WorldWideScience

Sample records for underlying neural pathways

  1. Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9{+-}4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7{+-} 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder.

  2. Developmental Pathway Genes and Neural Plasticity Underlying Emotional Learning and Stress-Related Disorders

    Science.gov (United States)

    Maheau, Marissa E.; Ressler, Kerry J.

    2017-01-01

    The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk…

  3. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  4. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

    Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

  5. Neural pathways in tactile object recognition.

    Science.gov (United States)

    Deibert, E; Kraut, M; Kremen, S; Hart, J

    1999-04-22

    To define further the brain regions involved in tactile object recognition using functional MRI (fMRI) techniques. The neural substrates involved in tactile object recognition (TOR) have not been elucidated. Studies of nonhuman primates and humans suggest that basic motor and somatosensory mechanisms are involved at a peripheral level; however, the mechanisms of higher order object recognition have not been determined. The authors investigated 11 normal volunteers utilizing fMRI techniques in an attempt to determine the neural pathways involved in TOR. Each individual performed a behavioral paradigm with the activated condition involving identification of objects by touch, with identification of rough/smooth as the control. Data suggest that in a majority of individuals, TOR involves the calcarine and extrastriatal cortex, inferior parietal lobule, inferior frontal gyrus, and superior frontal gyrus-polar region. TOR may utilize visual systems to access an internal object representation. The parietal cortices and inferior frontal regions may be involved in a concomitant lexical strategy of naming the object being examined. Frontal polar activation likely serves a role in visuospatial working memory or in recognizing unusual representations of objects. Overall, these findings suggest that TOR could involve a network of cortical regions subserving somatosensory, motor, visual, and, at times, lexical processing. The primary finding suggests that in this normal study population, the visual cortices may be involved in the topographic spatial processing of TOR.

  6. 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 ...

  7. Dopamine system: Manager of neural pathways

    Directory of Open Access Journals (Sweden)

    Simon eHong

    2013-12-01

    Full Text Available There are a growing number of roles that midbrain dopamine (DA neurons assume, such as, reward, aversion, alerting and vigor. Here I propose a theory that may be able to explain why the suggested functions of DA came about. It has been suggested that largely parallel cortico-basal ganglia-thalamo-cortico loops exist to control different aspects of behavior. I propose that (1 the midbrain DA system is organized in a similar manner, with different groups of DA neurons corresponding to these parallel neural pathways (NPs. The DA system can be viewed as the manager of these parallel NPs in that it recruits and activates only the task-relevant NPs when they are needed. It is likely that the functions of those NPs that have been consistently activated by the corresponding DA groups are facilitated. I also propose that (2 there are two levels of DA roles: the How and What roles. The How role is encoded in tonic and phasic DA neuron firing patterns and gives a directive to its target NP: how vigorously its function needs to be carried out. The tonic DA firing is to maintain a certain level of DA in the target NPs to support their expected behavioral and mental functions; it is only when a sudden unexpected boost or suppression of activity is required by the relevant target NP that DA neurons in the corresponding NP act in a phasic manner. The What role is the implementational aspect of the role of DA in the target NP, such as binding to D1 receptors to boost working memory. This What aspect of DA explains why DA seems to assume different functions depending on the region of the brain in which it is involved. In terms of the role of the lateral habenula (LHb, the LHb is expected to suppress maladaptive behaviors and mental processes by controlling the DA system. The demand-based smart management by the DA system may have given animals an edge in evolution with adaptive behaviors and a better survival rate in resource-scarce situations.

  8. Neural dynamics underlying emotional transmissions between individuals.

    Science.gov (United States)

    Golland, Yulia; Levit-Binnun, Nava; Hendler, Talma; Lerner, Yulia

    2017-08-01

    Emotional experiences are frequently shaped by the emotional responses of co-present others. Research has shown that people constantly monitor and adapt to the incoming social-emotional signals, even without face-to-face interaction. And yet, the neural processes underlying such emotional transmissions have not been directly studied. Here, we investigated how the human brain processes emotional cues which arrive from another, co-attending individual. We presented continuous emotional feedback to participants who viewed a movie in the scanner. Participants in the social group (but not in the control group) believed that the feedback was coming from another person who was co-viewing the same movie. We found that social-emotional feedback significantly affected the neural dynamics both in the core affect and in the medial pre-frontal regions. Specifically, the response time-courses in those regions exhibited increased similarity across recipients and increased neural alignment with the timeline of the feedback in the social compared with control group. Taken in conjunction with previous research, this study suggests that emotional cues from others shape the neural dynamics across the whole neural continuum of emotional processing in the brain. Moreover, it demonstrates that interpersonal neural alignment can serve as a neural mechanism through which affective information is conveyed between individuals. © The Author (2017). Published by Oxford University Press.

  9. The neural pathway underlying a numerical working memory task in abacus-trained children and associated functional connectivity in the resting brain.

    Science.gov (United States)

    Li, Yongxin; Hu, Yuzheng; Zhao, Ming; Wang, Yunqi; Huang, Jian; Chen, Feiyan

    2013-11-20

    Training can induce significant changes in brain functioning and behavioral performance. One consequence of training is changing the pattern of brain activation. Abacus training is of interest because abacus experts gain the ability to handle digits with unusual speed and accuracy. However, the neural correlates of numerical memory in abacus-trained children remain unknown. In the current study, we aimed to detect a training effect of abacus-based mental calculations on numerical working memory in children. We measured brain functional magnetic resonance imaging (fMRI) activation patterns in 17 abacus-trained children and 17 control children as they performed two numerical working memory tasks (digits and beads). Functional MRI results revealed higher activation in abacus-trained children than in the controls in the right posterior superior parietal lobule/superior occipital gyrus (PSPL/SOG) and the right supplementary motor area (SMA) in both tasks. When these regions were used as seeds in a functional connectivity analysis of the resting brain, the abacus-trained children showed significantly enhanced integration between the right SMA and the right inferior frontal gyrus (IFG). The IFG is considered to be the key region for the control of attention. These findings demonstrate that extensive engagement of the fronto-parietal network occurs during numerical memory tasks in the abacus-trained group. Furthermore, abacus training may increase the functional integration of visuospatial-attention circuitry, which and thus enhances high-level cognitive process. © 2013 Elsevier B.V. All rights reserved.

  10. Neural pathways for visual speech perception

    Directory of Open Access Journals (Sweden)

    Lynne E Bernstein

    2014-12-01

    Full Text Available This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1 The visual perception of speech relies on visual pathway representations of speech qua speech. (2 A proposed site of these representations, the temporal visual speech area (TVSA has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS. (3 Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  11. Neural dynamics underlying emotional transmissions between individuals

    OpenAIRE

    Golland, Yulia; Levit-Binnun, Nava; Hendler, Talma; Lerner, Yulia

    2017-01-01

    Abstract Emotional experiences are frequently shaped by the emotional responses of co-present others. Research has shown that people constantly monitor and adapt to the incoming social–emotional signals, even without face-to-face interaction. And yet, the neural processes underlying such emotional transmissions have not been directly studied. Here, we investigated how the human brain processes emotional cues which arrive from another, co-attending individual. We presented continuous emotional...

  12. Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory.

    Science.gov (United States)

    Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian; Zhang, Min; Li, Wanhe; Zhong, Yi

    2015-12-01

    Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β'1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts.

  13. Neural Population Dynamics Underlying Motor Learning Transfer.

    Science.gov (United States)

    Vyas, Saurabh; Even-Chen, Nir; Stavisky, Sergey D; Ryu, Stephen I; Nuyujukian, Paul; Shenoy, Krishna V

    2018-03-07

    Covert motor learning can sometimes transfer to overt behavior. We investigated the neural mechanism underlying transfer by constructing a two-context paradigm. Subjects performed cursor movements either overtly using arm movements, or covertly via a brain-machine interface that moves the cursor based on motor cortical activity (in lieu of arm movement). These tasks helped evaluate whether and how cortical changes resulting from "covert rehearsal" affect overt performance. We found that covert learning indeed transfers to overt performance and is accompanied by systematic population-level changes in motor preparatory activity. Current models of motor cortical function ascribe motor preparation to achieving initial conditions favorable for subsequent movement-period neural dynamics. We found that covert and overt contexts share these initial conditions, and covert rehearsal manipulates them in a manner that persists across context changes, thus facilitating overt motor learning. This transfer learning mechanism might provide new insights into other covert processes like mental rehearsal. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Neural circuit components of the Drosophila OFF motion vision pathway.

    Science.gov (United States)

    Meier, Matthias; Serbe, Etienne; Maisak, Matthew S; Haag, Jürgen; Dickson, Barry J; Borst, Alexander

    2014-02-17

    Detecting the direction of visual motion is an essential task of the early visual system. The Reichardt detector has been proven to be a faithful description of the underlying computation in insects. A series of recent studies addressed the neural implementation of the Reichardt detector in Drosophila revealing the overall layout in parallel ON and OFF channels, its input neurons from the lamina (L1→ON, and L2→OFF), and the respective output neurons to the lobula plate (ON→T4, and OFF→T5). While anatomical studies showed that T4 cells receive input from L1 via Mi1 and Tm3 cells, the neurons connecting L2 to T5 cells have not been identified so far. It is, however, known that L2 contacts, among others, two neurons, called Tm2 and L4, which show a pronounced directionality in their wiring. We characterized the visual response properties of both Tm2 and L4 neurons via Ca(2+) imaging. We found that Tm2 and L4 cells respond with an increase in activity to moving OFF edges in a direction-unselective manner. To investigate their participation in motion vision, we blocked their output while recording from downstream tangential cells in the lobula plate. Silencing of Tm2 and L4 completely abolishes the response to moving OFF edges. Our results demonstrate that both cell types are essential components of the Drosophila OFF motion vision pathway, prior to the computation of directionality in the dendrites of T5 cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Neural correlates underlying micrographia in Parkinson's disease.

    Science.gov (United States)

    Wu, Tao; Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Two distinct neural mechanisms underlying indirect reciprocity.

    Science.gov (United States)

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  17. Genes and (common pathways underlying drug addiction.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2008-01-01

    Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

  18. Neural correlates underlying musical semantic memory.

    Science.gov (United States)

    Groussard, M; Viader, F; Landeau, B; Desgranges, B; Eustache, F; Platel, H

    2009-07-01

    Numerous functional imaging studies have examined the neural basis of semantic memory mainly using verbal and visuospatial materials. Musical material also allows an original way to explore semantic memory processes. We used PET imaging to determine the neural substrates that underlie musical semantic memory using different tasks and stimuli. The results of three PET studies revealed a greater involvement of the anterior part of the temporal lobe. Concerning clinical observations and our neuroimaging data, the musical lexicon (and most widely musical semantic memory) appears to be sustained by a temporo-prefrontal cerebral network involving right and left cerebral regions.

  19. Neural processes underlying the orienting of attention without awareness.

    Science.gov (United States)

    Giattino, Charles M; Alam, Zaynah M; Woldorff, Marty G

    2017-07-22

    Despite long being of interest to both philosophers and scientists, the relationship between attention and perceptual awareness is not well understood, especially to what extent they are even dissociable. Previous studies have shown that stimuli of which we are unaware can orient spatial attention and affect behavior. Yet, relatively little is understood about the neural processes underlying such unconscious orienting of attention, and how they compare to conscious orienting. To directly compare the cascade of attentional processes with and without awareness of the orienting stimulus, we employed a spatial-cueing paradigm and used object-substitution masking to manipulate subjects' awareness of the cues. We recorded EEG during the task, from which we extracted hallmark event-related-potential (ERP) indices of attention. Behaviorally, there was a 61 ms validity effect (invalidly minus validly cued target RTs) on cue-aware trials. On cue-unaware trials, subjects also had a robust validity effect of 20 ms, despite being unaware of the cue. An N2pc to the cue, a hallmark ERP index of the lateralized orienting of attention, was observed for cue-aware but not cue-unaware trials, despite the latter showing a clear behavioral validity effect. Finally, the P1 sensory-ERP response to the targets was larger when validly versus invalidly cued, even when subjects were unaware of the preceding cue, demonstrating enhanced sensory processing of targets following subliminal cues. These results suggest that subliminal stimuli can orient attention and lead to subsequent enhancements to both stimulus sensory processing and behavior, but through different neural mechanisms (such as via a subcortical pathway) than stimuli we perceive. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Review of the Neural Oscillations Underlying Meditation

    Directory of Open Access Journals (Sweden)

    Darrin J. Lee

    2018-03-01

    Full Text Available Objective: Meditation is one type of mental training that has been shown to produce many cognitive benefits. Meditation practice is associated with improvement in concentration and reduction of stress, depression, and anxiety symptoms. Furthermore, different forms of meditation training are now being used as interventions for a variety of psychological and somatic illnesses. These benefits are thought to occur as a result of neurophysiologic changes. The most commonly studied specific meditation practices are focused attention (FA, open-monitoring (OM, as well as transcendental meditation (TM, and loving-kindness (LK meditation. In this review, we compare the neural oscillatory patterns during these forms of meditation.Method: We performed a systematic review of neural oscillations during FA, OM, TM, and LK meditation practices, comparing meditators to meditation-naïve adults.Results: FA, OM, TM, and LK meditation are associated with global increases in oscillatory activity in meditators compared to meditation-naïve adults, with larger changes occurring as the length of meditation training increases. While FA and OM are related to increases in anterior theta activity, only FA is associated with changes in posterior theta oscillations. Alpha activity increases in posterior brain regions during both FA and OM. In anterior regions, FA shows a bilateral increase in alpha power, while OM shows a decrease only in left-sided power. Gamma activity in these meditation practices is similar in frontal regions, but increases are variable in parietal and occipital regions.Conclusions: The current literature suggests distinct differences in neural oscillatory activity among FA, OM, TM, and LK meditation practices. Further characterizing these oscillatory changes may better elucidate the cognitive and therapeutic effects of specific meditation practices, and potentially lead to the development of novel neuromodulation targets to take advantage of their

  1. Neural mechanisms and models underlying joint action.

    Science.gov (United States)

    Chersi, Fabian

    2011-06-01

    Humans, in particular, and to a lesser extent also other species of animals, possess the impressive capability of smoothly coordinating their actions with those of others. The great amount of work done in recent years in neuroscience has provided new insights into the processes involved in joint action, intention understanding, and task sharing. In particular, the discovery of mirror neurons, which fire both when animals execute actions and when they observe the same actions done by other individuals, has shed light on the intimate relationship between perception and action elucidating the direct contribution of motor knowledge to action understanding. Up to date, however, a detailed description of the neural processes involved in these phenomena is still mostly lacking. Building upon data from single neuron recordings in monkeys observing the actions of a demonstrator and then executing the same or a complementary action, this paper describes the functioning of a biologically constraint neural network model of the motor and mirror systems during joint action. In this model, motor sequences are encoded as independent neuronal chains that represent concatenations of elementary motor acts leading to a specific goal. Action execution and recognition are achieved through the propagation of activity within specific chains. Due to the dual property of mirror neurons, the same architecture is capable of smoothly integrating and switching between observed and self-generated action sequences, thus allowing to evaluate multiple hypotheses simultaneously, understand actions done by others, and to respond in an appropriate way.

  2. Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex pathway in depression.

    Science.gov (United States)

    Zheng, C; Zhang, T

    2015-04-30

    It is believed that phase synchronization facilitates neural communication and neural plasticity throughout the hippocampal-cortical network, and further supports cognition and memory. The pathway from the ventral hippocampus to the medial prefrontal cortex (mPFC) is thought to play a significant role in emotional memory processing. Therefore, the information transmission on the pathway was hypothesized to be disrupted in the depressive state, which could be related to its impaired synaptic plasticity. In this study, local field potentials (LFPs) from both ventral CA1 (vCA1) and mPFC were recorded in both normal and chronic unpredictable stress (CUS) model rats under urethane anesthesia. LFPs of all rats were recorded before and after the long-term potentiation (LTP) induced on the vCA1-mPFC pathway in order to figure out the correlation of oscillatory synchronization of LFPs and synaptic plasticity. Our results showed the vCA1-to-mPFC unidirectional phase coupling of the theta rhythm, rather than the power of either region, was significantly enhanced by LTP induction, with less enhancement in the CUS model rats compared to that in the normal rats. In addition, theta phase coupling was positively correlated with synaptic plasticity on vCA1-mPFC pathway. Moreover, the theta-slow gamma phase-amplitude coupling in vCA1 was long-term enhanced after high frequency stimulation. These results suggest that the impaired synaptic plasticity in vCA1-mPFC pathway could be reflected by the attenuated theta phase coupling and theta-gamma cross frequency coupling of LFPs in the depression state. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. A dual-pathway neural architecture for specific temporal prediction.

    Science.gov (United States)

    Schwartze, Michael; Kotz, Sonja A

    2013-12-01

    Efficient behavior depends in part on the ability to predict the type and the timing of events in the environment. Specific temporal predictions require an internal representation of the temporal structure of events. Here we propose that temporal prediction recruits adaptive and non-adaptive oscillatory mechanisms involved in establishing such an internal representation. Partial structural and functional convergence of the underlying mechanisms allows speculation about an extended subcortico-cortical network. This network develops around a dual-pathway architecture, which establishes the basis for preparing the organism for perceptual integration, for the generation of specific temporal predictions, and for optimizing the brain's allocation of its limited resources. Key to these functions is rapid cerebellar transmission of an adaptively-filtered, event-based representation of temporal structure. Rapid cerebellar transmission engages a pathway comprising connections from early sensory processing stages to the cerebellum and from there to the thalamus, effectively bypassing more central stages of classical sensory pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Antagonistic neural networks underlying differentiated leadership roles

    Science.gov (United States)

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  5. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis

    2014-03-01

    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  6. Antagonistic neural networks underlying differentiated leadership roles.

    Science.gov (United States)

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  7. The Neural Baroreflex Pathway in Subjects With Metabolic Syndrome

    Science.gov (United States)

    Zanoli, Luca; Empana, Jean-Philippe; Estrugo, Nicolas; Escriou, Guillaume; Ketthab, Hakim; Pruny, Jean-Francois; Castellino, Pietro; Laude, Dominique; Thomas, Frederique; Pannier, Bruno; Jouven, Xavier; Boutouyrie, Pierre; Laurent, Stephane

    2016-01-01

    Abstract The mechanisms that link metabolic syndrome (MetS) to increased cardiovascular risk are incompletely understood. We examined whether MetS is associated with the neural baroreflex pathway (NBP) and whether any such associations are independent of blood pressure values. This study involved the cross-sectional analysis of data on 2835 subjects aged 50 to 75 years from the Paris Prospective Study 3. The prevalence of MetS was defined according to the American Heart Association/National Heart Blood and Lung Institute definition. NBP values were calculated from the fluctuation of the common carotid distension rate and heart rate using fast Fourier transformation and cross-spectral analysis. The prevalence of MetS was 20.1% in men and 10.4% in women. Compared with controls, subjects with MetS (≥3 components), and those at risk for MetS (1–2 components) had lower NBP (−5.3% and −2.3%, respectively) and higher carotid stiffness (+13.5% and +6.8%, respectively). The negative association between MetS components and NBP was confirmed, even after adjustment for age, sex, and carotid stiffness. After stratification for blood pressure (BP) levels, NBP was reduced only in MetS subjects and those at risk with high BP. The NBP was positively associated with carotid stiffness in controls and subjects at risk for MetS. This association was lost in subjects with MetS, regardless of BP levels. Subjects with MetS had reduced NBP values. The role of BP is fundamental in the reduction of NBP. The mechanisms that link carotid stiffness and NBP are inactive in subjects with MetS, independent of BP levels. PMID:26765449

  8. 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…

  9. Neural mechanisms underlying context-dependent shifts in risk preferences

    NARCIS (Netherlands)

    Losecaat Vermeer, A.B.; Boksem, M.A.S.; Sanfey, A.G.

