted co-activations of right fronto-parieto-temporal areas. However, the physiological foundation of these irregularities is not accessible with MRI. Complementary, transcranial magnetic stimulation (TMS) reveals local excitatory and inhibitory regulation of cortical dynamics. Applied to a speech motor area, TMS revealed reduced speech-planning-related neuronal dynamics at the level of the primary motor cortex in stuttering. Together, this review provides a focused view of the neurobiology of stuttering to date and may guide the rational design of future research. This future needs to account for the perpetual dynamic interactions between auditory, somatosensory, and speech motor circuits that shape fluent speech.

  16. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  17. Ferroelastic domain switching dynamics under electrical and mechanical excitations.

    Science.gov (United States)

    Gao, Peng; Britson, Jason; Nelson, Christopher T; Jokisaari, Jacob R; Duan, Chen; Trassin, Morgan; Baek, Seung-Hyub; Guo, Hua; Li, Linze; Wang, Yiran; Chu, Ying-Hao; Minor, Andrew M; Eom, Chang-Beom; Ramesh, Ramamoorthy; Chen, Long-Qing; Pan, Xiaoqing

    2014-05-02

    In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.

  18. Quasi-nano wear mechanism under repeated impact contact loading

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A new quasi-nano wear mechanism (QNWM) has been proposed in this paper based on the facts of wear curve turning under high energy impact contact loading.Its characteristic is that the wear rate of QNWM is only 1/10-1/3 that of delamination mechanism at the same energy density.The diameters of wear debris and pits on the worn surfaces fall into the quasi-nanometer scale (about 50-120 nm).The necessary and sufficient conditions,which bring about the QNWM,are:(i) the nano-structure (nano-crystalline + amorphous phase) in impact contact surface layer has formed by the intensive impact strain;(ii) the delamination wear cracking in sub-surface layer must be restrained;(iii) the microcracks of QNWM are produced in amorphous phase of surface nano-structure layer rather than in nano-crystalline.

  19. Mechanical Design of AM Fabricated Prismatic Rods under Torsion

    Directory of Open Access Journals (Sweden)

    Manzhirov Alexander V.

    2017-01-01

    Full Text Available We study the stress-strain state of viscoelastic prismatic rods fabricated or repaired by additive manufacturing technologies under torsion. An adequate description of the processes involved is given by methods of a new scientific field, mechanics of growing solids. Three main stages of the deformation process (before the beginning of growth, in the course of growth, and after the termination of growth are studied. Two versions of statement of two problems are given: (i given the torque, find the stresses, displacements, and torsion; (ii given the torsion, find the stresses, displacements, and torque. Solution methods using techniques of complex analysis are presented. The results can be used in mechanical and instrument engineering.

  20. Underlying mechanisms and the evolving influence of diet

    DEFF Research Database (Denmark)

    Larsen, Lesli Hingstrup

    2012-01-01

    sizes and accurate measurements of exposures and outcomes. In addition to SNPs, epigenetic changes have been suggested to account for some of the missing heritability, and epigenetic changes have been shown to be induced by dietary intake of mothers, in utero conditions, and early nutrition and can lead...... to increased risk of developing obesity. Recently, the intestinal microbiome, the collected genome of the bacteria, also has been associated with obesity and with specific dietary profiles. The underlying mechanisms determining the susceptibility to obesity do not only include the genome but also the epigenome...

  1. THE NEUROBIOLOGY OF PAIR BONDING: INSIGHTS FROM A SOCIALLY MONOGAMOUS RODENT

    Science.gov (United States)

    Young, Kimberly A.; Gobrogge, Kyle L.; Liu, Yan; Wang, Zuoxin

    2010-01-01

    The formation of enduring relationships between adult mates (i.e., pair bonds) is an integral aspect of human social behavior and has been implicated in both physical and psychological health. However, due to the inherent complexity of these bonds and the relative rarity with which they are formed in other mammalian species, we know surprisingly little about their underlying neurobiology. Over the past few decades, the prairie vole (Microtus ochrogaster) has emerged as an animal model of pair bonding. Research in this socially monogamous rodent has provided valuable insights into the neurobiological mechanisms that regulate pair bonding behaviors. Here, we review these studies and discuss the neural regulation of three behaviors inherent to pair bonding: the formation of partner preferences, the subsequent development of selective aggression toward unfamiliar conspecifics, and the bi-parental care of young. We focus on the role of vasopressin, oxytocin, and dopamine in the regulation of these behaviors, but also discuss the involvement of other neuropeptides, neurotransmitters, and hormones. These studies may not only contribute to the understanding of pair bonding in our own species, but may also offer insight into the underlying causes of social deficits noted in several mental health disorders. PMID:20688099

  2. Crystal nucleation mechanism in melts of short polymer chains under quiescent conditions and under shear flow

    Science.gov (United States)

    Anwar, Muhammad; Berryman, Joshua T.; Schilling, Tanja

    2014-09-01

    We present a molecular dynamics simulation study of crystal nucleation from undercooled melts of n-alkanes, and we identify the molecular mechanism of homogeneous crystal nucleation under quiescent conditions and under shear flow. We compare results for n-eicosane (C20) and n-pentacontahectane (C150), i.e., one system below the entanglement length and one above, at 20%-30% undercooling. Under quiescent conditions, we observe that entanglement does not have an effect on the nucleation mechanism. For both chain lengths, the chains first align and then straighten locally, then the local density increases and finally positional ordering sets in. At low shear rates the nucleation mechanism is the same as under quiescent conditions, while at high shear rates the chains align and straighten at the same time. We report on the effects of shear rate and temperature on the nucleation rates and estimate the critical shear rates, beyond which the nucleation rates increase with the shear rate. In agreement with previous experimental observation and theoretical work, we find that the critical shear rate corresponds to a Weissenberg number of order 1. Finally, we show that the viscosity of the system is not affected by the crystalline nuclei.

  3. Getting the phenotypes right: an essential ingredient for understanding aetiological mechanisms underlying persistent violence and developing effective treatments

    Directory of Open Access Journals (Sweden)

    Sheilagh Hodgins

    2009-11-01

    Full Text Available In order to reduce societal levels of violence, it is essential to advance understanding of the neurobiological mechanisms involved in initiating and maintaining individual patterns of physical aggression. New technologies such as Magnetic Resonance Imagining and analyses of DNA provide tools for identifying these mechanisms. The reliability and validity of the results of studies using these tools depend not only on aspects of the technology, but also on the methodological rigour with which the studies are conducted, particularly with respect to characterizing the phenotype. The present article discusses five challenges confronting scientists who aim to advance understanding of the neurobiological mechanisms associated with persistent violence. These challenges are: (1 to develop evidence-based hypotheses and to design studies that test alternate hypotheses; (2 to recruit samples that are homogeneous with respect to variables that may be linked to neurobiological mechanisms underpinning violent behaviour; (3 to use reliable and valid measures in order to fully characterize participants so that the external validity of the results is evident; (4 to restrict the range of age of participants so as not to confuse developmental change with group differences; and (5 to take account of sex. Our goal is to contribute to elevating methodological standards in this new field of research and to thereby improve the validity of results and move closer to finding effective ways to reduce violence

  4. Age differences in the underlying mechanisms of stereotype threat effects.

    Science.gov (United States)

    Popham, Lauren E; Hess, Thomas M

    2015-03-01

    The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Older adults' performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Is Lead Exposure in Early Life An Environmental Risk Factor for Schizophrenia? Neurobiological Connections and Testable Hypotheses

    Science.gov (United States)

    Guilarte, Tomás R.; Opler, Mark; Pletnikov, Mikhail

    2013-01-01

    Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb2+) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb2+ exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb2+ exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders. PMID:22178136

  6. Electrochemical mechanism of tin membrane electrodeposition under ultrasonic waves.

    Science.gov (United States)

    Nan, Tianxiang; Yang, Jianguang; Chen, Bing

    2018-04-01

    Tin was electrodeposited from chloride solutions using a membrane cell under ultrasonic waves. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CHR), and chronopotentiometry were applied to investigate the electrochemical mechanism of tin electrodeposition under ultrasonic field. Chronoamperometry curves showed that the initial process of tin electrodeposition followed the diffusion controlled three-dimensional nucleation and grain growth mechanism. The analysis of the cyclic voltammetry and linear sweep voltammetry diagrams showed that the application of ultrasound can change the tin membrane electro-deposition reaction from diffusion to electrochemical control, and the optimum parameters for tin electrodeposition were H + concentration 3.5 mol·L -1 , temperature 35 °C and ultrasonic power 100 W. The coupling ultrasonic field played a role in refining the grain in this process. The growth of tin crystals showed no orientation preferential, and the tin deposition showed a tendency to form a regular network structure after ultrasonic coupling. While in the absence of ultrasonic coupling, the growth of tin crystals has a high preferential orientation, and the tin deposition showed a tendency to form tin whiskers. Ultrasonic coupling was more favorable for obtaining a more compact and smoother cathode tin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  8. Behavior of duplex stainless steel casting defects under mechanical loadings

    Energy Technology Data Exchange (ETDEWEB)

    Jayet-Gendrot, S. [Electricite de France, 77 - Moret-sur-Loing (France). Dept. of Materials Study; Gilles, P.; Migne, C. [Societe Franco-Americaine de Constructions Atomiques (FRAMATOME), 92 - Paris-La-Defense (France)

    1997-04-01

    Several components in the primary circuit of pressurized water reactors are made of cast duplex stainless steels. This material contains small casting defects, mainly shrinkage cavities, due to the manufacturing process. In safety analyses, the structural integrity of the components is studied. In order to assess the real severity of the casting defects under mechanical loadings, an experimental program was carried out. It consisted of testing, under both cyclic and monotonic solicitations, three-point bend specimens containing either a natural defect (in the form of a localized cluster of cavities) or a machined notch having the dimensions of the cluster`s envelope. The tests are analyzed in order to develop a method that takes into account the behavior of castings defects in a more realistic fashion than by an envelope crack. Various approaches are investigated, including the search of equivalent defects or of criteria based on continuum mechanics concepts, and compared with literature data. This study shows the conservatism of current safety analyses in modelling casting defects by envelope semi-elliptical cracks and contributes to the development of alternative approaches. (author) 18 refs.

  9. Etiopathogenesis and Neurobiology of Narcolepsy: A Review

    Science.gov (United States)

    Kumar, Swarup; Sagili, Haritha

    2014-01-01

    Narcolepsy is a chronic lifelong sleep disorder and it often leaves a debilitating effect on the quality of life of the sufferer. This disorder is characterized by a tetrad of excessive daytime sleepiness, cataplexy (brief loss of muscle tone following strong emotion), hypnogogic hallucinations and sleep paralysis. There are two distinct subgroups of Narcolepsy: Narcolepsy with cataplexy and Narcolepsy without cataplexy. For over 100 years, clinicians have recognised narcolepsy, but only in the last few decades have scientists been able to shed light on the true cause and pathogenesis of narcolepsy. Recent studies have shown that a loss of the hypothalamic neuropeptide Hypocretin/Orexincauses Narcolepsy with cataplexy and that an autoimmune mechanism may be responsible for this loss. Our understanding of the neurophysiologic aspect of narcolepsy has also significantly improved. The basic neural mechanisms behind sleepiness and cataplexy, the two defining symptoms of narcolepsy have started to become clearer. In this review, we have provided a detailed account of the key aspects of etiopathogenesis and neurobiology of narcolepsy, along with a critical appraisal of the more recent and interesting causal associations.We have also looked at the contributions of neuroimaging to the etiopathogenesis of Narcolepsy. PMID:24701532

  10. The neurobiology of pleasure, reward processes, addiction and their health implications.

    Science.gov (United States)

    Esch, Tobias; Stefano, George B

    2004-08-01

    Modern science begins to understand pleasure as a potential component of salutogenesis. Thereby, pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. Further, health implications related to pleasurable activities are analyzed. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors, i.e., motivational toxicity. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, endorphin and endogenous morphinergic mechanisms may play a role. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex and reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways. Thus, the concrete outcome of pleasant experiences may be a question of dose. Moderate pleasurable experiences are able to enhance biological flexibility and health. Hence, pleasure can be a resistance resource or may serve salutogenesis. Natural rewards are mediated by sensory organ stimulation, thereby exhibiting a potential association with complementary medical approaches. Trust and belief can be part of a self-healing potential connected with rewarding stimuli. Further, the placebo response physiologically resembles pleasure phenomena, since both involve brain's reward circuitry stimulation and subjective feelings of well-being. Pleasurable activities can stimulate

  11. Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

    Directory of Open Access Journals (Sweden)

    Vanessa Cohignac

    2014-07-01

    Full Text Available The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s still remain(s unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

  12. Effects of manual hyperinflation in preterm newborns under mechanical ventilation.

    Science.gov (United States)

    Viana, Camila Chaves; Nicolau, Carla Marques; Juliani, Regina Celia Turola Passos; Carvalho, Werther Brunow de; Krebs, Vera Lucia Jornada

    2016-09-01

    To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver.

  13. Effects of manual hyperinflation in preterm newborns under mechanical ventilation

    Science.gov (United States)

    Viana, Camila Chaves; Nicolau, Carla Marques; Juliani, Regina Celia Turola Passos; de Carvalho, Werther Brunow; Krebs, Vera Lucia Jornada

    2016-01-01

    Objective To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Methods Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Results Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Conclusion Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver. PMID:27737427

  14. Response mechanism of post-earthquake slopes under heavy rainfall

    Science.gov (United States)

    Qiu, Hong-zhi; Kong, Ji-ming; Wang, Ren-chao; Cui, Yun; Huang, Sen-wang

    2017-07-01

    This paper uses the catastrophic landslide that occurred in Zhongxing Town, Dujiangyan City, as an example to study the formation mechanism of landslides induced by heavy rainfall in the post-Wenchuan earthquake area. The deformation characteristics of a slope under seismic loading were investigated via a shaking table test. The results show that a large number of cracks formed in the slope due to the tensile and shear forces of the vibrations, and most of the cracks had angles of approximately 45° with respect to the horizontal. A series of flume tests were performed to show how the duration and intensity of rainfall influence the responses of the shaken and non-shaken slopes. Wetting fronts were recorded under different rainfall intensities, and the depth of rainfall infiltration was greater in the shaken slope than in the non-shaken slope because the former experienced a greater extreme rainfall intensity under the same early rainfall and rainfall duration conditions. At the beginning of the rainfall infiltration experiment, the pore water pressure in the slope was negative, and settling occurred at the top of the slope. With increasing rainfall, the pore water pressure changed from negative to positive, and cracks were observed on the back surface of the slope and the shear outlet of the landslide on the front of the slope. The shaken slope was more susceptible to crack formation than the non-shaken slope under the same rainfall conditions. A comparison of the responses of the shaken and non-shaken slopes under heavy rainfall revealed that cracks formed by earthquakes provided channels for infiltration. Soil particles in the cracks of slopes were washed away, and the pore water pressure increased rapidly, especially the transient pore water pressure in the slope caused by short-term concentrated rainfall which decreased rock strength and slope stability.

  15. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  16. The neuropathology and neurobiology of traumatic brain injury.

    Science.gov (United States)

    Blennow, Kaj; Hardy, John; Zetterberg, Henrik

    2012-12-06

    The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and neural mechanisms associated with TBI, drawing on findings from sports-induced TBI in athletes, in whom acute TBI damages axons and elicits both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE). We also consider how the neuropathology and neurobiology of CTE in many ways resembles other neurodegenerative illnesses such as Alzheimer's disease, particularly with respect to mismetabolism and aggregation of tau, β-amyloid, and TDP-43. Finally, we explore how translational research in animal models of acceleration/deceleration types of injury relevant for concussion together with clinical studies employing imaging and biochemical markers may further elucidate the neurobiology of TBI and CTE. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. SCWISh network is essential for survival under mechanical pressure.

    Science.gov (United States)

    Delarue, Morgan; Poterewicz, Gregory; Hoxha, Ori; Choi, Jessica; Yoo, Wonjung; Kayser, Jona; Holt, Liam; Hallatschek, Oskar

    2017-12-19

    Cells that proliferate within a confined environment build up mechanical compressive stress. For example, mechanical pressure emerges in the naturally space-limited tumor environment. However, little is known about how cells sense and respond to mechanical compression. We developed microfluidic bioreactors to enable the investigation of the effects of compressive stress on the growth of the genetically tractable model organism Saccharomyces cerevisiae We used this system to determine that compressive stress is partly sensed through a module consisting of the mucin Msb2 and the cell wall protein Sho1, which act together as a sensor module in one of the two major osmosensing pathways in budding yeast. This signal is transmitted via the MAPKKK kinase Ste11. Thus, we term this mechanosensitive pathway the "SMuSh" pathway, for Ste11 through Mucin/Sho1 pathway. The SMuSh pathway delays cells in the G1 phase of the cell cycle and improves cell survival in response to growth-induced pressure. We also found that the cell wall integrity (CWI) pathway contributes to the response to mechanical compressive stress. These latter results are confirmed in complimentary experiments in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA, 10.1073/pnas.1709079114]. When both the SMuSh and the CWI pathways are deleted, cells fail to adapt to compressive stress, and all cells lyse at relatively low pressure when grown in confinement. Thus, we define a network that is essential for cell survival during growth under pressure. We term this mechanosensory system the SCWISh (survival through the CWI and SMuSh) network.

  18. The neurobiology of empathy in borderline personality disorder.

    Science.gov (United States)

    Ripoll, Luis H; Snyder, Rebekah; Steele, Howard; Siever, Larry J

    2013-03-01

    We present a neurobiological model of empathic dysfunction in borderline personality disorder (BPD) to guide future empirical research. Empathy is a necessary component of interpersonal functioning, involving two distinct, parallel neural networks. One form of empathic processing relies on shared representations (SR) of others' mental states, while the other is associated with explicit mental state attribution (MSA). SR processing is visceral and automatic, contributing to attunement, but also emotional contagion. MSA processing contributes to deliberate, perspectival forms of empathic understanding. Empathic dysfunction in BPD may involve hyper-reactivity of SR networks and impairment of MSA networks. Nevertheless, this empathic dysfunction is subtle, but contributes to interpersonal difficulties. Interaction between genetic factors and traumatic attachment stressors may contribute to development of BPD, with painful attachment insecurity and disorganization affecting SR and MSA network functioning. Future avenues for BPD research will include developmental assessment of attachment and neurobiological functioning under varying conditions.

  19. Neurobiological Correlates of the Attitude Toward Human Empathy

    Directory of Open Access Journals (Sweden)

    Claudio Gentili

    2015-04-01

    Full Text Available Over the last decade, integrated philosophical and neuroscientific studies of empathy have been steadily growing, because of the pivotal role that empathy plays in social cognition and ethics, as well as in the understanding of human behavior both under physiological conditions and in the presence of mental disorders. The umbrella concept of empathy embraces multi-faceted characteristics, including affective and cognitive processes, such as so-called emotional contagion and concern and perspective-taking. In this paper, we review the state-of-the-art of knowledge about the neurobiology of empathy. Specifically, we examine studies regarding empathy for pain, emotional imitation and expression and their alterations in psychopathological conditions. We also consider studies on the theory of mind (ToM and the mirror neuron system (MNS. Finally, we propose measures of brain resting state activity as a potential neurobiological marker of proneness to be empathic.

  20. Neurobiology of premature brain injury.

    Science.gov (United States)

    Salmaso, Natalina; Jablonska, Beata; Scafidi, Joseph; Vaccarino, Flora M; Gallo, Vittorio

    2014-03-01

    Every year in the United States, an estimated 500,000 babies are born preterm (before 37 completed weeks of gestation), and this number is rising, along with the recognition of brain injuries due to preterm delivery. A common underlying pathogenesis appears to be perinatal hypoxia induced by immature lung development, which causes injury to vulnerable neurons and glia. Abnormal growth and maturation of susceptible cell types, particularly neurons and oligodendrocytes, in preterm babies with very low birth weight is associated with decreased cerebral and cerebellar volumes and increases in cerebral ventricular size. Here we reconcile these observations with recent studies using models of perinatal hypoxia that show perturbations in the maturation and function of interneurons, oligodendrocytes and astroglia. Together, these findings suggest that the global mechanism by which perinatal hypoxia alters development is through a delay in maturation of affected cell types, including astroglia, oligodendroglia and neurons.

  1. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    is still not clear. In this work the crude oil/seawater ions interaction at different temperatures, pressures and sulfate ion concentrations is investigated. Our results show that sulfate ions may help decrease the crude oil viscosity when brine is contacted with oil under high temperature and pressure. We...... have also observed formation of a microemulsion phase between brine and oil with the increase in sulfate ion concentration at high temperature and pressure. In addition, sulfate ions can reduce interfacial tension (IFT) between oil and water. We propose that the decrease in viscosity and formation...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies....

  2. Degradation Mechanisms of Transparent Polyurethane Interlayer under UV Irradiation

    Directory of Open Access Journals (Sweden)

    OU Yingchun

    2017-01-01

    Full Text Available According to the ageing problem of laminated transparency, the trasparent polyurethane film used as interlayer had been irradiated by fluorescent ultraviolet lamp for 0 h, 200 h, 300 h, and 500 h respectively. With the aid of ultraviolet/visible spectrophotometer, FTIR and SEM etc., the color, structure and morphology of the materials were studied. SEM shows that when the irradiation time is increased to 500 h, the film surface cracks. The UV degradation mechanisms are that -CH2- of the position connecting the O and N from hard segment and the soft segment are easy to oxidize and produce hydrogen peroxide under UV and oxygen, which is furtherly oxidized to CO, and some part of the C-O and C-N bonds is cracked through β scission, and then the materials are fractured.

  3. Conserved Molecular Mechanisms Underlying Homeostasis of the Golgi Complex

    Directory of Open Access Journals (Sweden)

    Cathal Wilson

    2010-01-01

    Full Text Available The Golgi complex performs a central function in the secretory pathway in the sorting and sequential processing of a large number of proteins destined for other endomembrane organelles, the plasma membrane, or secretion from the cell, in addition to lipid metabolism and signaling. The Golgi apparatus can be regarded as a self-organizing system that maintains a relatively stable morphofunctional organization in the face of an enormous flux of lipids and proteins. A large number of the molecular players that operate in these processes have been identified, their functions and interactions defined, but there is still debate about many aspects that regulate protein trafficking and, in particular, the maintenance of these highly dynamic structures and processes. Here, we consider how an evolutionarily conserved underlying mechanism based on retrograde trafficking that uses lipids, COPI, SNAREs, and tethers could maintain such a homeodynamic system.

  4. POSSIBLE MECHANISMS UNDERLYING THE THERAPEUTIC EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION

    Directory of Open Access Journals (Sweden)

    Alexander eChervyakov

    2015-06-01

    Full Text Available Transcranial magnetic stimulation (TMS is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation (LTP and long-term depression (LTD. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor (BDNF concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals. It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

  5. Data on the mechanisms underlying succinate-induced aortic contraction

    Directory of Open Access Journals (Sweden)

    Natália A. Gonzaga

    2016-12-01

    Full Text Available We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled “Pharmacological characterization of the mechanisms underlying the vascular effects of succinate” (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016 [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, “Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors” (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004 [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor, SP600125 (JNK inhibitor and Y27632 (Rho-kinase inhibitor reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor, H7 (protein kinase C inhibitor, verapamil (Ca2+ channel blocker and tiron (superoxide anion scavenger.

  6. Simulated airplane headache: a proxy towards identification of underlying mechanisms.

    Science.gov (United States)

    Bui, Sebastian Bao Dinh; Petersen, Torben; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

    2017-12-01

    Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E2 (PGE2), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE2, cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE2, and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

  7. Nonlinear Mechanics of MEMS Rectangular Microplates under Electrostatic Actuation

    KAUST Repository

    Saghir, Shahid

    2016-12-01

    The first objective of the dissertation is to develop a suitable reduced order model capable of investigating the nonlinear mechanical behavior of von-Karman plates under electrostatic actuation. The second objective is to investigate the nonlinear static and dynamic behavior of rectangular microplates under small and large actuating forces. In the first part, we present and compare various approaches to develop reduced order models for the nonlinear von-Karman rectangular microplates actuated by nonlinear electrostatic forces. The reduced-order models aim to investigate the static and dynamic behavior of the plate under small and large actuation forces. A fully clamped microplate is considered. Different types of basis functions are used in conjunction with the Galerkin method to discretize the governing equations. First we investigate the convergence with the number of modes retained in the model. Then for validation purpose, a comparison of the static results is made with the results calculated by a nonlinear finite element model. The linear eigenvalue problem for the plate under the electrostatic force is solved for a wide range of voltages up to pull-in. In the second part, we present an investigation of the static and dynamic behavior of a fully clamped microplate. We investigate the effect of different non-dimensional design parameters on the static response. The forced-vibration response of the plate is then investigated when the plate is excited by a harmonic AC load superimposed to a DC load. The dynamic behavior is examined near the primary and secondary (superharmonic and subharmonic) resonances. The microplate shows a strong hardening behavior due to the cubic nonlinearity of midplane stretching. However, the behavior switches to softening as the DC load is increased. Next, near-square plates are studied to understand the effect of geometric imperfections of microplates. In the final part of the dissertation, we investigate the mechanical behavior of

  8. Using Drosophila to discover mechanisms underlying type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ronald W. Alfa

    2016-04-01

    Full Text Available Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positioned Drosophila as an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis.

  9. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Nguyen Quoc Vuong Tran

    2017-01-01

    Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  10. Thermal stability of nafion membranes under mechanical stress

    Energy Technology Data Exchange (ETDEWEB)

    Quintilii, M.; Struis, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-06-01

    The feasibility of adequately modified fluoro-ionomer membranes (NAFION{sup R}) is demonstrated for the selective separation of methanol synthesis products from the raw reactor gas at temperatures around 200{sup o}C. For an economically relevant application of this concept on a technical scale the Nafion membranes should be thin ({approx_equal}10 {mu}m) and thermally stable over a long period of time (1-2 years). In cooperation with industry (Methanol Casale SA, Lugano (CH)), we test the thermal stability of Nafion hollow fibers and supported Nafion thin sheet membranes at temperatures between 160 and 200{sup o}C under mechanical stress by applying a gas pressure difference over the membrane surface ({Delta}P{<=} 40 bar). Tests with the hollow fibers revealed that Nafion has visco-elastic properties. Tests with 50 {mu}m thin Nafion sheets supported by a porous metal carrier at 200{sup o}C and {Delta}P=39 bar showed no mechanical defects over a period of 92 days. (author) 5 figs., 4 refs.

  11. Mechanisms underlying temperature extremes in Iberia: a Lagrangian perspective

    Directory of Open Access Journals (Sweden)

    João A. Santos

    2015-04-01

    Full Text Available The mechanisms underlying the occurrence of temperature extremes in Iberia are analysed considering a Lagrangian perspective of the atmospheric flow, using 6-hourly ERA-Interim reanalysis data for the years 1979–2012. Daily 2-m minimum temperatures below the 1st percentile and 2-m maximum temperatures above the 99th percentile at each grid point over Iberia are selected separately for winter and summer. Four categories of extremes are analysed using 10-d backward trajectories initialized at the extreme temperature grid points close to the surface: winter cold (WCE and warm extremes (WWE, and summer cold (SCE and warm extremes (SWE. Air masses leading to temperature extremes are first transported from the North Atlantic towards Europe for all categories. While there is a clear relation to large-scale circulation patterns in winter, the Iberian thermal low is important in summer. Along the trajectories, air mass characteristics are significantly modified through adiabatic warming (air parcel descent, upper-air radiative cooling and near-surface warming (surface heat fluxes and radiation. High residence times over continental areas, such as over northern-central Europe for WCE and, to a lesser extent, over Iberia for SWE, significantly enhance these air mass modifications. Near-surface diabatic warming is particularly striking for SWE. WCE and SWE are responsible for the most extreme conditions in a given year. For WWE and SCE, strong temperature advection associated with important meridional air mass transports are the main driving mechanisms, accompanied by comparatively minor changes in the air mass properties. These results permit a better understanding of mechanisms leading to temperature extremes in Iberia.

  12. Different neurophysiological mechanisms underlying word and rule extraction from speech.

    Directory of Open Access Journals (Sweden)

    Ruth De Diego Balaguer

    Full Text Available The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400 in the central electrodes is related to word-learning and development of a frontal positivity (P2 is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity and clear lexical effects when presented in isolation (N400 modulation. The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language.

  13. Understanding and Imitating Unfamiliar Actions: Distinct Underlying Mechanisms

    Science.gov (United States)

    Carmo, Joana C.; Rumiati, Raffaella I.; Vallesi, Antonino

    2012-01-01

    The human “mirror neuron system” has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one’s own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1) whether the ultimate goal is to imitate or understand the presented actions and 2) whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions. PMID:23071668

  14. Mechanical properties and failure mechanisms of graphene under a central load.

    Science.gov (United States)

    Wang, Shuaiwei; Yang, Baocheng; Zhang, Shouren; Yuan, Jinyun; Si, Yubing; Chen, Houyang

    2014-09-15

    By employing molecular dynamics simulations, the evolution of deformation of a monolayer graphene sheet under a central transverse loading are investigated. Dependence of mechanical responses on the symmetry (shape) of the loading domain, on the size of the graphene sheet, and on temperature, is determined. It is found that the symmetry of the loading domain plays a central role in fracture strength and strain. By increasing the size of the graphene sheet or increasing temperature, the tensile strength and fracture strain decrease. The results have demonstrated that the breaking force and breaking displacement are sensitive to both temperature and the symmetry of the loading domain. In addition, we find that the intrinsic strength of graphene under a central load is much smaller than that of graphene under a uniaxial load. By examining the deformation processes, two failure mechanisms are identified namely, brittle bond breaking and plastic relaxation. In the second mechanism, the Stone-Wales transformation occurs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Microcracking in composite laminates under thermal and mechanical loading. Thesis

    Science.gov (United States)

    Maddocks, Jason R.