    2014-01-01

    Studies of risky decision-making have demonstrated that humans typically prefer risky options after incurring a financial loss, while generally preferring safer options after a monetary gain. Here, we examined the neural processes underlying these inconsistent risk preferences by investigating the

  10. AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.

    Science.gov (United States)

    Zingg, Brian; Chou, Xiao-Lin; Zhang, Zheng-Gang; Mesik, Lukas; Liang, Feixue; Tao, Huizhong Whit; Zhang, Li I

    2017-01-04

    To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we discovered that adeno-associated viruses (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drives Cre-dependent transgene expression in selected postsynaptic neuronal targets, thus allowing axonal tracing and functional manipulations of the latter input-defined neuronal population. Its application in superior colliculus (SC) reveals that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drive flight and freezing, two different types of defense behavior, respectively. Together with an intersectional approach, AAV-mediated anterograde transsynaptic tagging can categorize neurons by their inputs and molecular identity, and allow forward screening of distinct functional neural pathways embedded in complex brain circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Neural Global Pattern Similarity Underlies True and False Memories.

    Science.gov (United States)

    Ye, Zhifang; Zhu, Bi; Zhuang, Liping; Lu, Zhonglin; Chen, Chuansheng; Xue, Gui

    2016-06-22

    The neural processes giving rise to human memory strength signals remain poorly understood. Inspired by formal computational models that posit a central role of global matching in memory strength, we tested a novel hypothesis that the strengths of both true and false memories arise from the global similarity of an item's neural activation pattern during retrieval to that of all the studied items during encoding (i.e., the encoding-retrieval neural global pattern similarity [ER-nGPS]). We revealed multiple ER-nGPS signals that carried distinct information and contributed differentially to true and false memories: Whereas the ER-nGPS in the parietal regions reflected semantic similarity and was scaled with the recognition strengths of both true and false memories, ER-nGPS in the visual cortex contributed solely to true memory. Moreover, ER-nGPS differences between the parietal and visual cortices were correlated with frontal monitoring processes. By combining computational and neuroimaging approaches, our results advance a mechanistic understanding of memory strength in recognition. What neural processes give rise to memory strength signals, and lead to our conscious feelings of familiarity? Using fMRI, we found that the memory strength of a given item depends not only on how it was encoded during learning, but also on the similarity of its neural representation with other studied items. The global neural matching signal, mainly in the parietal lobule, could account for the memory strengths of both studied and unstudied items. Interestingly, a different global matching signal, originated from the visual cortex, could distinguish true from false memories. The findings reveal multiple neural mechanisms underlying the memory strengths of events registered in the brain. Copyright © 2016 the authors 0270-6474/16/366792-11$15.00/0.

  12. 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.

  13. Neural mechanisms underlying neurooptometric rehabilitation following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hudac CM

    2012-01-01

    Full Text Available Caitlin M Hudac1, Srinivas Kota1, James L Nedrow2, Dennis L Molfese1,31Department of Psychology, University of Nebraska-Lincoln, 2Oculi Vision Rehabilitation, 3Center for Brain, Biology, and Behavior, University of Nebraska-Lincoln, Lincoln, NEAbstract: Mild to severe traumatic brain injuries have lasting effects on everyday functioning. Issues relating to sensory problems are often overlooked or not addressed until well after the onset of the injury. In particular, vision problems related to ambient vision and the magnocellular pathway often result in posttrauma vision syndrome or visual midline shift syndrome. Symptoms from these syndromes are not restricted to the visual domain. Patients commonly experience proprioceptive, kinesthetic, vestibular, cognitive, and language problems. Neurooptometric rehabilitation often entails the use of corrective lenses, prisms, and binasal occlusion to accommodate the unstable magnocellular system. However, little is known regarding the neural mechanisms engaged during neurooptometric rehabilitation, nor how these mechanisms impact other domains. Event-related potentials from noninvasive electrophysiological recordings can be used to assess rehabilitation progress in patients. In this case report, high-density visual event-related potentials were recorded from one patient with posttrauma vision syndrome and secondary visual midline shift syndrome during a pattern reversal task, both with and without prisms. Results indicate that two factors occurring during the end portion of the P148 component (168–256 milliseconds poststimulus onset map onto two separate neural systems that were engaged with and without neurooptometric rehabilitation. Without prisms, neural sources within somatosensory, language, and executive brain regions engage inefficient magnocellular system processing. However, when corrective prisms were worn, primary visual areas were appropriately engaged. The impact of using early

  14. Protein signaling pathways in differentiation of neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Vodička, Petr; Pelech, S.; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2008-01-01

    Roč. 8, - (2008), s. 4547-4559 ISSN 1615-9853 R&D Projects: GA MŠk 1M0538 Institutional research plan: CEZ:AV0Z50450515 Keywords : antibody microarray * differentiation * neural stem cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.586, year: 2008

  15. Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy

    NARCIS (Netherlands)

    Willemze, Rose A.; Luyer, Misha D.; Buurman, Wim A.; de Jonge, Wouter J.

    2015-01-01

    Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes.

  16. Neural processes underlying cultural differences in cognitive persistence.

    Science.gov (United States)

    Telzer, Eva H; Qu, Yang; Lin, Lynda C

    2017-08-01

    Self-improvement motivation, which occurs when individuals seek to improve upon their competence by gaining new knowledge and improving upon their skills, is critical for cognitive, social, and educational adjustment. While many studies have delineated the neural mechanisms supporting extrinsic motivation induced by monetary rewards, less work has examined the neural processes that support intrinsically motivated behaviors, such as self-improvement motivation. Because cultural groups traditionally vary in terms of their self-improvement motivation, we examined cultural differences in the behavioral and neural processes underlying motivated behaviors during cognitive persistence in the absence of extrinsic rewards. In Study 1, 71 American (47 females, M=19.68 years) and 68 Chinese (38 females, M=19.37 years) students completed a behavioral cognitive control task that required cognitive persistence across time. In Study 2, 14 American and 15 Chinese students completed the same cognitive persistence task during an fMRI scan. Across both studies, American students showed significant declines in cognitive performance across time, whereas Chinese participants demonstrated effective cognitive persistence. These behavioral effects were explained by cultural differences in self-improvement motivation and paralleled by increasing activation and functional coupling between the inferior frontal gyrus (IFG) and ventral striatum (VS) across the task among Chinese participants, neural activation and coupling that remained low in American participants. These findings suggest a potential neural mechanism by which the VS and IFG work in concert to promote cognitive persistence in the absence of extrinsic rewards. Thus, frontostriatal circuitry may be a neurobiological signal representing intrinsic motivation for self-improvement that serves an adaptive function, increasing Chinese students' motivation to engage in cognitive persistence. Copyright © 2017 Elsevier Inc. All rights

  17. Parallel and interrelated neural systems underlying adaptive navigation.

    Science.gov (United States)

    Mizumori, Sheri J Y; Canfield, James G; Yeshenko, Oksana

    2005-06-01

    The ability to process in parallel multiple forms of sensory information, and link sensory-sensory associations to behavior, presumably allows for the opportunistic use of the most reliable and predictive sensory modalities in diverse behavioral contexts. Evolutionary considerations indicate that such processing may represent a fundamental operating principle underlying complex sensory associations and sensory-motor integration. Here, we suggest that animal navigation is a particularly useful model of such opportunistic use of sensory and motor information because it is possible to study directly the effects of memory on neural system functions. First, comparative evidence for parallel processing across multiple brain structures during navigation is provided from the literatures on fish and rodent navigation. Then, based on neurophysiological evidence of coordinated, multiregional processing, we provide a neurobiological explanation of learning and memory effects on neural circuitry mediating navigation.

  18. Distinct pathways of neural coupling for different basic emotions.

    Science.gov (United States)

    Tettamanti, Marco; Rognoni, Elena; Cafiero, Riccardo; Costa, Tommaso; Galati, Dario; Perani, Daniela

    2012-01-16

    Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience. Copyright © 2011. Published by Elsevier Inc.

  19. Similar judgment method of brain neural pathway using DT-MRI

    International Nuclear Information System (INIS)

    Watashiba, Yasuhiro; Sakamoto, Naohisa; Sakai, Koji; Koyamada, Koji; Kanazawa, Masanori; Doi, Akio

    2008-01-01

    Nowadays, the visualization of brain neural pathway extracted by the tractography technology is thought as a useful effective tool for the detection of involved area and the analysis of sick cause by comparison of difference of normal and patient's nerve fiber configurations and for the support of the surgery planning and the forecast of progress after an operation. So far, for the observation of the brain neural pathway, the method of the user's subjectively judging the 3D shape of them displayed in the image has been used. However, in this kind of subjective observation, verification of the propriety for the diagnostic result is difficult, in addition it cannot obtain sufficient reliability. Therefore, we think that the system to compare the shape based on a quantitative evaluation is necessary. To resolve this problem, we propose the system that enables the shape of the brain neural pathway extracted by the tractography technology to be compared quantitatively. The proposed system realized to calculate similarity between two neural pathways, and to display the difference area according to the similarity. (author)

  20. Neural changes underlying early stages of L2 vocabulary acquisition.

    Science.gov (United States)

    Pu, He; Holcomb, Phillip J; Midgley, Katherine J

    2016-11-01

    Research has shown neural changes following second language (L2) acquisition after weeks or months of instruction. But are such changes detectable even earlier than previously shown? The present study examines the electrophysiological changes underlying the earliest stages of second language vocabulary acquisition by recording event-related potentials (ERPs) within the first week of learning. Adult native English speakers with no previous Spanish experience completed less than four hours of Spanish vocabulary training, with pre- and post-training ERPs recorded to a backward translation task. Results indicate that beginning L2 learners show rapid neural changes following learning, manifested in changes to the N400 - an ERP component sensitive to lexicosemantic processing and degree of L2 proficiency. Specifically, learners in early stages of L2 acquisition show growth in N400 amplitude to L2 words following learning as well as a backward translation N400 priming effect that was absent pre-training. These results were shown within days of minimal L2 training, suggesting that the neural changes captured during adult second language acquisition are more rapid than previously shown. Such findings are consistent with models of early stages of bilingualism in adult learners of L2 ( e.g. Kroll and Stewart's RHM) and reinforce the use of ERP measures to assess L2 learning.

  1. 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.

  2. Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

    Directory of Open Access Journals (Sweden)

    Hideo eOtsuna

    2014-02-01

    Full Text Available Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

  3. Dimensions of childhood adversity have distinct associations with neural systems underlying executive functioning.

    Science.gov (United States)

    Sheridan, Margaret A; Peverill, Matthew; Finn, Amy S; McLaughlin, Katie A

    2017-12-01

    Childhood adversity is associated with increased risk for psychopathology. Neurodevelopmental pathways underlying this risk remain poorly understood. A recent conceptual model posits that childhood adversity can be deconstructed into at least two underlying dimensions, deprivation and threat, that are associated with distinct neurocognitive consequences. This model argues that deprivation (i.e., a lack of cognitive stimulation and learning opportunities) is associated with poor executive function (EF), whereas threat is not. We examine this hypothesis in two studies measuring EF at multiple levels: performance on EF tasks, neural recruitment during EF, and problems with EF in daily life. In Study 1, deprivation (low parental education and child neglect) was associated with greater parent-reported problems with EF in adolescents (N = 169; 13-17 years) after adjustment for levels of threat (community violence and abuse), which were unrelated to EF. In Study 2, low parental education was associated with poor working memory (WM) performance and inefficient neural recruitment in the parietal and prefrontal cortex during high WM load among adolescents (N = 51, 13-20 years) after adjusting for abuse, which was unrelated to WM task performance and neural recruitment during WM. These findings constitute strong preliminary evidence for a novel model of the neurodevelopmental consequences of childhood adversity.

  4. Renewable Fuel Pathways II Final Rule to Identify Additional Fuel Pathways under Renewable Fuel Standard Program

    Science.gov (United States)

    This final rule describes EPA’s evaluation of biofuels derived from biogas fuel pathways under the RFS program and other minor amendments related to survey requirements associated with ULSD program and misfueling mitigation regulations for E15.

  5. Adaptive neural network motion control for aircraft under uncertainty conditions

    Science.gov (United States)

    Efremov, A. V.; Tiaglik, M. S.; Tiumentsev, Yu V.

    2018-02-01

    We need to provide motion control of modern and advanced aircraft under diverse uncertainty conditions. This problem can be solved by using adaptive control laws. We carry out an analysis of the capabilities of these laws for such adaptive systems as MRAC (Model Reference Adaptive Control) and MPC (Model Predictive Control). In the case of a nonlinear control object, the most efficient solution to the adaptive control problem is the use of neural network technologies. These technologies are suitable for the development of both a control object model and a control law for the object. The approximate nature of the ANN model was taken into account by introducing additional compensating feedback into the control system. The capabilities of adaptive control laws under uncertainty in the source data are considered. We also conduct simulations to assess the contribution of adaptivity to the behavior of the system.

  6. Hearing loss impacts neural alpha oscillations under adverse listening conditions

    Directory of Open Access Journals (Sweden)

    Eline Borch Petersen

    2015-02-01

    Full Text Available Degradations in external, acoustic stimulation have long been suspected to increase the load on working memory. One neural signature of working memory load is enhanced power of alpha oscillations (6 ‒ 12 Hz. However, it is unknown to what extent common internal, auditory degradation, that is, hearing impairment, affects the neural mechanisms of working memory when audibility has been ensured via amplification. Using an adapted auditory Sternberg paradigm, we varied the orthogonal factors memory load and background noise level, while the electroencephalogram (EEG was recorded. In each trial, participants were presented with 2, 4, or 6 spoken digits embedded in one of three different levels of background noise. After a stimulus-free delay interval, participants indicated whether a probe digit had appeared in the sequence of digits. Participants were healthy older adults (62 – 86 years, with normal to moderately impaired hearing. Importantly, the background noise levels were individually adjusted and participants were wearing hearing aids to equalize audibility across participants. Irrespective of hearing loss, behavioral performance improved with lower memory load and also with lower levels of background noise. Interestingly, the alpha power in the stimulus-free delay interval was dependent on the interplay between task demands (memory load and noise level and hearing loss; while alpha power increased with hearing loss during low and intermediate levels of memory load and background noise, it dropped for participants with the relatively most severe hearing loss under the highest memory load and background noise level. These findings suggest that adaptive neural mechanisms for coping with adverse listening conditions break down for higher degrees of hearing loss, even when adequate hearing aid amplification is in place.

  7. Neural correlates underlying micrographia in Parkinson’s disease

    Science.gov (United States)

    Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson’s disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. PMID:26525918

  8. Ontogeny of neural circuits underlying spatial memory in the rat

    Directory of Open Access Journals (Sweden)

    James Alexander Ainge

    2012-03-01

    Full Text Available Spatial memory is a well characterised psychological function in both humans and rodents. The combined computations of a network of systems including place cells in the hippocampus, grid cells in the medial entorhinal cortex and head direction cells found in numerous structures in the brain have been suggested to form the neural instantiation of the cognitive map as first described by Tolman in 1948. However, while our understanding of the neural mechanisms underlying spatial representations in adults is relatively sophisticated, we know substantially less about how this network develops in young animals. In this article we review studies examining the developmental timescale that these systems follow. Electrophysiological recordings from very young rats show that directional information is at adult levels at the outset of navigational experience. The systems supporting allocentric memory, however, take longer to mature. This is consistent with behavioural studies of young rats which show that spatial memory based on head direction develops very early but that allocentric spatial memory takes longer to mature. We go on to report new data demonstrating that memory for associations between objects and their spatial locations is slower to develop than memory for objects alone. This is again consistent with previous reports suggesting that adult like spatial representations have a protracted development in rats and also suggests that the systems involved in processing non-spatial stimuli come online earlier.

  9. Neural basis of increased costly norm enforcement under adversity.

    Science.gov (United States)

    Wu, Yan; Yu, Hongbo; Shen, Bo; Yu, Rongjun; Zhou, Zhiheng; Zhang, Guoping; Jiang, Yushi; Zhou, Xiaolin

    2014-12-01

    Humans are willing to punish norm violations even at a substantial personal cost. Using fMRI and a variant of the ultimatum game and functional magnetic resonance imaging, we investigated how the brain differentially responds to fairness in loss and gain domains. Participants (responders) received offers from anonymous partners indicating a division of an amount of monetary gain or loss. If they accept, both get their shares according to the division; if they reject, both get nothing or lose the entire stake. We used a computational model to derive perceived fairness of offers and participant-specific inequity aversion. Behaviorally, participants were more likely to reject unfair offers in the loss (vs gain) domain. Neurally, the positive correlation between fairness and activation in ventral striatum was reduced, whereas the negative correlations between fairness and activations in dorsolateral prefrontal cortex were enhanced in the loss domain. Moreover, rejection-related dorsal striatum activation was higher in the loss domain. Furthermore, the gain-loss domain modulates costly punishment only when unfair behavior was directed toward the participants and not when it was directed toward others. These findings provide neural and computational accounts of increased costly norm enforcement under adversity and advanced our understanding of the context-dependent nature of fairness preference. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Auditory pathway encoding and neural plasticity in children with learning problems.

    Science.gov (United States)

    Kraus, N

    2001-01-01

    An inability to process auditory information, especially speech, characterizes many children with learning and attention problems. Our working hypothesis is that these speech-sound perception problems arise, at least in some cases, from faulty representation of the speech signal in central auditory centers. Preconscious neurophysiologic representation of sound structure by central auditory pathway neurons can be reflected by subcortical and cortical aggregate neural responses. These neurophysiologic responses can be modified by perceptual learning. Our research has shown that some children with learning problems demonstrate abnormal perception and neural representation of certain speech sounds. Differences between normal and learning-impaired groups can be attributable to aspects of neural synchrony that are reflected in aggregate neural responses. Deficiencies in neural synchrony in these children are apparent in subcortical (as well as cortical) representations of speech-sound structure, and these timing deficits are related to performance on speech-sound perception and learning measures. Moreover, impaired perception and neurophysiologic encoding of speech sounds can be improved with cue enhancement and can be modified by perceptual learning associated with auditory training. Copyright 2001 S. Karger AG, Basel

  11. Neural mechanisms underlying cognitive inflexibility in Parkinson's disease.

    Science.gov (United States)

    Lange, Florian; Seer, Caroline; Loens, Sebastian; Wegner, Florian; Schrader, Christoph; Dressler, Dirk; Dengler, Reinhard; Kopp, Bruno

    2016-12-01

    Cognitive inflexibility is a hallmark of executive dysfunction in Parkinson's disease (PD). This deficit consistently manifests itself in a PD-related increase in the number of perseverative errors committed on the Wisconsin Card Sorting Test (WCST). However, the neural processes underlying perseverative WCST performance in PD are still largely unknown. The present study is the first to investigate the event-related potential (ERP) correlates of cognitive inflexibility on the WCST in PD patients. Thirty-two PD patients and 35 matched control participants completed a computerized version of the WCST while the electroencephalogram (EEG) was recorded. Behavioral results revealed the expected increase in perseverative errors in patients with PD. ERP analysis focused on two established indicators of executive processes: the fronto-central P3a as an index of attentional orienting and the sustained parietal positivity (SPP) as an index of set-shifting processes. In comparison to controls, P3a amplitudes were significantly attenuated in PD patients. Regression analysis further revealed that P3a and SPP amplitudes interactively contributed to the prediction of perseverative errors in PD patients: The number of perseverative errors was only increased when both ERP amplitudes were attenuated. Notably, the two ERP markers of executive processes accounted for more than 40% of the variance in perseverative errors in PD patients. We conclude that cognitive inflexibility in PD occurs when the neural bases of multiple executive processes are affected by the pathophysiology of PD. The combined measurement of P3a and SPP might yield an electrophysiological marker of cognitive inflexibility in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Neural Mechanisms Underlying Hyperphagia in Prader-Willi Syndrome

    Science.gov (United States)

    Holsen, Laura M.; Zarcone, Jennifer R.; Brooks, William M.; Butler, Merlin G.; Thompson, Travis I.; Ahluwalia, Jasjit S.; Nollen, Nicole L.; Savage, Cary R.

    2006-01-01

    Objective Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Research Methods and Procedures Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Results Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Discussion Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and para-limbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC). PMID:16861608

  13. Neural mechanisms underlying hyperphagia in Prader-Willi syndrome.

    Science.gov (United States)

    Holsen, Laura M; Zarcone, Jennifer R; Brooks, William M; Butler, Merlin G; Thompson, Travis I; Ahluwalia, Jasjit S; Nollen, Nicole L; Savage, Cary R

    2006-06-01

    Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC).

  14. Neural mechanisms underlying the induction and relief of perceptual curiosity

    Directory of Open Access Journals (Sweden)

    Marieke eJepma

    2012-02-01

    Full Text Available Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (i the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex, brain regions sensitive to conflict and arousal; (ii the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (iii the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory.

  15. 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.

  16. Cyclosporin A enhances neural precursor cell survival in mice through a calcineurin-independent pathway

    Directory of Open Access Journals (Sweden)

    Nadia Sachewsky

    2014-08-01

    Full Text Available Cyclosporin A (CsA has direct effects on neural stem and progenitor cells (together termed neural precursor cells; NPCs in the adult central nervous system. Administration of CsA in vitro or in vivo promotes the survival of NPCs and expands the pools of NPCs in mice. Moreover, CsA administration is effective in promoting NPC activation, tissue repair and functional recovery in a mouse model of cortical stroke. The mechanism(s by which CsA mediates this cell survival effect remains unknown. Herein, we examined both calcineurin-dependent and calcineurin-independent pathways through which CsA might mediate NPC survival. To examine calcineurin-dependent pathways, we utilized FK506 (Tacrolimus, an immunosuppressive molecule that inhibits calcineurin, as well as drugs that inhibit cyclophilin A-mediated activation of calcineurin. To evaluate the calcineurin-independent pathway, we utilized NIM811, a non-immunosuppressive CsA analog that functions independently of calcineurin by blocking mitochondrial permeability transition pore formation. We found that only NIM811 can entirely account for the pro-survival effects of CsA on NPCs. Indeed, blocking signaling pathways downstream of calcineurin activation using nNOS mice did not inhibit CsA-mediated cell survival, which supports the proposal that the effects are calcinuerin-independent. In vivo studies revealed that NIM811 administration mimics the pro-survival effects of CsA on NPCs and promotes functional recovery in a model of cortical stroke, identical to the effects seen with CsA administration. We conclude that CsA mediates its effect on NPC survival through calcineurin-independent inhibition of mitochondrial permeability transition pore formation and suggest that this pathway has potential therapeutic benefits for developing NPC-mediated cell replacement strategies.

  17. Analytic Treatment of Deep Neural Networks Under Additive Gaussian Noise

    KAUST Repository

    Alfadly, Modar M.

    2018-04-12

    Despite the impressive performance of deep neural networks (DNNs) on numerous vision tasks, they still exhibit yet-to-understand uncouth behaviours. One puzzling behaviour is the reaction of DNNs to various noise attacks, where it has been shown that there exist small adversarial noise that can result in a severe degradation in the performance of DNNs. To rigorously treat this, we derive exact analytic expressions for the first and second moments (mean and variance) of a small piecewise linear (PL) network with a single rectified linear unit (ReLU) layer subject to general Gaussian input. We experimentally show that these expressions are tight under simple linearizations of deeper PL-DNNs, especially popular architectures in the literature (e.g. LeNet and AlexNet). Extensive experiments on image classification show that these expressions can be used to study the behaviour of the output mean of the logits for each class, the inter-class confusion and the pixel-level spatial noise sensitivity of the network. Moreover, we show how these expressions can be used to systematically construct targeted and non-targeted adversarial attacks. Then, we proposed a special estimator DNN, named mixture of linearizations (MoL), and derived the analytic expressions for its output mean and variance, as well. We employed these expressions to train the model to be particularly robust against Gaussian attacks without the need for data augmentation. Upon training this network on a loss that is consolidated with the derived output probabilistic moments, the network is not only robust under very high variance Gaussian attacks but is also as robust as networks that are trained with 20 fold data augmentation.

  18. Tracting the neural basis of music: Deficient structural connectivity underlying acquired amusia.

    Science.gov (United States)

    Sihvonen, Aleksi J; Ripollés, Pablo; Särkämö, Teppo; Leo, Vera; Rodríguez-Fornells, Antoni; Saunavaara, Jani; Parkkola, Riitta; Soinila, Seppo

    2017-12-01

    Acquired amusia provides a unique opportunity to investigate the fundamental neural architectures of musical processing due to the transition from a functioning to defective music processing system. Yet, the white matter (WM) deficits in amusia remain systematically unexplored. To evaluate which WM structures form the neural basis for acquired amusia and its recovery, we studied 42 stroke patients longitudinally at acute, 3-month, and 6-month post-stroke stages using DTI [tract-based spatial statistics (TBSS) and deterministic tractography (DT)] and the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Non-recovered amusia was associated with structural damage and subsequent degeneration in multiple WM tracts including the right inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and frontal aslant tract (FAT), as well as in the corpus callosum (CC) and its posterior part (tapetum). In a linear regression analysis, the volume of the right IFOF was the main predictor of MBEA performance across time. Overall, our results provide a comprehensive picture of the large-scale deficits in intra- and interhemispheric structural connectivity underlying amusia, and conversely highlight which pathways are crucial for normal music perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Hearing loss impacts neural alpha oscillations under adverse listening conditions

    OpenAIRE

    Petersen, Eline B.; Wöstmann, Malte; Obleser, Jonas; Stenfelt, Stefan; Lunner, Thomas

    2015-01-01

    Degradations in external, acoustic stimulation have long been suspected to increase the load on working memory (WM). One neural signature of WM load is enhanced power of alpha oscillations (6–12 Hz). However, it is unknown to what extent common internal, auditory degradation, that is, hearing impairment, affects the neural mechanisms of WM when audibility has been ensured via amplification. Using an adapted auditory Sternberg paradigm, we varied the orthogonal factors memory load and backgrou...

  20. All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways

    Directory of Open Access Journals (Sweden)

    Fang Bo

    2009-07-01

    Full Text Available Abstract Background All-trans retinoic acid (RA is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs, we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture. Results Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation. Conclusion RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.

  1. Neural Cell Apoptosis Induced by Microwave Exposure Through Mitochondria-dependent Caspase-3 Pathway

    Science.gov (United States)

    Zuo, Hongyan; Lin, Tao; Wang, Dewen; Peng, Ruiyun; Wang, Shuiming; Gao, Yabing; Xu, Xinping; Li, Yang; Wang, Shaoxia; Zhao, Li; Wang, Lifeng; Zhou, Hongmei

    2014-01-01

    To determine whether microwave (MW) radiation induces neural cell apoptosis, differentiated PC12 cells and Wistar rats were exposed to 2.856GHz for 5min and 15min, respectively, at an average power density of 30 mW/cm2. JC-1 and TUNEL staining detected significant apoptotic events, such as the loss of mitochondria membrane potential and DNA fragmentation, respectively. Transmission electron microscopy and Hoechst staining were used to observe chromatin ultrastructure and apoptotic body formation. Annexin V-FITC/PI double staining was used to quantify the level of apoptosis. The expressions of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and PARP were examined by immunoblotting or immunocytochemistry. Caspase-3 activity was measured using an enzyme-linked immunosorbent assay. The results showed chromatin condensation and apoptotic body formation in neural cells 6h after microwave exposure. Moreover, the mitochondria membrane potential decreased, DNA fragmentation increased, leading to an increase in the apoptotic cell percentage. Furthermore, the ratio of Bax/Bcl-2, expression of cytochrome c, cleaved caspase-3 and PARP all increased. In conclusion, microwave radiation induced neural cell apoptosis via the classical mitochondria-dependent caspase-3 pathway. This study may provide the experimental basis for further investigation of the mechanism of the neurological effects induced by microwave radiation. PMID:24688304

  2. The neural pathways mediating color shifts induced by temporally varying light.

    Science.gov (United States)

    Christiansen, Jens H; D'Antona, Anthony D; Shevell, Steven K

    2009-05-28

    In natural viewing, an object's background often changes over time. Temporally varying backgrounds were investigated here with a steady test field within a time-varying surrounding chromaticity. With slow surround variation (below approximately 3 Hz), the color appearance of a steady test is also perceived to fluctuate. At somewhat higher temporal frequencies, however, temporal variation of the surround is visible but the test appears steady (R. L. De Valois, M. A. Webster, K. K. De Valois, & B. Lingelbach, 1986); also above approximately 3 Hz, temporal chromatic variation along the l- or s-axis of the MacLeod-Boynton space (symmetric about equal-energy-spectrum "white") shifts the steady appearance of the test field toward redness or yellowness, respectively (A. D. D'Antona & S. K. Shevell, 2006). In the study here, color shifts were measured with temporal surround modulation at 6 Hz or greater along axes intermediate to the l and s directions. Varying the relative phase of simultaneous surround variation in l and s should not change responses within independent l and s pathways but should differentially excite neural representations that combine l and s signals (so-called higher order chromatic mechanisms). Varying the phase of l and s showed that the induced color shifts were accounted for by neural responses both from nearly independent l and s pathways and from higher order chromatic mechanisms.

  3. Neural correlates underlying true and false associative memories.

    Science.gov (United States)

    Dennis, Nancy A; Johnson, Christina E; Peterson, Kristina M

    2014-07-01

    Despite the fact that associative memory studies produce a large number of false memories, neuroimaging analyses utilizing this paradigm typically focus only on neural activity mediating successful retrieval. The current study sought to expand on this prior research by examining the neural basis of both true and false associative memories. Though associative false memories are substantially different than those found in semantic or perceptual false memory paradigms, results suggest that associative false memories are mediated by similar neural mechanisms. Specifically, we found increased frontal activity that likely represents enhanced monitoring and evaluation compared to that needed for true memories and correct rejections. Results also indicated that true, and not false associative memories, are mediated by neural activity in the MTL, specifically the hippocampus. Finally, while activity in early visual cortex distinguished true from false memories, a lack of neural differences between hits and correct rejections failed to support previous findings suggesting that activity in early visual cortex represents sensory reactivation of encoding-related processing. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The long reach of early adversity: Parenting, stress, and neural pathways to antisocial behavior in adulthood.

    Science.gov (United States)

    Gard, Arianna M; Waller, Rebecca; Shaw, Daniel S; Forbes, Erika E; Hariri, Ahmad R; Hyde, Luke W

    2017-10-01

    Early life adversities including harsh parenting, maternal depression, neighborhood deprivation, and low family economic resources are more prevalent in low-income urban environments and are potent predictors of psychopathology, including, for boys, antisocial behavior (AB). However, little research has examined how these stressful experiences alter later neural function. Moreover, identifying genetic markers of greater susceptibility to adversity is critical to understanding biopsychosocial pathways from early adversity to later psychopathology. Within a sample of 310 low-income boys followed from age 1.5 to 20, multimethod assessments of adversities were examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial expressions was assessed using fMRI, and symptoms of Antisocial Personality Disorder were assessed via structured clinical interview. Genetic variability in cortisol signaling ( CRHR1 ) was examined as a moderator of pathways to amygdala reactivity. Observed parenting and neighborhood deprivation at age 2 each uniquely predicted amygdala reactivity to emotional faces at age 20 over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically-significant symptoms of AB via less amygdala reactivity to fearful facial expressions and this pathway was moderated by genetic variation in CRHR1 . These results elucidate a pathway linking early adversity to less amygdala reactivity to social signals of interpersonal distress 18 years later, which in turn increased risk for serious AB. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.

  5. Identifying the Neural Correlates Underlying Social Pain: Implications for Developmental Processes

    Science.gov (United States)

    Eisenberger, Naomi I.

    2006-01-01

    Although the need for social connection is critical for early social development as well as for psychological well-being throughout the lifespan, relatively little is known about the neural processes involved in maintaining social connections. The following review summarizes what is known regarding the neural correlates underlying feeling of…

  6. Enhanced food anticipatory activity associated with enhanced activation of extrahypothalamic neural pathways in serotonin2C receptor null mutant mice.

    Directory of Open Access Journals (Sweden)

    Jennifer L Hsu

    Full Text Available The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity. However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin(2C receptor (5-HT2CR null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.

  7. Neural mechanisms underlying probalistic category learning in normal aging.

    NARCIS (Netherlands)

    Fera, F.; Weickert, T.W.; Goldberg, T.E.; Tessitore, A.; Hariri, A.; Das, S.; Lee, S.; Zoltick, B.; Meeter, M.; Gluck, M.A.; Weinberger, D.A.; Matta, V.S.

    2005-01-01

    Probabilistic category learning engages neural circuitry that includes the prefrontal cortex and caudate nucleus, two regions that show prominent changes with normal aging. However, the specific contributions of these brain regions are uncertain, and the effects of normal aging have not been

  8. Neural suppression of irrelevant information underlies optimal working memory performance.

    Science.gov (United States)

    Zanto, Theodore P; Gazzaley, Adam

    2009-03-11

    Our ability to focus attention on task-relevant information and ignore distractions is reflected by differential enhancement and suppression of neural activity in sensory cortex (i.e., top-down modulation). Such selective, goal-directed modulation of activity may be intimately related to memory, such that the focus of attention biases the likelihood of successfully maintaining relevant information by limiting interference from irrelevant stimuli. Despite recent studies elucidating the mechanistic overlap between attention and memory, the relationship between top-down modulation of visual processing during working memory (WM) encoding, and subsequent recognition performance has not yet been established. Here, we provide neurophysiological evidence in healthy, young adults that top-down modulation of early visual processing (performance, such that the likelihood of successfully remembering relevant information is associated with limiting interference from irrelevant stimuli. The consequences of a failure to ignore distractors on recognition performance was replicated for two types of feature-based memory, motion direction and color. Moreover, attention to irrelevant stimuli was reflected neurally during the WM maintenance period as an increased memory load. These results suggest that neural enhancement of relevant information is not the primary determinant of high-level performance, but rather optimal WM performance is dependent on effectively filtering irrelevant information through neural suppression to prevent overloading a limited memory capacity.

  9. Neural processing of reward magnitude under varying attentional demands.

    Science.gov (United States)

    Stoppel, Christian Michael; Boehler, Carsten Nicolas; Strumpf, Hendrik; Heinze, Hans-Jochen; Hopf, Jens-Max; Schoenfeld, Mircea Ariel

    2011-04-06

    Central to the organization of behavior is the ability to represent the magnitude of a prospective reward and the costs related to obtaining it. Therein, reward-related neural activations are discounted in dependence of the effort required to resolve a given task. Varying attentional demands of the task might however affect reward-related neural activations. Here we employed fMRI to investigate the neural representation of expected values during a monetary incentive delay task with varying attentional demands. Following a cue, indicating at the same time the difficulty (hard/easy) and the reward magnitude (high/low) of the upcoming trial, subjects performed an attention task and subsequently received feedback about their monetary reward. Consistent with previous results, activity in anterior-cingulate, insular/orbitofrontal and mesolimbic regions co-varied with the anticipated reward-magnitude, but also with the attentional requirements of the task. These activations occurred contingent on action-execution and resembled the response time pattern of the subjects. In contrast, cue-related activations, signaling the forthcoming task-requirements, were only observed within attentional control structures. These results suggest that anticipated reward-magnitude and task-related attentional demands are concurrently processed in partially overlapping neural networks of anterior-cingulate, insular/orbitofrontal, and mesolimbic regions. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Age-related neural correlates of cognitive task performance under increased postural load

    NARCIS (Netherlands)

    Van Impe, A; Bruijn, S M; Coxon, J P; Wenderoth, N; Sunaert, S; Duysens, J; Swinnen, S P

    2013-01-01

    Behavioral studies suggest that postural control requires increased cognitive control and visuospatial processing with aging. Consequently, performance can decline when concurrently performing a postural and a demanding cognitive task. We aimed to identify the neural substrate underlying this

  11. Neural mechanisms underlying migrating motor complex formation in mouse isolated colon

    Science.gov (United States)

    Brierley, Stuart M; Nichols, Kim; Grasby, Dallas J; Waterman, Sally A

    2001-01-01

    Little is known about the intrinsic enteric reflex pathways associated with migrating motor complex (MMC) formation. Acetylcholine (ACh) mediates the rapid component of the MMC, however a non-cholinergic component also exists. The present study investigated the possible role of endogenous tachykinins (TKs) in the formation of colonic MMCs and the relative roles of excitatory and inhibitory pathways.MMCs were recorded from the circular muscle at four sites (proximal, proximal-mid, mid-distal and distal) along the mouse colon using force transducers.The tachykinin (NK1 and NK2) receptor antagonists SR-140 333 (250 nM) and SR-48 968 (250 nM) reduced the amplitude of MMCs at all recording sites, preferentially abolishing the long duration contraction. Residual MMCs were abolished by the subsequent addition of atropine (1 μM).The neuronal nitric oxide synthase inhibitor, Nωnitro-L-arginine (L-NOARG, 100 μM), increased MMC amplitude in the distal region, whilst reducing the amplitude in the proximal region. In preparations where MMCs did not migrate to the distal colon, addition of L-NOARG resulted in the formation of MMCs. Subsequent addition of apamin (250 nM) or suramin (100 μM) further increased MMC amplitude in the distal region, whilst suramin increased MMC amplitude in the mid-distal region. Apamin but not suramin reduced MMC amplitude in the proximal region. Subsequent addition of SR-140 333 and SR-48 968 reduced MMC amplitude at all sites. Residual MMCs were abolished by atropine (1 μM).In conclusion, TKs, ACh, nitric oxide (NO) and ATP are involved in the neural mechanisms underlying the formation of MMCs in the mouse colon. Tachykinins mediate the long duration component of the MMC via NK1 and NK2 receptors. Inhibitory pathways may be involved in determining whether MMCs are formed. PMID:11159701

  12. Parallel pathways of ethoxylated alcohol biodegradation under aerobic conditions

    International Nuclear Information System (INIS)

    Zembrzuska, Joanna; Budnik, Irena; Lukaszewski, Zenon

    2016-01-01

    Non-ionic surfactants (NS) are a major component of the surfactant flux discharged into surface water, and alcohol ethoxylates (AE) are the major component of this flux. Therefore, biodegradation pathways of AE deserve more thorough investigation. The aim of this work was to investigate the stages of biodegradation of homogeneous oxyethylated dodecanol C 12 E 9 having 9 oxyethylene subunits, under aerobic conditions. Enterobacter strain Z3 bacteria were chosen as biodegrading organisms under conditions with C 12 E 9 as the sole source of organic carbon. Bacterial consortia of river water were used in a parallel test as an inoculum for comparison. The LC-MS technique was used to identify the products of biodegradation. Liquid-liquid extraction with ethyl acetate was selected for the isolation of C 12 E 9 and metabolites from the biodegradation broth. The LC-MS/MS technique operating in the multiple reaction monitoring (MRM) mode was used for quantitative determination of C 12 E 9 , C 12 E 8 , C 12 E 7 and C 12 E 6 . Apart from the substrate, the homologues C 12 E 8 , C 12 E 7 and C 12 E 6 , being metabolites of C 12 E 9 biodegradation by shortening of the oxyethylene chain, as well as intermediate metabolites having a carboxyl end group in the oxyethylene chain (C 12 E 8 COOH, C 12 E 7 COOH, C 12 E 6 COOH and C 12 E 5 COOH), were identified. Poly(ethylene glycols) (E) having 9, 8 and 7 oxyethylene subunits were also identified, indicating parallel central fission of C 12 E 9 and its metabolites. Similar results were obtained with river water as inoculum. It is concluded that AE, under aerobic conditions, are biodegraded via two parallel pathways: by central fission with the formation of PEG, and by Ω-oxidation of the oxyethylene chain with the formation of carboxylated AE and subsequent shortening of the oxyethylene chain by a single unit. - Highlights: • Two parallel biodegradation pathways of alcohol ethoxylates have been discovered. • Apart from central

  13. Neural Partial Differentiation for Aircraft Parameter Estimation Under Turbulent Atmospheric Conditions

    Science.gov (United States)

    Kuttieri, R. A.; Sinha, M.