    1995-01-01

    Composites used in space structures are exposed to both extremes in temperature and applied mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. The goal of the present investigation is to develop a predictive methodology to quantify microcracking in general composite laminates under both thermal and mechanical loading. This objective is successfully met through a combination of analytical modeling and experimental investigation. In the analysis, the stress and displacement distributions in the vicinity of a crack are determined using a shear lag model. These are incorporated into an energy based cracking criterion to determine the favorability of crack formation. A progressive damage algorithm allows the inclusion of material softening effects and temperature-dependent material properties. The analysis is implemented by a computer code which gives predicted crack density and degraded laminate properties as functions of any thermomechanical load history. Extensive experimentation provides verification of the analysis. AS4/3501-6 graphite/epoxy laminates are manufactured with three different layups to investigate ply thickness and orientation effects. Thermal specimens are cooled to progressively lower temperatures down to -184 C. After conditioning the specimens to each temperature, cracks are counted on their edges using optical microscopy and in their interiors by sanding to incremental depths. Tensile coupons are loaded monotonically to progressively higher loads until failure. Cracks are counted on the coupon edges after each loading. A data fit to all available results provides input parameters for the analysis and shows them to be material properties, independent of geometry and loading. Correlation between experiment and analysis is generally very good under both thermal and mechanical loading, showing the methodology to be a powerful, unified tool. Delayed crack initiation observed in a few cases is attributed to a

  16. Quantification of Age‐Related Lung Tissue Mechanics under Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    JongWon Kim

    2017-09-01

    Full Text Available Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator‐induced lung injury (VILI in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator‐induced lung injuries. Two age‐related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50‐year‐old (normal and second is for an 80‐year old (aged model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s decreased by about 40% in the alveolar sac (G23 and 27% in the bronchiole (G20, respectively, for the 80‐year‐old as compared to the 50‐year‐old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain over G20 and G23 for the 80‐year‐old decreased by about 64% (three‐fold and 80% (four‐fold, respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold in lung compliance for the 80‐year‐old in comparison to the 50‐year‐old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

  17. Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation.

    Science.gov (United States)

    Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

    2017-09-29

    Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

  18. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    Science.gov (United States)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  19. Mechanical Modeling of a WIPP Drum Under Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeffrey A. [Sandia National Laboratories, Albuquerque, NM (United States)

    2014-11-25

    Mechanical modeling was undertaken to support the Waste Isolation Pilot Plant (WIPP) technical assessment team (TAT) investigating the February 14th 2014 event where there was a radiological release at the WIPP. The initial goal of the modeling was to examine if a mechanical model could inform the team about the event. The intention was to have a model that could test scenarios with respect to the rate of pressurization. It was expected that the deformation and failure (inability of the drum to contain any pressure) would vary according to the pressurization rate. As the work progressed there was also interest in using the mechanical analysis of the drum to investigate what would happen if a drum pressurized when it was located under a standard waste package. Specifically, would the deformation be detectable from camera views within the room. A finite element model of a WIPP 55-gallon drum was developed that used all hex elements. Analyses were conducted using the explicit transient dynamics module of Sierra/SM to explore potential pressurization scenarios of the drum. Theses analysis show similar deformation patterns to documented pressurization tests of drums in the literature. The calculated failure pressures from previous tests documented in the literature vary from as little as 16 psi to 320 psi. In addition, previous testing documented in the literature shows drums bulging but not failing at pressures ranging from 69 to 138 psi. The analyses performed for this study found the drums failing at pressures ranging from 35 psi to 75 psi. When the drums are pressurized quickly (in 0.01 seconds) there is significant deformation to the lid. At lower pressurization rates the deformation of the lid is considerably less, yet the lids will still open from the pressure. The analyses demonstrate the influence of pressurization rate on deformation and opening pressure of the drums. Analyses conducted with a substantial mass on top of the closed drum demonstrate that the

  20. Neurobiological effects of physical exercise in schizophrenia: a systematic review.

    Science.gov (United States)

    Vancampfort, Davy; Probst, Michel; De Hert, Marc; Soundy, Andrew; Stubbs, Brendon; Stroobants, Marc; De Herdt, Amber

    2014-01-01

    The aim of the present systematic review was to provide a summary of neurobiological effects of physical exercise for people with schizophrenia. A systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searches were conducted up to April 2013 across three databases: Medline, PsycINFO, and Embase. A methodological quality assessment using the Downs and Black Quality Index was carried out with all of the included studies. Of the 654 initial data search results, two studies reported in 3 articles including 48 patients (six women) with schizophrenia, met the eligibility criteria. The methodological quality of each study was high. Data on hippocampal volume changes following physical exercise were conflicting while physical exercise-induced changes in other brain areas were absent. Increases in hippocampal volume following physical exercise were correlated with improvements in aerobic fitness and short-term memory. Future research is needed to investigate whether brain health in people with schizophrenia is activity-dependent. Additionally, research that considers the neurobiological mechanisms and associated functional outcomes of physical exercise in individuals with schizophrenia is required. Understanding the neurobiological effects of physical exercise in patients with schizophrenia may contribute to the development of new rehabilitation strategies. There is currently insufficient evidence to determine if physical exercise has a beneficial influence on the brain health of people with schizophrenia.

  1. Neurobiologically-based treatments in Rett syndrome: opportunities and challenges

    Science.gov (United States)

    Kaufmann, Walter E.; Stallworth, Jennifer L.; Everman, David B.; Skinner, Steven A.

    2016-01-01

    ABSTRACT Introduction: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that primarily affects females, typically resulting in a period of developmental regression in early childhood followed by stabilization and severe chronic cognitive, behavioral, and physical disability. No known treatment exists beyond symptomatic management, and while insights into the genetic cause, pathophysiology, neurobiology, and natural history of RTT have been gained, many challenges remain. Areas covered: Based on a comprehensive survey of the primary literature on RTT, this article describes and comments upon the general and unique features of the disorder, genetic and neurobiological bases of drug development, and the history of clinical trials in RTT, with an emphasis on drug trial design, outcome measures, and implementation. Expert opinion: Neurobiologically based drug trials are the ultimate goal in RTT, and due to the complexity and global nature of the disorder, drugs targeting both general mechanisms (e.g., growth factors) and specific systems (e.g., glutamate modulators) could be effective. Trial design should optimize data on safety and efficacy, but selection of outcome measures with adequate measurement properties, as well as innovative strategies, such as those enhancing synaptic plasticity and use of biomarkers, are essential for progress in RTT and other neurodevelopmental disorders. PMID:28163986

  2. Integrated neurobiology of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Vladimir eMaletic

    2014-08-01

    Full Text Available From a neurobiological perspective there is no such thing as bipolar disorder. Rather, it is almost certainly the case that many somewhat similar, but subtly different, pathological conditions produce a disease state that we currently diagnose as bipolarity. This heterogeneity—reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition—limits attempts to articulate an integrated perspective on bipolar disorder. However, despite these challenges, scientific findings in recent years are beginning to offer a provisional unified field theory of the disease. This theory sees bipolar disorder as a suite of related neurodevelopmental conditions with interconnected functional abnormalities that often appear early in life and worsen over time. In addition to accelerated loss of volume in brain areas known to be essential for mood regulation and cognitive function, consistent findings have emerged at a cellular level, providing evidence that bipolar disorder is reliably associated with dysregulation of glial-neuronal interactions. Among these glial elements are microglia—the brain’s primary immune elements, which appear to be overactive in the context of bipolarity. Multiple studies now indicate that inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness, with at least some return to normality in the euthymic state. These findings are consistent with changes in the HPA axis, which are known to drive inflammatory activation. In summary, the very fact that no single gene, pathway or brain abnormality is likely to ever account for the condition is itself an extremely important first step in better articulating an integrated perspective on both its ontological status and pathogenesis. Whether this perspective will translate into the discovery of innumerable more homogeneous forms of bipolarity is one of the great

  3. Alcohol-related aggression-social and neurobiological factors.

    Science.gov (United States)

    Beck, Anne; Heinz, Andreas

    2013-10-01

    Alcohol-related aggression and violence are a widespread cause of personal suffering with high socioeconomic costs. In 2011, nearly one in three violent acts in Germany was committed under the influence of alcohol (31.8%). The link between alcohol consumption and aggression is promoted by various interacting factors. In this review, based on a selective search for pertinent literature in PubMed, we analyze and summarize information from original articles, reviews, and book chapters about alcohol and aggression and discuss the neurobiological basis of aggressive behavior. Aggression is promoted both by the cognitive deficits arising in connection with acute or chronic alcohol use and by prior experience of violence in particular situations where alcohol was drunk. Only a minority of persons who drink alcohol become aggressive. On the other hand, alcohol abuse and dependence together constitute the second most commonly diagnosed cause of suicide (15-43%). Current research indicates that the individual tendency toward alcohol-induced aggression depends not just on neurobiological factors, but also on personal expectations of the effects of alcohol, on prior experience of violent conflicts, and on the environmental conditions of early childhood, especially social exclusion and discrimination. Gene-environment interactions affecting the serotonergic and other neurotransmitter systems play an important role. Potential (but not yet adequately validated) therapeutic approaches involve reinforcing cognitive processes or pharmacologically modulating serotonergic neurotransmission (and other target processes). Alcohol-related aggression has manifold social and neurobiological causes. Specific treatments must be tested in controlled trials.

  4. Video analysis of concussion injury mechanism in under-18 rugby

    Science.gov (United States)

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Background Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Methods Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative ‘control’ sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. Results All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact, 43% had a ‘down’ position, 29% the ‘up and forward’ and 29% the ‘away’ position (n=7). The speed of the injured tackler was observed as ‘slow’ in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of ‘support’ (n=2) or as the ‘jackal’ (n=1). Conclusions Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury. PMID:27900149

  5. Mechanisms underlying recovery of zooplankton in Lake Orta after liming

    Directory of Open Access Journals (Sweden)

    Roberta Piscia

    2016-04-01

    Full Text Available The goal of this study was to improve the understanding of the large-scale mechanisms underlying the recovery of the zooplankton of Lake Orta from historical contamination, following reduced input of ammonia and metals and the subsequent 1989/90 liming intervention. The industrial pollution had been severe and long-lasting (1929-1990. Zooplankton biodiversity has improved, but most of the new taxa appearing in our counts are rotifers, while many calanoids and the large cladoceran predators (Bythotrephes and Leptodora that are common in the nearby Lake Maggiore, were still absent from Lake Orta 17 years after liming. To aid understanding of the large-scale mechanisms controlling changes in annual richness, we assessed the annual persistence (P of Crustacea and Rotifera taxa as an estimator of whether propagules that survived introduction, as result of the natural recolonization process, also thrived. We found that the rate of introduction of zooplankton colonists and their persistence in the water column of Lake Orta changed from 1971 to 2007. New rotifer taxa appeared in the lake after the mid-1980s, when discharge of toxic substances decreased, but their annual persistence was low (P<0.5 until the turn of the century. The numerical values of rotifer and crustacean persistence in Lake Orta were unexpectedly high in 2001 and 2007 (0.55 and 0.72 for rotifers, 0.85 and 0.86 for crustacean, respectively, much higher than in limed lakes in Sudbury, Canada, and in adjacent Lake Maggiore. We hypothesize this could be related to the lack of Cladoceran predators and zooplanktivorous fish in the pelagic waters of Lake Orta.

  6. Rules and mechanisms governing octahedral tilts in perovskites under pressure

    Science.gov (United States)

    Xiang, H. J.; Guennou, Mael; Íñiguez, Jorge; Kreisel, Jens; Bellaiche, L.

    2017-08-01

    The rotation of octahedra (octahedral tilting) is common in A B O3 perovskites and relevant to many physical phenomena, ranging from electronic and magnetic properties, metal-insulator transitions to improper ferroelectricity. Hydrostatic pressure is an efficient way to tune and control octahedral tiltings. However, the pressure behavior of such tiltings can dramatically differ from one material to another, with the origins of such differences remaining controversial. In this paper, we discover several new mechanisms and formulate a set of simple rules that allow us to understand how pressure affects oxygen octahedral tiltings via the use and analysis of first-principles results for a variety of compounds. Besides the known A -O interactions, we reveal that the interactions between specific B ions and oxygen ions contribute to the tilting instability. We explain the previously reported trend that the derivative of the oxygen octahedral tilting with respect to pressure (dR /dP ) usually decreases with both the tolerance factor and the ionization state of the A ion by illustrating the key role of A -O interactions and their change under pressure. Furthermore, three new mechanisms/rules are discovered, namely that (i) the octahedral rotations in A B O3 perovskites with empty low-lying d states on the B site are greatly enhanced by pressure, in order to lower the electronic kinetic energy; (ii) dR /dP is enhanced when the system possesses weak tilt instabilities, and (iii) for the most common phase exhibited by perovskites—the orthorhombic Pbnm state—the in-phase and antiphase octahedral rotations are not automatically both suppressed or both enhanced by the application of pressure because of a trilinear coupling between these two rotation types and an antipolar mode involving the A ions. We further predict that the polarization associated with the so-called hybrid improper ferroelectricity could be manipulated by hydrostatic pressure by indirectly controlling the

  7. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  8. Underlying Mechanisms of Tinnitus: Review and Clinical Implications

    Science.gov (United States)

    Henry, James A.; Roberts, Larry E.; Caspary, Donald M.; Theodoroff, Sarah M.; Salvi, Richard J.

    2016-01-01

    Background The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. Purpose The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. Results It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. Conclusions Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions. PMID:24622858

  9. Video analysis of concussion injury mechanism in under-18 rugby.

    Science.gov (United States)

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative 'control' sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact , 43% had a 'down' position, 29% the 'up and forward' and 29% the 'away' position (n=7). The speed of the injured tackler was observed as 'slow' in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of 'support' (n=2) or as the 'jackal' (n=1). Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury.

  10. The behavior of the planetary rings under the Kozai Mechanism

    Science.gov (United States)

    Sucerquia, M. A.; Ramírez, C. V.; Zuluaga, J. I.

    2017-07-01

    Rings are one of the main feature of almost all giant planets in the Solar System. Even though thousands of exoplanets have been discovered to date, no evidence of exoplanetary rings have been found despite the effort made in the development and enhancing of techniques and methods for direct or indirect detection. In the transit of a ringed planet, the dynamic of the ring itself could play a meaningful role due to the so called Kozai Mechanism (KM) acting on each particle of it. When some specific initial conditions of the ring are fulfilled (as a ring inclination greater than ˜ 39°), KM generates short periodic changes in the inclination and eccentricity of each particle, leading to a meaningful characteristic collective behavior of the ring: it changes its width, inclination and optical depth. These changes induce periodic variations on the eclipsed area of the parent star, generating slight changes in the observed transit signal. Under this mechanism, light curves depths and shapes oscillate according to the fluctuations of the ring. To show this effect we have performed numerical simulations of the dynamic of a system of particles to asses the ring inclination and width variations over time. We have calculated the expected variations in the transit depth and finally, we have estimated the effect on the light curve of a hypothetical ringed exoplanet affected by the KM. The detection of this effect could be used as an alternative method to detect/confirm exoplanetary rings, and also it could be considered as a way to explain anomalous light curves patterns of exoplanets, as the case of KIC 8462852 star.

  11. Failure mechanisms of aluminium foams under compressive loads

    Directory of Open Access Journals (Sweden)

    Sáenz, E.

    2000-08-01

    Full Text Available The purpose of this paper is the investigation of the major failure mechanisms of aluminium foams, which were obtained by powder metallurgy route, under compressive loads. The study was focused on two commonly aluminium alloys AlMg1Si or A 6061 and AlSi12. Due to the fact that the failure mechanisms strongly depend on the density and the macrostructural properties of the material, the mechanical properties always have to be correlated to the structural properties. Therefore, macrostructural investigations were used as a basis to establish the correlation between structural and mechanical properties. This was done with a commercially available image analysis system. The average cell size, the cell size distribution and the cell density (number of cells/area were obtained. In order to evaluate the influence of foaming direction on the cell morphology, some cross sections parallel to the foaming direction were prepared. For the characterization of the mechanical compression properties the compressive or upper yield strength (UYS, the densification strain (eD, the energy absorption (Ea and the efficiency (Eff were obtained. Furthermore, the failure behavior of the samples was in-situ observed with a digital video camera and continuously recorded during the test.

    El objetivo de este estudio es investigar los principales mecanismos de fallo de espumas de aluminio sometidas a cargas de compresión. Las espumas metálicas fueron obtenidas mediante el proceso pulvimetalúrgico, utilizándose como materia prima dos aleaciones comerciales AlMg1Si o A 6061 y AlSi12. Debido a que los mecanismos de fallo en este tipo de materiales depende fuertemente de la densidad y las características macroestructurales del material, en este estudio se busca correlacionar las propiedades mecánicas con estas características. La macroestructura se caracterizó mediante análisis de imagen. El tamaño de celda promedio, la distribución de tamaño y la densidad de

  12. Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

    Directory of Open Access Journals (Sweden)

    Li Han

    2014-01-01

    Full Text Available Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA and oleanolic acid (OA at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0 to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT, and diacylglycerol acyltransferase (DGAT in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

  13. Hypotheses on mechanisms underlying observational learning in animals.

    Science.gov (United States)

    Pallaud, B

    1984-07-01

    Learning through observation or vicarious learning has been systematically studied in a variety of animal species for only 20 years. Demonstrating in animals a capacity to benefit from a conspecific's experience, this type of acquisition was first thought to require superior cognitive processes and thus to be restricted to primates, if possible at all in animals. The concept of imitation was commonly applied in this line of study to any social transmission. Later, experiments on vicarious learning showed that numerous species (rodents, cats, birds, primates, etc.) learn more quickly to perform an act whenever they have the opportunity of watching a conspecific performing that act. The principal characteristic of this acquisition is that it occurs during the observation period when the observer has no opportunity of either performing a response or receiving reinforcement. Four hypothesis have been put forward to explain the mechanisms underlying this type of acquisition : local enhancement, the opportunity for mediate responses, a sensory preconditioning, and the monitoring of the observer's response by some quantitative and/or qualitative aspects of the model's response. The fact that animals prove to have such a capacity is moreover a factor to be kept in mind in all studies in the eco-ethological field (particularly those concerning the predator-prey relation). Copyright © 1984. Published by Elsevier B.V.

  14. CFRP Mechanical Anchorage for Externally Strengthened RC Beams under Flexure

    Science.gov (United States)

    Ali, Alnadher; Abdalla, Jamal; Hawileh, Rami; Galal, Khaled

    De-bonding of carbon fiber reinforced polymers (CFRP) sheets and plates from the concrete substrate is one of the major reasons behind premature failures of beams that are externally strengthened with such CFRP materials. To delay or prevent de-bonding and therefore enhancing the load carrying capacity of strengthened beams, several anchorage systems were developed and used. This paper investigates the use of CFRP mechanical anchorage of CFRP sheets and plates used to externally strengthen reinforced concrete beams under flexure. The pin-and-fan shape CFRP anchor, which is custom-made from typical rolled fiber sheets and bundles of loose fiber is used. Several reinforced concrete beams were casted and tested in standard four-point bending scheme to study the effectiveness of this anchorage system. The beams were externally strengthened in flexure with bonded CFRP sheets and plates and then fastened to the soffit of the beams' using various patterns of CFRP anchors. It is observed that the CFRP plates begins to separate from the beams as soon as de-bonding occurs in specimens without CFRP anchors, while in beams with CFRP anchors de-bonding was delayed leading to increase in the load carrying capacity over the un-anchored strengthened beams.

  15. Axonal Degeneration in Tauopathies: Disease Relevance and Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Andrew Kneynsberg

    2017-10-01

    Full Text Available Tauopathies are a diverse group of diseases featuring progressive dying-back neurodegeneration of specific neuronal populations in association with accumulation of abnormal forms of the microtubule-associated protein tau. It is well-established that the clinical symptoms characteristic of tauopathies correlate with deficits in synaptic function and neuritic connectivity early in the course of disease, but mechanisms underlying these critical pathogenic events are not fully understood. Biochemical in vitro evidence fueled the widespread notion that microtubule stabilization represents tau's primary biological role and that the marked atrophy of neurites observed in tauopathies results from loss of microtubule stability. However, this notion contrasts with the mild phenotype associated with tau deletion. Instead, an analysis of cellular hallmarks common to different tauopathies, including aberrant patterns of protein phosphorylation and early degeneration of axons, suggests that alterations in kinase-based signaling pathways and deficits in axonal transport (AT associated with such alterations contribute to the loss of neuronal connectivity triggered by pathogenic forms of tau. Here, we review a body of literature providing evidence that axonal pathology represents an early and common pathogenic event among human tauopathies. Observations of axonal degeneration in animal models of specific tauopathies are discussed and similarities to human disease highlighted. Finally, we discuss potential mechanistic pathways other than microtubule destabilization by which disease-related forms of tau may promote axonopathy.

  16. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves

    Science.gov (United States)

    Ford, Kevin J.; Félix, Aude L.; Feller, Marla B.

    2012-01-01

    Prior to vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development. PMID:22262883

  17. Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

    Science.gov (United States)

    Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

    2017-11-01

    Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. Mechanisms underlying the antihypertensive effects of garlic bioactives.

    Science.gov (United States)

    Shouk, Reem; Abdou, Aya; Shetty, Kalidas; Sarkar, Dipayan; Eid, Ali H

    2014-02-01

    Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants.

    Science.gov (United States)

    Zhang, Zhaoliang; Liao, Hong; Lucas, William J

    2014-03-01

    As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehensive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies. © 2014 Institute of Botany, Chinese Academy of Sciences.

  20. Recent experimental developments concerning the mechanisms underlying dust emission

    Science.gov (United States)

    McKenna Neuman, C. L.; Sanderson, R. S.; O'Brien, P.

    2012-12-01

    Field based studies have been invaluable in elucidating the great variability and complexity in natural surfaces that emit dust. Spanning hours to days, and meters to kilometers, measurements of the regional and global characteristics of dust emission and transport are contributing to a clearer understanding of these phenomena. This work has been complimented by the development of increasingly more sophisticated atmospheric dispersion models. Only very recently, however, has much attention been paid to the physics of dust emission from the bed surface that necessarily require precise, high frequency measurements over fractions of millimeters under carefully manipulated conditions. This paper provides an overview of recent advances in our understanding of the mechanisms of dust emission, as derived from experiments carried out in the Trent boundary layer wind tunnel by a variety of workers. Energy transfer to the bed surface through the impacts of saltating particles has long been recognized as crucial for the ejection of silt and clay sized particles from surfaces where interparticle bonding is significant. Using Particle Tracking Velocimetry (PTV) and laser Doppler anemometry (LDA), we are now able to measure the energy transfer to the surface and the consequent deformation/rupture for both loose and consolidated beds of silt. The coefficient of restitution is found to decrease with particle impact speed, although some compaction may also occur with plowing and displacement of loose bed material (Gordon and McKenna Neuman, 2009). Further consideration is given to wind pumping as an alternate mechanism for dust entrainment from surfaces that are armored; that is, where insufficient sand supply is available to the support the development of a saltation cloud. LDA and pressure tap measurements confirm that turbulent structures measured in the atmospheric boundary layer are able to penetrate into the pores of gravel sized material, and specifically, the smelter waste

  1. Integrated Neurobiology of Bipolar Disorder

    Science.gov (United States)

    Maletic, Vladimir; Raison, Charles

    2014-01-01

    From a neurobiological perspective there is no such thing as bipolar disorder. Rather, it is almost certainly the case that many somewhat similar, but subtly different, pathological conditions produce a disease state that we currently diagnose as bipolarity. This heterogeneity – reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition – limits attempts to articulate an integrated perspective on bipolar disorder. However, despite these challenges, scientific findings in recent years are beginning to offer a provisional “unified field theory” of the disease. This theory sees bipolar disorder as a suite of related neurodevelopmental conditions with interconnected functional abnormalities that often appear early in life and worsen over time. In addition to accelerated loss of volume in brain areas known to be essential for mood regulation and cognitive function, consistent findings have emerged at a cellular level, providing evidence that bipolar disorder is reliably associated with dysregulation of glial–neuronal interactions. Among these glial elements are microglia – the brain’s primary immune elements, which appear to be overactive in the context of bipolarity. Multiple studies now indicate that inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness, with at least some return to normality in the euthymic state. These findings are consistent with changes in the hypothalamic–pituitary–adrenal axis, which are known to drive inflammatory activation. In summary, the very fact that no single gene, pathway, or brain abnormality is likely to ever account for the condition is itself an extremely important first step in better articulating an integrated perspective on both its ontological status and pathogenesis. Whether this perspective will translate into the discovery of innumerable more homogeneous forms of

  2. Role of Serotonin and Dopamine System Interactions in the Neurobiology of Impulsive Aggression and its Comorbidity with other Clinical Disorders.

    Science.gov (United States)

    Seo, Dongju; Patrick, Christopher J; Kennealy, Patrick J

    2008-10-01

    Impulsive aggression is characterized by an inability to regulate affect as well as aggressive impulses, and is highly comorbid with other mental disorders including depression, suicidal behavior, and substance abuse. In an effort to elucidate the neurobiological underpinnings of impulsive aggression and to help account for its connections with these other disorders, this paper reviews relevant biochemical, brain imaging, and genetic studies. The review suggests that dysfunctional interactions between serotonin and dopamine systems in the prefrontal cortex may be an important mechanism underlying the link between impulsive aggression and its comorbid disorders. Specifically, serotonin hypofunction may represent a biochemical trait that predisposes individuals to impulsive aggression, with dopamine hyperfunction contributing in an additive fashion to the serotonergic deficit. The current paper proposes a modified diathesis-stress model of impulsive aggression in which the underlying biological diathesis may be deficient serotonergic function in the ventral prefrontal cortex. This underlying disposition can be manifested behaviorally as impulsive aggression towards oneself and others, and as depression under precipitating life stressors. Substance abuse associated with impulsive aggression is understood in the context of dopamine dysregulation resulting from serotonergic deficiency. Also discussed are future research directions in the neurobiology of impulsive aggression and its comorbid disorders.

  3. Anxiety: a systematic review of neurobiology, traditional pharmaceuticals and novel alternatives from medicinal plants.

    Science.gov (United States)

    Gelfuso, Érica Aparecida; Rosa, Daiane Santos; Fachin, Ana Lúcia; Mortari, Márcia Renata; Cunha, Alexandra Olimpio Siqueira; Beleboni, Rene Oliveira

    2014-02-01

    Pathologic anxiety is a disproportional reaction of individuals to anticipation or misinterpretation of a potential danger, which affects individual social and personal life. Despite the advances already accomplished, further studies are still necessary in order to understand the mechanisms involved in anxiety. These may provide more effective and safer treatments to aid in the control of anxiety and improve patient quality of life. In this work, we review the current issue about anxiety disorders, covering general aspects such as basic epidemiology and classification, an overview of the pharmacological treatments employed and the current search for natural anxiolytics. Also, a compilation of data investigating the neurobiology that underlies anxiety disorders and a brief discussion evolving the most usual animal experimental models to study anxiety is presented.

  4. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    Energy Technology Data Exchange (ETDEWEB)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C. [Stuttgart Univ. (Germany). Materials Testing Inst.

    2013-07-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  5. Mechanisms underlying the antihypertensive properties of Urtica dioica.

    Science.gov (United States)

    Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

    2016-09-01

    Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

  6. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

    Directory of Open Access Journals (Sweden)

    Daniela Fanni

    2014-06-01

    better understanding of the underlying pathological mechanisms of BPD might provide insight into development of new therapeutic and preventive strategies.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  7. Mechanisms underlying the link between cannabis use and prospective memory.

    Directory of Open Access Journals (Sweden)

    Carrie Cuttler

    Full Text Available While the effects of cannabis use on retrospective memory have been extensively examined, only a limited number of studies have focused on the links between cannabis use and prospective memory. We conducted two studies to examine the links between cannabis use and both time-based and event-based prospective memory as well as potential mechanisms underlying these links. For the first study, 805 students completed an online survey designed to assess cannabis consumption, problems with cannabis use indicative of a disorder, and frequency of experiencing prospective memory failures. The results showed small to moderate sized correlations between cannabis consumption, problems with cannabis use, and prospective memory. However, a series of mediation analyses revealed that correlations between problems with cannabis use and prospective memory were driven by self-reported problems with retrospective memory. For the second study, 48 non-users (who had never used cannabis, 48 experimenters (who had used cannabis five or fewer times in their lives, and 48 chronic users (who had used cannabis at least three times a week for one year were administered three objective prospective memory tests and three self-report measures of prospective memory. The results revealed no objective deficits in prospective memory associated with chronic cannabis use. In contrast, chronic cannabis users reported experiencing more internally-cued prospective memory failures. Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs. Although our samples were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders, leaving open the possibility that these variables may play a role in the detected relationships, the present findings indicate that cannabis use has a modest effect on self-reported problems with

  8. Cognitive mechanisms underlying instructed choice exploration of small city maps

    Directory of Open Access Journals (Sweden)

    Sofia eSakellaridi

    2015-03-01

    Full Text Available We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S. city maps with two locations highlighted on the circumference, as possible choices for a post office (targets. At the beginning of a trial, subjects fixated a spot at the center of the map and ultimately chose one of the two locations. A space syntax analysis of the map paths (from the center to each target revealed that the chosen location was associated with the less convoluted path, as if subjects navigated mentally the paths in an ant’s way, i.e. by staying within street boundaries, and ultimately choosing the target that could be reached from the center in the shortest way, and the fewest turns and intersections. The subjects’ strategy for map exploration and decision making was investigated by monitoring eye position during the task. This revealed a restricted exploration of the map delimited by the location of the two alternative options and the center of the map. Specifically, subjects explored the areas around the two target options by repeatedly looking at them before deciding which one to choose, presumably implementing an evaluation and decision-making process. The ultimate selection of a specific target was significantly associated with the time spent exploring the area around that target. Finally, an analysis of the sequence of eye fixations revealed that subjects tended to look systematically towards the target ultimately chosen even from the beginning of the trial. This finding indicates an early cognitive selection bias for the ensuing decision process.