    2012-07-01

    An approach based on neural partial differentiation is suggested for aircraft parameter estimation using the flight data gathered under turbulent atmospheric conditions. The classical methods such as output error and equation error methods suffer from severe convergence issues; resulting in biased, inaccurate, and inconsistent estimates. Though filter error method yields better estimates while dealing with the flight data having process noise, it has few demerits like computational overheads and it allows estimation of a single set of process noise distribution matrix. The proposed neural method does not face any such problem of the classical methods. Moreover, the neural method does not require parameter initialization and a priori knowledge of the model structure. The neural network maps the aircraft state and control variables into the output variables corresponding to aerodynamic forces and moments. The parameter estimation, pertaining to lateral-directional motion, of the research aircraft de Havilland DHC-2 with simulated process noise, is presented. The results obtained using the neural partial differentiation are compared with the nominal values given in literature and with the classical methods. The neural method yields the aerodynamic derivatives very close to the nominal values and having quite low standard deviation. The neural methodology is also validated by comparing actual output variables with the neural predicted and neural reconstructed variables.

  14. Pathways of the Maillard reaction under physiological conditions.

    Science.gov (United States)

    Henning, Christian; Glomb, Marcus A

    2016-08-01

    Initially investigated as a color formation process in thermally treated foods, nowadays, the relevance of the Maillard reaction in vivo is generally accepted. Many chronic and age-related diseases such as diabetes, uremia, atherosclerosis, cataractogenesis and Alzheimer's disease are associated with Maillard derived advanced glycation endproducts (AGEs) and α-dicarbonyl compounds as their most important precursors in terms of reactivity and abundance. However, the situation in vivo is very challenging, because Maillard chemistry is paralleled by enzymatic reactions which can lead to both, increases and decreases in certain AGEs. In addition, mechanistic findings established under the harsh conditions of food processing might not be valid under physiological conditions. The present review critically discusses the relevant α-dicarbonyl compounds as central intermediates of AGE formation in vivo with a special focus on fragmentation pathways leading to formation of amide-AGEs.

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

    Science.gov (United States)

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

    2011-11-01

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

  16. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H

    2010-01-01

    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions......, as measured by c-Fos immunoreactivity, a marker of neuronal activation. Selective depletion of these cholinergic neurons abolishes the SSR180711-induced activation of the mPFC but not the ACCshell, demonstrating their critical importance for alpha(7) nAChR-dependent activation of the mPFC. Contrarily......, selective depletion of dopaminergic neurons in the ventral tegmental area abolishes the SSR180711-induced activation of the ACCshell but not the mPFC or HDB. These results demonstrate 2 distinct neural pathways activated by SSR180711. The BF and mPFC are important for attentional function and may subserve...

  17. Future changes in global warming potentials under representative concentration pathways

    Energy Technology Data Exchange (ETDEWEB)

    Reisinger, Andy [New Zealand Agricultural Greenhouse Gas Research Centre, PO Box 10002, Wellington 6143 (New Zealand); Meinshausen, Malte [Earth System Analysis, Potsdam Institute for Climate Impact Research (Germany); Manning, Martin, E-mail: andy.reisinger@nzagrc.org.nz [Climate Change Research Institute, Victoria University of Wellington (New Zealand)

    2011-04-15

    Global warming potentials (GWPs) are the metrics currently used to compare emissions of different greenhouse gases under the United Nations Framework Convention on Climate Change. Future changes in greenhouse gas concentrations will alter GWPs because the radiative efficiencies of marginal changes in CO{sub 2}, CH{sub 4} and N{sub 2}O depend on their background concentrations, the removal of CO{sub 2} is influenced by climate-carbon cycle feedbacks, and atmospheric residence times of CH{sub 4} and N{sub 2}O also depend on ambient temperature and other environmental changes. We calculated the currently foreseeable future changes in the absolute GWP of CO{sub 2}, which acts as the denominator for the calculation of all GWPs, and specifically the GWPs of CH{sub 4} and N{sub 2}O, along four representative concentration pathways (RCPs) up to the year 2100. We find that the absolute GWP of CO{sub 2} decreases under all RCPs, although for longer time horizons this decrease is smaller than for short time horizons due to increased climate-carbon cycle feedbacks. The 100-year GWP of CH{sub 4} would increase up to 20% under the lowest RCP by 2100 but would decrease by up to 10% by mid-century under the highest RCP. The 100-year GWP of N{sub 2}O would increase by more than 30% by 2100 under the highest RCP but would vary by less than 10% under other scenarios. These changes are not negligible but are mostly smaller than the changes that would result from choosing a different time horizon for GWPs, or from choosing altogether different metrics for comparing greenhouse gas emissions, such as global temperature change potentials.

  18. The neural bases underlying social risk perception in purchase decisions.

    Science.gov (United States)

    Yokoyama, Ryoichi; Nozawa, Takayuki; Sugiura, Motoaki; Yomogida, Yukihito; Takeuchi, Hikaru; Akimoto, Yoritaka; Shibuya, Satoru; Kawashima, Ryuta

    2014-05-01

    Social considerations significantly influence daily purchase decisions, and the perception of social risk (i.e., the anticipated disapproval of others) is crucial in dissuading consumers from making purchases. However, the neural basis for consumers' perception of social risk remains undiscovered, and this novel study clarifies the relevant neural processes. A total of 26 volunteers were scanned while they evaluated purchase intention of products (purchase intention task) and their anticipation of others' disapproval for possessing a product (social risk task), using functional magnetic resonance imaging (fMRI). The fMRI data from the purchase intention task was used to identify the brain region associated with perception of social risk during purchase decision making by using subjective social risk ratings for a parametric modulation analysis. Furthermore, we aimed to explore if there was a difference between participants' purchase decisions and their explicit evaluations of social risk, with reference to the neural activity associated with social risk perception. For this, subjective social risk ratings were used for a parametric modulation analysis on fMRI data from the social risk task. Analysis of the purchase intention task revealed a significant positive correlation between ratings of social risk and activity in the anterior insula, an area of the brain that is known as part of the emotion-related network. Analysis of the social risk task revealed a significant positive correlation between ratings of social risk and activity in the temporal parietal junction and the medial prefrontal cortex, which are known as theory-of-mind regions. Our results suggest that the anterior insula processes consumers' social risk implicitly to prompt consumers not to buy socially unacceptable products, whereas ToM-related regions process such risk explicitly in considering the anticipated disapproval of others. These findings may prove helpful in understanding the mental

  19. 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.

  20. The behavioral and neural mechanisms underlying the tracking of expertise.

    Science.gov (United States)

    Boorman, Erie D; O'Doherty, John P; Adolphs, Ralph; Rangel, Antonio

    2013-12-18

    Evaluating the abilities of others is fundamental for successful economic and social behavior. We investigated the computational and neurobiological basis of ability tracking by designing an fMRI task that required participants to use and update estimates of both people and algorithms' expertise through observation of their predictions. Behaviorally, we find a model-based algorithm characterized subject predictions better than several alternative models. Notably, when the agent's prediction was concordant rather than discordant with the subject's own likely prediction, participants credited people more than algorithms for correct predictions and penalized them less for incorrect predictions. Neurally, many components of the mentalizing network-medial prefrontal cortex, anterior cingulate gyrus, temporoparietal junction, and precuneus-represented or updated expertise beliefs about both people and algorithms. Moreover, activity in lateral orbitofrontal and medial prefrontal cortex reflected behavioral differences in learning about people and algorithms. These findings provide basic insights into the neural basis of social learning. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

    Science.gov (United States)

    Duric, Vanja

    2014-01-01

    Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response. PMID:22585060

  2. Parallel pathways of ethoxylated alcohol biodegradation under aerobic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Zembrzuska, Joanna, E-mail: Joanna.Zembrzuska@put.poznan.pl; Budnik, Irena, E-mail: Irena.Budnik@gmail.com; Lukaszewski, Zenon, E-mail: zenon.lukaszewski@put.poznan.pl

    2016-07-01

    Non-ionic surfactants (NS) are a major component of the surfactant flux discharged into surface water, and alcohol ethoxylates (AE) are the major component of this flux. Therefore, biodegradation pathways of AE deserve more thorough investigation. The aim of this work was to investigate the stages of biodegradation of homogeneous oxyethylated dodecanol C{sub 12}E{sub 9} having 9 oxyethylene subunits, under aerobic conditions. Enterobacter strain Z3 bacteria were chosen as biodegrading organisms under conditions with C{sub 12}E{sub 9} as the sole source of organic carbon. Bacterial consortia of river water were used in a parallel test as an inoculum for comparison. The LC-MS technique was used to identify the products of biodegradation. Liquid-liquid extraction with ethyl acetate was selected for the isolation of C{sub 12}E{sub 9} and metabolites from the biodegradation broth. The LC-MS/MS technique operating in the multiple reaction monitoring (MRM) mode was used for quantitative determination of C{sub 12}E{sub 9}, C{sub 12}E{sub 8}, C{sub 12}E{sub 7} and C{sub 12}E{sub 6}. Apart from the substrate, the homologues C{sub 12}E{sub 8}, C{sub 12}E{sub 7} and C{sub 12}E{sub 6}, being metabolites of C{sub 12}E{sub 9} biodegradation by shortening of the oxyethylene chain, as well as intermediate metabolites having a carboxyl end group in the oxyethylene chain (C{sub 12}E{sub 8}COOH, C{sub 12}E{sub 7}COOH, C{sub 12}E{sub 6}COOH and C{sub 12}E{sub 5}COOH), were identified. Poly(ethylene glycols) (E) having 9, 8 and 7 oxyethylene subunits were also identified, indicating parallel central fission of C{sub 12}E{sub 9} and its metabolites. Similar results were obtained with river water as inoculum. It is concluded that AE, under aerobic conditions, are biodegraded via two parallel pathways: by central fission with the formation of PEG, and by Ω-oxidation of the oxyethylene chain with the formation of carboxylated AE and subsequent shortening of the oxyethylene chain by a

  3. Serotonin activates overall feeding by activating two separate neural pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Song, Bo-mi; Avery, Leon

    2012-02-08

    Food intake in the nematode Caenorhabditis elegans requires two distinct feeding motions, pharyngeal pumping and isthmus peristalsis. Bacteria, the natural food of C. elegans, activate both feeding motions (Croll, 1978; Horvitz et al., 1982; Chiang et al., 2006). The mechanisms by which bacteria activate the feeding motions are largely unknown. To understand the process, we studied how serotonin, an endogenous pharyngeal pumping activator whose action is triggered by bacteria, activates feeding motions. Here, we show that serotonin, like bacteria, activates overall feeding by activating isthmus peristalsis as well as pharyngeal pumping. During active feeding, the frequencies and the timing of onset of the two motions were distinct, but each isthmus peristalsis was coupled to the preceding pump. We found that serotonin activates the two feeding motions mainly by activating two separate neural pathways in response to bacteria. For activating pumping, the SER-7 serotonin receptor in the MC motor neurons in the feeding organ activated cholinergic transmission from MC to the pharyngeal muscles by activating the Gsα signaling pathway. For activating isthmus peristalsis, SER-7 in the M4 (and possibly M2) motor neuron in the feeding organ activated the G(12)α signaling pathway in a cell-autonomous manner, which presumably activates neurotransmission from M4 to the pharyngeal muscles. Based on our results and previous calcium imaging of pharyngeal muscles (Shimozono et al., 2004), we propose a model that explains how the two feeding motions are separately regulated yet coupled. The feeding organ may have evolved this way to support efficient feeding.

  4. Projecting Drivers of Human Vulnerability under the Shared Socioeconomic Pathways

    Directory of Open Access Journals (Sweden)

    Guillaume Rohat

    2018-03-01

    Full Text Available The Shared Socioeconomic Pathways (SSPs are the new set of alternative futures of societal development that inform global and regional climate change research. They have the potential to foster the integration of socioeconomic scenarios within assessments of future climate-related health impacts. To date, such assessments have primarily superimposed climate scenarios on current socioeconomic conditions only. Until now, the few assessments of future health risks that employed the SSPs have focused on future human exposure—i.e., mainly future population patterns—, neglecting future human vulnerability. This paper first explores the research gaps—mainly linked to the paucity of available projections—that explain such a lack of consideration of human vulnerability under the SSPs. It then highlights the need for projections of socioeconomic variables covering the wide range of determinants of human vulnerability, available at relevant spatial and temporal scales, and accounting for local specificities through sectoral and regional extended versions of the global SSPs. Finally, this paper presents two innovative methods of obtaining and computing such socioeconomic projections under the SSPs—namely the scenario matching approach and an approach based on experts’ elicitation and correlation analyses—and applies them to the case of Europe. They offer a variety of possibilities for practical application, producing projections at sub-national level of various drivers of human vulnerability such as demographic and social characteristics, urbanization, state of the environment, infrastructure, health status, and living arrangements. Both the innovative approaches presented in this paper and existing methods—such as the spatial disaggregation of existing projections and the use of sectoral models—show great potential to enhance the availability of relevant projections of determinants of human vulnerability. Assessments of future climate

  5. Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

    Directory of Open Access Journals (Sweden)

    Tatsuya eKobayashi

    2015-02-01

    Full Text Available Sexual behavior is suppressed by various types of stressors. We previously demonstrated that an alarm pheromone released by stressed male Wistar rats is a stressor to other rats, increases the number of mounts needed for ejaculation, and decreases the hit rate (described as the number of intromissions/sum of the mounts and intromissions. This deterioration in sexual behavior was ameliorated by pretreatment with the opioid receptor antagonist naloxone. However, the neural mechanism underlying this remains to be elucidated. Here, we examined Fos expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the alarm pheromone increased the number of mounts and decreased the hit rate. In addition, Fos expression was increases in the anterior medial division, anterior lateral division and posterior division of the bed nucleus of the stria terminalis, parvocellular part of the paraventricular nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Fos expression decreased in the magnocellular part of the paraventricular nucleus of the hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in Fos expression in the magnocellular part of the paraventricular nucleus of the hypothalamus, ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Based on these results, we hypothesize that the alarm pheromone deteriorated sexual behavior by activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis cluster and suppressing the magnocellular part of the paraventricular nucleus of the hypothalamus via the opioidergic pathway.

  6. Group Membership Modulates the Neural Circuitry Underlying Third Party Punishment.

    Science.gov (United States)

    Morese, Rosalba; Rabellino, Daniela; Sambataro, Fabio; Perussia, Felice; Valentini, Maria Consuelo; Bara, Bruno G; Bosco, Francesca M

    2016-01-01

    This research aims to explore the neural correlates involved in altruistic punishment, parochial altruism and anti-social punishment, using the Third-Party Punishment (TPP) game. In particular, this study considered these punishment behaviors in in-group vs. out-group game settings, to compare how people behave with members of their own national group and with members of another national group. The results showed that participants act altruistically to protect in-group members. This study indicates that norm violation in in-group (but not in out-group) settings results in increased activity in the medial prefrontal cortex and temporo-parietal junction, brain regions involved in the mentalizing network, as the third-party attempts to understand or justify in-group members' behavior. Finally, exploratory analysis during anti-social punishment behavior showed brain activation recruitment of the ventromedial prefrontal cortex, an area associated with altered regulation of emotions.

  7. Climate Change and Health under the Shared Socioeconomic Pathway Framework

    Directory of Open Access Journals (Sweden)

    Samuel Sellers

    2017-12-01

    Full Text Available A growing body of literature addresses how climate change is likely to have substantial and generally adverse effects on population health and health systems around the world. These effects are likely to vary within and between countries and, importantly, will vary depending on different socioeconomic development patterns. Transitioning to a more resilient and sustainable world to prepare for and manage the effects of climate change is likely to result in better health outcomes. Sustained fossil fuel development will likely result in continued high burdens of preventable conditions, such as undernutrition, malaria, and diarrheal diseases. Using a new set of socioeconomic development trajectories, the Shared Socioeconomic Pathways (SSPs, along with the World Health Organization’s Operational Framework for Building Climate Resilient Health Systems, we extend existing storylines to illustrate how various aspects of health systems are likely to be affected under each SSP. We also discuss the implications of our findings on how the burden of mortality and the achievement of health-related Sustainable Development Goal targets are likely to vary under different SSPs.

  8. Managing coastal environments under climate change: Pathways to adaptation.

    Science.gov (United States)

    Sánchez-Arcilla, Agustín; García-León, Manuel; Gracia, Vicente; Devoy, Robert; Stanica, Adrian; Gault, Jeremy

    2016-12-01

    This paper deals with the question of how to manage vulnerable coastal systems so as to make them sustainable under present and future climates. This is interpreted in terms of the coastal functionality, mainly natural services and support for socio-economic activities. From here we discuss how to adapt for long term trends and for short terms episodic events using the DPSIR framework. The analysis is presented for coastal archetypes from Spain, Ireland and Romania, sweeping a range of meteo-oceanographic and socio-economic pressures, resulting in a wide range of fluxes among them those related to sediment. The analysis emphasizes the variables that provide a higher level of robustness. That means mean sea level for physical factors and population density for human factors. For each of the studied cases high and low sustainability practices, based on stakeholders preferences, are considered and discussed. This allows proposing alternatives and carrying out an integrated assessment in the last section of the paper. This assessment permits building a sequence of interventions called adaptation pathway that enhances the natural resilience of the studied coastal systems and therefore increases their sustainability under present and future conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. The neural underpinnings of music listening under different attention conditions.

    Science.gov (United States)

    Jäncke, Lutz; Leipold, Simon; Burkhard, Anja

    2018-05-02

    Most studies examining the neural underpinnings of music listening have no specific instruction on how to process the presented musical pieces. In this study, we explicitly manipulated the participants' focus of attention while they listened to the musical pieces. We used an ecologically valid experimental setting by presenting the musical stimuli simultaneously with naturalistic film sequences. In one condition, the participants were instructed to focus their attention on the musical piece (attentive listening), whereas in the second condition, the participants directed their attention to the film sequence (passive listening). We used two instrumental musical pieces: an electronic pop song, which was a major hit at the time of testing, and a classical musical piece. During music presentation, we measured electroencephalographic oscillations and responses from the autonomic nervous system (heart rate and high-frequency heart rate variability). During passive listening to the pop song, we found strong event-related synchronizations in all analyzed frequency bands (theta, lower alpha, upper alpha, lower beta, and upper beta). The neurophysiological responses during attentive listening to the pop song were similar to those of the classical musical piece during both listening conditions. Thus, the focus of attention had a strong influence on the neurophysiological responses to the pop song, but not on the responses to the classical musical piece. The electroencephalographic responses during passive listening to the pop song are interpreted as a neurophysiological and psychological state typically observed when the participants are 'drawn into the music'.

  10. Neural correlates underlying change in state self-esteem.

    Science.gov (United States)

    Kawamichi, Hiroaki; Sugawara, Sho K; Hamano, Yuki H; Kitada, Ryo; Nakagawa, Eri; Kochiyama, Takanori; Sadato, Norihiro

    2018-01-29

    State self-esteem, the momentary feeling of self-worth, functions as a sociometer involved in maintenance of interpersonal relations. How others' appraisal is subjectively interpreted to change state self-esteem is unknown, and the neural underpinnings of this process remain to be elucidated. We hypothesized that changes in state self-esteem are represented by the mentalizing network, which is modulated by interactions with regions involved in the subjective interpretation of others' appraisal. To test this hypothesis, we conducted task-based and resting-state fMRI. Participants were repeatedly presented with their reputations, and then rated their pleasantness and reported their state self-esteem. To evaluate the individual sensitivity of the change in state self-esteem based on pleasantness (i.e., the subjective interpretation of reputation), we calculated evaluation sensitivity as the rate of change in state self-esteem per unit pleasantness. Evaluation sensitivity varied across participants, and was positively correlated with precuneus activity evoked by reputation rating. Resting-state fMRI revealed that evaluation sensitivity was positively correlated with functional connectivity of the precuneus with areas activated by negative reputation, but negatively correlated with areas activated by positive reputation. Thus, the precuneus, as the part of the mentalizing system, serves as a gateway for translating the subjective interpretation of reputation into state self-esteem.

  11. Dissociable neural processes underlying risky decisions for self versus other

    Directory of Open Access Journals (Sweden)

    Daehyun eJung

    2013-03-01

    Full Text Available Previous neuroimaging studies on decision making have mainly focused on decisions on behalf of oneself. Considering that people often make decisions on behalf of others, it is intriguing that there is little neurobiological evidence on how decisions for others differ from those for self. Thus, the present study focused on the direct comparison between risky decisions for self and those for other using functional magnetic resonance imaging (fMRI. Participants (N = 23 were asked to perform a gambling task for themselves (decision-for-self condition or for another person (decision-for-other condition while in the scanner. Their task was to choose between a low-risk option (i.e., win or lose 10 points and a high-risk option (i.e., win or lose 90 points. The winning probabilities of each option varied from 17% to 83%. Compared to choices for others, choices for self were more risk-averse at lower winning probability and more risk-seeking at higher winning probability, perhaps due to stronger affective process during risky decision for self compared to other. The brain activation pattern changed according to the target of the decision, such that reward-related regions were more active in the decision-for-self condition than in the decision-for-other condition, whereas brain regions related to the theory of mind (ToM showed greater activation in the decision-for-other condition than in the decision-for-self condition. A parametric modulation analysis reflecting each individual’s decision model revealed that activation of the amygdala and the dorsomedial prefrontal cortex (DMPFC were associated with value computation for self and for other, respectively, during a risky financial decision. The present study suggests that decisions for self and other may recruit fundamentally distinctive neural processes, which can be mainly characterized by dominant affective/impulsive and cognitive/regulatory processes, respectively.

  12. Cortical Neural Activity Predicts Sensory Acuity Under Optogenetic Manipulation.

    Science.gov (United States)

    Briguglio, John J; Aizenberg, Mark; Balasubramanian, Vijay; Geffen, Maria N

    2018-02-21

    Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have predicted that suppression of inhibition in such excitatory-inhibitory networks can lead to either an increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex of male mice could evoke such a variety of effects in tone-evoked responses and in behavioral frequency discrimination acuity. We found that, indeed, the effects of optogenetic manipulation on stimulus selectivity and behavior varied in both magnitude and sign across subjects, possibly reflecting differences in circuitry or expression of optogenetic factors. Changes in neural population responses consistently predicted behavioral changes for individuals separately, including improvement and impairment in acuity. This correlation between cortical and behavioral change demonstrates that, despite the complex and varied effects that these manipulations can have on neuronal dynamics, the resulting changes in cortical activity account for accompanying changes in behavioral acuity. SIGNIFICANCE STATEMENT Excitatory and inhibitory interactions determine stimulus specificity and tuning in sensory cortex, thereby controlling perceptual discrimination acuity. Modeling has predicted that suppressing the activity of inhibitory neurons can lead to increased or, paradoxically, decreased excitatory activity depending on the architecture of the network. Here, we capitalized on differences between subjects to test whether suppressing/activating inhibition and excitation can in fact exhibit such paradoxical effects for both stimulus sensitivity and behavioral discriminability. Indeed, the same optogenetic manipulation in the auditory cortex of different mice could improve or impair frequency discrimination

  13. A segregated neural pathway for prefrontal top-down control of tactile discrimination.

    Science.gov (United States)

    Gogulski, Juha; Boldt, Robert; Savolainen, Petri; Guzmán-López, Jessica; Carlson, Synnöve; Pertovaara, Antti

    2015-01-01

    It has proven difficult to separate functional areas in the prefrontal cortex (PFC), an area implicated in attention, memory, and distraction handling. Here, we assessed in healthy human subjects whether PFC subareas have different roles in top-down regulation of sensory functions by determining how the neural links between the PFC and the primary somatosensory cortex (S1) modulate tactile perceptions. Anatomical connections between the S1 representation area of the cutaneous test site and the PFC were determined using probabilistic tractography. Single-pulse navigated transcranial magnetic stimulation of the middle frontal gyrus-S1 link, but not that of the superior frontal gyrus-S1 link, impaired the ability to discriminate between single and twin tactile pulses. The impairment occurred within a restricted time window and skin area. The spatially and temporally organized top-down control of tactile discrimination through a segregated PFC-S1 pathway suggests functional specialization of PFC subareas in fine-tuned regulation of information processing. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. The sleep and circadian modulation of neural reward pathways: a protocol for a pair of systematic reviews.

    Science.gov (United States)

    Byrne, Jamie E M; Murray, Greg

    2017-12-02

    Animal research suggests that neural reward activation may be systematically modulated by sleep and circadian function. Whether humans also exhibit sleep and circadian modulation of neural reward pathways is unclear. This area is in need of further research, as it has implications for the involvement of sleep and circadian function in reward-related disorders. The aim of this paper is to describe the protocol for a pair of systematic literature reviews to synthesise existing literature related to (1) sleep and (2) circadian modulation of neural reward pathways in healthy human populations. A systematic review of relevant online databases (Scopus, PubMed, Web of Science, ProQuest, PsycINFO and EBSCOhost) will be conducted. Reference lists, relevant reviews and supplementary data will be searched for additional articles. Articles will be included if (a) they contain a sleep- or circadian-related predictor variable with a neural reward outcome variable, (b) use a functional magnetic resonance imaging protocol and (c) use human samples. Articles will be excluded if study participants had disorders known to affect the reward system. The articles will be screened by two independent authors. Two authors will complete the data extraction form, with two authors independently completing the quality assessment tool for the selected articles, with a consensus reached with a third author if needed. Narrative synthesis methods will be used to analyse the data. The findings from this pair of systematic literature reviews will assist in the identification of the pathways involved in the sleep and circadian function modulation of neural reward in healthy individuals, with implications for disorders characterised by dysregulation in sleep, circadian rhythms and reward function. PROSPERO CRD42017064994.

  15. Gene expression profile of adult human olfactory bulb and embryonic neural stem cell suggests distinct signaling pathways and epigenetic control.

    Directory of Open Access Journals (Sweden)

    Hany E S Marei

    Full Text Available Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC, and adult human olfactory bulb-derived neural stem cells (OBNSCs, to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2, progenitor marker genes (LMX1a, ALDH1A1, SOX10, proliferation of neural progenitors (WNT1 and WNT3a, neuroplastin (NPTN, POU3F1 (OCT6, neuroligin (NLGN4X, MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC categories, 45 out of the 620 investigated Molecular Function (MF categories, and 239 out of the 2948 investigated Biological Process (BP categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults.

  16. Optogenetic dissection of neural circuit underlying locomotory decision-making in Caenorhabditis Elegans

    Science.gov (United States)

    Kocabas, Askin; Guo, Zengcai; Ramanathan, Sharad

    2011-03-01

    Despite the knowledge of the physical connectivity of the entire nervous system of C.elegans, we know little about how neuronal dynamics results in decision-making. Detailed understanding of functional and dynamic relations of the neural circuitry requires spatiotemporal control of the neuronal activity. Recent discoveries of light gated ion channels have allowed temporal optical control of neural activity. However, excitation of a specific neuron from among many expressing the channel has been a challenge. By combining optogenetic tools, micro mirror array technology and fast real time image processing, we have developed a technique to activate specific single or multiple neurons in an intact crawling animal while tracking its behavior. Using this setup we traced the neural pathway controlling the gradual turning of the animal during the locomotion. We found that the activity of a specific neuronal circuit that receives inputs from sensory neurons is coordinated with head movement. This coordination allows the animal to turn left or right based on the variation of sensory stimulus during head movement. By directly modulating the activity of the neural circuit, we can force the animal to turn in a specific direction independent of sensory stimuli. Human Frontier Science Program.

  17. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Makiko Okada

    2010-10-01

    Full Text Available Our previous study indicated that both 17β-estradiol (E2, known to be an endogenous estrogen, and bisphenol A (BPA, known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs. The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2, which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1 the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2 the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane‑associated ERs.

  18. Neural Correlates of Sensory Substitution in Vestibular Pathways Following Complete Vestibular Loss

    Science.gov (United States)

    Sadeghi, Soroush G.; Minor, Lloyd B.; Cullen, Kathleen E.

    2012-01-01

    Sensory substitution is the term typically used in reference to sensory prosthetic devices designed to replace input from one defective modality with input from another modality. Such devices allow an alternative encoding of sensory information that is no longer directly provided by the defective modality in a purposeful and goal-directed manner. The behavioral recovery that follows complete vestibular loss is impressive and has long been thought to take advantage of a natural form of sensory substitution in which head motion information is no longer provided by vestibular inputs, but instead by extra-vestibular inputs such as proprioceptive and motor efference copy signals. Here we examined the neuronal correlates of this behavioral recovery after complete vestibular loss in alert behaving monkeys (Macaca mulata). We show for the first time that extra-vestibular inputs substitute for the vestibular inputs to stabilize gaze at the level of single neurons in the VOR premotor circuitry. The summed weighting of neck proprioceptive and efference copy information was sufficient to explain simultaneously observed behavioral improvements in gaze stability. Furthermore, by altering correspondence between intended and actual head movement we revealed a four-fold increase in the weight of neck motor efference copy signals consistent with the enhanced behavioral recovery observed when head movements are voluntary versus unexpected. Thus, taken together our results provide direct evidence that the substitution by extra-vestibular inputs in vestibular pathways provides a neural correlate for the improvements in gaze stability that are observed following the total loss of vestibular inputs. PMID:23077054

  19. 78 FR 41703 - Regulation of Fuels and Fuel Additives: Additional Qualifying Renewable Fuel Pathways Under the...

    Science.gov (United States)

    2013-07-11

    ... Regulation of Fuels and Fuel Additives: Additional Qualifying Renewable Fuel Pathways Under the Renewable Fuel Standard Program; Final Rule Approving Renewable Fuel Pathways for Giant Reed (Arundo Donax) and.... SUMMARY: This final rule approves pathways for production of renewable fuel from giant reed (Arundo donax...

  20. 2010 Carl Ludwig Distinguished Lectureship of the APS Neural Control and Autonomic Regulation Section: Central neural pathways for thermoregulatory cold defense.

    Science.gov (United States)

    Morrison, Shaun F

    2011-05-01

    Central neural circuits orchestrate the homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the research leading to a model representing our current understanding of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for control of heat loss, and brown adipose tissue, skeletal muscle, and the heart for thermogenesis. The activation of these effectors is regulated by parallel but distinct, effector-specific core efferent pathways within the central nervous system (CNS) that share a common peripheral thermal sensory input. The thermal afferent circuit from cutaneous thermal receptors includes neurons in the spinal dorsal horn projecting to lateral parabrachial nucleus neurons that project to the medial aspect of the preoptic area. Within the preoptic area, warm-sensitive, inhibitory output neurons control heat production by reducing the discharge of thermogenesis-promoting neurons in the dorsomedial hypothalamus. The rostral ventromedial medulla, including the raphe pallidus, receives projections form the dorsomedial hypothalamus and contains spinally projecting premotor neurons that provide the excitatory drive to spinal circuits controlling the activity of thermogenic effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus sympathetic premotor neurons controlling cutaneous vasoconstriction. The model proposed for central thermoregulatory control provides a platform for further understanding of the functional organization of central thermoregulation.

  1. Potential neural mechanisms underlying the effectiveness of early intervention for children with autism spectrum disorder

    Science.gov (United States)

    Sullivan, Katherine; Stone, Wendy L.; Dawson, Geraldine

    2014-01-01

    Although evidence supports the efficacy of early intervention for improving outcomes for children with autism spectrum disorder (ASD), the mechanisms underlying their effectiveness remain poorly understood. This paper reviews the research literature on the neural bases of the early core deficits in ASD and proposes three key features of early intervention related to the neural mechanisms that may contribute to its effectiveness in improving deficit areas. These features include (1) the early onset of intensive intervention which capitalizes on the experience-expectant plasticity of the immature brain, (2) the use of treatment strategies that address core deficits in social motivation through an emphasis on positive social engagement and arousal modulation, and (3) promotion of complex neural networks and connectivity through thematic, multi-sensory and multi-domain teaching approaches. Understanding the mechanisms of effective early intervention will enable us to identify common or foundational active ingredients for promoting optimal outcomes in children with ASD. PMID:25108609

  2. Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yan Liang

    2017-01-01

    Full Text Available Adipose tissue-derived stromal cells (ADSCs are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9. Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

  3. Studies of Neuronal Gene Regulation Controlling the Molecular Mechanisms Underlying Neural Plasticity.

    Science.gov (United States)

    Fukuchi, Mamoru

    2017-01-01

    The regulation of the development and function of the nervous system is not preprogramed but responds to environmental stimuli to change neural development and function flexibly. This neural plasticity is a characteristic property of the nervous system. For example, strong synaptic activation evoked by environmental stimuli leads to changes in synaptic functions (known as synaptic plasticity). Long-lasting synaptic plasticity is one of the molecular mechanisms underlying long-term learning and memory. Since discovering the role of the transcription factor cAMP-response element-binding protein in learning and memory, it has been widely accepted that gene regulation in neurons contributes to long-lasting changes in neural functions. However, it remains unclear how synaptic activation is converted into gene regulation that results in long-lasting neural functions like long-term memory. We continue to address this question. This review introduces our recent findings on the gene regulation of brain-derived neurotrophic factor and discusses how regulation of the gene participates in long-lasting changes in neural functions.

  4. Neural network model for evaluation of seedling vigour under clinostated conditions

    Science.gov (United States)

    Zaidi, M.; Murase, H.

    A hierarchical neural net can be applied to simulate nonlinear phenomena found in biological systems. The learning process of the hierarchical neural net can be used as an algorithm for nonlinear multivariate analysis. The non- invasive technique for monitoring the plant's growth stage is one part of the required technology of the bio-response feedback control system. The stage of a plant's growth can be identified or quantified by measuring physical indices. Automated monitoring is also necessary in the clinostat experiment and neural networks are used for the calibration of lettuce plant growth. A back propagation neural network was trained to evaluate the plant growth in terms of plant growth characteristics, with a network consisting of 4, 8 and 1 processing units in the input, hidden and output layers, respectively. Sixteen sets of training data were used. The training was terminated after 800 times of iterative calculations at the RMS error value equal to 3.35x10-3 . Four sets of validation data were used to calculate the prediction error. The ability of the neural network models to predict the required information is very accurate. As a result, there is potential for the present technique to be applied to seedling vigour evaluating system under the clinostated conditions.

  5. Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD.

    Directory of Open Access Journals (Sweden)

    Yuanquan Song

    2009-12-01

    Full Text Available In humans, mutations in electron transfer flavoprotein (ETF or electron transfer flavoprotein dehydrogenase (ETFDH lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention.

  6. Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

    Directory of Open Access Journals (Sweden)

    J. Antunes-Rodrigues

    2013-12-01

    Full Text Available Several forebrain and brainstem neurochemical circuitries interact with peripheral neural and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Although much progress has been made over the past decades in the understanding of complex mechanisms underlying neuroendocrine control of hydromineral homeostasis, several issues still remain to be clarified. The use of techniques such as molecular biology, neuronal tracing, electrophysiology, immunohistochemistry, and microinfusions has significantly improved our ability to identify neuronal phenotypes and their signals, including those related to neuron-glia interactions. Accordingly, neurons have been shown to produce and release a large number of chemical mediators (neurotransmitters, neurohormones and neuromodulators into the interstitial space, which include not only classic neurotransmitters, such as acetylcholine, amines (noradrenaline, serotonin and amino acids (glutamate, GABA, but also gaseous (nitric oxide, carbon monoxide and hydrogen sulfide and lipid-derived (endocannabinoids mediators. This efferent response, initiated within the neuronal environment, recruits several peripheral effectors, such as hormones (glucocorticoids, angiotensin II, estrogen, which in turn modulate central nervous system responsiveness to systemic challenges. Therefore, in this review, we shall evaluate in an integrated manner the physiological control of body fluid homeostasis from the molecular aspects to the systemic and integrated responses.