  9. Cognitive mechanisms underlying instructed choice exploration of small city maps.

    Science.gov (United States)

    Sakellaridi, Sofia; Christova, Peka; Christopoulos, Vassilios N; Vialard, Alice; Peponis, John; Georgopoulos, Apostolos P

    2015-01-01

    We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S. city maps with two locations highlighted on the circumference, as possible choices for a post office ("targets"). At the beginning of a trial, subjects fixated a spot at the center of the map and ultimately chose one of the two locations. A space syntax analysis of the map paths (from the center to each target) revealed that the chosen location was associated with the less convoluted path, as if subjects navigated mentally the paths in an "ant's way," i.e., by staying within street boundaries, and ultimately choosing the target that could be reached from the center in the shortest way, and the fewest turns and intersections. The subjects' strategy for map exploration and decision making was investigated by monitoring eye position during the task. This revealed a restricted exploration of the map delimited by the location of the two alternative options and the center of the map. Specifically, subjects explored the areas around the two target options by repeatedly looking at them before deciding which one to choose, presumably implementing an evaluation and decision-making process. The ultimate selection of a specific target was significantly associated with the time spent exploring the area around that target. Finally, an analysis of the sequence of eye fixations revealed that subjects tended to look systematically toward the target ultimately chosen even from the beginning of the trial. This finding indicates an early cognitive selection bias for the ensuing decision process.

  10. Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure

    Directory of Open Access Journals (Sweden)

    Wouter A. A. de Steenhuijsen Piters

    2016-03-01

    Full Text Available The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1:e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting.

  11. Different underlying mechanisms for deficits in concept formation in dementia.

    Science.gov (United States)

    Giovannetti, T; Lamar, M; Cloud, B S; Swenson, R; Fein, D; Kaplan, E; Libon, D J

    2001-08-01

    We investigated the different mechanisms that may underlie deficits in verbal concept formation among patients with Alzheimer's disease (AD) and ischaemic vascular dementia (IVD) associated with periventricular and deep white matter alterations. Concept formation was assessed with the WAIS-R Similarities subtest (SIM). Two types of errors were re-coded from the 0-point responses as scored by the WAIS-R manual. In set errors (e.g., dog-lion "they're alive") were coded when patients reported a very vague superordinate concept for the word pair. Out of set responses (e.g., dog-lion "the lion roars and the dog barks") were coded when a response was clearly out of mental set, i.e., when participants were unable to provide a superordinate concept for the word pair. Between-group comparisons demonstrated no difference in SIM test performance according to the scoring system described in the WAIS-R manual. Nonetheless, AD patients produced a greater proportion of in set errors, while IVD patients produced a greater proportion of out of set errors. Out of set errors were highly associated with measures of executive function, while in set errors were associated with measures related to delayed recognition memory and semantic intrusion errors. We conclude that the underlying deficits that contribute to poor concept formation differ between AD and IVD patients. In IVD impaired concept formation is related to deficits in the executive systems necessary to monitor responses and sustain mental set. In AD, by contrast, the deficit appears to be secondary to impaired verbal response selection.

  12. Neurobiology of Consciousness: Current Research and Perspectives

    Directory of Open Access Journals (Sweden)

    Płonka Beata

    2015-12-01

    Full Text Available Scientific, objective approach to consciousness has allowed to obtain some experimental data concerning brain activity, ignoring, however, the longstanding philosophical tradition. Spectacular development of neuroscience which has been observed recently made this dissonance particularly noticeable. The paper addresses the main problems of discrepancy between neurobiological research and philosophical perspective. Current opinions concerning neural correlates and models of consciousness are discussed, as well as the problems of working memory, attention, self, and disorders of consciousness. A new neurobiological approach to describe brain function in terms of brain connectivity (so-called connectome is also presented. Finally, the need to introduce at least some aspects of philosophical approach directly into neurobiological research of consciousness is postulated.

  13. The clinical neurobiology of drug craving.

    Science.gov (United States)

    Sinha, Rajita

    2013-08-01

    Drug craving has re-emerged as a relevant and important construct in the pathophysiology of addiction with its inclusion in DSM-V as a key clinical symptom of addictive disorders. This renewed focus has been due in part to the recent neurobiological evidence on craving-related neural activation and clinical evidence supporting its association with drug use, relapse, and recovery processes. This review covers the neurobiology of drug craving and relapse risk with a primary focus on cocaine addiction and a secondary emphasis on alcohol addiction. A conceptualization of drug craving on the continuum of healthy desire and compulsive seeking, and the associated neurobiological adaptations associated with the development of an increased craving/wanting state is presented. Altered dopamine neurochemistry as well as disrupted prefrontal control and hyperactive striatal-limbic responses in experiencing drug cues, stress, drug intake and in basal relaxed states are identified as neurobiological signatures that predict drug craving and drug use. Thus, the clinical and neurobiological features of the craving/wanting state are presented with specific attention to alterations in these cortico-limbic-striatal and prefrontal self-control circuits that predict drug craving and relapse risk. The methodological challenges that need to be addressed to further develop the evolving conceptual approach to the neuroscience of drug craving is presented, with a focus on identification and validation of biomarkers associated with the craving state and treatment approaches that may be of benefit in reversing the neurobiological adaptations associated with drug craving to improve treatment outcomes in addiction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Plant-insect interactions under bacterial influence: ecological implications and underlying mechanisms.

    Science.gov (United States)

    Sugio, Akiko; Dubreuil, Géraldine; Giron, David; Simon, Jean-Christophe

    2015-02-01

    Plants and insects have been co-existing for more than 400 million years, leading to intimate and complex relationships. Throughout their own evolutionary history, plants and insects have also established intricate and very diverse relationships with microbial associates. Studies in recent years have revealed plant- or insect-associated microbes to be instrumental in plant-insect interactions, with important implications for plant defences and plant utilization by insects. Microbial communities associated with plants are rich in diversity, and their structure greatly differs between below- and above-ground levels. Microbial communities associated with insect herbivores generally present a lower diversity and can reside in different body parts of their hosts including bacteriocytes, haemolymph, gut, and salivary glands. Acquisition of microbial communities by vertical or horizontal transmission and possible genetic exchanges through lateral transfer could strongly impact on the host insect or plant fitness by conferring adaptations to new habitats. Recent developments in sequencing technologies and molecular tools have dramatically enhanced opportunities to characterize the microbial diversity associated with plants and insects and have unveiled some of the mechanisms by which symbionts modulate plant-insect interactions. Here, we focus on the diversity and ecological consequences of bacterial communities associated with plants and herbivorous insects. We also highlight the known mechanisms by which these microbes interfere with plant-insect interactions. Revealing such mechanisms in model systems under controlled environments but also in more natural ecological settings will help us to understand the evolution of complex multitrophic interactions in which plants, herbivorous insects, and micro-organisms are inserted. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions

  15. Diagnosis, treatment, and neurobiology of autism in children.

    Science.gov (United States)

    Lainhart, J E; Piven, J

    1995-08-01

    Autism is a developmental neuropsychiatric disorder defined by the presence of social and communicative deficits, restricted and repetitive behaviors and interests, and a characteristic course. Research suggests that hereditary factors play a principal role in the etiology of most cases. A phenotype broader than autism, including milder social and language-based cognitive deficits, appears to be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms clearly underlie the disorder. Neuropathologic studies have demonstrated abnormalities in limbic structures, the cerebellum, and the cortex. New advances in behavioral therapies and pharmacologic treatment are important components of successful multidisciplinary treatment of this disorder.

  16. Sleep neurobiology and critical care illness.

    Science.gov (United States)

    Drouot, Xavier; Quentin, Solene

    2015-07-01

    The intensive care unit (ICU) environment is not propitious for restoring sleep and many studies have reported that critically ill patients have severe sleep disruptions. However, sleep alterations in critically ill patients are specific and differ significantly from those in ambulatory patients. Polysomnographic patterns of normal sleep are frequently lacking in critically ill patients and the neurobiology of sleep is important to consider regarding alternative methods to quantify sleep in the ICU. This article discusses elements of sleep neurobiology affecting the specificity of sleep patterns and sleep alterations in patients admitted to the ICU. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The neurobiological basis of temperament: towards a better understanding of psychopathology.

    Science.gov (United States)

    Whittle, Sarah; Allen, Nicholas B; Lubman, Dan I; Yücel, Murat

    2006-01-01

    The ability to characterise psychopathologies on the basis of their underlying neurobiology is critical in improving our understanding of disorder etiology and making more effective diagnostic and treatment decisions. Given the well-documented relationship between temperament (i.e. core personality traits) and psychopathology, research investigating the neurobiological substrates that underlie temperament is potentially key to our understanding of the biological basis of mental disorder. We present evidence that specific areas of the prefrontal cortex (including the dorsolateral prefrontal, anterior cingulate, and orbitofrontal cortices) and limbic structures (including the amygdala, hippocampus and nucleus accumbens) are key regions associated with three fundamental dimensions of temperament: Negative Affect, Positive Affect, and Constraint. Proposed relationships are based on two types of research: (a) research into the neurobiological correlates of affective and cognitive processes underlying these dimensions; and (b) research into the neurobiology of various psychopathologies, which have been correlated with these dimensions. A model is proposed detailing how these structures might comprise neural networks whose functioning underlies the three temperaments. Recommendations are made for future research into the neurobiology of temperament, including the need to focus on neural networks rather than individual structures, and the importance of prospective, longitudinal, multi-modal imaging studies in at-risk youth.

  18. Neurobiology of Escalated Aggression and Violence

    Science.gov (United States)

    Miczek, Klaus A.; de Almeida, Rosa M. M.; Kravitz, Edward A.; Rissman, Emilie F.; de Boer, Sietse F.; Raine, Adrian

    2009-01-01

    Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and its escalation with greater precision; second, the prefrontal cortex (PFC) and brainstem structures emerge as pivotal nodes in the limbic circuitry mediating escalated aggressive behavior. The neurochemical and molecular work focuses on the genes that enable invertebrate aggression in males and females and genes that are expressed or suppressed as a result of aggressive experiences in mammals. The fruitless gene, immediate early genes in discrete serotonin neurons, or sex chromosome genes identify sexually differentiated mechanisms for escalated aggression. Male, but not female, fruit flies establish hierarchical relationships in fights and learn from previous fighting experiences. By manipulating either the fruitless or transformer genes in the brains of male or female flies, patterns of aggression can be switched with males using female patterns and vice versa. Work with Sts or Sry genes suggests so far that other genes on the X chromosomes may have a more critical role in female mouse aggression. New data from feral rats point to the regulatory influences on mesocortical serotonin circuits in highly aggressive animals via feedback to autoreceptors and via GABAergic and glutamatergic inputs. Imaging data lead to the hypothesis that antisocial, violent, and psychopathic behavior may in part be attributable to impairments in some of the brain structures (dorsal and ventral PFC, amygdala, and angular gyrus) subserving moral cognition and emotion. PMID:17978016

  19. [Neural mechanism underlying autistic savant and acquired savant syndrome].

    Science.gov (United States)

    Takahata, Keisuke; Kato, Motoichiro

    2008-07-01

    , especially that of the prefrontal cortex and the posterior regions of the brain. (3) Autistic models, including those based on weak central coherence theory (Frith, 1989), that focus on how savant skills emerge from an autistic brain. Based on recent neuroimaging studies of ASD, Just et al. (2004) suggested the underconnectivity theory, which emphasizes the disruption of long-range connectivity and the relative intact or even more enhanced local connectivity in the autistic brain. All the models listed above have certain advantages and shortcomings. At the end of this review, we propose another integrative model of savant syndrome. In this model, we predict an altered balance of local/global connectivity patterns that contribute to an altered functional segregation/integration ratio. In particular, we emphasize the crucial role played by the disruption of global connectivity in a parallel distributed cortical network, which might result in impairment in integrated cognitive processing, such as impairment in executive function and social cognition. On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing. The disruption of connectivity between the prefrontal cortex and other regions is considered to be a particularly important factor because the prefrontal region shows the most influential inhibitory control on other cortical areas. We propose that these neural mechanisms as the underlying causes for the emergence of savant ability in ASD and FTD patients.

  20. [Study on main pharmacodynamics and underlying mechanisms of 999 Ganmaoling].

    Science.gov (United States)

    Xu, Qi-Hua; He, Rong; Peng, Bo; Ye, Zu-Guang; Li, Jian-Rong; Zhang, Yue-Fei; Dai, Zhi

    2016-04-01

    To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their anti-inflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, non-specific pleurisy induced by carrageenan in rats, and yeast induced fever in rats. Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes. The results showed that compared with control group, GML could reduce exudation amount of Evans-Blue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects. The concentration of TNF-α and IL-1β of rat pleural effusion in GML, CMM and WMM group decreased significantly. The concentration of TNF-α, IL-1β and IL-8 in GML group, TNF-α, IL-8 in WMM group and IL-8 in CMM in rats serum decreased significantly. The body temperature in rats decreased significantly in GML and WMM group after 4-8 h of administration. CMM group showed no significant difference in rat body temperature compare with control. Compared with control group, GML (55-13.75 g•L⁻¹) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm. CMM (45-22.5 g•L⁻¹) and WMM (10 g•L⁻¹) could also inhibit KPN biofilm formation and reduce number of viable cells (P<0.01). Result of SEM also showed that GML (55 g•L⁻¹) and its CMM (45 g•L⁻¹) and WMM (10 g•L⁻¹) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix. GML and its CMM & WMM could inhibit the formation of KPN biofilm, CMM & WMM in GML showed synergism and complementation in inhibit KPN biofilm. Results showed that GML had obvious anti-inflammatory and

  1. Reducing the stigma of depression through neurobiology-based psychoeducation: a randomized controlled trial.

    Science.gov (United States)

    Han, Der-Yan; Chen, Sue-Huei

    2014-09-01

    Attribution theory claims that people who are stigmatized experience more negative emotional and behavioral reactions from others when they are thought to be responsible for their problems. Accordingly, this study proposed a neurobiology-based psychoeducational intervention, which attempted to reduce people's blameworthy attitudes toward and social distance from depressed individuals. One hundred and thirty-two college students were randomly assigned to an experimental and control group. Participants in the experimental group received a 30-min lecture on neurobiology-based psychoeducation for depressive disorders, and were asked to fill out questionnaires before and 2 weeks after the intervention. The control group, with no intervention, also filled out the same questionnaires before and 2 weeks after the experiment. The main contents of the neurobiology-based psychoeducation concerned the neurotransmission processes and biological mechanisms of depression, in order to emphasize the biological attribution of depression. An ancova indicated that the neurobiology-based psychoeducational intervention significantly elevated the biological attribution of depression and reduced the social distance from depressed individuals. Psychological blameworthy attitudes toward depression, however, did not significantly change. Through a brief psychoeducation program about depression, knowledge of neuroscience could lead to positive benefits. Public awareness that depression can be effectively prevented and treated may be a way in which people can accept depressed individuals. Further studies are needed to certify the mechanisms of the effect of neurobiology-based psychoeducation. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  2. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  3. Neurobiology of bipolar disorder - lessons from migraine disorders.

    Science.gov (United States)

    Holland, Janathon; Agius, Mark

    2011-09-01

    Treatment for Bipolar Affective Disorder is at present largely empirical, in the lack of a definitive understanding of the biological basis of the condition. Many theories have been proposed regarding the underlying neurobiology. These have included aetiologies relating to altered neurotrophic factor expression, mitochondrial endoplasmic reticulum dysfunction with related calcium changes, and loss of inhibitory interneurons. Here an attempt is made to integrate such current understanding, in part by considering the changes observed in migraine - a condition which has a number of similarities with bipolar disorder.

  4. BBGKY hierarchy underlying many-particle quantum mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Kaniadakis, G

    2003-04-28

    Recently, the one-particle quantum mechanics has been obtained in the framework of an entirely classical subquantum kinetics. In the present Letter we argue that, within the same scheme and without any additional assumption, it is possible to obtain also the n-particle non-relativistic quantum mechanics. The main goal of the present effort is to show that the classical BBGKY hierarchical equation, for the n-particle reduced distribution function, is the ancestor of the n-particle Schroedinger equation. On the other hand we show that within the scenario of the subquantum structure of quantum particle, the Fisher information measure emerges naturally in quantum mechanics.

  5. Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus.

    Science.gov (United States)

    Panadero, Juan Alberto; Sencadas, Vitor; Silva, Sonia C M; Ribeiro, Clarisse; Correia, Vitor; Gama, Francisco M; Gomez Ribelles, José Luis; Lanceros-Mendez, Senentxu

    2016-02-01

    In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro-pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in poly-ε-caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading-unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements. © 2015 Wiley Periodicals, Inc.

  6. Mechanics of stretchable electronics on balloon catheter under extreme deformation

    National Research Council Canada - National Science Library

    Su, Yewang; Liu, Zhuangjian; Wang, Shuodao; Ghaffari, Roozbeh; Kim, Dae-Hyeong; Hwang, Keh-Chih; Rogers, John A; Huang, Yonggang

    2014-01-01

    ... ([approximately equal to]vacuum) and outside of the balloon (pressure [approximately equal to]1atm). The balloon catheter, on which microelectrodes and interconnects are printed, undergoes extreme mechanical deformation during its inflation and deflation...

  7. Peer influence: Neural mechanisms underlying in-group conformity

    National Research Council Canada - National Science Library

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan

    2013-01-01

    .... However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI...

  8. Neurobiology of Anxious Depression: A Review

    OpenAIRE

    Ionescu, Dawn F; Niciu, Mark J; Mathews, Daniel C; Richards, Erica M; Zarate, Carlos A

    2013-01-01

    Anxious depression is a common, distinct clinical subtype of major depressive disorder (MDD). This review summarizes current neurobiological knowledge regarding anxious depression. Peer-reviewed articles published January 1970 through September 2012 were identified via PUBMED, EMBASE, and Cochrane Library, using the following key words: anxious depression electroencephalography (EEG), anxious depression functional magnetic resonance imaging (fMRI), anxious depression genetics, anxious depress...

  9. Neurobiology of escalated aggression and violence

    NARCIS (Netherlands)

    Miczek, Klaus A.; de Almeida, Rosa M. M.; Kravitz, Edward A.; Rissman, Emilie F.; de Boer, Sietse F.; Raine, Adrian

    2007-01-01

    Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and

  10. The Neurobiology of Trust and Schooling

    Science.gov (United States)

    Sankey, Derek

    2018-01-01

    Are there neurobiological reasons why we are willing to trust other people and why "trust" and moral values such as "care" play a quite pivotal role in our social lives and the judgements we make, including our social interactions and judgements made in the context of schooling? In pursuing this question, this paper largely…

  11. Molecular neurobiology in neurology and psychiatry

    Energy Technology Data Exchange (ETDEWEB)

    Kandel, E.R.

    1987-01-01

    This book contains 14 selections. Some of the titles are: An Introduction to Ion Channels; Molecular Neurobiology of the Myelinated Nerve Fiber: Ion-Channel Distributions and Their Implications for Demyelinating Diseases; A Molecular Genetic Approach to Huntington's Disease; and Molecular Features of Cell Adhesion Molecules Involved in Neural Development.

  12. Features wear nodes mechanization wing aircraft operating under dynamic loads

    Directory of Open Access Journals (Sweden)

    А.М. Хімко

    2009-03-01

    Full Text Available  The conducted researches of titanic alloy ВТ-22 at dynamic loading with cycled sliding and dynamic loading in conditions of rolling with slipping. It is established that roller jamming in the carriage increases wear of rod of mechanization of a wing to twenty times. The optimum covering for strengthening wearied sites and restoration of working surfaces of wing’s mechanization rod is defined.

  13. Culturing functional cartilage tissue under a novel bionic mechanical condition.

    Science.gov (United States)

    Sun, Minglin; Lv, Dan; Zhang, Chunqiu; Zhu, Lei

    2010-12-01

    Bioreactor, which is used for in vitro construction of tissue-engineered cartilage, has been extensively studied by researchers. The growth and development of articular cartilage tissue are affected by biomechanical and biochemical factors, especially mechanical condition. Kinds of mechanical conditions including compressive and shear force, fluid flow, hydrostatic pressure, and tissue deformation, were developed in the past years. However, most mechanical conditions of improved bioreactor involve only one or two external force, which is merely partial for engineering cartilage tissue. No bioreactor which can simulate a normal articular cartilage in terms of structure and function has been reported. Consequently, simulation of bionic mechanical environment of a normal articular cartilage is considered to be the optimal environment for culturing the functional articular cartilage in vitro. Based upon this purpose, we designed a rolling-compression loading bioreactor. It could provide cultures with multi-mechanical stimulations and sufficiently mimic the complex mechanical environment of a normal articular cartilage. We propose that this comprehensive rolling-compression loading bioreactor can enhance the cultivation of functional cartilage constructs in vitro. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Mechanisms of disease: mechanism-based classification of neuropathic pain - a critical analysis

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Jensen, Troels Staehelin

    2006-01-01

    Classification of neuropathic pain according to etiology or localization has clear limitations. The discovery of specific molecular and cellular events following experimental nerve injury has raised the possibility of classifying neuropathic pain on the basis of the underlying neurobiological...... mechanisms. Application of this approach in the clinic is problematic, however, owing to a lack of precise tools to assess symptoms and signs, and difficulties in correlating symptoms and signs with mechanisms. Development and validation of diagnostic methods to identify mechanisms, together...

  15. Numerical investigation of pulmonary drug delivery under mechanical ventilation conditions

    Science.gov (United States)

    Banerjee, Arindam; van Rhein, Timothy

    2012-11-01

    The effects of mechanical ventilation waveform on fluid flow and particle deposition were studied in a computer model of the human airways. The frequency with which aerosolized drugs are delivered to mechanically ventilated patients demonstrates the importance of understanding the effects of ventilation parameters. This study focuses specifically on the effects of mechanical ventilation waveforms using a computer model of the airways of patient undergoing mechanical ventilation treatment from the endotracheal tube to generation G7. Waveforms were modeled as those commonly used by commercial mechanical ventilators. Turbulence was modeled with LES. User defined particle force models were used to model the drag force with the Cunningham correction factor, the Saffman lift force, and Brownian motion force. The endotracheal tube (ETT) was found to be an important geometric feature, causing a fluid jet towards the right main bronchus, increased turbulence, and a recirculation zone in the right main bronchus. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by the ETT. Authors acknowledge financial support through University of Missouri Research Board Award.

  16. Mechanism and kinetics of mineral weathering under acid conditions

    NARCIS (Netherlands)

    Anbeek, C.

    1994-01-01

    This study deals with the relationships between crystal structure, grain diameter, surface morphology and dissolution kinetics for feldspar and quartz under acid conditions.

    Intensively ground samples from large, naturally weathered mineral fragments are frequently used in

  17. [Pleasure: Neurobiological conception and Freudian conception].

    Science.gov (United States)

    Chenu, A; Tassin, J-P

    2014-04-01

    Despite many controversies the debate between psychoanalysis and neuroscience remains intense, all the more since the Freudian theory stands as a reference for a number of medical practitioners and faculty psychiatrists, at least in France. Instead of going on arguing we think that it may be more constructive to favour dialogue through the analysis of a precise concept developed in each discipline. The Freudian theory of pleasure, because it is based on biological principles, appears an appropriate topic to perform this task. In this paper, we aim at comparing Freud's propositions to those issued from recent findings in Neuroscience. Like all emotions, pleasure is acknowledged as a motivating factor in contemporary models. Pleasure can indeed be either rewarding when it follows satisfaction, or incentive when it reinforces behaviours. The Freudian concept of pleasure is more univocal. In Freud's theory, pleasure is assumed to be the result of the discharge of the accumulated excitation which will thus reduce the tension. This quantitative approach corresponds to the classical scheme that associates satisfaction and pleasure. Satisfaction of a need would induce both a decrease in tension and the development of pleasure. However, clinical contradictions to this model, such as the occasional co-existence between pleasure and excitation, drove Freud to suggest different theoretical reversals. Freud's 1905 publication, which describes how preliminary sexual pleasures contribute to an increased excitation and a sexual satisfaction, is the only analysis which provides an adapted answer to the apparent paradox of pleasure and excitation co-existence. Studies on the neurobiological mechanisms responsible for the development of pleasure may help to fill this gap in the Freudian theory. Activity of the mesolimbic dopaminergic pathway is strongly associated with the reward system. Experimental studies performed in animals have shown that increased dopaminergic activity in the

  18. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  19. Mechanisms underlying KCNQ1channel cell volume sensitivity

    DEFF Research Database (Denmark)

    Hammami, Sofia

    volume alterations is not yet fully understood. The KCNQ1 channel belonging to the voltage gated KCNQ family is considered a precise sensor of volume changes. The goal of this thesis was to elucidate the mechanism that induces cell volume sensitivity. Until now, a number of investigators have implicitly......) osmotic cell swelling and (2) local membrane stretch on the highly volume sensitive KCNQ1 channel and the highly stretch sensitive BK channel. In this study we present evidence against this assumption by showing that activation of BK channels by local membrane stretch is not mimicked by cell swelling......, and activation of KCNQ1 channels by cell volume increase is not mimicked by stretch of the cell membrane. Thus, we conclude that stretch- and volume-sensitivity can be considered two independent regulatory mechanisms. Alternatively, volume-activation of ion channels could be mediated by an autocrine mechanism...

  20. The neurobiology of the emotional adolescent: From the inside out.

    Science.gov (United States)

    Guyer, Amanda E; Silk, Jennifer S; Nelson, Eric E

    2016-11-01

    Adolescents are commonly portrayed as highly emotional, with their behaviors often hijacked by their emotions. Research on the neural substrates of adolescent affective behavior is beginning to paint a more nuanced picture of how neurodevelopmental changes in brain function influence affective behavior, and how these influences are modulated by external factors in the environment. Recent neurodevelopmental models suggest that the brain is designed to promote emotion regulation, learning, and affiliation across development, and that affective behavior reciprocally interacts with age-specific social demands and different social contexts. In this review, we discuss current findings on neurobiological mechanisms of adolescents' affective behavior and highlight individual differences in and social-contextual influences on adolescents' emotionality. Neurobiological mechanisms of affective processes related to anxiety and depression are also discussed as examples. As the field progresses, it will be critical to test new hypotheses generated from the foundational empirical and conceptual work and to focus on identifying more precisely how and when neural networks change in ways that promote or thwart adaptive affective behavior during adolescence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Survival under stress: molecular mechanisms of metabolic rate ...

    African Journals Online (AJOL)

    Studies in my laboratory are analysing the molecular mechanisms and regulatory events that underlie transitions to and from hypometabolic states In systems including ... Our newest research targets two areas: the role of protein kinases in regulating metabolic adjustments and the role of stress-induced gene expression in ...

  2. A review of mechanisms underlying anticarcinogenicity by brassica vegetables

    NARCIS (Netherlands)

    Verhoeven, D.T.H.; Verhagen, H.; Goldbohm, R.A.; Brandt, P.A. van den; Poppel, G. van

    1997-01-01

    The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in this paper. Brassicas, including all types of cabbages, broccoli, cauliflower and Brussels sprouts, may be protective against cancer due to their relatively high glucosinolate content. Glucosinolates are

  3. Mechanical behaviour of adhesive joint under tensile and shear loading

    NARCIS (Netherlands)

    Jiang, X.; Kolstein, M.H.; Bijlaard, F.S.K.

    2013-01-01

    Due to various advantages of Fibre-Reinforced Polymer (FRP) decks, the FRP to steel composite bridge system is being increasingly used in new bridge structures as well as rehabilitation projects for old bridges. This paper focuses on the mechanical behaviours and failure modes of the

  4. Cellular mechanisms underlying acute graft rejection: time for reassessment

    NARCIS (Netherlands)

    Alegre, Maria-Luisa; Florquin, Sandrine; Goldman, Michel

    2007-01-01

    Rejection of transplanted organs depends on an orchestrated immune response to histocompatibility antigens expressed by the grafted tissue. Effector mechanisms primarily responsible for the rejection process classically involve type 1 helper CD4(+) T cells, cytotoxic CD8(+) T cells and antibodies.

  5. Peer influence: neural mechanisms underlying in-group conformity

    NARCIS (Netherlands)

    Stallen, M.; Smidts, A.; Sanfey, A.G.

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed

  6. Peer influence: Neural mechanisms underlying in-group conformity

    NARCIS (Netherlands)

    M. Stallen (Mirre); A. Smidts (Ale); A.G. Sanfey (Alan)

    2013-01-01

    textabstractPeople often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI).

  7. Mechanisms underlying social inequality in post-menopausal breast cancer.

    Science.gov (United States)

    Hvidtfeldt, Ulla Arthur

    2014-10-01

    This thesis is based on studies conducted in the period 2010-2014 at Department of Public Health, University of Copenhagen and at Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York. The results are presented in three scientific papers and a synopsis. The main objective of the thesis was to determine mechanisms underlying social inequality (defined by educational level) in postmenopausal breast cancer (BC) by addressing mediating effects through hormone therapy (HT) use, BMI, lifestyle and reproductive factors. The results of previous studies suggest that the higher risk of postmenopausal BC among women of high socioeconomic position (SEP) may be explained by reproductive factors and health behaviors. Women of higher SEP generally have fewer children and give birth at older ages than women of low SEP, and these factors have been found to affect the risk of BC - probably through altered hormone levels. Adverse effects on BC risk have also been documented for modifiable health behaviors that may affect hormone levels, such as alcohol consumption, high BMI, physical inactivity, and HT use. Alcohol consumption and HT use are likewise more common among women of higher SEP. The analyses were based on the Social Inequality in Cancer (SIC) cohort and a subsample of the Women's Health Initiative Observational Study (WHI-OS). The SIC cohort was derived by pooling 6 individual studies from the Copenhagen area including 33,562 women (1,733 BC cases) aged 50-70 years at baseline. The subsample of WHI-OS consisted of two case-cohort studies with measurements of endogenous estradiol (N = 1,601) and insulin (N = 791). Assessment of mediation often relies on comparing multiplicative models with and without the potential mediator. Such approaches provide potentially biased results, because they do not account for mediator-outcome confounding, exposure-dependent mediator-outcome confounding, exposure-mediator interaction and interactions

  8. Dislocation mechanism of deuterium retention in tungsten under plasma implantation.

    Science.gov (United States)

    Dubinko, V I; Grigorev, P; Bakaev, A; Terentyev, D; van Oost, G; Gao, F; Van Neck, D; Zhurkin, E E

    2014-10-01

    We have developed a new theoretical model for deuterium (D) retention in tungsten-based alloys on the basis of its being trapped at dislocations and transported to the surface via the dislocation network with parameters determined by ab initio calculations. The model is used to explain experimentally observed trends of D retention under sub-threshold implantation, which does not produce stable lattice defects to act as traps for D in conventional models. Saturation of D retention with implantation dose and effects due to alloying of tungsten with, e.g. tantalum, are evaluated, and comparison of the model predictions with experimental observations under high-flux plasma implantation conditions is presented.