  7. The role of automaticity and attention in neural processes underlying empathy for happiness, sadness, and anxiety

    Directory of Open Access Journals (Sweden)

    Sylvia A. Morelli

    2013-05-01

    Full Text Available Although many studies have examined the neural basis of experiencing empathy, relatively little is known about how empathic processes are affected by different attentional conditions. Thus, we examined whether instructions to empathize might amplify responses in empathy-related regions and whether cognitive load would diminish the involvement of these regions. 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing happy, sad, and anxious events. Stimuli were presented under three conditions: watching naturally, while instructed to empathize, and under cognitive load. Across analyses, we found evidence for a core set of neural regions that support empathic processes (dorsomedial prefrontal cortex, DMPFC; medial prefrontal cortex, MPFC; temporoparietal junction, TPJ; amygdala; ventral anterior insula, AI; septal area, SA. Two key regions – the ventral AI and SA – were consistently active across all attentional conditions, suggesting that they are automatically engaged during empathy. In addition, watching versus empathizing with targets was not markedly different and instead led to similar subjective and neural responses to others’ emotional experiences. In contrast, cognitive load reduced the subjective experience of empathy and diminished neural responses in several regions related to empathy (DMPFC, MPFC, TPJ, amygdala and social cognition. The current results reveal how attention impacts empathic processes and provides insight into how empathy may unfold in everyday interactions.

  8. Concise Review: Reprogramming, Behind the Scenes: Noncanonical Neural Stem Cell Signaling Pathways Reveal New, Unseen Regulators of Tissue Plasticity With Therapeutic Implications.

    Science.gov (United States)

    Poser, Steven W; Chenoweth, Josh G; Colantuoni, Carlo; Masjkur, Jimmy; Chrousos, George; Bornstein, Stefan R; McKay, Ronald D; Androutsellis-Theotokis, Andreas

    2015-11-01

    Interest is great in the new molecular concepts that explain, at the level of signal transduction, the process of reprogramming. Usually, transcription factors with developmental importance are used, but these approaches give limited information on the signaling networks involved, which could reveal new therapeutic opportunities. Recent findings involving reprogramming by genetic means and soluble factors with well-studied downstream signaling mechanisms, including signal transducer and activator of transcription 3 (STAT3) and hairy and enhancer of split 3 (Hes3), shed new light into the molecular mechanisms that might be involved. We examine the appropriateness of common culture systems and their ability to reveal unusual (noncanonical) signal transduction pathways that actually operate in vivo. We then discuss such novel pathways and their importance in various plastic cell types, culminating in their emerging roles in reprogramming mechanisms. We also discuss a number of reprogramming paradigms (mouse induced pluripotent stem cells, direct conversion to neural stem cells, and in vivo conversion of acinar cells to β-like cells). Specifically for acinar-to-β-cell reprogramming paradigms, we discuss the common view of the underlying mechanism (involving the Janus kinase-STAT pathway that leads to STAT3-tyrosine phosphorylation) and present alternative interpretations that implicate STAT3-serine phosphorylation alone or serine and tyrosine phosphorylation occurring in sequential order. The implications for drug design and therapy are important given that different phosphorylation sites on STAT3 intercept different signaling pathways. We introduce a new molecular perspective in the field of reprogramming with broad implications in basic, biotechnological, and translational research. Reprogramming is a powerful approach to change cell identity, with implications in both basic and applied biology. Most efforts involve the forced expression of key transcription

  9. Neural sensitivity to statistical regularities as a fundamental biological process that underlies auditory learning: the role of musical practice.

    Science.gov (United States)

    François, Clément; Schön, Daniele

    2014-02-01

    There is increasing evidence that humans and other nonhuman mammals are sensitive to the statistical structure of auditory input. Indeed, neural sensitivity to statistical regularities seems to be a fundamental biological property underlying auditory learning. In the case of speech, statistical regularities play a crucial role in the acquisition of several linguistic features, from phonotactic to more complex rules such as morphosyntactic rules. Interestingly, a similar sensitivity has been shown with non-speech streams: sequences of sounds changing in frequency or timbre can be segmented on the sole basis of conditional probabilities between adjacent sounds. We recently ran a set of cross-sectional and longitudinal experiments showing that merging music and speech information in song facilitates stream segmentation and, further, that musical practice enhances sensitivity to statistical regularities in speech at both neural and behavioral levels. Based on recent findings showing the involvement of a fronto-temporal network in speech segmentation, we defend the idea that enhanced auditory learning observed in musicians originates via at least three distinct pathways: enhanced low-level auditory processing, enhanced phono-articulatory mapping via the left Inferior Frontal Gyrus and Pre-Motor cortex and increased functional connectivity within the audio-motor network. Finally, we discuss how these data predict a beneficial use of music for optimizing speech acquisition in both normal and impaired populations. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. The molecular pathways underlying host resistance and tolerance to pathogens.

    Science.gov (United States)

    Glass, Elizabeth J

    2012-01-01

    Breeding livestock that are better able to withstand the onslaught of endemic- and exotic pathogens is high on the wish list of breeders and farmers world-wide. However, the defense systems in both pathogens and their hosts are complex and the degree of genetic variation in resistance and tolerance will depend on the trade-offs that they impose on host fitness as well as their life-histories. The genes and pathways underpinning resistance and tolerance traits may be distinct or intertwined as the outcome of any infection is a result of a balance between collateral damage of host tissues and control of the invading pathogen. Genes and molecular pathways associated with resistance are mainly expressed in the mucosal tract and the innate immune system and control the very early events following pathogen invasion. Resistance genes encode receptors involved in uptake of pathogens, as well as pattern recognition receptors (PRR) such as the toll-like receptor family as well as molecules involved in strong and rapid inflammatory responses which lead to rapid pathogen clearance, yet do not lead to immunopathology. In contrast tolerance genes and pathways play a role in reducing immunopathology or enhancing the host's ability to protect against pathogen associated toxins. Candidate tolerance genes may include cytosolic PRRs and unidentified sensors of pathogen growth, perturbation of host metabolism and intrinsic danger or damage associated molecules. In addition, genes controlling regulatory pathways, tissue repair and resolution are also tolerance candidates. The identities of distinct genetic loci for resistance and tolerance to infectious pathogens in livestock species remain to be determined. A better understanding of the mechanisms involved and phenotypes associated with resistance and tolerance should ultimately help to improve livestock health and welfare.

  11. The molecular pathways underlying host resistance and tolerance to pathogens

    Directory of Open Access Journals (Sweden)

    Elizabeth Janet Glass

    2012-12-01

    Full Text Available Breeding livestock that are better able to withstand the onslaught of endemic and exotic pathogens is high on the wish list of breeders and farmers world-wide. However the defence systems in both pathogens and their hosts are complex and the degree of genetic variation in resistance and tolerance will depend on the trade-offs that they impose on host fitness as well as their life-histories. The genes and pathways underpinning resistance and tolerance traits may be distinct or intertwined as the outcome of any infection is a result of a balance between collateral damage of host tissues and control of the invading pathogen. Genes and molecular pathways associated with resistance are mainly expressed in the mucosal tract and the innate immune system and control the very early events following pathogen invasion. Resistance genes encode receptors involved in uptake of pathogens, as well as pattern recognition receptors (PRR such as the toll-like receptor family as well as molecules involved in strong and rapid inflammatory responses which lead to rapid pathogen clearance yet do not lead to immunopathology. In contrast tolerance genes and pathways play a role in reducing immunopathology or enhancing the host’s ability to protect against pathogen associated toxins. Candidate tolerance genes may include cytosolic PRRs and unidentified sensors of pathogen growth, perturbation of host metabolism and intrinsic danger or damage associated molecules. In addition, genes controlling regulatory pathways, tissue repair and resolution are also tolerance candidates. The identities of distinct genetic loci for resistance and tolerance to infectious pathogens in livestock species remain to be determined. A better understanding of the mechanisms involved and phenotypes associated with resistance and tolerance should ultimately help to improve livestock health and welfare.

  12. Integrating resource defence theory with a neural nonapeptide pathway to explain territory-based mating systems.

    Science.gov (United States)

    Oldfield, Ronald G; Harris, Rayna M; Hofmann, Hans A

    2015-01-01

    The ultimate-level factors that drive the evolution of mating systems have been well studied, but an evolutionarily conserved neural mechanism involved in shaping behaviour and social organization across species has remained elusive. Here, we review studies that have investigated the role of neural arginine vasopressin (AVP), vasotocin (AVT), and their receptor V1a in mediating variation in territorial behaviour. First, we discuss how aggression and territoriality are a function of population density in an inverted-U relationship according to resource defence theory, and how territoriality influences some mating systems. Next, we find that neural AVP, AVT, and V1a expression, especially in one particular neural circuit involving the lateral septum of the forebrain, are associated with territorial behaviour in males of diverse species, most likely due to their role in enhancing social cognition. Then we review studies that examined multiple species and find that neural AVP, AVT, and V1a expression is associated with territory size in mammals and fishes. Because territoriality plays an important role in shaping mating systems in many species, we present the idea that neural AVP, AVT, and V1a expression that is selected to mediate territory size may also influence the evolution of different mating systems. Future research that interprets proximate-level neuro-molecular mechanisms in the context of ultimate-level ecological theory may provide deep insight into the brain-behaviour relationships that underlie the diversity of social organization and mating systems seen across the animal kingdom.

  13. Neural correlates underlying mental calculation in abacus experts: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Hanakawa, Takashi; Honda, Manabu; Okada, Tomohisa; Fukuyama, Hidenao; Shibasaki, Hiroshi

    2003-06-01

    Experts of abacus operation demonstrate extraordinary ability in mental calculation. There is psychological evidence that abacus experts utilize a mental image of an abacus to remember and manipulate large numbers in solving problems; however, the neural correlates underlying this expertise are unknown. Using functional magnetic resonance imaging, we compared the neural correlates associated with three mental-operation tasks (numeral, spatial, verbal) among six experts in abacus operations and eight nonexperts. In general, there was more involvement of neural correlates for visuospatial processing (e.g., right premotor and parietal areas) for abacus experts during the numeral mental-operation task. Activity of these areas and the fusiform cortex was correlated with the size of numerals used in the numeral mental-operation task. Particularly, the posterior superior parietal cortex revealed significantly enhanced activity for experts compared with controls during the numeral mental-operation task. Comparison with the other mental-operation tasks indicated that activity in the posterior superior parietal cortex was relatively specific to computation in 2-dimensional space. In conclusion, mental calculation of abacus experts is likely associated with enhanced involvement of the neural resources for visuospatial information processing in 2-dimensional space.

  14. Anger under control: neural correlates of frustration as a function of trait aggression.

    Science.gov (United States)

    Pawliczek, Christina M; Derntl, Birgit; Kellermann, Thilo; Gur, Ruben C; Schneider, Frank; Habel, Ute

    2013-01-01

    Antisocial behavior and aggression are prominent symptoms in several psychiatric disorders including antisocial personality disorder. An established precursor to aggression is a frustrating event, which can elicit anger or exasperation, thereby prompting aggressive responses. While some studies have investigated the neural correlates of frustration and aggression, examination of their relation to trait aggression in healthy populations are rare. Based on a screening of 550 males, we formed two extreme groups, one including individuals reporting high (n=21) and one reporting low (n=18) trait aggression. Using functional magnetic resonance imaging (fMRI) at 3T, all participants were put through a frustration task comprising unsolvable anagrams of German nouns. Despite similar behavioral performance, males with high trait aggression reported higher ratings of negative affect and anger after the frustration task. Moreover, they showed relatively decreased activation in the frontal brain regions and the dorsal anterior cingulate cortex (dACC) as well as relatively less amygdala activation in response to frustration. Our findings indicate distinct frontal and limbic processing mechanisms following frustration modulated by trait aggression. In response to a frustrating event, HA individuals show some of the personality characteristics and neural processing patterns observed in abnormally aggressive populations. Highlighting the impact of aggressive traits on the behavioral and neural responses to frustration in non-psychiatric extreme groups can facilitate further characterization of neural dysfunctions underlying psychiatric disorders that involve abnormal frustration processing and aggression.

  15. Anger under control: neural correlates of frustration as a function of trait aggression.

    Directory of Open Access Journals (Sweden)

    Christina M Pawliczek

    Full Text Available Antisocial behavior and aggression are prominent symptoms in several psychiatric disorders including antisocial personality disorder. An established precursor to aggression is a frustrating event, which can elicit anger or exasperation, thereby prompting aggressive responses. While some studies have investigated the neural correlates of frustration and aggression, examination of their relation to trait aggression in healthy populations are rare. Based on a screening of 550 males, we formed two extreme groups, one including individuals reporting high (n=21 and one reporting low (n=18 trait aggression. Using functional magnetic resonance imaging (fMRI at 3T, all participants were put through a frustration task comprising unsolvable anagrams of German nouns. Despite similar behavioral performance, males with high trait aggression reported higher ratings of negative affect and anger after the frustration task. Moreover, they showed relatively decreased activation in the frontal brain regions and the dorsal anterior cingulate cortex (dACC as well as relatively less amygdala activation in response to frustration. Our findings indicate distinct frontal and limbic processing mechanisms following frustration modulated by trait aggression. In response to a frustrating event, HA individuals show some of the personality characteristics and neural processing patterns observed in abnormally aggressive populations. Highlighting the impact of aggressive traits on the behavioral and neural responses to frustration in non-psychiatric extreme groups can facilitate further characterization of neural dysfunctions underlying psychiatric disorders that involve abnormal frustration processing and aggression.

  16. Anger under Control: Neural Correlates of Frustration as a Function of Trait Aggression

    Science.gov (United States)

    Pawliczek, Christina M.; Derntl, Birgit; Kellermann, Thilo; Gur, Ruben C.; Schneider, Frank; Habel, Ute

    2013-01-01

    Antisocial behavior and aggression are prominent symptoms in several psychiatric disorders including antisocial personality disorder. An established precursor to aggression is a frustrating event, which can elicit anger or exasperation, thereby prompting aggressive responses. While some studies have investigated the neural correlates of frustration and aggression, examination of their relation to trait aggression in healthy populations are rare. Based on a screening of 550 males, we formed two extreme groups, one including individuals reporting high (n=21) and one reporting low (n=18) trait aggression. Using functional magnetic resonance imaging (fMRI) at 3T, all participants were put through a frustration task comprising unsolvable anagrams of German nouns. Despite similar behavioral performance, males with high trait aggression reported higher ratings of negative affect and anger after the frustration task. Moreover, they showed relatively decreased activation in the frontal brain regions and the dorsal anterior cingulate cortex (dACC) as well as relatively less amygdala activation in response to frustration. Our findings indicate distinct frontal and limbic processing mechanisms following frustration modulated by trait aggression. In response to a frustrating event, HA individuals show some of the personality characteristics and neural processing patterns observed in abnormally aggressive populations. Highlighting the impact of aggressive traits on the behavioral and neural responses to frustration in non-psychiatric extreme groups can facilitate further characterization of neural dysfunctions underlying psychiatric disorders that involve abnormal frustration processing and aggression. PMID:24205247

  17. Overexpression of miR‑21 promotes neural stem cell proliferation and neural differentiation via the Wnt/β‑catenin signaling pathway in vitro.

    Science.gov (United States)

    Zhang, Wei-Min; Zhang, Zhi-Ren; Yang, Xi-Tao; Zhang, Yong-Gang; Gao, Yan-Sheng

    2018-01-01

    The primary aim of the present study was to examine the effects of microRNA‑21 (miR‑21) on the proliferation and differentiation of rat primary neural stem cells (NSCs) in vitro. miR‑21 was overexpressed in NSCs by transfection with a miR‑21 mimic. The effects of miR‑21 overexpression on NSC proliferation were revealed by Cell Counting kit 8 and 5‑ethynyl‑2'‑deoxyuridine incorporation assay, and miR‑21 overexpression was revealed to increase NSC proliferation. miR‑21 overexpression was confirmed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). mRNA and protein expression levels of key molecules (β‑catenin, cyclin D1, p21 and miR‑21) in the Wnt/β‑catenin signaling pathway were studied by RT‑qPCR and western blot analysis. RT‑qPCR and western blot analyses revealed that miR‑21 overexpression increased β‑catenin and cyclin D1 expression, and decreased p21 expression. These results suggested that miR‑21‑induced increase in proliferation was mediated by activation of the Wnt/β‑catenin signaling pathway, since overexpression of miR‑21 increased β‑catenin and cyclin D1 expression and reduced p21 expression. Furthermore, inhibition of the Wnt/β‑catenin pathway with FH535 attenuated the influence of miR‑21 overexpression on NSC proliferation, indicating that the factors activated by miR‑21 overexpression were inhibited by FH535 treatment. Furthermore, overexpression of miR‑21 enhanced the differentiation of NSCs into neurons and inhibited their differentiation into astrocytes. The present study indicated that in primary rat NSCs, overexpression of miR‑21 may promote proliferation and differentiation into neurons via the Wnt/β‑catenin signaling pathway in vitro.

  18. Sea level rise under the Shared Socioeconomic Pathways (SSPs)

    Science.gov (United States)

    Schleussner, C. F.; Nauels, A.; Rogelj, J.; Mengel, M.; Meinshausen, M.

    2017-12-01

    In order to assess future sea level rise and its impacts, we need to study climate change pathways combined with different scenarios of socioeconomic development. Here, we present Sea Level Rise (SLR) projections for the Shared Socioeconomic Pathway (SSP) storylines and different year-2100 radiative Forcing Targets (FTs). Future SLR is estimated with a comprehensive SLR emulator that accounts for latest research on additional Antarctic rapid discharge dynamics from hydrofracturing and ice cliff instability. Across all baseline scenario realizations (no dedicated climate mitigation), we find 2100 median SLR relative to 1986-2005 of 102 cm (likely range: 77 to 135 cm) for SSP1, 118 cm (90 to 151 cm) for SSP2, 118 cm (91 to 149 cm) for SSP3, 107 cm (81 to 137 cm) for SSP4, and 144 cm (112 to 184 cm) for SSP5. The 2100 sea level responses for combined SSP-FT scenarios is dominated by the mitigation targets and yield median estimates of 68 cm (56 to 87 cm) for FT 2.6 Wm-2, 76 cm (61 to 107 cm) for FT 3.4 Wm-2, 90 cm (68 to 120 cm) for FT 4.5 Wm-2, and 105 cm (79 to 136 cm) for FT 6.0 Wm-2. Average 2081-2100 annual rates of SLR are 6 mm/yr and 19 mm/yr for the FT 2.6 Wm-2 and the baseline scenarios, respectively. Our model setup allows linking scenario-specific emission and socioeconomic indicators to projected SLR. For limiting median 2100 SSP SLR projections to below 80 cm, we find that 2050 cumulative CO2 emissions since pre-industrial should not exceed around 860 GtC, with the global coal phase-out nearly completed. For SSP mitigation scenarios, the median 2050 carbon price of 90 US$2005 tCO2-1 would correspond to a median 2100 SLR of around 80 cm. Our results confirm that rapid and early emission reductions are essential for limiting 2100 SLR.

  19. Suppression of anomalous synchronization and nonstationary behavior of neural network under small-world topology

    Science.gov (United States)

    Boaretto, B. R. R.; Budzinski, R. C.; Prado, T. L.; Kurths, J.; Lopes, S. R.

    2018-05-01

    It is known that neural networks under small-world topology can present anomalous synchronization and nonstationary behavior for weak coupling regimes. Here, we propose methods to suppress the anomalous synchronization and also to diminish the nonstationary behavior occurring in weakly coupled neural network under small-world topology. We consider a network of 2000 thermally sensitive identical neurons, based on the model of Hodgkin-Huxley in a small-world topology, with the probability of adding non local connection equal to p = 0 . 001. Based on experimental protocols to suppress anomalous synchronization, as well as nonstationary behavior of the neural network dynamics, we make use of (i) external stimulus (pulsed current); (ii) biologic parameters changing (neuron membrane conductance changes); and (iii) body temperature changes. Quantification analysis to evaluate phase synchronization makes use of the Kuramoto's order parameter, while recurrence quantification analysis, particularly the determinism, computed over the easily accessible mean field of network, the local field potential (LFP), is used to evaluate nonstationary states. We show that the methods proposed can control the anomalous synchronization and nonstationarity occurring for weak coupling parameter without any effect on the individual neuron dynamics, neither in the expected asymptotic synchronized states occurring for large values of the coupling parameter.

  20. Prisoners' rights under the Nigerian law: legal pathways to ...

    African Journals Online (AJOL)

    Some rights are denied the prisoners by the prison administrators and, by extension, the State by lack of will to promote enabling environment and treatment to the prisoners. It is against this backdrop that this article appraises prisoners' rights that are to be respected, protected and fulfilled under the law, at national, regional ...

  1. Behavioral and Physiological Neural Network Analyses: A Common Pathway toward Pattern Recognition and Prediction

    Science.gov (United States)

    Ninness, Chris; Lauter, Judy L.; Coffee, Michael; Clary, Logan; Kelly, Elizabeth; Rumph, Marilyn; Rumph, Robin; Kyle, Betty; Ninness, Sharon K.

    2012-01-01

    Using 3 diversified datasets, we explored the pattern-recognition ability of the Self-Organizing Map (SOM) artificial neural network as applied to diversified nonlinear data distributions in the areas of behavioral and physiological research. Experiment 1 employed a dataset obtained from the UCI Machine Learning Repository. Data for this study…

  2. Combined use of the canine adenovirus-2 and DREADD-technology to activate specific neural pathways in vivo.

    Directory of Open Access Journals (Sweden)

    Arjen J Boender

    Full Text Available We here describe a technique to transiently activate specific neural pathways in vivo. It comprises the combined use of a CRE-recombinase expressing canine adenovirus-2 (CAV-2 and an adeno-associated virus (AAV-hSyn-DIO-hM3D(Gq-mCherry that contains the floxed inverted sequence of the designer receptor exclusively activated by designer drugs (DREADD hM3D(Gq-mCherry. CAV-2 retrogradely infects projection neurons, which allowed us to specifically express hM3D(Gq-mCherry in neurons that project from the ventral tegmental area (VTA to the nucleus accumbens (Acb, the majority of which were dopaminergic. Activation of hM3D(Gq-mCherry by intraperitoneal (i.p. injections of clozapine-N-oxide (CNO leads to increases in neuronal activity, which enabled us to specifically activate VTA to Acb projection neurons. The VTA to Acb pathway is part of the mesolimbic dopamine system and has been implicated in behavioral activation and the exertion of effort. Injections of all doses of CNO led to increases in progressive ratio (PR performance. The effect of the lowest dose of CNO was suppressed by administration of a DRD1-antagonist, suggesting that CNO-induced increases in PR-performance are at least in part mediated by DRD1-signaling. We hereby validate the combined use of CAV-2 and DREADD-technology to activate specific neural pathways and determine consequent changes in behaviorally relevant paradigms.

  3. Neural mechanisms underlying transcranial direct current stimulation in aphasia: A feasibility study.

    Directory of Open Access Journals (Sweden)

    Lena eUlm

    2015-10-01

    Full Text Available Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI. We employed a single subject, cross-over, sham-tDCS controlled design and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus (IFG and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioural stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS-effects on brain functions in aphasia.

  4. The impact of abacus training on working memory and underlying neural correlates in young adults.

    Science.gov (United States)

    Dong, Shanshan; Wang, Chunjie; Xie, Ye; Hu, Yuzheng; Weng, Jian; Chen, Feiyan

    2016-09-22

    Abacus-based mental calculation (AMC) activates the frontoparietal areas largely overlapping with the working memory (WM) network. Given the critical role of WM in cognition, how to improve WM capability has attracted intensive attention in past years. However, it is still unclear whether WM could be enhanced by AMC training. The current research thus explored the impact of AMC training on verbal and visuospatial WM, as well as the underlying neural basis. Participants were randomly assigned to an abacus group and a control group. Their verbal WM was evaluated by digit/letter memory span (DMS/LMS) tests, and visuospatial WM was assessed by a visuospatial n-back task. Neural activity during the n-back task was examined using functional MRI. Our results showed reliable improvements of both verbal and visuospatial WM in the abacus group after 20-day AMC training but not in the control. In addition, the n-back task-induced activations in the right frontoparietal circuitry and left occipitotemporal junction (OTJ) declined as a result of training. Notably, the decreases in activity were positively correlated with performance gains across trained participants. These results suggest AMC training not only improves calculating skills but also have the potential to promote individuals' WM capabilities, which is associated with the functional plasticity of the common neural substrates. Copyright © 2016 IBRO. All rights reserved.

  5. Spatially Nonlinear Interdependence of Alpha-Oscillatory Neural Networks under Chan Meditation

    Directory of Open Access Journals (Sweden)

    Pei-Chen Lo

    2013-01-01

    Full Text Available This paper reports the results of our investigation of the effects of Chan meditation on brain electrophysiological behaviors from the viewpoint of spatially nonlinear interdependence among regional neural networks. Particular emphasis is laid on the alpha-dominated EEG (electroencephalograph. Continuous-time wavelet transform was adopted to detect the epochs containing substantial alpha activities. Nonlinear interdependence quantified by similarity index S(X∣Y, the influence of source signal Y on sink signal X, was applied to the nonlinear dynamical model in phase space reconstructed from multichannel EEG. Experimental group involved ten experienced Chan-Meditation practitioners, while control group included ten healthy subjects within the same age range, yet, without any meditation experience. Nonlinear interdependence among various cortical regions was explored for five local neural-network regions, frontal, posterior, right-temporal, left-temporal, and central regions. In the experimental group, the inter-regional interaction was evaluated for the brain dynamics under three different stages, at rest (stage R, pre-meditation background recording, in Chan meditation (stage M, and the unique Chakra-focusing practice (stage C. Experimental group exhibits stronger interactions among various local neural networks at stages M and C compared with those at stage R. The intergroup comparison demonstrates that Chan-meditation brain possesses better cortical inter-regional interactions than the resting brain of control group.

  6. Neural network remodeling underlying motor map reorganization induced by rehabilitative training after ischemic stroke.

    Science.gov (United States)

    Okabe, Naohiko; Shiromoto, Takashi; Himi, Naoyuki; Lu, Feng; Maruyama-Nakamura, Emi; Narita, Kazuhiko; Iwachidou, Nobuhisa; Yagita, Yoshiki; Miyamoto, Osamu

    2016-12-17

    Motor map reorganization is believed to be one mechanism underlying rehabilitation-induced functional recovery. Although the ipsilesional secondary motor area has been known to reorganize motor maps and contribute to rehabilitation-induced functional recovery, it is unknown how the secondary motor area is reorganized by rehabilitative training. In the present study, using skilled forelimb reaching tasks, we investigated neural network remodeling in the rat rostral forelimb area (RFA) of the secondary motor area during 4weeks of rehabilitative training. Following photothrombotic stroke in the caudal forelimb area (CFA), rehabilitative training led to task-specific recovery and motor map reorganization in the RFA. A second injury to the RFA resulted in reappearance of motor deficits. Further, when both the CFA and RFA were destroyed simultaneously, rehabilitative training no longer improved task-specific recovery. In neural tracer studies, although rehabilitative training did not alter neural projection to the RFA from other brain areas, rehabilitative training increased neural projection from the RFA to the lower spinal cord, which innervates the muscles in the forelimb. Double retrograde tracer studies revealed that rehabilitative training increased the neurons projecting from the RFA to both the upper cervical cord, which innervates the muscles in the neck, trunk, and part of the proximal forelimb, and the lower cervical cord. These results suggest that neurons projecting to the upper cervical cord provide new connections to the denervated forelimb area of the spinal cord, and these new connections may contribute to rehabilitation-induced task-specific recovery and motor map reorganization in the secondary motor area. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Neural substrates underlying motor skill learning in chronic hemiparetic stroke patients

    Directory of Open Access Journals (Sweden)

    Stephanie eLefebvre

    2015-06-01

    Full Text Available Motor skill learning is critical in post-stroke motor recovery, but little is known about its underlying neural substrates. Recently, using a new visuomotor skill learning paradigm involving a speed/accuracy trade-off in healthy individuals we identified three subpopulations based on their behavioral trajectories: fitters (in whom improvement in speed or accuracy coincided with deterioration in the other parameter, shifters (in whom speed and/or accuracy improved without degradation of the other parameter, and non-learners. We aimed to identify the neural substrates underlying the first stages of motor skill learning in chronic hemiparetic stroke patients and to determine whether specific neural substrates were recruited in shifters versus fitters. During functional magnetic resonance imaging (fMRI, 23 patients learned the visuomotor skill with their paretic upper limb. In the whole-group analysis, correlation between activation and motor skill learning was restricted to the dorsal prefrontal cortex of the damaged hemisphere (DLPFCdamh: r=-0.82 and the dorsal premotor cortex (PMddamh: r=0.70; the correlations was much lesser (-0.160.25 in the other regions of interest. In a subgroup analysis, significant activation was restricted to bilateral posterior parietal cortices of the fitters and did not correlate with motor skill learning. Conversely, in shifters significant activation occurred in the primary sensorimotor cortexdamh and supplementary motor areadamh and in bilateral PMd where activation changes correlated significantly with motor skill learning (r=0.91. Finally, resting-state activity acquired before learning showed a higher functional connectivity in the salience network of shifters compared with fitters (qFDR<0.05. These data suggest a neuroplastic compensatory reorganization of brain activity underlying the first stages of motor skill learning with the paretic upper limb in chronic hemiparetic stroke patients, with a key role of

  8. Opposite feedbacks in the Hippo pathway for growth control and neural fate.

    Science.gov (United States)

    Jukam, David; Xie, Baotong; Rister, Jens; Terrell, David; Charlton-Perkins, Mark; Pistillo, Daniela; Gebelein, Brian; Desplan, Claude; Cook, Tiffany

    2013-10-11

    Signaling pathways are reused for multiple purposes in plant and animal development. The Hippo pathway in mammals and Drosophila coordinates proliferation and apoptosis via the coactivator and oncoprotein YAP/Yorkie (Yki), which is homeostatically regulated through negative feedback. In the Drosophila eye, cross-repression between the Hippo pathway kinase LATS/Warts (Wts) and growth regulator Melted generates mutually exclusive photoreceptor subtypes. Here, we show that this all-or-nothing neuronal differentiation results from Hippo pathway positive feedback: Yki both represses its negative regulator, warts, and promotes its positive regulator, melted. This postmitotic Hippo network behavior relies on a tissue-restricted transcription factor network-including a conserved Otx/Orthodenticle-Nrl/Traffic Jam feedforward module-that allows Warts-Yki-Melted to operate as a bistable switch. Altering feedback architecture provides an efficient mechanism to co-opt conserved signaling networks for diverse purposes in development and evolution.

  9. At-risk for pathological gambling: imaging neural reward processing under chronic dopamine agonists.

    Science.gov (United States)

    Abler, Birgit; Hahlbrock, Roman; Unrath, Alexander; Grön, Georg; Kassubek, Jan

    2009-09-01

    Treatment with dopamine receptor agonists has been associated with impulse control disorders and pathological gambling (PG) secondary to medication in previously unaffected patients with Parkinson's disease or restless legs syndrome (RLS). In a within-subjects design, we investigated the underlying neurobiology in RLS patients using functional magnetic resonance imaging. We scanned 12 female RLS patients without a history of PG. All patients were scanned twice: once whilst taking their regular medication with low dose dopamine receptor agonists and once after a washout phase interval. They performed an established gambling game task involving expectation and receipt or omission of monetary rewards at different levels of probabilities. Upon expectation of rewards, reliable ventral striatal activation was detected only when patients were on, but not when patients were off medication. Upon receipt or omission of rewards, the observed ventral striatal signal under medication differed markedly from its predicted pattern which by contrast was apparent when patients were off medication. Orbitofrontal activation was not affected by medication. Chronic dopamine receptor agonist medication changed the neural signalling of reward expectation predisposing the dopaminergic reward system to mediate an increased appetitive drive. Even without manifest PG, chronic medication with dopamine receptor agonists led to markedly changed neural processing of negative consequences probably mediating dysfunctional learning of contingencies. Intact orbitofrontal functioning, potentially moderating impulse control, may explain why none of the patients actually developed PG. Our results support the notion of a general medication effect in patients under dopamine receptor agonists in terms of a sensitization towards impulse control disorders.

  10. Experimental study and artificial neural network modeling of tartrazine removal by photocatalytic process under solar light.

    Science.gov (United States)

    Sebti, Aicha; Souahi, Fatiha; Mohellebi, Faroudja; Igoud, Sadek

    2017-07-01

    This research focuses on the application of an artificial neural network (ANN) to predict the removal efficiency of tartrazine from simulated wastewater using a photocatalytic process under solar illumination. A program is developed in Matlab software to optimize the neural network architecture and select the suitable combination of training algorithm, activation function and hidden neurons number. The experimental results of a batch reactor operated under different conditions of pH, TiO 2 concentration, initial organic pollutant concentration and solar radiation intensity are used to train, validate and test the networks. While negligible mineralization is demonstrated, the experimental results show that under sunlight irradiation, 85% of tartrazine is removed after 300 min using only 0.3 g/L of TiO 2 powder. Therefore, irradiation time is prolonged and almost 66% of total organic carbon is reduced after 15 hours. ANN 5-8-1 with Bayesian regulation back-propagation algorithm and hyperbolic tangent sigmoid transfer function is found to be able to predict the response with high accuracy. In addition, the connection weights approach is used to assess the importance contribution of each input variable on the ANN model response. Among the five experimental parameters, the irradiation time has the greatest effect on the removal efficiency of tartrazine.

  11. Bridging the Gap: Towards a Cell-Type Specific Understanding of Neural Circuits Underlying Fear Behaviors

    Science.gov (United States)

    McCullough, KM; Morrison, FG; Ressler, KJ

    2016-01-01

    Fear and anxiety-related disorders are remarkably common and debilitating, and are often characterized by dysregulated fear responses. Rodent models of fear learning and memory have taken great strides towards elucidating the specific neuronal circuitries underlying the learning of fear responses. The present review addresses recent research utilizing optogenetic approaches to parse circuitries underlying fear behaviors. It also highlights the powerful advances made when optogenetic techniques are utilized in a genetically defined, cell-type specific, manner. The application of next-generation genetic and sequencing approaches in a cell-type specific context will be essential for a mechanistic understanding of the neural circuitry underlying fear behavior and for the rational design of targeted, circuit specific, pharmacologic interventions for the treatment and prevention of fear-related disorders. PMID:27470092

  12. Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

    Directory of Open Access Journals (Sweden)

    Yosefu Arime

    Full Text Available Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days of either saline or PCP (10 mg/kg: (1 a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2 brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

  13. The sacral networks and neural pathways used to elicit lumbar motor rhythm in the rodent spinal cord

    Directory of Open Access Journals (Sweden)

    Meir eCherniak

    2014-12-01

    Full Text Available Identification of neural networks and pathways involved in activation and modulation of spinal central pattern generators (CPGs in the absence of the descending control from the brain is important for further understanding of neural control of movement and for developing innovative therapeutic approaches to improve the mobility of spinal cord injury patients. Activation of the hindlimb innervating segments by sacrocaudal afferent input and by specific application of neurochemicals to the sacral networks is feasible in the isolated spinal cord preparation of the newborn rat. Here we review our recent studies of sacral relay neurons with lumbar projections and evaluate their role in linking the sacral and thoracolumbar networks during different motor behaviors. Our major findings show that: 1 Heterogeneous groups of dorsal, intermediate and ventral sacral-neurons with ventral and lateral ascending funicular projections mediate the activation of the locomotor central pattern generators through sacral sensory input, and 2 Rhythmic excitation of lumbar flexor motoneurons, produced by bath application of alpha-1 adrenoceptor agonists to the sacral segments is mediated exclusively by ventral clusters of sacral-neurons with lumbar projections through the ventral funiculus.

  14. Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray

    Directory of Open Access Journals (Sweden)

    You Ning

    2013-01-01

    Full Text Available Adult neural stem cells (NSCs persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia L., on NSC behaviors and the underlying mechanisms. The self-renewal and proliferation of NSC were examined. We detected neuron- and/or astrocyte-specific markers using immunofluorescence and Western blotting, which could evaluate NSC differentiation. Psoralen treatment significantly inhibited neurosphere formation in a dose-dependent manner. Psoralen treatment increased the expression of the astrocyte-specific marker but decreased neuron-specific marker expression. These results suggested that Psoralen was a differentiation inducer in astrocyte. Differential gene expression following Psoralen treatment was screened using DNA microarray and confirmed by quantitative real-time PCR. Our microarray study demonstrated that Psoralen could effectively regulate the specific gene expression profile of NSC. The genes involved in the classification of cellular differentiation, proliferation, and metabolism, the transcription factors belonging to Ets family, and the hedgehog pathway may be closely related to the regulation.

  15. Associations between proprioceptive neural pathway structural connectivity and balance in people with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Brett W Fling

    2014-10-01

    Full Text Available Mobility and balance impairments are a hallmark of multiple sclerosis (MS, affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to 1 map the cortical proprioceptive pathway in-vivo using diffusion weighted imaging and 2 assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls. Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere’s proprioceptive pathway was significantly correlated with overall balance performance in healthy controls, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon 1 cerebellar-regulated proprioceptive control, 2 the vestibular system, and/or 3 the visual system.