  9. [Neurobiological, psychological and sociological approach to sexual desire and sexual satisfaction].

    Science.gov (United States)

    Bianchi-Demicheli, Francesco; Ammar, Nadia; Bolmont, Mylène; Dosch, Alessandra; Favez, Nicolas; Van der Linden, Martial; Widmer, Eric

    2016-03-16

    In the last years, University Fund Maurice Chalumeau (FUMC) launched a dynamic of research designed to promote scientific excellence and the development of Sexology with particular interest regarding sexual desire. The FUMC has supported a research project entitled "Neurobiological, psychological and sociological approach to sexual desire and sexual satisfaction". This project, sampled on 600 people (300 men and 300 women) aged between 25 and 46 years, was structured around three studies: a broad sociological study and two more specific ones, focused on some psychological mechanisms and neurobiological factors involved in sexual desire. The results show how the secondary socialization, personal expectations, beliefs and values in sexuality, sexual motivations, body image, as well as the neurobiological foundations and visual patterns, are of vital importance in the dynamics of sexual desire.

  10. Peer influence: Neural mechanisms underlying in-group conformity

    Directory of Open Access Journals (Sweden)

    Mirre eStallen

    2013-03-01

    Full Text Available People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI. Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  11. Partitioning-based mechanisms under personalized differential privacy.

    Science.gov (United States)

    Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

    2017-05-01

    Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t-round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms.

  12. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  13. Peer influence: neural mechanisms underlying in-group conformity.

    Science.gov (United States)

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  14. Mental imagery in music performance: underlying mechanisms and potential benefits.

    Science.gov (United States)

    Keller, Peter E

    2012-04-01

    This paper examines the role of mental imagery in music performance. Self-reports by musicians, and various other sources of anecdotal evidence, suggest that covert auditory, motor, and/or visual imagery facilitate multiple aspects of music performance. The cognitive and motor mechanisms that underlie such imagery include working memory, action simulation, and internal models. Together these mechanisms support the generation of anticipatory images that enable thorough action planning and movement execution that is characterized by efficiency, temporal precision, and biomechanical economy. In ensemble performance, anticipatory imagery may facilitate interpersonal coordination by enhancing online predictions about others' action timing. Overlap in brain regions subserving auditory imagery and temporal prediction is consistent with this view. It is concluded that individual differences in anticipatory imagery may be a source of variation in expressive performance excellence and the quality of ensemble cohesion. Engaging in effortful musical imagery is therefore justified when artistic perfection is the goal. © 2012 New York Academy of Sciences.

  15. Critical fracturing phenomenon in heterogeneous materials under external mechanical stress

    Science.gov (United States)

    Jei, Y.; Ouaskit, S.; Nassif et, R.; Boughaleb, Y.; Nechad, H.; El Guerjouma, R.

    2005-12-01

    We analyzed experiments designed for industrial applications in order to test the concept that in heterogeneous materials such as fiber composites concrete subjected to an external mechanical stress rupture is a genuine critical point. This prediction has been tested extensively on heterogeneous materials bases polymer from acoustic emission measurements. The investigating consists in simulating the two-dimensional model of a spring network. Also the bond percolation concept has been very helpful in the interpretation of the numerical results.

  16. The Survival Advantage: Underlying Mechanisms and Extant Limitations

    Directory of Open Access Journals (Sweden)

    Stephanie A. Kazanas

    2015-04-01

    Full Text Available Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007, the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.. However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007 original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.

  17. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress.

    Science.gov (United States)

    Girard, Olivier; Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P; Périard, Julien D

    2017-01-01

    Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Mean skin (37.2±0.7 vs. 32.7±0.8°C; Pvertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both Pvertical (-2.6±5.5%; Pvertical stiffness (-12.9±2.3%; Pvertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations.

  18. The Central Role of Recognition in Auditory Perception: A Neurobiological Model

    Science.gov (United States)

    McLachlan, Neil; Wilson, Sarah

    2010-01-01

    The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior…

  19. The sweetest pill to swallow: how patient neurobiology can be harnessed to maximise placebo effects.

    NARCIS (Netherlands)

    Jubb, J.; Bensing, J.M.

    2013-01-01

    The burgeoning interest in placebo effects over the last 10-15 years has fallen into two main research areas: elucidation of the neurobiological mechanisms recruited following placebo administration, and investigations into the situations and contexts in which placebo effects are evoked. There has

  20. Historical Overview on Plant Neurobiology

    OpenAIRE

    Stahlberg, Rainer

    2006-01-01

    The review tracks the history of electrical long-distance signals from the first recordings of action potentials (APs) in sensitive Dionea and Mimosa plants at the end of the 19th century to their re-discovery in common plants in the 1950's, from the first intracellular recordings of APs in giant algal cells to the identification of the ionic mechanisms by voltage-clamp experiments. An important aspect is the comparison of plant and animal signals and the resulting theoretical implications th...

  1. Putative physiological mechanisms underlying tDCS analgesic effects

    OpenAIRE

    Knotkova, Helena; Nitsche, Michael A.; Cruciani, Ricardo A.

    2013-01-01

    Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits. It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analge...

  2. Can understanding the neurobiology of body dysmorphic disorder (BDD) inform treatment?

    Science.gov (United States)

    Rossell, Susan L; Harrison, Ben J; Castle, David

    2015-08-01

    We aim to provide a clinically focused review of the neurobiological literature in body dysmorphic disorder (BDD), with a focus on structural and functional neuroimaging. There has been a recent influx of studies examining the underlying neurobiology of BDD using structural and functional neuroimaging methods. Despite obvious symptom similarities with obsessive-compulsive disorder (OCD), no study to date has directly compared the two groups using neuroimaging techniques. Studies have established that there are limbic and visual cortex abnormalities in BDD, in contrast to fronto-striatal differences in OCD. Such data suggests affect or visual training maybe useful in BDD. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  3. Hindered dissolution of fibrin formed under mechanical stress.

    Science.gov (United States)

    Varjú, I; Sótonyi, P; Machovich, R; Szabó, L; Tenekedjiev, K; Silva, M M C G; Longstaff, C; Kolev, K

    2011-05-01

    Recent data indicate that stretching forces cause a dramatic decrease in clot volume accompanied by gross conformational changes of fibrin structure. The present study attempts to characterize the lytic susceptibility of fibrin exposed to mechanical stress as a model for fibrin structures observed in vivo. The relevance of stretched fibrin models was substantiated by scanning electron microscopic (SEM) evaluation of human thrombi removed during surgery, where surface fibrin fibers were observed to be oriented in the direction of shear forces, whereas interior fibers formed a random spatial meshwork. These structural variations were modeled in vitro with fibrin exposed to adjustable mechanical stress. After two- and three-fold longitudinal stretching (2 × S, 3 × S) the median fiber diameter and pore area in SEM images of fibrin decreased two- to three-fold. Application of tissue plasminogen activator (tPA) to the surface of model clots, which contained plasminogen, resulted in plasmin generation which was measured in the fluid phase. After 30-min activation 12.6 ± 0.46 pmol mm(-2) plasmin was released from the non-stretched clot (NS), 5.5 ± 1.11 pmol mm(-2) from 2 × S and 2.3 ± 0.36 pmol mm(-2) from 3 × S clot and this hampered plasmin generation was accompanied by decreased release of fibrin degradation products from stretched fibrins. Confocal microscopic images showed that a green fluorescent protein-fusion variant of tPA accumulated in the superficial layer of NS, but not in stretched fibrin. Mechanical stress confers proteolytic resistance to fibrin, which is a result of impaired plasminogen activation coupled to lower plasmin sensitivity of the denser fibrin network. © 2011 International Society on Thrombosis and Haemostasis.

  4. Believing versus interacting: Behavioural and neural mechanisms underlying interpersonal coordination

    DEFF Research Database (Denmark)

    Konvalinka, Ivana; Bauer, Markus; Kilner, James

    When two people engage in a bidirectional interaction with each other, they use both bottom-up sensorimotor mechanisms such as monitoring and adapting to the behaviour of the other, as well as top-down cognitive processes, modulating their beliefs and allowing them to make decisions. Most research...... was measured from one co-actor, with the other co-actor seated outside the scanner. Our findings show frontal alpha suppression during anticipation of the task with a person vs. a computer, and frontal-sensorimotor suppression during task execution with the person vs. computer. This provides insight...

  5. Peer influence: neural mechanisms underlying in-group conformity

    OpenAIRE

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G.

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is ...

  6. Obesity and cancer--mechanisms underlying tumour progression and recurrence.

    Science.gov (United States)

    Park, Jiyoung; Morley, Thomas S; Kim, Min; Clegg, Deborah J; Scherer, Philipp E

    2014-08-01

    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment.

  7. Obesity and cancer—mechanisms underlying tumour progression and recurrence

    Science.gov (United States)

    Kim, Min; Clegg, Deborah J.; Scherer, Philipp E.

    2015-01-01

    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment. PMID:24935119

  8. Mechanisms underlying probucol-induced hERG-channel deficiency.

    Science.gov (United States)

    Shi, Yuan-Qi; Yan, Cai-Chuan; Zhang, Xiao; Yan, Meng; Liu, Li-Rong; Geng, Huai-Ze; Lv, Lin; Li, Bao-Xin

    2015-01-01

    The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (I Kr), which is important for cardiac repolarization. Reduction of I hERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes) or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on I hERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.

  9. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  10. Mechanisms of patulin toxicity under conditions that inhibit yeast growth.

    Science.gov (United States)

    Iwahashi, Yumiko; Hosoda, Hiroshi; Park, Ji-Hyun; Lee, Joo-Hee; Suzuki, Yoshiteru; Kitagawa, Emiko; Murata, Satomi Mizukami; Jwa, Nam-Soo; Gu, Man-Bock; Iwahashi, Hitoshi

    2006-03-08

    Patulin, 4-hydroxy-4H-furo[3,2c]pyran-2(6H)-one, is one of the best characterized and most widely disseminated mycotoxins found in agricultural products. Nonetheless, the mechanisms by which patulin causes toxicity are not well understood. Thus, the cytotoxicity of patulin was characterized by analysis of the yeast transcriptome upon challenge with patulin. Interestingly, patulin-induced yeast gene expression profiles were found to be similar to gene expression patterns obtained after treatment with the antifungal agricultural chemicals thiuram, maneb, and zineb. Moreover, patulin treatment was found to activate protein degradation, especially proteasome activities, sulfur amino acid metabolism, and the defense system for oxidative stress. Damage to DNA by alkylation was also suggested, and this seemed to be repaired by recombinational and excision repair mechanisms. Furthermore, the results provide potential biomarker genes for the detection of patulin in agricultural products. The results suggest the possibility of applying the yeast transcriptome system for the evaluation of chemicals, especially for natural chemicals that are difficult to get by organic synthesis.

  11. Partitioning-based mechanisms under personalized differential privacy

    Science.gov (United States)

    Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

    2017-01-01

    Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t-round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms. PMID:28932827

  12. Neurobiology and treatment of compulsive hoarding.

    Science.gov (United States)

    Saxena, Sanjaya

    2008-09-01

    Compulsive hoarding is a common and often disabling neuropsychiatric disorder. This article reviews the phenomenology, etiology, neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part of a discrete clinical syndrome that includes difficulty discarding, urges to save, clutter, excessive acquisition, indecisiveness, perfectionism, procrastination, disorganization, and avoidance. Epidemiological and taxometric studies indicate that compulsive hoarding is a separate but related obsessive-compulsive spectrum disorder that is frequently comorbid with obsessive-compulsive disorder (OCD). Compulsive hoarding is a genetically discrete, strongly heritable phenotype. Neuroimaging and neuropsychological studies indicate that compulsive hoarding is neurobiologically distinct from OCD and implicate dysfunction of the anterior cingulate cortex and other ventral and medial prefrontal cortical areas that mediate decision-making, attention, and emotional regulation. Effective treatments for compulsive hoarding include pharmacotherapy and cognitive-behavioral therapy. More research will be required to determine the etiology and pathophysiology of compulsive hoarding, and to develop better treatments for this disorder.

  13. The neurobiology of the human memory.

    Science.gov (United States)

    Fietta, Pierluigi; Fietta, Pieranna

    2011-01-01

    Memory can be defined as the ability to acquire, process, store, and retrieve information. Memory is indispensable for learning, adaptation, and survival of every living organism. In humans, the remembering process has acquired great flexibility and complexity, reaching close links with other mental functions, such as thinking and emotions. Changes in synaptic connectivity and interactions among multiple neural networks provide the neurobiological substrates for memory encoding, retention, and consolidation. Memory may be categorized as short-term and long-term memory (according to the storage temporal duration), as implicit and explicit memory (with respect to the consciousness of remembering), as declarative (knowing that [fact]) and procedural (knowing how [skill]) memory, or as sensory (echoic, iconic and haptil), semantic, and episodic memory (according to the various remembering domains). Significant advances have been obtained in understanding memory neurobiology, but much remains to be learned in its cognitive, psychological, and phenomenological aspects.

  14. Neurobiology of depression: A neurodevelopmental approach.

    Science.gov (United States)

    Lima-Ojeda, Juan M; Rupprecht, Rainer; Baghai, Thomas C

    2017-03-03

    The main aims of this paper are to review and evaluate the neurobiology of the depressive syndrome from a neurodevelopmental perspective. An English language literature search was performed using PubMed. Depression is a complex syndrome that involves anatomical and functional changes that have an early origin in brain development. In subjects with genetic risk for depression, early stress factors are able to mediate not only the genetic risk but also gene expression. There is evidence that endocrine and immune interactions have an important impact on monoamine function and that the altered monoamine signalling observed in the depressive syndrome has a neuro-endocrino-immunological origin early in the development. Neurodevelopment is a key aspect to understand the whole neurobiology of depression.

  15. Neurobiological Consequences of Sleep Deprivation

    Science.gov (United States)

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-01-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed. PMID:24179461

  16. Neurobiological consequences of sleep deprivation.

    Science.gov (United States)

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-05-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.

  17. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress.

    Directory of Open Access Journals (Sweden)

    Olivier Girard

    Full Text Available Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C and CON (25°C conditions.Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting.Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001 and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05 temperatures, together with thermal comfort (P<0.001 were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001 and contact time (+3.2±2.4%; P<0.01 higher in HOT for the mean of sets 1-3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001, with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06. Mean vertical (-2.6±5.5%; P<0.01, horizontal (-9.1±4.4%; P<0.001 and resultant ground reaction forces (-3.0±2.8%; P<0.01 along with vertical stiffness (-12.9±2.3%; P<0.001 and leg stiffness (-8.4±2.7%; P<0.01 decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001, with lower propulsive power values in set 2 (-6.6%; P<0.05 in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise.Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations.

  18. The Neurobiological Impact of Ghrelin Suppression after Oesophagectomy

    Directory of Open Access Journals (Sweden)

    Conor F. Murphy

    2016-12-01

    Full Text Available Ghrelin, discovered in 1999, is a 28-amino-acid hormone, best recognized as a stimulator of growth hormone secretion, but with pleiotropic functions in the area of energy homeostasis, such as appetite stimulation and energy expenditure regulation. As the intrinsic ligand of the growth hormone secretagogue receptor (GHS-R, ghrelin appears to have a broad array of effects, but its primary role is still an area of debate. Produced mainly from oxyntic glands in the stomach, but with a multitude of extra-metabolic roles, ghrelin is implicated in complex neurobiological processes. Comprehensive studies within the areas of obesity and metabolic surgery have clarified the mechanism of these operations. As a stimulator of growth hormone (GH, and an apparent inducer of positive energy balance, other areas of interest include its impact on carcinogenesis and tumour proliferation and its role in the cancer cachexia syndrome. This has led several authors to study the hormone in the cancer setting. Ghrelin levels are acutely reduced following an oesophagectomy, a primary treatment modality for oesophageal cancer. We sought to investigate the nature of this postoperative ghrelin suppression, and its neurobiological implications.

  19. Attachment, neurobiology, and mentalizing along the psychosis continuum

    Directory of Open Access Journals (Sweden)

    Martin Debbané

    2016-08-01

    Full Text Available In this review article, we outline the evidence linking attachment adversity to the psychosis, from the premorbid stages of the disorder to its clinical forms. To better understand the neurobiological mechanisms through which insecure attachment may contribute to psychosis, we identify at least five neurobiological pathways linking attachment to risk for developing psychosis. Besides its well documented influence on the hypothalamic-pituary-adrenal (HPA axis, insecure attachment may also contribute to neurodevelopmental risk through the dopaminergic and oxytonergic systems, as well as bear influence on neuroinflammation and oxidative stress responses. We further consider the neuroscientific and behavioural studies that underpin mentalization as a suite of processes potentially moderating the risk to transition to psychotic disorders. In particular, mentalization may help the individual compensate for endophenotypical impairments in the integration of sensory and metacognitive information. We propose a model where embodied mentalization would lie at the core of a protective, resilience response mitigating the adverse and potentially pathological influence of the neurodevelopmental cascade of risk for psychosis.

  20. Bridging Philosophy of Technology and Neurobiological Research: Interpreting Images from the "Slam Freezer"

    Science.gov (United States)

    Rosenberger, Robert

    2005-01-01

    The swiftly growing field of neurobiological research utilizes highly advanced technologies (e.g., magnetic resonance imaging, electron microscopy) to mediate between investigators and the brains they investigate. Here, the author analyzes a device called the "slam freezer" that quick-freezes neurons to be studied under the microscope. Employing…

  1. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.

    Science.gov (United States)

    Davis, Brian W; Seabury, Christopher M; Brashear, Wesley A; Li, Gang; Roelke-Parker, Melody; Murphy, William J

    2015-10-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-03-17

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  3. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2012-02-01

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  4. Wire bond degradation under thermo- and pure mechanical loading

    DEFF Research Database (Denmark)

    Pedersen, Kristian Bonderup; Nielsen, Dennis Achton; Czerny, Bernhard

    2017-01-01

    This paper presents a fundamental study on degradation of heavy Al bond wires typically used in high power modules. Customized samples are designed to only consist of Al bond wires on standard Si diodes. These samples are subjected to pure mechanical and passive thermal cycling to investigate...... the bond degradation behavior on a simple system as well as compare these two test methods. Although an appreciable difference in fracture behavior is observed between these two methods, both provide correlation between the number of cycles and degree of degradation, especially in the case of the passive...... thermal test. To enable investigation of degradation rate a large number of bond interfaces is analyzed and they are found to follow conventional accepted fracture laws like Paris-Erdogan. With additional work this could enable the possibility of obtaining empirical parameters to be used in actual physics...

  5. Mechanical characterization of stomach tissue under uniaxial tensile action.

    Science.gov (United States)

    Jia, Z G; Li, W; Zhou, Z R

    2015-02-26

    In this article, the tensile properties of gastric wall were investigated by using biomechanical test and theoretical analysis. The samples of porcine stomach strips from smaller and greater curvature of the stomach were cut in longitudinal and circumferential direction, respectively. The loading-unloading, stress relaxation, strain creep, tensile fracture tests were performed at mucosa-submucosa, serosa-muscle and intact layer, respectively. Results showed that the biomechanical properties of the porcine stomach depended on the layers, orientations and locations of the gastric wall and presented typical viscoelastic, nonlinear and anisotropic mechanical properties. During loading-unloading test, the stress of serosa-muscle layer in the longitudinal direction was 15-20% more than that in the circumferential direction at 12% stretch ratio, while it could reach about 40% for the intact layer and 50% for the mucosa-submucosa layer. The results of stress relaxation and strain creep showed that the variation degree was obviously faster in the circumferential direction than that in the longitudinal direction, and the ultimate residual values were also different for the different layers, orientations and locations. In the process of fracture test, the serosa-muscle layer fractured firstly followed by the mucosa-submucosa layer when the intact layer was tested, the longitudinal strips firstly began to fracture and the required stress value was about twice as much as that in the circumferential strips. The anisotropy and heterogeneity of mechanical characterization of the porcine stomach were related to its complicated geometry, structure and functions. The results would help us to understand the biomechanics of soft organ tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Mechanisms underlying probucol-induced hERG-channel deficiency

    Directory of Open Access Journals (Sweden)

    Shi YQ

    2015-07-01

    Full Text Available Yuan-Qi Shi,1,* Cai-Chuan Yan,1,* Xiao Zhang,1 Meng Yan,1 Li-Rong Liu,1 Huai-Ze Geng,1 Lin Lv,1 Bao-Xin Li1,21Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workAbstract: The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (IKr, which is important for cardiac repolarization. Reduction of IhERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on IhERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.Keywords: long QT, hERG potassium channels, probucol, SGK1, Nedd4-2

  7. The chronobiology and neurobiology of winter seasonal affective disorder

    Science.gov (United States)

    Levitan, Robert D.

    2007-01-01

    This review summarizes research on the chronobiology and neurobiology of winter seasonal affective disorder (SAD), a recurrent subtype of depression characterized by a predictable onset in the fall/winter months and spontaneous remission in the spring/summer period. Chronobiological mechanisms related to circadian rhythms, melatonin, and photoperiodism play a significant role in many cases of SAD, and treatment of SAD can be optimized by considering individual differences in key chronobiological markers. Converging evidence also points to a role for the major monoamine neurotransmitters serotonin, norepinephrine, and dopamine in one or more aspects of SAD. Ultimately, as with other psychiatric illnesses, SAD is best considered as a complex disorder resulting from the interaction of several vulnerability factors acting at different levels, the various genetic mechanisms that underlie them, and the physical environment. Models of SAD that emphasize its potential role in human evolution will also be discussed. PMID:17969868

  8. Neurobiological findings related to Internet use disorders.

    Science.gov (United States)

    Park, Byeongsu; Han, Doug Hyun; Roh, Sungwon

    2017-07-01

    In the last 10 years, numerous neurobiological studies have been conducted on Internet addiction or Internet use disorder. Various neurobiological research methods - such as magnetic resonance imaging; nuclear imaging modalities, including positron emission tomography and single photon emission computed tomography; molecular genetics; and neurophysiologic methods - have made it possible to discover structural or functional impairments in the brains of individuals with Internet use disorder. Specifically, Internet use disorder is associated with structural or functional impairment in the orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. These regions are associated with the processing of reward, motivation, memory, and cognitive control. Early neurobiological research results in this area indicated that Internet use disorder shares many similarities with substance use disorders, including, to a certain extent, a shared pathophysiology. However, recent studies suggest that differences in biological and psychological markers exist between Internet use disorder and substance use disorders. Further research is required for a better understanding of the pathophysiology of Internet use disorder. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  9. Algorithmic mechanisms for reliable crowdsourcing computation under collusion.

    Science.gov (United States)

    Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A; Pareja, Daniel

    2015-01-01

    We consider a computing system where a master processor assigns a task for execution to worker processors that may collude. We model the workers' decision of whether to comply (compute the task) or not (return a bogus result to save the computation cost) as a game among workers. That is, we assume that workers are rational in a game-theoretic sense. We identify analytically the parameter conditions for a unique Nash Equilibrium where the master obtains the correct result. We also evaluate experimentally mixed equilibria aiming to attain better reliability-profit trade-offs. For a wide range of parameter values that may be used in practice, our simulations show that, in fact, both master and workers are better off using a pure equilibrium where no worker cheats, even under collusion, and even for colluding behaviors that involve deviating from the game.

  10. Neural mechanisms underlying melodic perception and memory for pitch.

    Science.gov (United States)

    Zatorre, R J; Evans, A C; Meyer, E

    1994-04-01

    The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.

  11. Separable mechanisms underlying global feature-based attention.

    Science.gov (United States)

    Bondarenko, Rowena; Boehler, Carsten N; Stoppel, Christian M; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Hopf, Jens-Max

    2012-10-31

    Feature-based attention is known to operate in a spatially global manner, in that the selection of attended features is not bound to the spatial focus of attention. Here we used electromagnetic recordings in human observers to characterize the spatiotemporal signature of such global selection of an orientation feature. Observers performed a simple orientation-discrimination task while ignoring task-irrelevant orientation probes outside the focus of attention. We observed that global feature-based selection, indexed by the brain response to unattended orientation probes, is composed of separable functional components. One such component reflects global selection based on the similarity of the probe with task-relevant orientation values ("template matching"), which is followed by a component reflecting selection based on the similarity of the probe with the orientation value under discrimination in the focus of attention ("discrimination matching"). Importantly, template matching occurs at ∼150 ms after stimulus onset, ∼80 ms before the onset of discrimination matching. Moreover, source activity underlying template matching and discrimination matching was found to originate from ventral extrastriate cortex, with the former being generated in more anterolateral and the latter in more posteromedial parts, suggesting template matching to occur in visual cortex higher up in the visual processing hierarchy than discrimination matching. We take these observations to indicate that the population-level signature of global feature-based selection reflects a sequence of hierarchically ordered operations in extrastriate visual cortex, in which the selection based on task relevance has temporal priority over the selection based on the sensory similarity between input representations.

  12. Molecular mechanism for cavitation in water under tension

    Science.gov (United States)

    Menzl, Georg; Gonzalez, Miguel A.; Geiger, Philipp; Caupin, Frédéric; Abascal, José L. F.; Dellago, Christoph

    2016-01-01

    Despite its relevance in biology and engineering, the molecular mechanism driving cavitation in water remains unknown. Using computer simulations, we investigate the structure and dynamics of vapor bubbles emerging from metastable water at negative pressures. We find that in the early stages of cavitation, bubbles are irregularly shaped and become more spherical as they grow. Nevertheless, the free energy of bubble formation can be perfectly reproduced in the framework of classical nucleation theory (CNT) if the curvature dependence of the surface tension is taken into account. Comparison of the observed bubble dynamics to the predictions of the macroscopic Rayleigh–Plesset (RP) equation, augmented with thermal fluctuations, demonstrates that the growth of nanoscale bubbles is governed by viscous forces. Combining the dynamical prefactor determined from the RP equation with CNT based on the Kramers formalism yields an analytical expression for the cavitation rate that reproduces the simulation results very well over a wide range of pressures. Furthermore, our theoretical predictions are in excellent agreement with cavitation rates obtained from inclusion experiments. This suggests that homogeneous nucleation is observed in inclusions, whereas only heterogeneous nucleation on impurities or defects occurs in other experiments. PMID:27803329

  13. Neural mechanisms underlying social conformity in an ultimatum game

    Directory of Open Access Journals (Sweden)

    Zhenyu eWei

    2013-12-01

    Full Text Available When individuals’ actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as social conformity. In the present study, we used event-related functional magnetic resonance imaging (fMRI to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

  14. Fracture mechanisms of glass particles under dynamic compression

    Energy Technology Data Exchange (ETDEWEB)

    Parab, Niranjan D.; Guo, Zherui; Hudspeth, Matthew C.; Claus, Benjamin J.; Fezzaa, Kamel; Sun, Tao; Chen, Weinong W.

    2017-08-01

    In this study, dynamic fracture mechanisms of single and contacting spherical glass particles were observed using high speed synchrotron X-ray phase contrast imaging. A modified Kolsky bar setup was used to apply controlled dynamic compressive loading on the soda-lime glass particles. Four different configurations of particle arrangements with one, two, three, and five particles were studied. In single particle experiments, cracking initiated near the contact area between the particle and the platen, subsequently fragmenting the particle in many small sub-particles. In multi-particle experiments, a crack was observed to initiate from the point just outside the contact area between two particles. The initiated crack propagated at an angle to the horizontal loading direction, resulting in separation of a fragment. However, this fragment separation did not affect the ability of the particle to withstand further contact loading. On further compression, large number of cracks initiated in the particle with the highest number of particle-particle contacts near one of the particle-particle contacts. The initiated cracks roughly followed the lines joining the contact points. Subsequently, the initiated cracks along with the newly developed sub-cracks bifurcated rapidly as they propagated through the particle and fractured the particle explosively into many small fragments, leaving the other particles nearly intact.

  15. The dynamic response of electrostatically driven resonators under mechanical shock

    Science.gov (United States)

    Ibrahim, Mahmoud I.; Younis, Mohammad I.

    2010-02-01

    This paper presents a theoretical and experimental investigation of the response of electrostatically actuated parallel-plate resonators when subjected to mechanical shock. Resonators are commonly employed in resonant sensors, where they are operated at low pressure for enhanced sensitivity making their response to external disturbances such as shock a critical issue. A single-degree-of-freedom system is used to model a resonator, which is electrostatically driven by a dc load superimposed to an ac harmonic load. Simulation results are demonstrated in a series of shock spectra that help indicate the combined influence of shock, dc and ac loads. The effect of the shock duration coinciding with the ac harmonic frequency is investigated. It is concluded that accounting for electrostatic forces, especially the ac load, is crucial when addressing the reliability and performance of resonators against shock. It is found that for specific shock and ac excitation conditions, a resonator may experience early dynamic pull-in instability. Experimental work has been conducted on a capacitive sensor to verify the obtained theoretical results. The sensor is mounted on top of a small shaker and then both are placed inside a vacuum chamber. Acceleration pulses were applied on the sensor while powered by dc and ac loads. The response of the device was monitored using a laser-Doppler vibrometer. The experimental data were compared to the theoretical results and were found to be in good agreement.

  16. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    Science.gov (United States)

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions. PMID:24474939

  17. Adhesive wear mechanism under combined electric diamond grinding

    Directory of Open Access Journals (Sweden)

    Popov Vyacheslav

    2017-01-01

    Full Text Available The article provides a scientific substantiation of loading of metal-bond diamond grinding wheels and describes the mechanism of contact interaction (interlocking of wheels with tool steel as well as its general properties having an influence on combined electric diamond grinding efficiency. The study concluded that a loaded layer can be formed in a few stages different by nature. It is known, that one of the causes of grinding degradation is a continuous loading of active grits (abrasive grinding tool by workpiece chips. It all affects the diamond grinding wheels efficiency and grinding ability with a result in increase of tool pressure, contact temperature and wheels specific removal rate. Science has partially identified some various methods to minimize grinding wheel loading, however, as to loading of metal-bond diamond grinding wheels the search is still in progress. Therefore, research people have to state, that in spite of the fact that the wheels made of cubic boron nitride are of little use as applied to ceramic, ultrahard, hard-alloyed hard-to-machine and nano-materials of the time, but manufactures have to apply cubic boron nitride wheels wherein diamond ones preferable.

  18. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Antonio F. Hernández

    2016-03-01

    Full Text Available Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation. Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  19. Metal uptake by microalgae: underlying mechanisms and practical applications.

    Science.gov (United States)

    Monteiro, Cristina M; Castro, Paula M L; Malcata, F Xavier

    2012-01-01

    Metal contamination of a few aquatic, atmospheric, and soil ecosystems has increased ever since the industrial revolution, owing to discharge of such elements via the effluents of some industrial facilities. Their presence to excessive levels in the environment will eventually lead to serious health problems in higher animals owing to accumulation throughout the food web. Current physicochemical methods available for recovery of metal pollutants (e.g., chemical precipitation, oxidation/reduction, or physical ion exchange) are either expensive or inefficient when they are present at very low concentrations. Consequently, removal of toxic metals by microorganisms has emerged as a potentially more economical alternative. Microalgae (in terms of both living and nonliving biomass) are an example of microorganisms suitable to recover metals and able to attain noteworthy percent removals. Their relatively high metal-binding capacities arise from the intrinsic composition of their cell walls, which contain negatively charged functional groups. Consequently, microalgal cells are particularly efficient in uptake of those contaminants when at low levels. Self-defense mechanisms developed by microalgal cells to survive in metal-containing media and environmental factors that affect their removal (e.g., pH, temperature, and biomass concentration) are reviewed here in a comprehensive way and further discussed in attempts to rationalize this form of remediation vis-a-vis with conventional nonbiological alternatives. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  20. Neural mechanisms underlying social conformity in an ultimatum game.

    Science.gov (United States)

    Wei, Zhenyu; Zhao, Zhiying; Zheng, Yong

    2013-01-01

    When individuals' actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as "social conformity." In the present study, we used event-related functional magnetic resonance imaging (fMRI) to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

  1. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  2. Risk factors for pancreatic cancer: underlying mechanisms and potential targets.

    Science.gov (United States)

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C

    2013-01-01

    Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  3. Raynaud's Phenomenon: a Brief Review of the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Manal Fardoun

    2016-11-01

    Full Text Available Raynaud's phenomenon (RP is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR. In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells (VSMCs orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α2C-AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in pre-menopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  4. Common neural mechanisms underlying reversal learning by reward and punishment.

    Science.gov (United States)

    Xue, Gui; Xue, Feng; Droutman, Vita; Lu, Zhong-Lin; Bechara, Antoine; Read, Stephen

    2013-01-01

    Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations.

  5. Color vision in primates: Neurobiology and behavior

    OpenAIRE

    Skalníková, Petra

    2015-01-01

    Trichromacy is the condition that involves three independent channels for processing color information based on three different cone types. Most mammals have dichromatic vision, trichromacy appears in primates of the Old World (including human) and partly in the New Wold primates. This thesis focuses on the mechanisms of trichromatic vision, its evolution in primates and the comparison of the primates of the Old and New World. The neuronal mechanisms underlying both trichromatic and dichromat...

  6. Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

    Science.gov (United States)

    Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

    2012-03-01

    Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

  7. 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).

  8. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    Directory of Open Access Journals (Sweden)

    Michele eBellesi

    2014-10-01

    Full Text Available Even modest sleep restriction, especially the loss of sleep slow wave activity, is invariably associated with slower EEG activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex, a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep enhancement.

  9. Design principles and developmental mechanisms underlying retinal mosaics.

    Science.gov (United States)

    Reese, Benjamin E; Keeley, Patrick W

    2015-08-01

    Most structures within the central nervous system (CNS) are composed of different types of neuron that vary in both number and morphology, but relatively little is known about the interplay between these two features, i.e. about the population dynamics of a given cell type. How such arrays of neurons are distributed within a structure, and how they differentiate their dendrites relative to each other, are issues that have recently drawn attention in the invertebrate nervous system, where the genetic and molecular underpinnings of these organizing principles are being revealed in exquisite detail. The retina is one of the few locations where these principles have been extensively studied in the vertebrate CNS, indeed, where the design principles of 'mosaic regularity' and 'uniformity of coverage' were first explicitly defined, quantified, and related to each other. Recent studies have revealed a number of genes that influence the formation of these histotypical features in the retina, including homologues of those invertebrate genes, although close inspection reveals that they do not always mediate comparable developmental processes nor elucidate fundamental design principles. The present review considers just how pervasive these features of 'mosaic regularity' and 'uniform dendritic coverage' are within the mammalian retina, discussing the means by which such features can be assessed in the mature and developing nervous system and examining the limitations associated with those assessments. We then address the extent to which these two design principles co-exist within different populations of neurons, and how they are achieved during development. Finally, we consider the neural phenotypes obtained in mutant nervous systems, to address whether a prospective gene of interest underlies those very design principles. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  10. Mechanism of attenuation of leptin signaling under chronic ligand stimulation

    Directory of Open Access Journals (Sweden)

    Bamberg-Lemper Simone

    2010-01-01

    Full Text Available Abstract Background Leptin is an adipocyte-derived hormone that acts via its hypothalamic receptor (LEPRb to regulate energy balance. A downstream effect essential for the weight-regulatory action of leptin is the phosphorylation and activation of the latent transcription factor STAT3 by LEPRb-associated Janus kinases (JAKs. Obesity is typically associated with chronically elevated leptin levels and a decreased ability of LEPRb to activate intracellular signal transduction pathways (leptin resistance. Here we have studied the roles of the intracellular tyrosine residues in the negative feedback regulation of LEPRb-signaling under chronic leptin stimulation. Results Mutational analysis showed that the presence of either Tyr985 and Tyr1077 in the intracellular domain of LEPRb was sufficient for the attenuation of STAT3 phosphorylation, whereas mutation of both tyrosines rendered LEPRb resistant to feedback regulation. Overexpression and RNA interference-mediated downregulation of suppressor of cytokine signaling 3 (SOCS3 revealed that both Tyr985 and Tyr1077 were capable of supporting the negative modulatory effect of SOCS3 in reporter gene assays. In contrast, the inhibitory effect of SOCS1 was enhanced by the presence of Tyr985 but not Tyr1077. Finally, the reduction of the STAT-phosphorylating activity of the LEPRb complex after 2 h of leptin stimulation was not accompanied by the dephosphorylation or degradation of LEPRb or the receptor-associated JAK molecule, but depended on Tyr985 and/or Tyr1077. Conclusions Both Tyr985 and Tyr1077 contribute to the negative regulation of LEPRb signaling. The inhibitory effects of SOCS1 and SOCS3 differ in the dependence on the tyrosine residues in the intracellular domain of LEPRb.

  11. [The social brain: neurobiological bases of clinical interest].

    Science.gov (United States)

    Álvaro-González, Luis C

    2015-11-16

    Human social capacities are developmentally late and unique. They allow for a specialisation that enhances the availability of resources and facilitates reproduction. Our social complexity rests on specific circuits and mechanisms, which are analysed here. The following are put into operation for those purposes: knowledge of the other by means of empathy, specific mechanisms that endow us with the capacity to detect defrauders, genetic and biochemical factors, and the autonomic nervous system. Empathy is the basic mechanism in sociability. It has different levels of complexity (emotional, cognitive, attribution), with specific anatomical differentiation. Social matters are linked to emotional ones, and this in turn to the homeostatic aspects. Hence, physical and social pain share an anatomical matrix and therapies. We are social beings of a selfish biological nature, which we adjust thanks to a special capacity to detect defrauders, which is dominant over those involving planning or abstraction. Oxytocin is the essential prosocial neurochemical mediator. Serotonin and the enzyme MAO are considered as having an antisocial capacity, which is dependent on the interaction with adverse environments. Finally, the vagal system, which is more recent phylogenetically speaking and myelinated, that of the dorsal nucleus of the vagus nerve, is a requirement for warm and leisurely social interaction. The neurobiology of social matters makes it possible to recognise disorders affecting this behaviour in structural injuries (vascular, of the white matter, dementias, etc.), neurodevelopmental disorders (autism), psychiatric illnesses (schizophrenia) or personality disorders. There are a number of promising therapeutic interventions (transcranial magnetic stimulation, drugs). The addition of cultural and environmental factors to the neurobiological ones introduces a greater amount of ecological complexity, but without lessening the validity of what it outlined.

  12. Mechanisms Underlying the Association Between Early-Life Adversity and Physical Health: Charting a Course for the Future.

    Science.gov (United States)

    Bush, Nicole R; Lane, Richard D; McLaughlin, Katie A

    Early-life adversities (ELA) are associated with subsequent pervasive alterations across a wide range of neurobiological systems and psychosocial factors that contribute to accelerated onset of health problems and diseases. In this article, we provide an integrated perspective on recent developments in research on ELA, based on the articles published in this Special Issue of Psychosomatic Medicine. We focus on the following: 1) the distinction between specific versus general aspects of ELA with regard to the nature of exposure (e.g., physical and sexual abuse, emotional abuse or neglect, relative socioeconomic deprivation), biological and behavioral correlates of ELA, and differences across diseases; 2) the importance of timing in the critical phases of exposure to ELA; and 3) adaptive versus dysfunctional responses to ELA and their consequences for biological and behavioral risk factors for adverse health outcomes. This article concludes with outlining important new targets for research in this area, including the neurobiology of affect as a mechanism linking ELA to adverse health outcomes, and the need for large-scale longitudinal investigations of multisystem processes relevant to ELA in diverse samples, starting prenatally, continuing to late adolescence, and with long-term follow-up assessments that enable evaluation of incident disease outcomes.

  13. The TFOS International Workshop on Contact Lens Discomfort: report of the subcommittee on neurobiology.

    Science.gov (United States)

    Stapleton, Fiona; Marfurt, Carl; Golebiowski, Blanka; Rosenblatt, Mark; Bereiter, David; Begley, Carolyn; Dartt, Darlene; Gallar, Juana; Belmonte, Carlos; Hamrah, Pedram; Willcox, Mark

    2013-10-18

    This report characterizes the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens-related discomfort. While there is limited evidence for the mechanisms involved in contact lens-related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the effect of hyperosmolarity on ocular surface nociceptors, and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented herein to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactorial, including components of osmolarity, solution effects, desiccation, thermal effects, inflammation, friction, and mechanical stimulation. Sensory input will arise from stimulation of the lid margin, palpebral and bulbar conjunctiva, and the cornea.

  14. Advances in the neurobiological bases for food 'liking' versus 'wanting'.

    Science.gov (United States)

    Castro, D C; Berridge, K C

    2014-09-01

    The neural basis of food sensory pleasure has become an increasingly studied topic in neuroscience and psychology. Progress has been aided by the discovery of localized brain subregions called hedonic hotspots in the early 2000s, which are able to causally amplify positive affective reactions to palatable tastes ('liking') in response to particular neurochemical or neurobiological stimulations. Those hedonic mechanisms are at least partly distinct from larger mesocorticolimbic circuitry that generates the incentive motivation to eat ('wanting'). In this review, we aim to describe findings on these brain hedonic hotspots, especially in the nucleus accumbens and ventral pallidum, and discuss their role in generating food pleasure and appetite. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. The neurobiology of relapse in schizophrenia.

    Science.gov (United States)

    Remington, Gary; Foussias, George; Agid, Ofer; Fervaha, Gagan; Takeuchi, Hiroyoshi; Hahn, Margaret

    2014-02-01

    Dopamine's proposed role in psychosis proved a starting point in our understanding of the neurobiology of relapse, fitting given the central role positive symptoms play. This link is reflected in early work examining neurotransmitter metabolite and drug (e.g. amphetamine, methylphenidate) challenge studies as a means of better understanding relapse and predictors. Since, lines of investigation have expanded (e.g. electrophysiological, immunological, hormonal, stress), an important step forward if relapse per se is the question. Arguably, perturbations in dopamine represent the final common pathway in psychosis but it is evident that, like schizophrenia, relapse is heterogeneous and multidimensional. In understanding the neurobiology of relapse, greater gains are likely to be made if these distinctions are acknowledged; for example, efforts to identify trait markers might better be served by distinguishing primary (i.e. idiopathic) and secondary (e.g. substance abuse, medication nonadherence) forms of relapse. Similarly, it has been suggested that relapse is 'neurotoxic', yet individuals do very well on clozapine after multiple relapses and the designation of treatment resistance. An alternative explanation holds that schizophrenia is characterized by different trajectories, at least to some extent biologically and/or structurally distinguishable from the outset, with differential patterns of response and relapse. Just as with schizophrenia, it seems naïve to conceptualize the neurobiology of relapse as a singular process. We propose that it is shaped by the form of illness and in place from the outset, modified by constitutional factors like resilience, as well as treatment, and confounded by secondary forms of relapse. © 2013 Elsevier B.V. All rights reserved.

  16. An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

    Science.gov (United States)

    Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

    2016-01-01

    Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644

  17. An update on CRF mechanisms underlying alcohol use disorders and dependence.

    Directory of Open Access Journals (Sweden)

    Isabel Marian Hartmann Quadros

    2016-10-01

    Full Text Available Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin Releasing Factor (CRF systems have been critically implied in the transition towards problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic-pituitary-adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF binding protein and Urocortins, a family of CRF-related peptides.

  18. An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence.

    Science.gov (United States)

    Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

    2016-01-01

    Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic-pituitary-adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides.

  19. Neurobiology of wisdom: a literature overview.

    Science.gov (United States)

    Meeks, Thomas W; Jeste, Dilip V

    2009-04-01

    Wisdom is a unique psychological trait noted since antiquity, long discussed in humanities disciplines, recently operationalized by psychology and sociology researchers, but largely unexamined in psychiatry or biology. To discuss recent neurobiological studies related to subcomponents of wisdom identified from several published definitions/descriptions of wisdom by clinical investigators in the field, ie, prosocial attitudes/behaviors, social decision making/pragmatic knowledge of life, emotional homeostasis, reflection/self-understanding, value relativism/tolerance, and acknowledgment of and dealing effectively with uncertainty. Literature focusing primarily on neuroimaging/brain localization and secondarily on neurotransmitters, including their genetic determinants. Studies involving functional neuroimaging or neurotransmitter functioning, examining human (rather than animal) subjects, and identified via a PubMed search using keywords from any of the 6 proposed subcomponents of wisdom were included. Studies were reviewed by both of us, and data considered to be potentially relevant to the neurobiology of wisdom were extracted. Functional neuroimaging permits exploration of neural correlates of complex psychological attributes such as those proposed to comprise wisdom. The prefrontal cortex figures prominently in several wisdom subcomponents (eg, emotional regulation, decision making, value relativism), primarily via top-down regulation of limbic and striatal regions. The lateral prefrontal cortex facilitates calculated, reason-based decision making, whereas the medial prefrontal cortex is implicated in emotional valence and prosocial attitudes/behaviors. Reward neurocircuitry (ventral striatum, nucleus accumbens) also appears important for promoting prosocial attitudes/behaviors. Monoaminergic activity (especially dopaminergic and serotonergic), influenced by several genetic polymorphisms, is critical to certain subcomponents of wisdom such as emotional

  20. Neuromorphic implementations of neurobiological learning algorithms for spiking neural networks.

    Science.gov (United States)

    Walter, Florian; Röhrbein, Florian; Knoll, Alois

    2015-12-01

    The application of biologically inspired methods in design and control has a long tradition in robotics. Unlike previous approaches in this direction, the emerging field of neurorobotics not only mimics biological mechanisms at a relatively high level of abstraction but employs highly realistic simulations of actual biological nervous systems. Even today, carrying out these simulations efficiently at appropriate timescales is challenging. Neuromorphic chip designs specially tailored to this task therefore offer an interesting perspective for neurorobotics. Unlike Von Neumann CPUs, these chips cannot be simply programmed with a standard programming language. Like real brains, their functionality is determined by the structure of neural connectivity and synaptic efficacies. Enabling higher cognitive functions for neurorobotics consequently requires the application of neurobiological learning algorithms to adjust synaptic weights in a biologically plausible way. In this paper, we therefore investigate how to program neuromorphic chips by means of learning. First, we provide an overview over selected neuromorphic chip designs and analyze them in terms of neural computation, communication systems and software infrastructure. On the theoretical side, we review neurobiological learning techniques. Based on this overview, we then examine on-die implementations of these learning algorithms on the considered neuromorphic chips. A final discussion puts the findings of this work into context and highlights how neuromorphic hardware can potentially advance the field of autonomous robot systems. The paper thus gives an in-depth overview of neuromorphic implementations of basic mechanisms of synaptic plasticity which are required to realize advanced cognitive capabilities with spiking neural networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Effect of Altered Gravity on the Neurobiology of Fish

    Science.gov (United States)

    Anken, R. H.; Rahmann, H.

    In vertebrates (including humans) altered gravitational environments such as weightlessness can induce malfunction of the inner ears due to a mismatch between canal and statolith afferents. This leads to an illusionary tilt because the inputs from the inner ear are not confirmed by the other sensory organs, which then results in intersensory conflict. Vertebrates in orbit therefore face severe orientation problems. In humans the intersensory conflict may additionally lead to a malaise commonly referred to as space motion sickness (SMS). After the initial days of weightlessness the orientation problems (and SMS) disappear as the brain develops a new interpretation of the available sensory data. The present contribution reviews the neurobiological responses, particularly those of fish, observed under altered gravitational states concerning behavior and neuroplastic reactivities. Investigations employing microgravity (spaceflight, parabolic aircraft flights, clinostat) and hypergravity (laboratory centrifuges as ground-based research tools) provide insights for understanding the basic phenomena, many of which remain only incompletely explained

  2. Neurobiology of Schemas and Schema-Mediated Memory.

    Science.gov (United States)

    Gilboa, Asaf; Marlatte, Hannah

    2017-08-01

    Schemas are superordinate knowledge structures that reflect abstracted commonalities across multiple experiences, exerting powerful influences over how events are perceived, interpreted, and remembered. Activated schema templates modulate early perceptual processing, as they get populated with specific informational instances (schema instantiation). Instantiated schemas, in turn, can enhance or distort mnemonic processing from the outset (at encoding), impact offline memory transformation and accelerate neocortical integration. Recent studies demonstrate distinctive neurobiological processes underlying schema-related learning. Interactions between the ventromedial prefrontal cortex (vmPFC), hippocampus, angular gyrus (AG), and unimodal associative cortices support context-relevant schema instantiation and schema mnemonic effects. The vmPFC and hippocampus may compete (as suggested by some models) or synchronize (as suggested by others) to optimize schema-related learning depending on the specific operationalization of schema memory. This highlights the need for more precise definitions of memory schemas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. What is so special about smell? Olfaction as a model system in neurobiology.

    Science.gov (United States)

    Barwich, Ann-Sophie

    2016-01-01

    Neurobiology studies mechanisms of cell signalling. A key question is how cells recognise specific signals. In this context, olfaction has become an important experimental system over the past 25 years. The olfactory system responds to an array of structurally diverse stimuli. The discovery of the olfactory receptors (ORs), recognising these stimuli, established the olfactory pathway as part of a greater group of signalling mechanisms mediated by G-protein-coupled receptors (GPCRs). GPCRs are the largest protein family in the mammalian genome and involved in numerous fundamental physiological processes. The OR family exhibits two characteristics that make them an excellent model system to understand GPCRs: its size and the structural diversity of its members. Research on the OR binding site investigates what amino acid sequences determine the receptor-binding capacity. This promises a better understanding of how the basic genetic makeup of GPCRs relates to their diversification in ligand-binding capacities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. The sweetest pill to swallow: how patient neurobiology can be harnessed to maximise placebo effects.

    Science.gov (United States)

    Jubb, Jayne; Bensing, Jozien M

    2013-12-01

    The burgeoning interest in placebo effects over the last 10-15 years has fallen into two main research areas: elucidation of the neurobiological mechanisms recruited following placebo administration, and investigations into the situations and contexts in which placebo effects are evoked. There has been little attention focused on bridging these two i.e. how to actively translate and apply these neurobiological mechanisms into daily clinical practice in a responsible way. This article addresses this gap, first through a narrative review of the last 15 years of neuroscience findings with special attention focussed on the elucidation of the neurotransmitters, pathways and mechanisms involved in placebo effects, and secondly, at how these psycho(neuro)biological effects could be harnessed in medical care. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Fundamental study of failure mechanisms of pressure vessels under thermo-mechanical cycling in multiphase environments

    Science.gov (United States)

    Penso Mula, Jorge Antonio

    Cracking and bulging in welded and internally lined pressure vessels that work in thermal-mechanical cycling services have been well known problems in the petrochemical, power and nuclear industries. Published literature and industry surveys show that similar problems have been occurring during the last 50 years. Understanding the causes of cracking and bulging would lead to improvements in the reliability of these pressure vessels. This study attempts to add information required for improving the knowledge and fundamental understanding of these problems. Cracking and bulging, most often in the weld areas, commonly experienced in delayed coking units (e.g. coke drums) in oil refineries are typical examples. The coke drum was selected for this study because of the existing field experience and past industrial investigation results that were available to serve as the baseline references for the analytical studies performed for this dissertation. Another reason for selecting the delayed coking units for this study was due to their high economical yields. Shutting down these units would cause a high negative economic impact on the refinery operations. Several failure mechanisms were hypothesized. The finite element method was used to analyze these significant variables and to verify the hypotheses. In conclusion, a fundamental explanation of the occurrence of bulging and cracking in pressure vessels in multiphase environments has been developed. Several important factors have been identified, including the high convection coefficient of the boiling layer during filling and quenching, the mismatch in physical, thermal and mechanical properties in the dissimilar weld of the clad plates and process conditions such as heating and quenching rate and warming time. Material selection for coke drums should consider not only fatigue strength but also corrosion resistance at high temperatures and low temperatures. Cracking occurs due to low cycle fatigue and corrosion. The FEA

  6. Adolescent neurobiological susceptibility to social context

    Directory of Open Access Journals (Sweden)

    Roberta A. Schriber

    2016-06-01

    Full Text Available Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment encountered (e.g., high vs. low parental warmth. Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. Ultimately, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes.

  7. PET and SPECT of neurobiological systems

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [Groningen Univ. (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Gent Univ. (Belgium). Dept. of Nuclear Medicine; Otte, Andreas [Univ. of Applied Sciences, Offenburg (Germany). Faculty of Electrical Engineering and Information Technology; Vries, Erik F.J. de; Waarde, Aren van (eds.) [Groningen Univ. (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging

    2014-04-01

    Addresses a variety of aspects of neurotransmission in the brain. Details the latest results in probe development. Emphasis on a multidisciplinary approach. Written by internationally acclaimed experts. PET and SPECT of Neurobiological Systems combines the expertise of renowned authors whose dedication to the development of novel probes and techniques for the investigation of neurobiological systems has achieved international recognition. Various aspects of neurotransmission in the brain are discussed, such as visualization and quantification of (more than 20 different) neuroreceptors, neuroinflammatory markers, transporters, and enzymes as well as neurotransmitter synthesis, ?-amyloid deposition, cerebral blood flow, and the metabolic rate of glucose. The latest results in probe development are also detailed. Most chapters are written jointly by radiochemists and nuclear medicine specialists to ensure a multidisciplinary approach. This state of the art compendium will be valuable to anyone in the field of clinical or preclinical neuroscience, from the radiochemist and radiologist/nuclear medicine specialist to the interested neurobiologist and general practitioner. It is the second volume of a trilogy on PET and SPECT imaging in the neurosciences. Other volumes focus on PET and SPECT in psychiatry and PET and SPECT in neurology''.

  8. The neurobiology of aggression and violence.

    Science.gov (United States)

    Rosell, Daniel R; Siever, Larry J

    2015-06-01

    Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.

  9. Adolescent Neurobiological Susceptibility to Social Context

    Science.gov (United States)

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  10. Social ‘wanting’ dysfunction in autism: neurobiological underpinnings and treatment implications

    Directory of Open Access Journals (Sweden)

    Kohls Gregor

    2012-06-01

    Full Text Available Abstract Most behavioral training regimens in autism spectrum disorders (ASD rely on reward-based reinforcement strategies. Although proven to significantly increase both cognitive and social outcomes and successfully reduce aberrant behaviors, this approach fails to benefit a substantial number of affected individuals. Given the enormous amount of clinical and financial resources devoted to behavioral interventions, there is a surprisingly large gap in our knowledge of the basic reward mechanisms of learning in ASD. Understanding the mechanisms for reward responsiveness and reinforcement-based learning is urgently needed to better inform modifications that might improve current treatments. The fundamental goal of this review is to present a fine-grained literature analysis of reward function in ASD with reference to a validated neurobiological model of reward: the ‘wanting’/’liking’ framework. Despite some inconsistencies within the available literature, the evaluation across three converging sets of neurobiological data (neuroimaging, electrophysiological recordings, and neurochemical measures reveals good evidence for disrupted reward-seeking tendencies in ASD, particularly in social contexts. This is most likely caused by dysfunction of the dopaminergic–oxytocinergic ‘wanting’ circuitry, including the ventral striatum, amygdala, and ventromedial prefrontal cortex. Such a conclusion is consistent with predictions derived from diagnostic criteria concerning the core social phenotype of ASD, which emphasize difficulties with spontaneous self-initiated seeking of social encounters (that is, social motivation. Existing studies suggest that social ‘wanting’ tendencies vary considerably between individuals with ASD, and that the degree of social motivation is both malleable and predictive of intervention response. Although the topic of reward responsiveness in ASD is very new, with much research still needed, the current data

  11. Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders.

    Science.gov (United States)

    Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

    2016-05-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

  12. Mechanisms of Oryza sativa (Poaceae) resistance to Tagosodes orizicolus (Homoptera: Delphacidae) under greenhouse condition in Venezuela

    National Research Council Canada - National Science Library

    González, Alex; Labrín, Natalia; Alvarez, Rosa M; Jayaro, Yorman; Gamboa, Carlos; Reyes, Edicta; Barrientos, Venancio

    2012-01-01

    ... of the "Rice hoja blanca virus". During 2006-2007 we carried out research under greenhouse conditions at Fundaci6n Danac, Venezuela, in order to determine the mechanisms of antixenosis, antibiosis and tolerance...

  13. Interactivity effects in social media marketing on brand engagement: an investigation of underlying mechanisms

    NARCIS (Netherlands)

    Antheunis, M.L.; van Noort, G.; Eisend, M.; Langner, T.

    2011-01-01

    Although, SNS advertising spending increases, research on SNS campaigning is still underexposed. First, this study aims to investigate the effect of SNS campaign interactivity on the receivers brand engagement, taking four underlying mechanisms into account (brand identification, campaign

  14. Mechanisms of Mining Seismicity under Large Scale Exploitation with Multikey Strata

    OpenAIRE

    Hu He; Linming Dou; Anye Cao; Jun Fan

    2015-01-01

    The dynamic disasters are aggravating with the increase of exploitation scale and intensity in Chinese coal mines, to further understand this problem, we studied the mechanisms of mining tremors induced by key strata movement and instability under large scale exploitation. First the mechanisms were categorized into two groups that is main key strata fracture and movement as well as subkey strata instability again under adjacent mining activities. Based on the key strata theory in ground contr...

  15. Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0652 TITLE: Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER W81XWH-16-1-0652 Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity 5b. GRANT NUMBER W81XWH...to stress fracture risk. In particular, in Study 1, we will perform advanced skeletal imaging along with gait-assessments in subjects with history of

  16. Plant neurobiology and green plant intelligence : science, metaphors and nonsense

    NARCIS (Netherlands)

    Struik, P.C.; Yin, X.; Meinke, H.B.

    2008-01-01

    This paper analyses the recent debates on the emerging science of plant neurobiology, which claims that the individual green plant should be considered as an intelligent organism. Plant neurobiology tries to use elements from animal physiology as elegant metaphors to trigger the imagination in

  17. A Neurobiological Basis for SLA and First Language Attrition.

    Science.gov (United States)

    de Bode, Stella

    The two-part paper examines the neurobiological processes of synapse overproduction, synapse elimination, and issues of language acquisition and attrition. The first part consists of diagrams and notes explaining some basic terms and concepts of neurobiology: cortex; white matter; neuron; synapse; synaptogenesis; and development and organization…

  18. Microbial Mechanisms Underlying Acidity-induced Reduction in Soil Respiration Under Nitrogen Fertilization

    Science.gov (United States)

    Niu, S.; Li, Y.

    2016-12-01

    Terrestrial ecosystems are receiving increasing amounts of reactive nitrogen (N) due to anthropogenic activities, which largely changes soil respiration and its feedback to climate change. N enrichment can not only increase N availability but also induce soil acidification, both may affect soil microbial activity and root growth with a consequent impact on soil respiration. However, it remains unclear whether elevated N availability or soil acidity has greater impact on soil respiration (Rs). We conducted a manipulative experiment to simulate N enrichment (10 g m-2 yr-1 NH4NO3) and soil acidity (0.552 mol H+ m-2 yr-1 sulfuric acid) and studied their effects on Rs and its components in a temperate forest. Our results showed that soil pH was reduced by 0.2 under N addition or acid addition treatment. Acid addition significantly decreased autotrophic respiration (Ra) and heterotrophic respiration (Rh) by 21.5% and 22.7% in 2014, 34.8% and 21.9% in 2015, respectively, resulting in a reduction of Rs by 22.2% in 2014 and 26.1% in 2015. Nitrogen enrichment reduced Ra, Rh, Rs by 21.9%, 16.2%, 18.6% in 2014 and 22.1%, 5.9%, 11.7% in 2015, respectively. The reductions of Rs and its components were attributable to decrease of fine root biomass, microbial biomass, and cellulose degrading enzymes. N addition did not change microbial community but acid addition increased both fungal and arbuscular mycorrhiza fungi PLFAs, and N plus acid addition significantly enhanced fungal to bacterial ratio. All the hydrolase enzymes were reduced more by soil acidity (43-50%) than nitrogen addition (30-39%). Structural equation model showed that soil acidity played more important role than N availability in reducing soil respiration mainly by changing microbial extracellular enzymes. We therefore suggest that N deposition induced indirect effect of soil acidification on microbial properties is critical and should be taken into account to better understand and predict ecosystem C cycling in

  19. Imaging the neurobiological substrate of atypical depression by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Salmaso, Dario [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Nardo, Davide [University of Rome La Sapienza, Department of Psychology, Rome (Italy); Jonsson, Cathrine; Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Gardner, Ann [Karolinska University Hospital Huddinge, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm (Sweden)

    2007-01-15

    Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in {sup 99m}Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders. (orig.)

  20. Mathematical methods in biology and neurobiology

    CERN Document Server

    Jost, Jürgen

    2014-01-01

    Mathematical models can be used to meet many of the challenges and opportunities offered by modern biology. The description of biological phenomena requires a range of mathematical theories. This is the case particularly for the emerging field of systems biology. Mathematical Methods in Biology and Neurobiology introduces and develops these mathematical structures and methods in a systematic manner. It studies:   • discrete structures and graph theory • stochastic processes • dynamical systems and partial differential equations • optimization and the calculus of variations.   The biological applications range from molecular to evolutionary and ecological levels, for example:   • cellular reaction kinetics and gene regulation • biological pattern formation and chemotaxis • the biophysics and dynamics of neurons • the coding of information in neuronal systems • phylogenetic tree reconstruction • branching processes and population genetics • optimal resource allocation • sexual recombi...

  1. Towards a new neurobiology of language.

    Science.gov (United States)

    Poeppel, David; Emmorey, Karen; Hickok, Gregory; Pylkkänen, Liina

    2012-10-10

    Theoretical advances in language research and the availability of increasingly high-resolution experimental techniques in the cognitive neurosciences are profoundly changing how we investigate and conceive of the neural basis of speech and language processing. Recent work closely aligns language research with issues at the core of systems neuroscience, ranging from neurophysiological and neuroanatomic characterizations to questions about neural coding. Here we highlight, across different aspects of language processing (perception, production, sign language, meaning construction), new insights and approaches to the neurobiology of language, aiming to describe promising new areas of investigation in which the neurosciences intersect with linguistic research more closely than before. This paper summarizes in brief some of the issues that constitute the background for talks presented in a symposium at the Annual Meeting of the Society for Neuroscience. It is not a comprehensive review of any of the issues that are discussed in the symposium.

  2. Neurobiology of the circadian system: meeting metabolism

    Directory of Open Access Journals (Sweden)

    Mendoza, Jorge

    2009-06-01

    Full Text Available The basic principles of physiology postulated the necessity of the constancy of the internal environment to maintain a physiological equilibrium and do not front serious consequences in health. Now we know that physiology is rhythmic and that a break of this rhythmicity can generate serious consequences in health which even could be lethal. Circadian clocks, headed by the suprachiasmatic nucleus in the central nervous system, are the responsible for the generation of circadian rhythms. These clocks are affected by external signals as light (day-night cycles and feeding. This review examines the basic principles of the circadian system and the current knowledge in the neurobiology of biological clocks, making emphasis in the relationship between the circadian system, feeding behaviour, nutrition and metabolism, and the consequences that occur when these systems are not coordinated each other, as the development of metabolic and circadian pathologies.

  3. Towards a new neurobiology of language

    Science.gov (United States)

    Poeppel, David; Emmorey, Karen; Hickok, Gregory; Pylkkänen, Liina

    2012-01-01

    Theoretical advances in language research and the availability of increasingly high-resolution experimental techniques in the cognitive neurosciences are profoundly changing how we investigate and conceive of the neural basis of speech and language processing. Recent work closely aligns language research with issues at the core of systems neuroscience, ranging from neurophysiological and neuroanatomic characterizations to questions about neural coding. Here we highlight, across different aspects of language processing (perception, production, sign language, meaning construction), new insights and approaches to the neurobiology of language, aiming to describe promising new areas of investigation in which the neurosciences intersect with linguistic research more closely than before. This paper summarizes in brief some of the issues that constitute the background for talks presented in a symposium at the annual meeting of the Society for Neuroscience. It is not a comprehensive review of any of the issues that are discussed in the symposium. PMID:23055482

  4. Autism spectrum disorders: from genes to neurobiology.

    Science.gov (United States)

    Willsey, A Jeremy; State, Matthew W

    2015-02-01

    Advances in genome-wide technology, coupled with the availability of large cohorts, are finally yielding a steady stream of autism spectrum disorder (ASD) genes carrying mutations of large effect. These findings represent important molecular clues, but at the same time present notable challenges to traditional strategies for moving from genes to neurobiology. A remarkable degree of genetic heterogeneity, the biological pleiotropy of ASD genes, and the tremendous complexity of the human brain are prompting the development of new strategies for translating genetic discoveries into therapeutic targets. Recent developments in systems biology approaches that 'contextualize' these genetic findings along spatial, temporal, and cellular axes of human brain development are beginning to bridge the gap between high-throughput gene discovery and testable pathophysiological hypotheses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The cognitive and neurobiological effects of daily stress in adolescents.

    Science.gov (United States)

    Rahdar, Ahrareh; Galván, Adriana

    2014-05-15

    Increased stress reactivity during adolescence coincides with maturation of cognitive abilities and development of the prefrontal cortex. Although the effects of early-life, chronic, and pervasive stress on cognition have been extensively explored across development, very little is known about the effects of naturalistic, daily stress on adolescent cognition. In this study, our goal was to use a naturalistic approach to determine whether participants' own stressful experiences from daily life impacted cognitive performance and associated neural correlates. Adolescent and adult participants provided daily ratings of stress and underwent functional magnetic resonance imaging (fMRI) twice: once under a self-reported "high-stress" state and once under a self-reported "low-stress" state. While in the scanner, participants performed a response inhibition task. Behaviorally, all participants exhibited worse response inhibition under high, versus low, stress states, an effect that was significantly stronger in adolescents. At the neural level, there was a significant age by stress interaction, such that adolescents exhibited less recruitment of the dorsolateral prefrontal cortex (DLPFC) during inhibition under high-stress versus low-stress; adults evinced the opposite activation pattern in DLPFC. These data suggest that the developing brain may be a more vulnerable target to the cognitive and neurobiological effects of daily stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. A neural systems-based neurobiology and neuropsychiatry course: integrating biology, psychodynamics, and psychology in the psychiatric curriculum.

    Science.gov (United States)

    Lacy, Timothy; Hughes, John D

    2006-01-01

    Psychotherapy and biological psychiatry remain divided in psychiatry residency curricula. Behavioral neurobiology and neuropsychiatry provide a systems-level framework that allows teachers to integrate biology, psychodynamics, and psychology. The authors detail the underlying assumptions and outline of a neural systems-based neuroscience course they teach at the National Capital Consortium Psychiatry Residency Program. They review course assessment reports and classroom observations. Self-report measures and teacher observations are encouraging. By the end of the course, residents are able to discuss both neurobiological and psychodynamic/psychological concepts of distributed biological neural networks. They verbalize an understanding that psychology is biology, that any distinction is artificial, and that both are valuable. A neuroscience curriculum founded on the underlying principles of behavioral neurobiology and neuropsychiatry is inherently anti-reductionistic and facilitates the acquisition of detailed information as well as critical thinking and cross-disciplinary correlations with psychological theories and psychotherapy.

  7. Nonlinear dynamical patterns as personality theory for neurobiology and psychiatry.

    Science.gov (United States)

    Mandell, A J; Selz, K A

    1995-11-01

    ADVANCES in the theory of nonlinear differential equations and their statistical representations have yielded a powerful, qualitatively descriptive yet quantitative language that captures characteristic patterns of behavior (what the psychoanalyst Roy Schafer calls "continuity, coherence, and consistency of action") that has begun to influence studies of complex systems in motion as diverse in specifics as signatory patterns of discharge of neurochemically defined single neurons and the dynamical structures characteristic of a particular composer's music. What might be called personality theories of neurobiological dynamics have arisen to replace neurobiological theories of personality. It is in this way that rigorously proven and powerful general mathematical insights have changed the face of determinism in research in brain and behavior. Two examples: (1) Very complicated looking behavior of neurobiological forced-dissipative (expanding and contracting) systems over time take place on low dimensional abstract surfaces on which only a few underlying abstract parameters control the action. (2) Independent of specific details (chemical, electrical, and/or behavioral), there exist a relatively few fundamental categories of behavior in time and transitions, among them a property called universality. Results from this new theoretical, in contrast with experimental, reductionism yield analogies with and new approaches to historically important dynamic ideas about personality and character patterns that are equally relevant to micro and macrocomplex systems such as neural membrane receptor proteins and individual personality styles. Research findings achieved over the past decade and a half in our laboratory and others in neurochemistry, neurophysiology, and animal and human behavior, as well as the results of a new demonstration experiment involving the prediction of dynamical category membership from abstract expressive motion in humans, are used to exemplify this use

  8. STED microscopy of living cells--new frontiers in membrane and neurobiology.

    Science.gov (United States)

    Eggeling, Christian; Willig, Katrin I; Barrantes, Francisco J

    2013-07-01

    Recent developments in fluorescence far-field microscopy such as STED microscopy have accomplished observation of the living cell with a spatial resolution far below the diffraction limit. Here, we briefly review the current approaches to super-resolution optical microscopy and present the implementation of STED microscopy for novel insights into live cell mechanisms, with a focus on neurobiology and plasma membrane dynamics. © 2013 International Society for Neurochemistry.

  9. Numerical investigation of aerosolized drug delivery in the human lungs under mechanical ventilator conditions

    Science.gov (United States)

    Vanrhein, Timothy; Banerjee, Arindam

    2010-11-01

    Particle deposition for aerosolized drug delivery in the human airways is heavily dependent upon flow conditions. Numerical modeling techniques have proven valuable for determining particle deposition characteristics under steady flow conditions. For the case of patients under mechanical ventilation, however, flow conditions change drastically and there is an increased importance to understand particle deposition characteristics. This study focuses on mechanically ventilated conditions in the upper trachea-bronchial (TB) region of the human airways. Solution of the continuous phase flow is done under ventilator waveform conditions with a suitable turbulence model in conjunction with a realistic model of upper TB airways. A discrete phase Euler-Lagrange approach is applied to solve for particle deposition characteristics with a focus on the effect of the ventilator inlet waveform. The purpose of this study is to accurately model flow conditions in the upper TB airways under mechanically ventilated conditions with a focus on real-time patient specific targeted aerosolized drug delivery.

  10. Genetics, Cognition and Neurobiology of Schizotypal Personality: A Review of the Overlap with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Ulrich eEttinger

    2014-02-01

    Full Text Available Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia. Evidence was corroborated that significant overlap exists between the two, covering the behavioural, brain structural and functional as well molecular levels. In particular, several studies showed that individuals with high levels of schizotypal traits exhibit alterations in neurocognitive task performance and underlying brain function similar to the deficits seen in patients with schizophrenia. Studies of brain structure have shown both volume reductions and increases in schizotypy, pointing to schizophrenia-like deficits as well as possible protective or compensatory mechanisms. Experimental pharmacological studies have shown that high levels of schizotypy are associated with (i enhanced dopaminergic response in striatum following administration of amphetamine and (ii improvement of cognitive performance following administration of antipsychotic compounds. Together, this body of work suggests that schizotypy shows overlap with schizophrenia across multiple behavioural and neurobiological domains, suggesting that the study of schizotypal traits may be useful in improving our understanding of the aetiology of schizophrenia.

  11. Defeating the fear: new insights into the neurobiology of stress susceptibility.

    Science.gov (United States)

    Krishnan, Vaishnav

    2014-11-01

    The psychopathological impact of emotional stress on a specific individual varies markedly: while most escape the development of post-traumatic stress disorder and/or major depression, a select group of individuals demonstrate a vulnerability to succumb to these conditions. The past decade has witnessed an explosion in animal research into the underlying neurobiological mechanisms that govern both vulnerability and resilience to such stressors. In the May 2014 issue, Chou and colleagues employ the mouse social defeat model of chronic stress to demonstrate that defeated susceptible mice display an exaggerated conditioned fear response associated with more pronounced autonomic changes. These physiological alterations were found to be mediated via local increases in the levels of brain derived neurotrophic factor (BDNF) within the basolateral amygdala and could be inhibited by the systemic administration of a beta adrenergic antagonist. This mini-review critically examines this manuscript's new mechanistic insights in light of previous results employing similar approaches. The strengths and limitations of the social defeat model, as well as the relevance of these findings to neurologic illness are discussed briefly. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections.

    Science.gov (United States)

    Duman, Ronald S

    2014-04-01

    Stress and depression are associated with atrophy and loss of neurons in limbic and cortical brain regions that could contribute to the symptoms of depression. Typical monoamine reuptake inhibitor antidepressants have only modest efficacy and require long-term treatment, and are only weakly effective in blocking or reversing these structural changes caused by stress. Recent findings demonstrate that ketamine, an NMDA receptor antagonist, produces rapid antidepressant actions in difficult to treat depressed patients. In addition, preclinical studies demonstrate that ketamine rapidly increases synaptic connections in the prefrontal cortex by increasing glutamate signaling and activation of pathways that control the synthesis of synaptic proteins. Moreover, ketamine rapidly reverses the synaptic deficits caused by exposure to chronic stress in rodent models. Studies of the signaling mechanisms underlying the actions of ketamine have provided novel approaches and targets for new rapid acting antidepressants with decreased side effects, as well as a better understanding of the neurobiology of stress, depression, and treatment response. © 2014 Wiley Periodicals, Inc.

  13. Using a Comparative Species Approach to Investigate the Neurobiology of Paternal Responses

    OpenAIRE

    Franssen, Catherine L.; Bardi, Massimo; Lambert, Kelly G.

    2011-01-01

    A goal of behavioral neuroscience is to identify underlying neurobiological factors that regulate specific behaviors. Using animal models to accomplish this goal, many methodological strategies require invasive techniques to manipulate the intensity of the behavior of interest (e.g., lesion methods, pharmacological manipulations, microdialysis techniques, genetically-engineered animal models). The utilization of a comparative species approach allows researchers to take advantage of naturally ...

  14. The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

    OpenAIRE

    Ramirez, Jan-Marino

    2014-01-01

    “Sighs, tears, grief, distress” expresses Johann Sebastian Bach in a musical example for the relationship between sighs and deep emotions. This review explores the neurobiological basis of the sigh and its relationship with psychology, physiology, and pathology. Sighs monitor changes in brain states, induce arousal, and reset breathing variability. These behavioral roles homeostatically regulate breathing stability under physiological and pathological conditions. Sighs evoked in hypoxia evoke...

  15. Neurobiology of Suicidal Behavior. An Integration of Biological and Clinical Findings

    OpenAIRE

    Carballo, Juan J.; Akamnonu, Chibuikem P.; Oquendo, Maria A.

    2008-01-01

    Suicide is among the top ten leading causes of death in individuals of all ages. An explanatory model for suicidal behavior that links clinical and psychological risk factors or endophenotypes, to the underlying neurobiological abnormalities associated with suicidal behavior may enhance prediction, help identify treatment options and have heuristic value. Our explanatory model proposes that developmental factors that are biological (genetics) and psychological or clinical (early childhood adv...

  16. Cadherin-11 modulates cell morphology and collagen synthesis in periodontal ligament cells under mechanical stress.

    Science.gov (United States)

    Feng, Lishu; Zhang, Yimei; Kou, Xiaoxing; Yang, Ruili; Liu, Dawei; Wang, Xuedong; Song, Yang; Cao, Haifeng; He, Danqing; Gan, Yehua; Zhou, Yanheng

    2017-03-01

    To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed β-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time- and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed β-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation.

  17. An investigation of the mechanism underlying teacher aggression : Testing I3 theory and the General Aggression Model

    NARCIS (Netherlands)

    Montuoro, Paul; Mainhard, Tim|info:eu-repo/dai/nl/30483517X

    2017-01-01

    Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression

  18. Energy intake, meal frequency, and health: a neurobiological perspective.

    Science.gov (United States)

    Mattson, Mark P

    2005-01-01

    The size and frequency of meals are fundamental aspects of nutrition that can have profound effects on the health and longevity of laboratory animals. In humans, excessive energy intake is associated with increased incidence of cardiovascular disease, diabetes, and certain cancers and is a major cause of disability and death in industrialized countries. On the other hand, the influence of meal frequency on human health and longevity is unclear. Both caloric (energy) restriction (CR) and reduced meal frequency/intermittent fasting can suppress the development of various diseases and can increase life span in rodents by mechanisms involving reduced oxidative damage and increased stress resistance. Many of the beneficial effects of CR and fasting appear to be mediated by the nervous system. For example, intermittent fasting results in increased production of brain-derived neurotrophic factor (BDNF), which increases the resistance of neurons in the brain to dysfunction and degeneration in animal models of neurodegenerative disorders; BDNF signaling may also mediate beneficial effects of intermittent fasting on glucose regulation and cardiovascular function. A better understanding of the neurobiological mechanisms by which meal size and frequency affect human health may lead to novel approaches for disease prevention and treatment.

  19. Visualization of hot spot formation in energetic materials under periodic mechanical excitation using phosphor thermography

    Science.gov (United States)

    Casey, Alex; Fenoglio, Gabriel; Detrinidad, Humberto

    2017-06-01

    Under mechanical excitation, energy is known to localize within an energetic material resulting in `hot spot' formation. While many formation mechanisms have been proposed, additional insight to heat generation mechanisms, the effect of binder/crystal interfaces, and predication capabilities can be gained by quantifying the initiation and growth of the hot spots. Phosphor thermography is a well established temperature sensing technique wherein an object's temperature is obtained by collecting the temperature dependent luminescence of an optically excited phosphor. Herein, the phosphor thermography technique has been applied to Dow Corning Sylgard® 184/octahydro 1,3,5,7 tetranitro 1,3,5,7 tetrazocine (HMX) composite materials under mechanical excitation in order to visualize the evolution of the temperature field, and thus hot spot formation, within the binder. Funded by AFOSR. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

  20. Transcriptome analyses reveal molecular mechanism underlying tapping panel dryness of rubber tree (Hevea brasiliensis)

    OpenAIRE

    Dejun Li; Xuncheng Wang; Zhi Deng; Hui Liu; Hong Yang; Guangming He

    2016-01-01

    Tapping panel dryness (TPD) is a serious threat to natural rubber yields from rubber trees, but the molecular mechanisms underlying TPD remain poorly understood. To identify TPD-related genes and reveal these molecular mechanisms, we sequenced and compared the transcriptomes of bark between healthy and TPD trees. In total, 57,760 assembled genes were obtained and analyzed in details. In contrast to healthy rubber trees, 5652 and 2485 genes were up- or downregulated, respectively, in TPD trees...

  1. Mechanisms Underlying Food-Drug Interactions: Inhibition of Intestinal Metabolism and Transport

    OpenAIRE

    Won, Christina S.; Oberlies, Nicholas H.; Paine, Mary F.

    2012-01-01

    Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have...

  2. Space, place and the midwife: exploring the relationship between the birth environment, neurobiology and midwifery practice.

    Science.gov (United States)

    Hammond, Athena; Foureur, Maralyn; Homer, Caroline S E; Davis, Deborah

    2013-12-01

    Research indicates that midwives and their practice are influenced by space and place and that midwives practice differently in different places. It is possible that one mechanism through which space and place influence midwifery practice is via neurobiological responses such as the production and release of oxytocin, which can be triggered by experiences and perceptions of the physical environment. To articulate the significance of space and place to midwifery and explore the relationship between the birth environment, neurobiology and midwifery practice. Quality midwifery care requires the facilitation of trusting social relationships and the provision of emotionally sensitive care to childbearing women. The neuropeptide oxytocin plays a critical role in human social and emotional behaviour by increasing trust, reducing stress and heightening empathy, reciprocity and generosity. Through its role as a trigger for oxytocin release, the birth environment may play a direct role in the provision of quality midwifery care. Copyright © 2013 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  3. Kindling and second messengers: an approach to the neurobiology of recurrence in bipolar disorder.

    Science.gov (United States)

    Ghaemi, S N; Boiman, E E; Goodwin, F K

    1999-01-15

    Since bipolar disorder is inherently a longitudinal illness characterized by recurrence and cycling of mood episodes, neurobiological theories involving kindlinglike phenomena appear to possess a certain explanatory power. An approach to understanding kindlinglike phenomena at the molecular level has been made possible by advances in research on second-messenger systems in the brain. The time frame of interest has shifted from the microseconds of presynaptic events to hours, days, months, and even years in the longer duration of events beyond the synapse--through second messengers, gene regulation, and synthesis of long-acting trophic factors. These complex interlocking systems may explain how environmental stress could interact over time with genetic vulnerability to produce illness. In its two sections, this paper will review an approach to understanding two major aspects of the neurobiology of bipolar disorder: kindling phenomena and second-messenger mechanisms. We will suggest that these two fields of research together help explain the biology of recurrence.

  4. Freeze for action: Neurobiological mechanisms in animal and human freezing

    NARCIS (Netherlands)

    Roelofs, K.

    2017-01-01

    Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions

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

    OpenAIRE

    Sandi Carmen; Haller József

    2015-01-01

    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 chang...

  6. 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.

  7. Neurobiological underpinnings of dogs' human-like social competence: How interactions between stress response systems and oxytocin mediate dogs' social skills.

    Science.gov (United States)

    Buttner, Alicia Phillips

    2016-12-01

    Domestic dogs (Canis familiaris) have been suggested as a natural model for human social cognition, possessing social skills that are in many ways functionally analogous to those of young humans. Researchers have debated the origins of dogs' human-like social competence and the underlying cognitive mechanisms, but only recently have researchers begun to explore their neurobiological underpinnings. In this review, findings from behavioral studies are integrated with what is known about the biological basis of dogs' human-directed social competence, with an emphasis on how stress-mediating systems, particularly the hypothalamic-pituitary-adrenal (HPA) axis, interact with oxytocin and underlying neural systems to facilitate dogs' interspecific social-cognitive abilities. The working model presented in this paper offers a biological explanation for many of the inconsistent findings from past work on social cognition in dogs and generates questions for future research in the field of canine social competence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. To what extent do neurobiological sleep-waking processes support psychoanalysis?

    Science.gov (United States)

    Gottesmann, Claude

    2010-01-01

    Sigmund Freud's thesis was that there is a censorship during waking that prevents memory of events, drives, wishes, and feelings from entering the consciousness because they would induce anxiety due to their emotional or ethical unacceptability. During dreaming, because the efficiency of censorship is decreased, latent thought contents can, after dream-work involving condensation and displacement, enter the dreamer's consciousness under the figurative form of manifest content. The quasi-closed dogma of psychoanalytic theory as related to unconscious processes is beginning to find neurobiological confirmation during waking. Indeed, there are active processes that suppress (repress) unwanted memories from entering consciousness. In contrast, it is more difficult to find neurobiological evidence supporting an organized dream-work that would induce meaningful symbolic content, since dream mentation most often only shows psychotic-like activities. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Progress in the genetics of polygenic brain disorders: significant new challenges for neurobiology.

    Science.gov (United States)

    McCarroll, Steven A; Hyman, Steven E

    2013-10-30

    Advances in genome analysis, accompanied by the assembly of large patient cohorts, are making possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Neurobiological Correlates in Forensic Assessment : A Systematic Review

    NARCIS (Netherlands)

    van der Gronde, Toon; Kempes, Maaike; van El, Carla; Rinne, Thomas; Pieters, Toine

    2014-01-01

    Background: With the increased knowledge of biological risk factors, interest in including this information in forensic assessments is growing. Currently, forensic assessments are predominantly focused on psychosocial factors. A better understanding of the neurobiology of violent criminal behaviour

  11. Quantum and Multidimensional Explanations in a Neurobiological Context of Mind

    NARCIS (Netherlands)

    Korf, Jakob

    This article examines the possible relevance of physical-mathematical multidimensional or quantum concepts aiming at understanding the (human) mind in a neurobiological context. Some typical features of the quantum and multidimensional concepts are briefly introduced, including entanglement,

  12. An embodied view of octopus neurobiology.

    Science.gov (United States)

    Hochner, Binyamin

    2012-10-23

    Octopuses have a unique flexible body and unusual morphology, but nevertheless they are undoubtedly a great evolutionary success. They compete successfully with vertebrates in their ecological niche using a rich behavioral repertoire more typical of an intelligent predator which includes extremely effective defensive behavior--fast escape swimming and an astonishing ability to adapt their shape and color to their environment. The most obvious characteristic feature of an octopus is its eight long and flexible arms, but these pose a great challenge for achieving the level of motor and sensory information processing necessary for their behaviors. First, coordinating motion is a formidable task because of the infinite degrees of freedom that have to be controlled; and second, it is hard to use body coordinates in this flexible animal to represent sensory information in a central control system. Here I will review experimental results suggesting that these difficulties, arising from the animal's morphology, have imposed the evolution of unique brain/body/behavior relationships best explained as intelligent behavior which emerges from the octopus's embodied organization. The term 'intelligent embodiment' comes from robotics and refers to an approach to designing autonomous robots in which the behavior emerges from the dynamic physical and sensory interactions of the agent's materials, morphology and environment. Consideration of the unusual neurobiology of the octopus in the light of its unique morphology suggests that similar embodied principles are instrumental for understanding the emergence of intelligent behavior in all biological systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. The neurobiology of neuropsychiatric syndromes in dementia.

    Science.gov (United States)

    Meeks, Thomas W; Ropacki, Susan A; Jeste, Dilip V

    2006-11-01

    Neuropsychiatric disturbances in dementia are prevalent, and research is uncovering their neurobiological correlates. Late-onset depression appears to be associated with Alzheimer's disease pathology at autopsy, and lifetime depression episodes may worsen Alzheimer's disease pathology in the hippocampus. Vascular disease and elevated homocysteine increase risk for both late-onset depression and Alzheimer's disease and may partly mediate their relationship. Monoamine changes are robust finding in Alzheimer's disease and may account for many observed depression symptoms. Risk of psychosis of Alzheimer's disease appears to be increased by several genes also implicated in schizophrenia (e.g., catechol-O-methyltransferase, neuregulin-1). Psychosis in dementia with Lewy bodies appears to be related to cholinergic deficits. Alzheimer's disease is associated with changes in the circadian sleep-wake cycles, including decreased night-time melatonin. Sleep apnea may be related to apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye movement sleep behavior disorder is intricately related to synucleinopathies, such as dementia with Lewy bodies, but synuclein changes may not totally explain this relationship. Neuropsychiatric disturbances are a core feature of dementia and worsen many clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies increasingly provide insight into the origins of these psychiatric symptoms in dementia.

  14. Neurobiological linkage between stress and sleep

    Science.gov (United States)

    Sanford, Larry D.; Wellman, Laurie L.

    2012-10-01

    Stress can have a significant negative impact on health and stress-induced alterations in sleep are implicated in both human sleep disorders and in psychiatric disorders in which sleep is affected. We have demonstrated that the amygdala, a region critical for regulating emotion, is a key modulator of sleep. Our current research is focused on understanding how the amygdala and stressful emotion affect sleep and on the role sleep plays in recovery from stress. We have implemented animal models to examine the how stress and stress-related memories impact sleep. Experiencing uncontrollable stress and reminders of uncontrollable stress can produce significant reductions in sleep, in particular rapid eye movement sleep. We are using these models to explore the neurobiology linking stress-related emotion and sleep. This research is relevant for sleep disorders such as insomnia and into mental disorders in which sleep is affected such as post-traumatic stress disorder (PTSD), which is typically characterized by a prominent sleep disturbance in the aftermath of exposure to a psychologically traumatic event.

  15. [Collective violence: neurobiological, psychosocial and sociological condition].

    Science.gov (United States)

    Möller-Leimkühler, A M; Bogerts, B

    2013-11-01

    Collective violence, despite its often disastrous consequences has widely been disregarded by psychiatry, as was the case for individual violence. Physical violence is not only an individual, mostly male phenomenon but manifests mainly as collective violence among men in multiple forms. Due to the plentitude of theories and findings on collective violence the present article is limited to a few relevant sociological and neurobiological aspects of collective violence as a group and intergroup phenomenon. A special focus is given to the association of the phylogenetic disposition to group violence and constructions of masculinity, to the potential relevance of mirror neurons for social contagion and to the influence of sociostructural factors for male adolescents joining violence-prone groups. In this context group dynamics such as in-group overevaluation and out-group devaluation are of central importance by stabilizing the male sense of self-worth and legitimizing, normalizing and internalizing violent behavior. Instead of mythologizing, biologizing or banalizing violence, transdisciplinary approaches are necessary to improve violence prevention on different ecological levels being obligated to a culture of nonviolent conflict management.

  16. A Neural Systems-Based Neurobiology and Neuropsychiatry Course: Integrating Biology, Psychodynamics, and Psychology in the Psychiatric Curriculum

    Science.gov (United States)

    Lacy, Timothy; Hughes, John D.

    2006-01-01

    Objective: Psychotherapy and biological psychiatry remain divided in psychiatry residency curricula. Behavioral neurobiology and neuropsychiatry provide a systems-level framework that allows teachers to integrate biology, psychodynamics, and psychology. Method: The authors detail the underlying assumptions and outline of a neural systems-based…

  17. Structural and Mechanical Properties of Intermediate Filaments under Extreme Conditions and Disease

    Science.gov (United States)

    Qin, Zhao

    Intermediate filaments are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that intermediate filament proteins play key roles to reinforce cells subjected to large-deformation as well as participate in signal transduction. However, it is still poorly understood how the nanoscopic structure, as well as the biochemical properties of these protein molecules contribute to their biomechanical functions. In this research we investigate the material function of intermediate filaments under various extreme mechanical conditions as well as disease states. We use a full atomistic model and study its response to mechanical stresses. Learning from the mechanical response obtained from atomistic simulations, we build mesoscopic models following the finer-trains-coarser principles. By using this multiple-scale model, we present a detailed analysis of the mechanical properties and associated deformation mechanisms of intermediate filament network. We reveal the mechanism of a transition from alpha-helices to beta-sheets with subsequent intermolecular sliding under mechanical force, which has been inferred previously from experimental results. This nanoscale mechanism results in a characteristic nonlinear force-extension curve, which leads to a delocalization of mechanical energy and prevents catastrophic fracture. This explains how intermediate filament can withstand extreme mechanical deformation of > 1 00% strain despite the presence of structural defects. We combine computational and experimental techniques to investigate the molecular mechanism of Hutchinson-Gilford progeria syndrome, a premature aging disease. We find that the mutated lamin tail .domain is more compact and stable than the normal one. This altered structure and stability may enhance the association of intermediate filaments with the nuclear membrane, providing a molecular mechanism of the disease. We study the nuclear membrane association

  18. Towards a neurobiological understanding of pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Søren S; Krauss, Theresa; Demir, Ihsan Ekin

    2017-01-01

    a chronic pain syndrome. Objectives: We aimed to characterize the neurobiological signature of pain associated with CP and to discuss its implications for treatment strategies. Methods: Relevant basic and clinical articles were selected for review following an extensive search of the literature. Results...... processing of pain at the peripheral and central level of the pain system. This neurobiological understanding of pain has important clinical implications for treatment and prevention of pain chronification....

  19. The Neurobiology of Moral Behavior: Review and Neuropsychiatric Implications

    OpenAIRE

    Mendez, Mario F.

    2009-01-01

    Morality may be innate to the human brain. This review examines the neurobiological evidence from research involving functional magnetic resonance imaging of normal subjects, developmental sociopathy, acquired sociopathy from brain lesions, and frontotemporal dementia. These studies indicate a “neuromoral” network for responding to moral dilemmas centered in the ventromedial prefrontal cortex and its connections, particularly on the right. The neurobiological evidence indicates the existence ...

  20. Neurobiology of dyslexia : A reinterpretation of the data

    OpenAIRE

    Ramus, Franck

    2004-01-01

    Theories of developmental dyslexia differ on how to best interpret the great variety of symptoms (linguistic, sensory, motor) observed in dyslexic individuals. One approach views dyslexia as a specific phonological deficit, which sometimes co-occurs with a more general sensorimotor syndrome. The present review of the neurobiology of dyslexia shows that neurobiological data are indeed consistent with this view, explaining both how a specific phonological deficit might arise, and why a sensorim...

  1. Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types.

    Science.gov (United States)

    Dacquino, Claudia; De Rossi, Pietro; Spalletta, Gianfranco

    2015-09-20

    Although diagnosis is a central issue in medical care, in psychiatry its value is still controversial. The function of diagnosis is to indicate treatments and to help clinicians take better care of patients. The fundamental role of diagnosis is to predict outcome and prognosis. To date serious concern persists regarding the clinical utility and predictive validity of the diagnosis system in psychiatry, which is at the most syndromal. Schizophrenia and bipolar disorder, which nosologists consider two distinct disorders, are the most discussed psychiatric illnesses. Recent findings in different fields of psychiatric research, such as neuroimaging, neuropathology, neuroimmunology, neuropsychology and genetics, have led to other conceptualizations. Individuals with schizophrenia or bipolar disorder vary greatly with regard to symptoms, illness course, treatment response, cognitive and functional impairment and biological correlates. In fact, it is possible to find heterogeneous correlates even within the same syndrome, i.e., from one stage of the disorder to another. Thus, it is possible to identify different subsyndromes, which share some clinical and neurobiological characteristics. The main goal of modern psychiatry is to ovethrow these barriers and to obtain a better understanding of the biological profiles underlying heterogeneous clinical features and thus reduce the variance and lead to a homogeneous definition. The translational research model, which connects the basic neuroscience research field with clinical experience in psychiatry, aims to investigate different neurobiological features of syndromes and of the shared neurobiological features between two syndromes. In fact, this approach should help us to better understand the neurobiological pathways underlying clinical entities, and even to distinguish different, more homogeneous, diagnostic subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Failure mechanisms of closed-cell aluminum foam under monotonic and cyclic loading

    NARCIS (Netherlands)

    Amsterdam, E.; De Hosson, J. Th. M.; Onck, P. R.

    2006-01-01

    This paper concentrates on the differences in failure mechanisms of Alporas closed-cell aluminum foam under either monotonic or cyclic loading. The emphasis lies on aspects of crack nucleation and crack propagation in relation to the microstructure. The cell wall material consists of Al dendrites

  3. Magnetic and mechanical AC loss of the ITER CSI model coil conductor under transverse cyclic loading

    NARCIS (Netherlands)

    Nijhuis, Arend; Noordman, Niels H.W.; ten Kate, Herman H.J.; Mitchell, Neil; Bruzzone, Pierluigi

    1998-01-01

    The magnetic field in a coil results in a transverse force on the strands pushing the cable towards one side of the jacket. A special cryogenic press has been built to study in a unique way the mechanical and electrical properties of full-size ITER Cable-in-Conduit (CIC) samples under a transverse,

  4. On the mechanical behaviour of a butt jointed thermoplastic composite under bending

    NARCIS (Netherlands)

    Baran, Ismet; Warnet, Laurent; Akkerman, Remko; Thomsen, O.T

    2015-01-01

    In the present work, the mechanical behavior of a recently developed novel butt jointed thermoplastic composite was investigated under bending conditions. The laminated skin and the web were made of carbon fiber (AS4) and polyetherketoneketone (PEKK). The butt joint (filler) was injection molded

  5. Nonlinear Dynamic Analysis of Telescopic Mechanism for Truss Structure Bridge Inspection Vehicle Under Pedestrian Excitation

    Directory of Open Access Journals (Sweden)

    Wenwen Sui

    Full Text Available Abstract Nonlinear dynamic analysis of an axially moving telescopic mechanism for truss structure bridge inspection vehicle under pedestrian excitation is carried out. A biomechanically inspired inverted-pendulum model is utilized to simplify the pedestrian. The nonlinear equations of motion for the beam-pedestrian system are derived using the Hamilton's principle. The equations are transformed into two ordinary differential equations by applying the Galerkin's method at the first two orders. The solutions to the equations are acquired by using the Newmark-β method associated with the Newton-Raphson method. The time-dependent feature of the eigenfunctions for the two beams are taken into consideration in the solutions. Accordingly, the equations of motion for a simplified system, in which the pedestrian is regarded as moving cart, are given. In the numerical examples, dynamic responses of the telescopic mechanism in eight conditions of different beam-telescoping and pedestrian-moving directions are simulated. Comparisons between the vibrations of the beams under pedestrian excitation and corresponding moving cart are carried out to investigate the influence of the pedestrian excitation on the telescopic mechanism. The results show that the displacement of the telescopic mechanism under pedestrian excitation is smaller than that under moving cart especially when the pedestrian approaches the beams end. Additionally, compared with moving cart, the pedestrian excitation can effectively strengthen the vibration when the beam extension is small or when the pedestrian is close to the beams end.

  6. Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional Chinese medicine.

    Science.gov (United States)

    Zhou, Xuezhong; Li, Yubing; Peng, Yonghong; Hu, Jingqing; Zhang, Runshun; He, Liyun; Wang, Yinghui; Jiang, Lijie; Yan, Shiyan; Li, Peng; Xie, Qi; Liu, Baoyan

    2014-09-01

    Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

  7. Hydration of Odd−Even Terminated Polyelectrolyte Multilayers under Mechanical Confinement

    NARCIS (Netherlands)

    Abbott, Stephen B.; de Vos, Wiebe Matthijs; Maers, Laura L. E.; Barker, Robert; Richardson, Robert M.; Prescott, Stuart W.

    2014-01-01

    Using a combination of neutron reflectivity and a surface force type apparatus, the hydration of polyelectrolyte multilayers, PEMs, is investigated under mechanical confinement. The samples consist of poly(styrenesulfonic acid), PSS, and poly(allylamine hydrochloride), PAH, which were formed by

  8. Mechanisms underlying prorenin actions on hypothalamic neurons implicated in cardiometabolic control

    Directory of Open Access Journals (Sweden)

    Soledad Pitra

    2016-10-01

    Conclusions: We identified novel neuronal targets and cellular mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in cardiometabolic regulation. This fundamental mechanistic information regarding central PR/PRR actions is essential for the development of novel RAS-based therapeutic targets for the treatment of cardiometabolic disorders in obesity and hypertension.

  9. Swallowing rehabilitation of dysphagic tracheostomized patients under mechanical ventilation in intensive care units: a feasibility study.

    Science.gov (United States)

    Rodrigues, Katia Alonso; Machado, Flávia Ribeiro; Chiari, Brasília Maria; Rosseti, Heloísa Baccaro; Lorenzon, Paula; Gonçalves, Maria Inês Rebelo

    2015-01-01

    The aim of the present study was to assess the feasibility of the early implementation of a swallowing rehabilitation program in tracheostomized patients under mechanical ventilation with dysphagia. This prospective study was conducted in the intensive care units of a university hospital. We included hemodynamically stable patients under mechanical ventilation for at least 48 hours following 48 hours of tracheostomy and with an appropriate level of consciousness. The exclusion criteria were previous surgery in the oral cavity, pharynx, larynx and/or esophagus, the presence of degenerative diseases or a past history of oropharyngeal dysphagia. All patients were submitted to a swallowing rehabilitation program. An oropharyngeal structural score, a swallowing functional score and an otorhinolaryngological structural and functional score were determined before and after swallowing therapy. We included 14 patients. The mean duration of the rehabilitation program was 12.4 ± 9.4 days, with 5.0 ± 5.2 days under mechanical ventilation. Eleven patients could receive oral feeding while still in the intensive care unit after 4 (2 - 13) days of therapy. All scores significantly improved after therapy. In this small group of patients, we demonstrated that the early implementation of a swallowing rehabilitation program is feasible even in patients under mechanical ventilation.

  10. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  11. Neurobiological candidate endophenotypes of social anxiety disorder.

    Science.gov (United States)

    Bas-Hoogendam, Janna Marie; Blackford, Jennifer U; Brühl, Annette B; Blair, Karina S; van der Wee, Nic J A; Westenberg, P Michiel

    2016-12-01

    Social anxiety disorder (SAD) is a disabling psychiatric disorder with a complex pathogenesis. Studies indicate a genetic component in the development of SAD, but the search for genetic mechanisms underlying this vulnerability is complicated. A focus on endophenotypes instead of the disorder itself may provide a fruitful path forward. Endophenotypes are measurable characteristics related to complex psychiatric disorders and reflective of genetically-based disease mechanisms, and could shed light on the ways by which genes contribute to the development of SAD. We review evidence for candidate MRI endophenotypes of SAD and discuss the extent to which they meet the criteria for an endophenotype, focussing on the amygdala, the medial prefrontal cortex, whole-brain functional connectivity and structural-anatomical changes. Strongest evidence is present for the primary endophenotype criterion of association between the candidate endophenotypes and SAD, while the other criteria, involving trait-stability, heritability and co-segregation of the endophenotype with the disorder within families, warrant further investigation. We highlight the potential of neuroimaging endophenotypes and stress the need for family studies into SAD endophenotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Compressive damage mechanism of GFRP composites under off-axis loading: Experimental and numerical investigations

    DEFF Research Database (Denmark)

    Zhou, H.W.; Li, H.Y.; Gui, L.L.

    2013-01-01

    Experimental and computational studies of the microscale mechanisms of damage formation and evolution in unidirectional glass fiber reinforced polymer composites (GFRP) under axial and off-axis compressive loading are carried out. A series of compressive testing of the composites with different....... With increasing the angle between the fiber and applied loading, failure of glass fibers is mainly controlled by shear cracking. For the computational analysis of the damage mechanisms, 3D multifiber unit cell models of GFRP composites and X-FEM approach to the fracture modeling were used. The computational...... angles between the loading vector and fiber direction were carried out under scanning electron microscopy (SEM) in situ observation. The damage mechanisms as well as stress strain curves were obtained in the experiments. It was shown that the compressive strength of composites drastically reduces when...

  13. Intercomparison of chemical mechanisms for air quality policy formulation and assessment under North American conditions.

    Science.gov (United States)

    Derwent, Richard

    2017-07-01

    The intercomparison of seven chemical mechanisms for their suitability for air quality policy formulation and assessment is described. Box modeling techniques were employed using 44 sets of background environmental conditions covering North America to constrain the chemical development of the longer lived species. The selected mechanisms were modified to enable an unbiased assessment of the adequacy of the parameterizations of photochemical ozone production from volatile organic compound (VOC) oxidation in the presence of NOx. Photochemical ozone production rates responded differently to 30% NOx and VOC reductions with the different mechanisms, despite the striking similarities between the base-case ozone production rates. The 30% reductions in NOx and VOCs also produced changes in OH. The responses in OH to 30% reductions in NOx and VOCs appeared to be more sensitive to mechanism choice, compared with the responses in the photochemical ozone production rates. Although 30% NOx reductions generally led to decreases in OH, 30% reductions in VOCs led to increases in OH, irrespective of mechanism choice and background environmental conditions. The different mechanisms therefore gave different OH responses to NOx and VOC reductions and so would give different responses in terms of changes in the fate and behavior of air toxics, acidification and eutrophication, and fine particle formation compared with others, in response to ozone control strategies. Policymakers need to understand that there are likely to be inherent differences in the responses to ozone control strategies between different mechanisms, depending on background environmental conditions and the extents of NOx and VOC reductions under consideration. The purpose of this paper is to compare predicted ozone responses to NOx and VOC reductions with seven chemical mechanisms under North American conditions. The good agreement found between the tested mechanisms should provide some support for their application

  14. Static and dynamic mechanical characteristic comparison research of v-type insulator string under gale condition

    Science.gov (United States)

    Wang, J. C.; Zhu, S. W.; Peng, B.; Duan, S. B.; Li, P.

    2017-04-01

    Application of V-type insulator string is most effective method in gale area to reduce wind deflection flashover, and dynamic characteristic of the V-type insulator string under action of pulse wind is an important factor to affect design of the V string. In order to clarify mechanical characteristic of the V-type insulator string under action of dynamic wind load, which is different to traditional rigid straight rod static mechanical method, finite element method is taken to calculate forcing of the V-type insulator string under action of pulse wind. Pulse wind speed time history with space relativity is considered and is converted to wind load time history, establishing non-linear finite element coupling model of insulator string - conductor, calculating mechanical characteristic of V-type insulator string under excitation of pulse wind, analyzing dynamic yield characteristic of the insulator under different angle of the V string, and providing theoretical basis for engineering design through comparison analysis between dynamic calculation result and static calculation result.

  15. Neurobiological signatures of alcohol dependence revealed by protein profiling.

    Directory of Open Access Journals (Sweden)

    Giorgio Gorini

    Full Text Available Alcohol abuse causes dramatic neuroadaptations in the brain, which contribute to tolerance, dependence, and behavioral modifications. Previous proteomic studies in human alcoholics and animal models have identified candidate alcoholism-related proteins. However, recent evidences suggest that alcohol dependence is caused by changes in co-regulation that are invisible to single protein-based analysis. Here, we analyze global proteomics data to integrate differential expression, co-expression networks, and gene annotations to unveil key neurobiological rearrangements associated with the transition to alcohol dependence modeled by a Chronic Intermittent Ethanol (CIE, two-bottle choice (2BC paradigm. We analyzed cerebral cortices (CTX and midbrains (MB from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. CIE induced significant changes in protein levels in dependent mice compared with their non-dependent controls. Multiple protein isoforms showed region-specific differential regulation as a result of post-translational modifications. Our integrative analysis identified modules of co-expressed proteins that were highly correlated with CIE treatment. We found that modules most related to the effects of CIE treatment coordinate molecular imbalances in endocytic- and energy-related pathways, with specific proteins involved, such as dynamin-1. The qRT-PCR experiments validated both differential and co-expression analyses, and the correspondence among our data and previous genomic and proteomic studies in humans and rodents substantiates our findings. The changes identified above may play a key role in the escalation of ethanol consumption associated with dependence. Our approach to alcohol addiction will advance knowledge of brain remodeling mechanisms and adaptive changes in response to drug abuse, contribute to

  16. The neurobiology of offensive aggression: Revealing a modular view.

    Science.gov (United States)

    de Boer, S F; Olivier, B; Veening, J; Koolhaas, J M

    2015-07-01

    Experimental studies aimed at understanding the neurobiology of aggression started in the early 20th century, and by employing increasingly sophisticated tools of functional neuroanatomy (i.e., from electric/chemical lesion and stimulation techniques to neurochemical mapping and manipulations) have provided the important framework for the functional brain circuit organization of aggressive behaviors. Recently, newly emerging technologies for mapping,measuring and manipulating neural circuitry at the level of molecular and genetically defined neuronal subtypes promise to further delineate the precise neural microcircuits mediating the initiation and termination of aggressive behavior, and characterize its dynamic neuromolecular functioning. This paper will review some of the behavioral, neuroanatomical and neurochemical evidence in support of a modular view of the neurobiology of offensive aggressive behavior. Although aggressive behavior likely arises from a specific concerted activity within a distributed neural network across multiple brain regions, emerging opto- and pharmacogenetic neuronal manipulation studies make it clear that manipulation of molecularly-defined neurons within a single node of this global interconnected network seems to be both necessary and sufficient to evoke aggressive attacks. However, the evidence so far also indicates that in addition to behavior-specific neurons there are neuronal systems that should be considered as more general behavioral control modules. The answer to the question of behavioral specificity of brain structures at the level of individual neurons requires a change of the traditional experimental setup. Studies using c-fos expression mapping usually compare the activation patterns induced by for example aggression with a home cage control. However, to reveal the behavioral specificity of this neuronal activation pattern, a comparison with other social and non-social related behaviors such as mating, defensive burying

  17. Dual mechanisms regulate ecosystem stability under decade-long warming and hay harvest.

    Science.gov (United States)

    Shi, Zheng; Xu, Xia; Souza, Lara; Wilcox, Kevin; Jiang, Lifen; Liang, Junyi; Xia, Jianyang; García-Palacios, Pablo; Luo, Yiqi

    2016-06-15

    Past global change studies have identified changes in species diversity as a major mechanism regulating temporal stability of production, measured as the ratio of the mean to the standard deviation of community biomass. However, the dominant plant functional group can also strongly determine the temporal stability. Here, in a grassland ecosystem subject to 15 years of experimental warming and hay harvest, we reveal that warming increases while hay harvest decreases temporal stability. This corresponds with the biomass of the dominant C4 functional group being higher under warming and lower under hay harvest. As a secondary mechanism, biodiversity also explains part of the variation in temporal stability of production. Structural equation modelling further shows that warming and hay harvest regulate temporal stability through influencing both temporal mean and variation of production. Our findings demonstrate the joint roles that dominant plant functional group and biodiversity play in regulating the temporal stability of an ecosystem under global change.

  18. The placebo response: neurobiological and clinical issues of neurological relevance.

    Science.gov (United States)

    Pollo, Antonella; Benedetti, Fabrizio

    2009-01-01

    The recent upsurge in placebo research has demonstrated the sound neurobiological substrate of a phenomenon once believed to be only patient mystification, or at best a variable to control in clinical trials, bringing about a new awareness of its potential exploitation to the patient's benefit and framing it as a positive context effect, with the power to influence the therapy outcome. Placebo effects have been described both in the experimental setting and in different clinical conditions, many of which are of neurological interest. Multiple mechanisms have been described, namely conditioning and cognitive factors like expectation, desire, and reward. A body of evidence from neurochemical, pharmacological, and neuroimaging studies points to the involvement of neural pathways specific to single conditions, such as the activation of the endogenous antinociceptive system during placebo analgesia or the release of dopamine in the striatum of parkinsonian patients experiencing placebo reduction of motor impairment. The possible clinical applications of placebo studies range from the design of clinical trials incorporating specific recommendations and minimizing the use of placebo arms to the optimization of the context surrounding the patient, in order to maximize the placebo component present in any treatment.

  19. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms.

    Science.gov (United States)

    Nohe, Christoph; Hertel, Guido

    2017-01-01

    Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

  20. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms

    Science.gov (United States)

    Nohe, Christoph; Hertel, Guido

    2017-01-01

    Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB. PMID:28848478

  1. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Christoph Nohe

    2017-08-01

    Full Text Available Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction and relational mediators (trust in leader, leader-member exchange; LMX of the positive relationship between transformational leadership and organizational citizenship behavior (OCB. Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall. When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

  2. Review of the damage mechanism in wind turbine gearbox bearings under rolling contact fatigue

    Science.gov (United States)

    Su, Yun-Shuai; Yu, Shu-Rong; Li, Shu-Xin; He, Yan-Ni

    2017-12-01

    Wind turbine gearbox bearings fail with the service life is much shorter than the designed life. Gearbox bearings are subjected to rolling contact fatigue (RCF) and they are observed to fail due to axial cracking, surface flaking, and the formation of white etching areas (WEAs). The current study reviewed these three typical failure modes. The underlying dominant mechanisms were discussed with emphasis on the formation mechanism of WEAs. Although numerous studies have been carried out, the formation of WEAs remains unclear. The prevailing mechanism of the rubbing of crack faces that generates WEAs was questioned by the authors. WEAs were compared with adiabatic shear bands (ASBs) generated in the high strain rate deformation in terms of microstructural compositions, grain refinement, and formation mechanism. Results indicate that a number of similarities exist between them. However, substantial evidence is required to verify whether or not WEAs and ASBs are the same matters.

  3. Titi Monkeys as a Novel Non-Human Primate Model for the Neurobiology of Pair Bonding
.

    Science.gov (United States)

    Bales, Karen L; Arias Del Razo, Rocío; Conklin, Quinn A; Hartman, Sarah; Mayer, Heather S; Rogers, Forrest D; Simmons, Trenton C; Smith, Leigh K; Williams, Alexia; Williams, Donald R; Witczak, Lynea R; Wright, Emily C

    2017-09-01

    It is now widely recognized that social bonds are critical to human health and well-being. One of the most important social bonds is the attachment relationship between two adults, known as the pair bond. The pair bond involves many characteristics that are inextricably linked to quality of health, including providing a secure psychological base and acting as a social buffer against stress. The majority of our knowledge about the neurobiology of pair bonding comes from studies of a socially monogamous rodent, the prairie vole (Microtus ochrogaster), and from human imaging studies, which inherently lack control. Here, we first review what is known of the neurobiology of pair bonding from humans and prairie voles. We then present a summary of the studies we have conducted in titi monkeys (Callicebus cupreus)-a species of socially monogamous New World primates. Finally, we construct a neural model based on the location of neuropeptide receptors in the titi monkey brain, as well as the location of neural changes in our imaging studies, with some basic assumptions based on the prairie vole model. In this model, we emphasize the role of visual mating stimuli as well as contributions of the dopaminergic reward system and a strong role for the lateral septum. This model represents an important step in understanding the neurobiology of social bonds in non-human primates, which will in turn facilitate a better understanding of these mechanisms in humans.

  4. Effects of delaying transplanting on agronomic traits and grain yield of rice under mechanical transplantation pattern.

    Directory of Open Access Journals (Sweden)

    Qihua Liu

    Full Text Available A delay in the mechanical transplantation (MT of rice seedlings frequently occurs in Huanghuai wheat-rice rotation cropping districts of China, due to the late harvest of wheat, the poor weather conditions and the insufficiency of transplanters, missing the optimum transplanting time and causing seedlings to age. To identify how delaying transplanting rice affects the agronomic characteristics including the growth duration, photosynthetic productivity and dry matter remobilization efficiency and the grain yield under mechanical transplanting pattern, an experiment with a split-plot design was conducted over two consecutive years. The main plot includes two types of cultivation: mechanical transplanting and artificial transplanting (AT. The subplot comprises four japonica rice cultivars. The results indicate that the rice jointing, booting, heading and maturity stages were postponed under MT when using AT as a control. The tiller occurrence number, dry matter weight per tiller, accumulative dry matter for the population, leaf area index, crop growth rate, photosynthetic potential, and dry matter remobilization efficiency of the leaf under MT significantly decreased compared to those under AT. In contrast, the reduction rate of the leaf area during the heading-maturity stage was markedly enhanced under MT. The numbers of effective panicles and filled grains per panicle and the grain yield significantly decreased under MT. A significant correlation was observed between the dry matter production, remobilization and distribution characteristics and the grain yield. We infer that, as with rice from old seedlings, the decrease in the tiller occurrence, the photosynthetic productivity and the assimilate remobilization efficiency may be important agronomic traits that are responsible for the reduced grain yield under MT.

  5. Neurobiology of aggression and violence in schizophrenia.

    Science.gov (United States)

    Soyka, Michael

    2011-09-01

    There is much evidence that schizophrenia patients have an increased risk for aggression and violent behavior, including homicide. The neurobiological basis and correlates of this risk have not been much studied. While genome-wide association studies are lacking, a number of candidate genes have been investigated. By far, the most intensively studied is the catechol-O-methyltransferase (COMT) gene on chromosome 22. COMT is involved in the metabolism of dopamine, a key neurotransmitter in schizophrenia pathophysiology. Several studies suggest that the Val158Met polymorphism of this gene affects COMT activity. Methionine (Met)/Met homozygote schizophrenia patients show 4- to 5-fold lower COMT activity than valine (Val)/Val homozygotes, and some but not all studies have found an association with aggression and violence. Recently, a new functional single-nucleotide polymorphism in the COMT gene, Ala72Ser, was found to be associated with homicidal behavior in schizophrenia, but this finding warrants further replication. Studies published so far indicate that an association with the monoamine oxidase A, B, or tryptophan hydroxylase 1 genes is unlikely. Data for the brain-derived neurotrophic factor gene are conflicting and limited. Data from the limited number of neuroimaging studies performed to date are interesting. Frontal and temporal lobe abnormalities are found consistently in aggressive schizophrenia patients. Positron emission tomography and single photon-emission computed tomography (SPECT) data indicate deficits also in the orbitofrontal and temporal cortex. Some functional magnetic resonance imaging studies found a negative association of violent behavior with frontal and right-sided inferior parietal activity. Neuroimaging studies may well help further elucidate the interrelationship between neurocognitive functioning, personality traits, and antisocial and violent behavior.

  6. Translation from neurobiological data to music parameters.

    Science.gov (United States)

    Minciacchi, Diego

    2003-11-01

    Composers have explored different ways to use biological information for the realization of music. Throughout the decades, biological findings have been repeatedly indicated as a source of inspiration or a reservoir of extramusical material for musical composition. More radical and fertile are attempts to produce music systematically using biological data in processes called data sonification or biofeedback techniques. Presented here is a novel strategy of translation where populations of neurobiological data are converted into relational structures from which sound objects are generated by flexible and homogeneous control of the sound parameters. All brain data originate from experiments performed with standard anatomical and physiological techniques, and results of studies based on these experimental materials have already been published. During the translation processes, the information for every sound parameter (such as pitch, duration, envelope, and dynamics) is never derived from fixed transcriptions of data properties. Rather, the space and/or the time interrelations of data populations are used to obtain indexes for sound construction. In this way, equivalent sets of information are exploited to model, or sculpt, the different parameters of sound objects. Three examples from the last decade's personal productions are given. The first refers to the microformal aspects of sound aggregation and is based on data from a microstimulation experiment in the motor cortex. The second describes the earliest translation process developed for live performance with conventional instruments and is based on experiments using a conventional tract tracing technique to compare selected spinal-projecting cell populations in two differently organized brains. The third outlines a recent music production for three pianos based on data from experiments using the multiple fluorescent tract-tracing technique to simultaneously label different populations of thalamocortical neurons

  7. Neurobiological Correlates of Coping through Emotional Approach

    Science.gov (United States)

    Master, Sarah L.; Amodio, David M.; Stanton, Annette L.; Yee, Cindy M.; Hilmert, Clayton J.; Taylor, Shelley E.

    2008-01-01

    This investigation considered possible health-related neurobiological processes associated with “emotional approach coping” (EAC), or intentional efforts to identify, process, and express emotions surrounding stressors. It was hypothesized that higher dispositional use of EAC strategies would be related to neural activity indicative of greater trait approach motivational orientation and to lower proinflammatory cytokine and cortisol responses to stress. To assess these relationships, 46 healthy participants completed a questionnaire assessing the two components of EAC (i.e., emotional processing and emotional expression), and their resting frontal cortical asymmetry was measured using electroencephalography (EEG). A subset (N = 22) of these participants’ levels of the soluble receptor for tumor necrosis factor-alpha (sTNFαRII), interleukin-6 (IL-6), and cortisol (all obtained from oral fluids) were also assessed before and after exposure to an acute laboratory stressor. Consistent with predictions, higher reported levels of emotional expression were significantly associated with greater relative left-sided frontal EEG asymmetry, indicative of greater trait approach motivation. Additionally, people who scored higher on EAC, particularly the emotional processing component, tended to show a less-pronounced TNF-α stress response. EAC was unrelated to levels of IL-6 and cortisol. Greater left-sided frontal EEG asymmetry was significantly related to lower baseline levels of IL-6 and to lower stress-related levels of sTNFαRII, and was marginally related to lower stress-related levels of IL-6. The findings suggest that the salubrious effects of EAC strategies for managing stress may be linked to an approach-oriented neurocognitive profile and to well-regulated proinflammatory cytokine responses to stress. PMID:18558470

  8. Neurobiology and clinical implications of lucid dreaming.

    Science.gov (United States)

    Mota-Rolim, Sérgio A; Araujo, John F

    2013-11-01

    Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Alcohol and Suicide: Neurobiological and Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Leo Sher

    2006-01-01

    Full Text Available Alcohol, primarily in the form of ethyl alcohol (ethanol, has occupied an important place in the history of humankind for at least 8,000 years. In most Western societies, at least 90% of people consume alcohol at some time during their lives, and 30% or more of drinkers develop alcohol-related problems. Severe alcohol-related life impairment, alcohol dependence (alcoholism, is observed at some time during their lives in about 10% of men and 3—5% of women. An additional 5—10% of each sex develops persistent, but less intense, problems that are diagnosed as alcohol abuse. It this review, neurobiological aspects of suicidal behavior in alcoholism is discussed. In individuals with comorbid depression and alcoholism, greater serotonergic impairment may be associated with higher risk of completed suicide. Dopaminergic dysfunction may play an important role in the pathophysiology of suicidal behavior in alcoholism. Brain damage and neurobehavioral deficits are associated with alcohol use disorders and may contribute to suicidal behavior in persons with alcohol dependence or abuse. Aggression/impulsivity and alcoholism severity affect risk for suicide among individuals with alcoholism. Major depressive episodes and stressful life events particularly, partner-relationship disruptions, may precipitate suicidal behavior in individuals with alcohol use disorders. Alcohol misuse and psychosocial adversity can combine to increase stress on the person, and, thereby, potentially, increase the risk for suicidal behavior. The management of suicidal patients with alcohol use disorders is also discussed. It is to be hoped that the efforts of clinicians will reduce morbidity and mortality associated with alcohol misuse.

  10. Mechanical behavior of an individual adherent MLO-Y4 osteocyte under shear flow.

    Science.gov (United States)

    Qiu, Jun; Li, Fang-Fang

    2017-02-01

    Mechanical properties of a single cell and its mechanical response under stimulation play an important role in regulating interactions between cell and extracellular matrix and affecting mechanotransduction. Osteocytes exhibit solid-like viscoelastic behavior in response to the interstitial fluid shear resulting from tissue matrix deformation. This study intends to quantitatively describe the mechanical behavior of osteocytes combining in vitro experiment and fluid-structure interaction (FSI) finite element (FE) model. The cell is configured in the FSI FE model using the observed data from quasi-3D images. Instead of simply assigning the cellular viscoelastic parameters by statistical data, the mechanical parameters are determined by an iterative algorithm comparing the experimental and the computational results from the FE model. The viscoelastic parameters of osteocytes are obtained as: the equilibrium elasticity modulus [Formula: see text], instantaneous elasticity modulus [Formula: see text], viscosity coefficient [Formula: see text]. A novel index to quantify the cell adhesion is also put forward. In addition, an interesting competition phenomenon is revealed on the cell surface concerning stress and strain, i.e., the place with high stress has low strain and that with low stress has high strain. The proposed method provides a novel technique to study the mechanical behavior of individual adherent cell in vitro. It is believed that this quantitative technique not only determines cell mechanical behavior but also helps elucidate the mechanism of mechanotransduction in various types of cells.

  11. Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.

    Science.gov (United States)

    Hammerling, Ulf; Bergman Laurila, Jonas; Grafström, Roland; Ilbäck, Nils-Gunnar

    2016-01-01

    Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

  12. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Anna Jarosz

    2016-01-01

    Full Text Available Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines.

  13. Mechanical failure of zigzag graphene nanoribbons under tensile strain induced by edge reconstruction

    KAUST Repository

    Cheng, Yingchun

    2012-10-01

    The structural and mechanical properties of graphene nanoribbons (GNRs) under uniaxial tensile strain are studied by density functional theory. The ideal strength of a zigzag GNR (120 GPa) is close to that of pristine graphene. However, for a GNR with both edges reconstructed to pentagon–heptagon pairs (from hexagon–hexagon pairs) it decreases to 94 GPa and the maximum tensile strain is reduced to 15%. Our results constitute a comprehensive picture of the edge structure effect on the mechanical properties of GNRs.

  14. Mechanics and mechanisms of surface damage in Al-Si alloys under ultra-mild wear conditions

    Science.gov (United States)

    Chen, Ming

    Al-Si alloys intended for use in engine components must operate under ultra-mild wear (UMW) conditions to fit an acceptable amount of wear during a typical vehicle life. This study simulated surface damage in a UMW regime on five chemically etched Al-Si alloy surfaces using a pin-on-disc tribometer at low loads (0.5-2.0 N) under boundary lubricated conditions. The five alloys contained 11 to 25 wt.% Si and differed in matrix hardness, silicon particle morphology, and size. The mechanisms leading to the UMW damage and the role that the matrix hardness and microstructure play on said mechanisms were studied. Quantitative measurement methods based on statistical analysis of particle height changes and material loss from elevated aluminum using a profilometer technique were developed and used to assess UMW. The Greenwood and Tripp's numerical model was adapted to analyze the contact that occurred between Al-Si alloys with silicon particles protruding above the aluminum and steel balls. The estimation of the real contact pressure applied to the silicon particles was used to rationalize the damage mechanisms. The UMW mechanisms consisted of (i) abrasive wear on the top of the silicon particle surfaces; (ii) sinking-in of the silicon particles; (iii) piling-up of the aluminium around sunken-in particles and (vi) wear of the aluminium by the counterface, which eventually led to the initiation of UMW-II. Increasing the size or areal density of silicon particles with small aspect ratios delayed the onset of UMW-II by providing resistance against the silicon particles sinking-in and the aluminum piling-up. The UMW wear rates, however, began to decrease after long sliding cycles once an oil residue layer supported by hardened ultra-fine subsurface grains formed on the deformed aluminium matrix. The layer formation depended on the microstructure and applied load. Overall experimental observations suggested that Al-11% Si with small silicon particles exhibited optimal long

  15. A study on the fracture mechanism of smart composite under thermal shock cycles using AE technique

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.K.; Lee, S.P. [School of Mechanical Engineering, Dongeui Univ., Busan (Korea); Park, Y.C. [School of Mechanical Engineering, Donga Univ., Busan (Korea)

    2005-07-01

    A smart material is used as spectacle frames and brassiere frames, and partly in medical supplies because of its shape memory effect. The smart composite can be used on the wing of an airplane instead of the existing aluminium to control crack propagation. In this study, the smart composite was fabricated by a hot press method. TiNi alloy as reinforcement and Al6061 as matrix were used, respectively. The mechanical properties of the smart composite under thermal shock cycles were evaluated. In addition, acoustic emission techniques were also used to clarify the damage behavior of the smart composite under thermal shock cycles nondestructively. (orig.)

  16. CISM course on mechanical behaviour of soils under environmentally induced cyclic loads

    CERN Document Server

    Wood, David; Mechanical Behaviour of Soils Under Environmentally Induced Cyclic Loads

    2012-01-01

    The book gives a comprehensive description of the mechanical response of soils (granular and cohesive materials) under cyclic loading. It provides the geotechnical engineer with the theoretical and analytical tools necessary for the evaluation of settlements developng with time under cyclic, einvironmentally idncued loads (such as wave motion, wind actions, water table level variation) and their consequences for the serviceability and durability of structures such as the shallow or deep foundations used in offshore engineering, caisson beakwaters, ballast and airport pavements and also to interpret monitoring data, obtained from both natural and artificial slopes and earth embankments, for the purposes of risk assessment and mitigation.

  17. ALCOHOL DEPENDENCE--NEUROBIOLOGY AND TREATMENT.

    Science.gov (United States)

    Michalak, Agnieszka; Biała, Grazyna

    2016-01-01

    The consequences of alcohol dependence concern serious health care, social and economic problems. The scope of many studies is to better understand mechanisms underlying alcohol addiction in order to work out new, more effective treatment strategies. Alcohol affects many neurotransmission systems within the brain. In general, acute alcohol enhances inhibitory transmission, up-regulating the GABAergic system and impairing glutamatergic function, therefore interfering the balance between excitatory and inhibitory synaptic inputs. Chronic alcohol consumption, meanwhile, in order to restore equilibrium leads to neuroadaptive changes caus- ing both decreased GABAergic and increased glutamatergic activity. Also function of other neurotransmitters and modulators is modified by the presence of alcohol, including glycine, adenosine, serotonin and dopamine. Moreover, a significant impact of alcohol on the endogenous opioid system, nicotinic cholinergic transmission and the endocannabinoids system has been also established. At present, only four medications are approved for the treatment of alcohol dependence in Europe, that is naltrexone, acamprosate, disulfiram and the most recent nalmefene. Among other promising strategies the following drugs are mentioned: baclofen, topiramate, ondansetron, aripiprazole, rimonabant and varenicline. Additionally, the role of appetite-regulating hormones, neuroimmune modulators or the body's stress-response system modulators in reducing alcohol consumption is currently of great interest, however, further investigations are needed.

  18. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    Science.gov (United States)

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

  19. Behavioral Effects of Upper Respiratory Tract Illnesses: A Consideration of Possible Underlying Cognitive Mechanisms

    Directory of Open Access Journals (Sweden)

    Andrew P. Smith

    2012-03-01

    Full Text Available Previous research has shown that both experimentally induced upper respiratory tract illnesses (URTIs and naturally occurring URTIs influence mood and performance. The present study investigated possible cognitive mechanisms underlying the URTI-performance changes. Those who developed a cold (N = 47 had significantly faster, but less accurate, performance than those who remained healthy (N = 54. Illness had no effect on manipulations designed to influence encoding, response organisation (stimulus-response compatilibility or response preparation. Similarly, there was no evidence that different components of working memory were impaired. Overall, the present research confirms that URTIs can have an effect on performance efficiency. Further research is required to identify the physiological and behavioral mechanisms underlying these effects.

  20. From Sound to Significance: Exploring the Mechanisms Underlying Emotional Reactions to Music.

    Science.gov (United States)

    Juslin, Patrik N; Barradas, Gonçalo; Eerola, Tuomas

    2015-01-01

    A common approach to studying emotional reactions to music is to attempt to obtain direct links between musical surface features such as tempo and a listener's responses. However, such an analysis ultimately fails to explain why emotions are aroused in the listener. In this article we explore an alternative approach, which aims to account for musical emotions in terms of a set of psychological mechanisms that are activated by different types of information in a musical event. This approach was tested in 4 experiments that manipulated 4 mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by selecting existing musical pieces that featured information relevant for each mechanism. The excerpts were played to 60 listeners, who were asked to rate their felt emotions on 15 scales. Skin conductance levels and facial expressions were measured, and listeners reported subjective impressions of relevance to specific mechanisms. Results indicated that the target mechanism conditions evoked emotions largely as predicted by a multimechanism framework and that mostly similar effects occurred across the experiments that included different pieces of music. We conclude that a satisfactory account of musical emotions requires consideration of how musical features and responses are mediated by a range of underlying mechanisms.

  1. Analytical Compliance Modeling of Serial Flexure-Based Compliant Mechanism Under Arbitrary Applied Load

    Science.gov (United States)

    Wang, Li-Ping; Jiang, Yao; Li, Tie-Min

    2017-07-01

    Analytical compliance model is vital to the flexure- based compliant mechanism in its mechanical design and motion control. The matrix is a common and effective approach in the compliance modeling while it is not well developed for the closed-loop serial and parallel compliant mechanisms and is not applicable to the situation when the external loads are applied on the flexure members. Concise and explicit analytical compliance models of the serial flexure-based compliant mechanisms under arbitrary loads are derived by using the matrix method. An equivalent method is proposed to deal with the situation when the external loads are applied on the flexure members. The external loads are transformed to concentrated forces applied on the rigid links, which satisfy the equations of static equilibrium and also guarantee that the deformations at the displacement output point remain unchanged. Then the matrix method can be still adopted for the compliance analysis of the compliant mechanism. Finally, several specific examples and an experimental test are given to verify the effectiveness of the compliance models and the force equivalent method. The research enriches the matrix method and provides concise analytical compliance models for the serial compliant mechanism.

  2. Physiological mechanisms contributing to increased water-use efficiency in winter wheat under organic fertilization.

    Science.gov (United States)

    Wang, Linlin; Wang, Shiwen; Chen, Wei; Li, Hongbing; Deng, Xiping

    2017-01-01

    Improving the efficiency of resource utilization has received increasing research attention in recent years. In this study, we explored the potential physiological mechanisms underlying improved grain yield and water-use efficiency of winter wheat (Triticum aestivum L.) following organic fertilizer application. Two wheat cultivars, ChangHan58 (CH58) and XiNong9871 (XN9871), were grown under the same nitrogen (N) fertilizer rate (urea-N, CK; and manure plus urea-N, M) and under two watering regimes (WW, well-watered; and WS, water stress) imposed after anthesis. The M fertilizer treatment had a higher Pn and lower gs and Tr than CK under both water conditions, in particular, it significantly increased WRC and Ψw, and decreased EWLR and MDA under WS. Also, the M treatment increased post-anthesis N uptake by 81.4 and 16.4% under WS and WW, thus increasing post-anthesis photosynthetic capacity and delaying leaf senescence. Consequently, the M treatment increased post-anthesis DM accumulation under WS and WW by 51.5 and 29.6%, WUEB by 44.5 and 50.9%, grain number per plant by 11.5 and 12.2% and 1000-grain weight by 7.3 and 3.6%, respectively, compared with CK. The grain yield under M treatment increased by 23 and 15%, and water use efficiency (WUEg) by 25 and 23%, respectively. The increased WUE under organic fertilizer treatment was due to elevated photosynthesis and decreased Tr and gs. Our results suggest that the organic fertilizer treatment enabled plants to use water more efficiently under drought stress.

  3. The chemical and mechanical behaviors of polymer / reactive metal systems under high strain rates

    Science.gov (United States)

    Shen, Yubin

    As one category of energetic materials, impact-initiated reactive materials are able to release a high amount of stored chemical energy under high strain rate impact loading, and are used extensively in civil and military applications. In general, polymers are introduced as binder materials to trap the reactive metal powders inside, and also act as an oxidizing agent for the metal ingredient. Since critical attention has been paid on the metal / metal reaction, only a few types of polymer / reactive metal interactions have been studied in the literature. With the higher requirement of materials resistant to different thermal and mechanical environments, the understanding and characterization of polymer / reactive metal interactions are in great demand. In this study, PTFE (Polytetrafluoroethylene) 7A / Ti (Titanium) composites were studied under high strain rates by utilizing the Taylor impact and SHPB tests. Taylor impact tests with different impact velocities, sample dimensions and sample configurations were conducted on the composite, equipped with a high-speed camera for tracking transient images during the sudden process. SHPB and Instron tests were carried out to obtain the stress vs. strain curves of the composite under a wide range of strain rates, the result of which were also utilized for fitting the constitutive relations of the composite based on the modified Johnson-Cook strength model. Thermal analyses by DTA tests under different flow rates accompanied with XRD identification were conducted to study the reaction mechanism between PTFE 7A and Ti when only heat was provided. Numerical simulations on Taylor impact tests and microstructural deformations were also performed to validate the constitutive model built for the composite system, and to investigate the possible reaction mechanism between two components. The results obtained from the high strain rate tests, thermal analyses and numerical simulations were combined to provide a systematic study on

  4. Neural mechanisms underlying the integration of situational information into attribution outcomes

    OpenAIRE

    Brosch, Tobias; Schiller, Daniela; Mojdehbakhsh, Rachel; Uleman, James S.; Phelps, Elizabeth A.

    2013-01-01

    When forming impressions and trying to figure out why other people behave the way they do, we should take into account not only dispositional factors (i.e. personality traits) but also situational constraints as potential causes for a behavior. However, in their attributions, people often ignore the importance of situational factors. To investigate the neural mechanisms underlying the integration of situational information into attributions, we decomposed the attribution process by separately...

  5. Mechanisms underlying dual effects of serotonin during development of Helisoma trivolvis (Mollusca).

    OpenAIRE

    Glebov, Konstantin; Voronezhskaya, Elena E.; Khabarova, Marina Yu; Ivashkin, Evgeny; Nezlin, Leonid P.; Ponimaskin, Evgeni G.

    2014-01-01

    BACKGROUND: Serotonin (5-HT) is well known as widely distributed modulator of developmental processes in both vertebrates and invertebrates. It is also the earliest neurotransmitter to appear during neuronal development. In aquatic invertebrates, which have larvae in their life cycle, 5-HT is involved in regulation of stages transition including larval metamorphosis and settlement. However, molecular and cellular mechanisms underlying developmental transition in aquatic invertebrate species a...

  6. Remodeling of Rural Public Service Supply Mechanism under the Background of New Village Construction

    OpenAIRE

    Lu, Mei

    2011-01-01

    Under the background of new village construction, the necessity of remodeling the supply mechanism of rural public service is expounded. It is conducive to improving the capability of public service to satisfy farmers' demand; to constructing a rural diversified public service system and improving the supply efficiency of rural public goods; to realizing the equalization of urban-rural public service to coordinate urban-rural development. Problems in the supply of Chinese rural public service...

  7. Mechanisms of Oryza sativa (Poaceae) resistance to Tagosodes orizicolus (Homoptera: Delphacidae) under greenhouse condition in Venezuela

    OpenAIRE

    Alex González; Natalia Labrín; Álvarez, Rosa M.; Yorman Jayaro; Carlos Gamboa; Edicta Reyes; Venancio Barrientos

    2012-01-01

    Tagosodes orizicolus is one of the main plagues of rice in tropical America causing two types of damages, the direct one, feeding and oviposition effect, and an indirect one, by the transmission of the “Rice hoja blanca virus”. During 2006-2007 we carried out research under greenhouse conditions at Fundación Danac, Venezuela, in order to determine the mechanisms of antixenosis, antibiosis and tolerance to T. orizicolus, which could be acting in commercial varieties and advanced li...

  8. Understanding Cellular Mechanisms Underlying Airway Epithelial Repair: Selecting the Most Appropriate Animal Models

    OpenAIRE

    Yahaya, B.

    2012-01-01

    Understanding the mechanisms underlying the process of regeneration and repair of airway epithelial structures demands close characterization of the associated cellular and molecular events. The choice of an animal model system to study these processes and the role of lung stem cells is debatable since ideally the chosen animal model should offer a valid comparison with the human lung. Species differences may include the complex three-dimensional lung structures, cellular composition of the l...

  9. Towards understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles

    OpenAIRE

    Ruwona, Tinashe B.; Xu, Haiyue; Li, Xu; Taylor, Amber; Shi, Yan-chun; Cui, Zhengrong

    2016-01-01

    Aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate are commonly used human vaccine adjuvants. In an effort to improve the adjuvant activity of aluminum salts, we previously showed that the adjuvant activity of aluminum oxyhydroxide nanoparticles is significantly more potent than that of aluminum oxyhydroxide microparticles. The present study was designed to i) understand the mechanism underlying the potent adjuvant activity of aluminum oxyhydroxide nanoparticles, relat...

  10. The Decision to Fight or Flee – Insights into Underlying Mechanism in Crickets

    OpenAIRE

    Paul Anthony eStevenson; Jan eRillich

    2012-01-01

    Ritualized fighting between conspecifics is an inherently dangerous behavioral strategy, optimized to secure limited resources at minimal cost and risk. To be adaptive, potential rewards, and costs of aggression must be assessed to decide when it would be more opportune to fight or flee. We summarize insights into the proximate mechanisms underlying this decision-making process in field crickets. As in other animals, cricket aggression is enhanced dramatically by motor activity, winning, and ...

  11. The effects and underlying mechanisms of mirror therapy – literature review

    OpenAIRE

    Urška Puh; Sonja Hlebš

    2013-01-01

    Background: Mirror therapy is a relatively new therapeutic modality, where movement of the unaffected limb is used to facilitate performance of the affected limb. Literature review of clinical studies regarding the effectiveness of mirror therapy in different groups of patients was performed. The review focussed on randomised controlled trials and studies, which explore the underlying mechanisms of mirror therapy. Conclusions: The majority of randomised controlled ...

  12. Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder.

    Science.gov (United States)

    Kim, Hyopil; Lim, Chae-Seok; Kaang, Bong-Kiun

    2016-01-20

    Autism spectrum disorder (ASD) refers to a broad spectrum of neurodevelopmental disorders characterized by three central behavioral symptoms: impaired social interaction, impaired social communication, and restricted and repetitive behaviors. However, the symptoms are heterogeneous among patients and a number of ASD mouse models have been generated containing mutations that mimic the mutations found in human patients with ASD. Each mouse model was found to display a unique set of repetitive behaviors. In this review, we summarize the repetitive behaviors of the ASD mouse models and variations found in their neural mechanisms including molecular and electrophysiological features. We also propose potential neuronal mechanisms underlying these repetitive behaviors, focusing on the role of the cortico-basal ganglia-thalamic circuits and brain regions associated with both social and repetitive behaviors. Further understanding of molecular and circuitry mechanisms of the repetitive behaviors associated with ASD is necessary to aid the development of effective treatments for these disorders.

  13. Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

    Science.gov (United States)

    Hara, Yusuke

    2017-06-01

    The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  14. FInal Report: First Principles Modeling of Mechanisms Underlying Scintillator Non-Proportionality

    Energy Technology Data Exchange (ETDEWEB)

    Aberg, Daniel [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sadigh, Babak [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zhou, Fei [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-01

    This final report presents work carried out on the project “First Principles Modeling of Mechanisms Underlying Scintillator Non-Proportionality” at Lawrence Livermore National Laboratory during 2013-2015. The scope of the work was to further the physical understanding of the microscopic mechanisms behind scintillator nonproportionality that effectively limits the achievable detector resolution. Thereby, crucial quantitative data for these processes as input to large-scale simulation codes has been provided. In particular, this project was divided into three tasks: (i) Quantum mechanical rates of non-radiative quenching, (ii) The thermodynamics of point defects and dopants, and (iii) Formation and migration of self-trapped polarons. The progress and results of each of these subtasks are detailed.

  15. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Directory of Open Access Journals (Sweden)

    Jinpeng Qi

    Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  16. Scaling laws and deformation mechanisms of nanoporous copper under adiabatic uniaxial strain compression

    Directory of Open Access Journals (Sweden)

    Fuping Yuan

    2014-12-01

    Full Text Available A series of large-scale molecular dynamics simulations were conducted to investigate the scaling laws and the related atomistic deformation mechanisms of Cu monocrystal samples containing randomly placed nanovoids under adiabatic uniaxial strain compression. At onset of yielding, plastic deformation is accommodated by dislocations emitted from void surfaces as shear loops. The collapse of voids are observed by continuous emissions of dislocations from void surfaces and their interactions with further plastic deformation. The simulation results also suggest that the effect modulus, the yield stress and the energy aborption density of samples under uniaxial strain are linearly proportional to the relative density ρ. Moreover, the yield stress, the average flow stress and the energy aborption density of samples with the same relative density show a strong dependence on the void diameter d, expressed by exponential relations with decay coefficients much higher than -1/2. The corresponding atomistic mechanisms for scaling laws of the relative density and the void diameter were also presented. The present results should provide insights for understanding deformation mechanisms of nanoporous metals under extreme conditions.

  17. Towards a neurobiological understanding of alexithymia

    Directory of Open Access Journals (Sweden)

    Nicolás Meza-Concha

    2017-05-01

    Full Text Available Resumen Si bien la literatura especializada sobre la etiología de la alexitimia es controvertida, la investigación neurobiológica sobre el fenómeno ha demostrado importantes avances. El objetivo de esta revisión es analizar la evidencia disponible en relación a las bases neurofisiológicas de la alexitimia. Se realizó una revisión exhaustiva de artículos disponibles en MEDLINE/PubMed, EBSCO y SciELO. Inicialmente, se vinculó a la alexitimia con una conexión cerebral interhemisférica reducida. Desde la perspectiva traumática infantil, la corteza prefrontal derecha y la red neuronal por defecto experimentarían alteraciones, primero hipermetabólicas (desregulación dopaminérgica y glutamatérgica y luego hipometabólicas-disociativas (desregulación serotoninérgica y opioide, resultando en una consciencia interoceptiva y emocional distorsionada. Las neuronas espejo son el sustrato neurobiológico fundamental de la teoría de la mente y la cognición social, intrínsecamente vinculadas con la alexitimia, involucrando cortezas como la parietal, la temporal, la premotora, la cingulada y el giro frontal inferior. Otras estructuras involucradas son amígdala (expresión facial y reactividad emocional, ínsula (interocepción, integración emocional y empatía y cerebelo (cerebelo límbico y consciencia somatosensorial. La genética molecular ha detectado polimorfismos en el gen del transportador de serotonina, en los genes de las enzimas del metabolismo dopaminérgico y del factor neurotrófico derivado del cerebro, mientras que el rol de la oxitocina es controvertido. En conclusión, numerosos estudios demuestran contundentemente la existencia de una neurobiología subyacente a la alexitimia. Sin embargo, la investigación es aún poco concluyente y debe considerar los factores ambientales, traumáticos, sociales y psicológicos que contribuyen al origen del fenómeno.

  18. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw.

    Science.gov (United States)

    Marotta, Denise M; Costa, Robson; Motta, Emerson M; Fernandes, Elizabeth S; Medeiros, Rodrigo; Quintão, Nara L M; Campos, Maria M; Calixto, João B

    2009-04-01

    Platelet-activating factor (PAF) is an inflammatory mediator widely known to exert relevant pathophysiological functions. However, the relevance of PAF in nociception has received much less attention. Herein, we have investigated the mechanisms underlying PAF-induced spontaneous nociception and mechanical hypersensitivity in the rat paw. PAF injection (1- 30 nmol/paw) resulted in a dose-related overt nociception, whilst only the dose of 10 nmol/ paw produced a significant and time-related mechanical hypersensitivity. Local coinjection of PAF antagonist WEB2086 significantly inhibited both spontaneous nociception and mechanical hypersensitivity. Moreover, the coinjection of the natural IL-1beta receptor antagonist (IRA) notably prevented both PAF-induced nociceptive responses, whilst these responses were not altered by anti-TNFalpha coinjection. Interestingly, pretreatment with the ultrapotent vaniloid agonist resiniferotoxin, coinjection of the TRPV1 receptor antagonist SB366791, or mast cell depletion with compound 48/80 markedly prevented PAF-induced spontaneous nociception. Conversely, PAF-elicited mechanical hypersensitivity was strikingly susceptible to distinct antineutrophil-related strategies, namely the antineutrophil antibody, the selectin blocker fucoidin, the chemokine CXCR2 receptor antagonist SB225002, and the C5a receptor antibody anti-CD88. Notably, the same antineutrophil migration strategies significantly prevented the increase of myeloperoxidase activity induced by PAF. The mechanical hypersensitivity caused by PAF was also prevented by the cyclooxygenase inhibitors indomethacin or celecoxib, and by the selective beta(1) adrenergic receptor antagonist atenolol. Collectively, the present results provide consistent evidence indicating that distinct mechanisms are involved in the spontaneous nociception and mechanical hypersensitivity caused by PAF. They also support the concept that selective PAF receptor antagonists might constitute interesting

  19. [Neurobiological consequences of child sexual abuse: a systematic review].

    Science.gov (United States)

    Pereda, Noemí; Gallardo-Pujol, David

    2011-01-01

    The results of several studies suggest that there is a critical timeframe during development in which experiences of maltreatment and sexual abuse may lead to permanent or long-lasting neurobiological changes that particularly affect the hypothalamus-pituitary-adrenal axis response. The aim of the present study was to provide an updated review on the main neurobiological consequences of child sexual abuse. We selected articles published between January 1999 and January 2010 in English or Spanish that focused on the neurobiological consequences of child sexual abuse available through Medline, Scopus and Web of Science. We also examined the references in published articles on the consequences of sexual victimization in childhood. In this review we included 34 studies on neurobiological consequences, indicating different kinds of effects, namely: neuroendocrine, structural, functional and neuropsychological consequences, which affect a large number of victims. The existing body of work on the neurobiological consequences of maltreatment shows the need to consider maltreatment and child sexual abuse as health problems that affect different areas of victims' lives, which would in turn favor the development of intervention and treatment programs that take these multiple effects into account. Copyright © 2010 SESPAS. Published by Elsevier Espana. All rights reserved.

  20. Experimental Evaluation of the Developmental Mechanism Underlying Fractures at the Adjacent Segment.

    Science.gov (United States)

    Özkaya, Mustafa; Demir, Teyfik; Yaman, Onur; Yaman, Mesut Emre; Özalp, Hakan; Dalbayrak, Sedat

    2016-02-01

    Compression fractures at adjacent mobile segments have been reported as adjacent segment disease under trauma in several studies. In this study, the occurrence of fractures at the adjacent segment was evaluated experimentally under trauma. Static testing of different fixation systems was performed to show their biomechanical performances. The ovine vertebrae fixed with rigid, dynamic, and semirigid systems were used as test samples. The stiffness values of the systems were obtained by testing the vertebrectomy models under compression bending, lateral bending, and torsion tests. In addition, their effects on the adjacent segments were experimentally evaluated within a drop mechanism. A free-fall drop mechanism was designed and manufactured. Next, 3.5-kg, 5-kg, and 7-kg weights were released from 1 m above the test samples to generate compression fractures. The occurrence of compression fractures was observed with the use of radiograph of test samples, which were obtained before and after the drop test. Dynamic and semirigid systems have advantages compared with rigid systems as the result of their lower stiffness values. Radiographs showed that epiphysis fractures occurred at fixed and adjacent mobile segments, which were fixed with semirigid fixation. In addition, dynamic fixation well preserved the fixed and adjacent mobile segments under trauma. The dynamic system with a polyetheretherketone rod can better preserve both adjacent and fixed segments. However, because of the cantilever beam effect, the semirigid system exhibits a great disadvantage. Copyright © 2016 Elsevier Inc. All rights reserved.