  16. Abnormal regional spontaneous neural activity in visual pathway in retinal detachment patients: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Huang X

    2017-11-01

    Full Text Available Xin Huang,1,2,* Dan Li,3,* Hai-Jun Li,3 Yu-Lin Zhong,1 Shelby Freeberg,4 Jing Bao,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Ophthalmology, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Objective: The aim of the study was to investigate changes of brain neural homogeneity in retinal detachment (RD patients using the regional homogeneity (ReHo method to understand their relationships with clinical features. Materials and methods: A total of 30 patients with RD (16 men and 14 women, and 30 healthy controls (HCs (16 men and 14 women closely matched in age and sex were recruited. Resting-state functional magnetic resonance imaging scans were performed for all subjects. The ReHo method was used to investigate the brain regional neural homogeneity. Patients with RD were distinguished from HCs by receiver operating characteristic curve. The relationships between the mean ReHo signal values in many brain regions and clinical features in RD patients were calculated by Pearson correlation analysis. Results: Compared with HCs, RD patients had significantly decreased ReHo values in the right occipital lobe, right superior temporal gyrus, bilateral cuneus and left middle frontal gyrus. Moreover, we found that the mean ReHo signal of the bilateral cuneus showed positive relationships with the duration of the RD (r=0.392, P=0.032. Conclusion: The RD patients showed brain neural homogeneity dysfunction in the visual pathway, which may underline the pathological mechanism

  17. Morphological covariance in anatomical MRI scans can identify discrete neural pathways in the brain and their disturbances in persons with neuropsychiatric disorders.

    Science.gov (United States)

    Bansal, Ravi; Hao, Xuejun; Peterson, Bradley S

    2015-05-01

    We hypothesize that coordinated functional activity within discrete neural circuits induces morphological organization and plasticity within those circuits. Identifying regions of morphological covariation that are independent of morphological covariation in other regions therefore may therefore allow us to identify discrete neural systems within the brain. Comparing the magnitude of these variations in individuals who have psychiatric disorders with the magnitude of variations in healthy controls may allow us to identify aberrant neural pathways in psychiatric illnesses. We measured surface morphological features by applying nonlinear, high-dimensional warping algorithms to manually defined brain regions. We transferred those measures onto the surface of a unit sphere via conformal mapping and then used spherical wavelets and their scaling coefficients to simplify the data structure representing these surface morphological features of each brain region. We used principal component analysis (PCA) to calculate covariation in these morphological measures, as represented by their scaling coefficients, across several brain regions. We then assessed whether brain subregions that covaried in morphology, as identified by large eigenvalues in the PCA, identified specific neural pathways of the brain. To do so, we spatially registered the subnuclei for each eigenvector into the coordinate space of a Diffusion Tensor Imaging dataset; we used these subnuclei as seed regions to track and compare fiber pathways with known fiber pathways identified in neuroanatomical atlases. We applied these procedures to anatomical MRI data in a cohort of 82 healthy participants (42 children, 18 males, age 10.5 ± 2.43 years; 40 adults, 22 males, age 32.42 ± 10.7 years) and 107 participants with Tourette's Syndrome (TS) (71 children, 59 males, age 11.19 ± 2.2 years; 36 adults, 21 males, age 37.34 ± 10.9 years). We evaluated the construct validity of the identified covariation in morphology

  18. Neural pathways for language in autism: the potential for music-based treatments

    OpenAIRE

    Wan, Catherine Y; Schlaug, Gottfried

    2010-01-01

    Language deficits represent the core diagnostic characteristics of autism, and some of these individuals never develop functional speech. The language deficits in autism may be due to structural and functional abnormalities in certain language regions (e.g., frontal and temporal), or due to altered connectivity between these brain regions. In particular, a number of anatomical pathways that connect auditory and motor brain regions (e.g., the arcuate fasciculus, the uncinate fasciculus and the...

  19. Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1.

    Science.gov (United States)

    Singh, Varsha; Aballay, Alejandro

    2012-09-28

    In response to pathogen infection, the host innate immune system activates microbial killing pathways and cellular stress pathways that need to be balanced because insufficient or excessive immune responses have deleterious consequences. Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the nervous system of Caenorhabditis elegans control immune homeostasis. To investigate further how GPCR signaling controls immune homeostasis at the organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor protein in C. elegans. The results indicate that ARR-1 is required for GPCR signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded protein response and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity. ARR-1 activity also controlled immunity through ADF chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore, we found that although ARR-1 played a key role in the control of immunity by AFD thermosensory neurons, it did not control longevity through these cells. However, ARR-1 partially controlled longevity through ADF neurons.

  20. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation.

    Science.gov (United States)

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

    2015-12-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcoholalcohol specifically increased proactive (unprovoked) but not reactive (provoked) aggression (alcohol × provocation interaction). However, investigation of inter-individual differences revealed (1) that pronounced alcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation.

  1. A neural network underlying intentional emotional facial expression in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Kelly A. Gola

    2017-01-01

    Full Text Available Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.

  2. Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.

    Science.gov (United States)

    Skeide, Michael A; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole; Brauer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D

    2015-09-01

    Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A neural network underlying intentional emotional facial expression in neurodegenerative disease.

    Science.gov (United States)

    Gola, Kelly A; Shany-Ur, Tal; Pressman, Peter; Sulman, Isa; Galeana, Eduardo; Paulsen, Hillary; Nguyen, Lauren; Wu, Teresa; Adhimoolam, Babu; Poorzand, Pardis; Miller, Bruce L; Rankin, Katherine P

    2017-01-01

    Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls) were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM) across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.

  4. Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways.

    Science.gov (United States)

    Dyall, S C; Mandhair, H K; Fincham, R E A; Kerr, D M; Roche, M; Molina-Holgado, F

    2016-08-01

    Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects. EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1β deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1β signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1β deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Modelling plant invasion pathways in protected areas under climate change: implication for invasion management

    Directory of Open Access Journals (Sweden)

    C.-J. Wang

    2017-12-01

    Full Text Available Global climate change may enable invasive plant species (IPS to invade protected areas (PAs, but plant invasion on a global scale has not yet been explicitly addressed. Here, we mapped the potential invasion pathways for IPS in PAs across the globe and explored potential factors determining the pathways of plant invasion under climate change. We used species distribution modelling to estimate the suitable habitats of 386 IPS and applied a corridor analysis to compute the potential pathways of IPS in PAs under climate change. Subsequently, we analysed the potential factors affecting the pathways in PAs. According to our results, the main potential pathways of IPS in PAs are in Europe, eastern Australia, New Zealand, southern Africa, and eastern regions of South America and are strongly influenced by changes in temperature and precipitation. Protected areas can play an important role in preventing and controlling the spread of IPS under climate change. This is due to the fact that measures are taken to monitor climate change in detail, to provide effective management near or inside PAs, and to control the introduction of IPS with a high capacity for natural dispersal. A review of conservation policies in PAs is urgently needed.

  6. The manipulative skill: Cognitive devices and their neural correlates underlying Machiavellian's decision making.

    Science.gov (United States)

    Bereczkei, Tamas

    2015-10-01

    Until now, Machiavellianism has mainly been studied in personality and social psychological framework, and little attention has been paid to the underlying cognitive and neural equipment. In light of recent findings, Machiavellian social skills are not limited to emotion regulation and "cold-mindedness" as many authors have recently stated, but linked to specific cognitive abilities. Although Machiavellians appear to have a relatively poor mindreading ability and emotional intelligence, they can efficiently exploit others which is likely to come from their flexible problem solving processes in changing environmental circumstances. The author proposed that Machiavellians have specialized cognitive domains of decision making, such as monitoring others' behavior, task orientation, reward seeking, inhibition of cooperative feelings, and choosing victims. He related the relevant aspects of cognitive functions to their neurological substrates, and argued why they make Machiavellians so successful in interpersonal relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Neural mechanisms underlying paradoxical performance for monetary incentives are driven by loss aversion.

    Science.gov (United States)

    Chib, Vikram S; De Martino, Benedetto; Shimojo, Shinsuke; O'Doherty, John P

    2012-05-10

    Employers often make payment contingent on performance in order to motivate workers. We used fMRI with a novel incentivized skill task to examine the neural processes underlying behavioral responses to performance-based pay. We found that individuals' performance increased with increasing incentives; however, very high incentive levels led to the paradoxical consequence of worse performance. Between initial incentive presentation and task execution, striatal activity rapidly switched between activation and deactivation in response to increasing incentives. Critically, decrements in performance and striatal deactivations were directly predicted by an independent measure of behavioral loss aversion. These results suggest that incentives associated with successful task performance are initially encoded as a potential gain; however, when actually performing a task, individuals encode the potential loss that would arise from failure. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. PREDICTION OF SITE RESPONSE SPECTRUM UNDER EARTHQUAKE VIBRATION USING AN OPTIMIZED DEVELOPED ARTIFICIAL NEURAL NETWORK MODEL

    Directory of Open Access Journals (Sweden)

    Reza Esmaeilabadi

    2016-06-01

    Full Text Available Site response spectrum is one of the key factors to determine the maximum acceleration and displacement, as well as structure behavior analysis during earthquake vibrations. The main objective of this paper is to develop an optimized model based on artificial neural network (ANN using five different training algorithms to predict nonlinear site response spectrum subjected to Silakhor earthquake vibrations is. The model output was tested for a specified area in west of Iran. The performance and quality of optimized model under all training algorithms have been examined by various statistical, analytical and graph analyses criteria as well as a comparison with numerical methods. The observed adaptabilities in results indicate a feasible and satisfactory engineering alternative method for predicting the analysis of nonlinear site response.

  9. Neural connectivity patterns underlying symbolic number processing indicate mathematical achievement in children.

    Science.gov (United States)

    Park, Joonkoo; Li, Rosa; Brannon, Elizabeth M

    2014-03-01

    In early childhood, humans learn culturally specific symbols for number that allow them entry into the world of complex numerical thinking. Yet little is known about how the brain supports the development of the uniquely human symbolic number system. Here, we use functional magnetic resonance imaging along with an effective connectivity analysis to investigate the neural substrates for symbolic number processing in young children. We hypothesized that, as children solidify the mapping between symbols and underlying magnitudes, important developmental changes occur in the neural communication between the right parietal region, important for the representation of non-symbolic numerical magnitudes, and other brain regions known to be critical for processing numerical symbols. To test this hypothesis, we scanned children between 4 and 6 years of age while they performed a magnitude comparison task with Arabic numerals (numerical, symbolic), dot arrays (numerical, non-symbolic), and lines (non-numerical). We then identified the right parietal seed region that showed greater blood-oxygen-level-dependent signal in the numerical versus the non-numerical conditions. A psychophysiological interaction method was used to find patterns of effective connectivity arising from this parietal seed region specific to symbolic compared to non-symbolic number processing. Two brain regions, the left supramarginal gyrus and the right precentral gyrus, showed significant effective connectivity from the right parietal cortex. Moreover, the degree of this effective connectivity to the left supramarginal gyrus was correlated with age, and the degree of the connectivity to the right precentral gyrus predicted performance on a standardized symbolic math test. These findings suggest that effective connectivity underlying symbolic number processing may be critical as children master the associations between numerical symbols and magnitudes, and that these connectivity patterns may serve as an

  10. Encoding neural and synaptic functionalities in electron spin: A pathway to efficient neuromorphic computing

    Science.gov (United States)

    Sengupta, Abhronil; Roy, Kaushik

    2017-12-01

    Present day computers expend orders of magnitude more computational resources to perform various cognitive and perception related tasks that humans routinely perform every day. This has recently resulted in a seismic shift in the field of computation where research efforts are being directed to develop a neurocomputer that attempts to mimic the human brain by nanoelectronic components and thereby harness its efficiency in recognition problems. Bridging the gap between neuroscience and nanoelectronics, this paper attempts to provide a review of the recent developments in the field of spintronic device based neuromorphic computing. Description of various spin-transfer torque mechanisms that can be potentially utilized for realizing device structures mimicking neural and synaptic functionalities is provided. A cross-layer perspective extending from the device to the circuit and system level is presented to envision the design of an All-Spin neuromorphic processor enabled with on-chip learning functionalities. Device-circuit-algorithm co-simulation framework calibrated to experimental results suggest that such All-Spin neuromorphic systems can potentially achieve almost two orders of magnitude energy improvement in comparison to state-of-the-art CMOS implementations.

  11. Sensory neural pathways revisited to unravel the temporal dynamics of the Simon effect: A model-based cognitive neuroscience approach.

    Science.gov (United States)

    Salzer, Yael; de Hollander, Gilles; Forstmann, Birte U

    2017-06-01

    The Simon task is one of the most prominent interference tasks and has been extensively studied in experimental psychology and cognitive neuroscience. Despite years of research, the underlying mechanism driving the phenomenon and its temporal dynamics are still disputed. Within the framework of the review, we adopt a model-based cognitive neuroscience approach. We first go over key findings in the literature of the Simon task, discuss competing qualitative cognitive theories and the difficulty of testing them empirically. We then introduce sequential sampling models, a particular class of mathematical cognitive process models. Finally, we argue that the brain architecture accountable for the processing of spatial ('where') and non-spatial ('what') information, could constrain these models. We conclude that there is a clear need to bridge neural and behavioral measures, and that mathematical cognitive models may facilitate the construction of this bridge and work towards revealing the underlying mechanisms of the Simon effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Temporal entrainment of cognitive functions: musical mnemonics induce brain plasticity and oscillatory synchrony in neural networks underlying memory.

    Science.gov (United States)

    Thaut, Michael H; Peterson, David A; McIntosh, Gerald C

    2005-12-01

    In a series of experiments, we have begun to investigate the effect of music as a mnemonic device on learning and memory and the underlying plasticity of oscillatory neural networks. We used verbal learning and memory tests (standardized word lists, AVLT) in conjunction with electroencephalographic analysis to determine differences between verbal learning in either a spoken or musical (verbal materials as song lyrics) modality. In healthy adults, learning in both the spoken and music condition was associated with significant increases in oscillatory synchrony across all frequency bands. A significant difference between the spoken and music condition emerged in the cortical topography of the learning-related synchronization. When using EEG measures as predictors during learning for subsequent successful memory recall, significantly increased coherence (phase-locked synchronization) within and between oscillatory brain networks emerged for music in alpha and gamma bands. In a similar study with multiple sclerosis patients, superior learning and memory was shown in the music condition when controlled for word order recall, and subjects were instructed to sing back the word lists. Also, the music condition was associated with a significant power increase in the low-alpha band in bilateral frontal networks, indicating increased neuronal synchronization. Musical learning may access compensatory pathways for memory functions during compromised PFC functions associated with learning and recall. Music learning may also confer a neurophysiological advantage through the stronger synchronization of the neuronal cell assemblies underlying verbal learning and memory. Collectively our data provide evidence that melodic-rhythmic templates as temporal structures in music may drive internal rhythm formation in recurrent cortical networks involved in learning and memory.

  13. Study Under AC Stimulation on Excitement Properties of Weighted Small-World Biological Neural Networks with Side-Restrain Mechanism

    International Nuclear Information System (INIS)

    Yuan Wujie; Luo Xiaoshu; Jiang Pinqun

    2007-01-01

    In this paper, we propose a new model of weighted small-world biological neural networks based on biophysical Hodgkin-Huxley neurons with side-restrain mechanism. Then we study excitement properties of the model under alternating current (AC) stimulation. The study shows that the excitement properties in the networks are preferably consistent with the behavior properties of a brain nervous system under different AC stimuli, such as refractory period and the brain neural excitement response induced by different intensities of noise and coupling. The results of the study have reference worthiness for the brain nerve electrophysiology and epistemological science.

  14. Bioavailability pathways underlying zinc-induced avoidance behavior and reproduction toxicity in Lumbricus rubellus earthworms.

    NARCIS (Netherlands)

    Ma, W.C.; Bonten, L.T.C.

    2011-01-01

    We investigated possible bioavailability pathways underlying zinc-induced avoidance behavior and sublethal reproduction impairment in Lumbricus rubellus. Clay-loam (pH 7.3) and sandy soil (three pH values of 4.3–6.0) were amended with zinc sulfate at six soil concentrations of total Zn ranging from

  15. Mapping Common Aphasia Assessments to Underlying Cognitive Processes and Their Neural Substrates.

    Science.gov (United States)

    Lacey, Elizabeth H; Skipper-Kallal, Laura M; Xing, Shihui; Fama, Mackenzie E; Turkeltaub, Peter E

    2017-05-01

    Understanding the relationships between clinical tests, the processes they measure, and the brain networks underlying them, is critical in order for clinicians to move beyond aphasia syndrome classification toward specification of individual language process impairments. To understand the cognitive, language, and neuroanatomical factors underlying scores of commonly used aphasia tests. Twenty-five behavioral tests were administered to a group of 38 chronic left hemisphere stroke survivors and a high-resolution magnetic resonance image was obtained. Test scores were entered into a principal components analysis to extract the latent variables (factors) measured by the tests. Multivariate lesion-symptom mapping was used to localize lesions associated with the factor scores. The principal components analysis yielded 4 dissociable factors, which we labeled Word Finding/Fluency, Comprehension, Phonology/Working Memory Capacity, and Executive Function. While many tests loaded onto the factors in predictable ways, some relied heavily on factors not commonly associated with the tests. Lesion symptom mapping demonstrated discrete brain structures associated with each factor, including frontal, temporal, and parietal areas extending beyond the classical language network. Specific functions mapped onto brain anatomy largely in correspondence with modern neural models of language processing. An extensive clinical aphasia assessment identifies 4 independent language functions, relying on discrete parts of the left middle cerebral artery territory. A better understanding of the processes underlying cognitive tests and the link between lesion and behavior may lead to improved aphasia diagnosis, and may yield treatments better targeted to an individual's specific pattern of deficits and preserved abilities.

  16. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways

    Directory of Open Access Journals (Sweden)

    Young Daniel L

    2006-08-01

    Full Text Available Abstract Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator – both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering – effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism

  17. Neural networks underlying language and social cognition during self-other processing in Autism spectrum disorders.

    Science.gov (United States)

    Kana, Rajesh K; Sartin, Emma B; Stevens, Carl; Deshpande, Hrishikesh D; Klein, Christopher; Klinger, Mark R; Klinger, Laura Grofer

    2017-07-28

    The social communication impairments defining autism spectrum disorders (ASD) may be built upon core deficits in perspective-taking, language processing, and self-other representation. Self-referential processing entails the ability to incorporate self-awareness, self-judgment, and self-memory in information processing. Very few studies have examined the neural bases of integrating self-other representation and semantic processing in individuals with ASD. The main objective of this functional MRI study is to examine the role of language and social brain networks in self-other processing in young adults with ASD. Nineteen high-functioning male adults with ASD and 19 age-sex-and-IQ-matched typically developing (TD) control participants made "yes" or "no" judgments of whether an adjective, presented visually, described them (self) or their favorite teacher (other). Both ASD and TD participants showed significantly increased activity in the medial prefrontal cortex (MPFC) during self and other processing relative to letter search. Analyses of group differences revealed significantly reduced activity in left inferior frontal gyrus (LIFG), and left inferior parietal lobule (LIPL) in ASD participants, relative to TD controls. ASD participants also showed significantly weaker functional connectivity of the anterior cingulate cortex (ACC) with several brain areas while processing self-related words. The LIFG and IPL are important regions functionally at the intersection of language and social roles; reduced recruitment of these regions in ASD participants may suggest poor level of semantic and social processing. In addition, poor connectivity of the ACC may suggest the difficulty in meeting the linguistic and social demands of this task in ASD. Overall, this study provides new evidence of the altered recruitment of the neural networks underlying language and social cognition in ASD. Published by Elsevier Ltd.

  18. Transcriptomic Analysis Of Purified Embryonic Neural Stem Cells From Zebrafish Embryos Reveals Signalling Pathways Involved In Glycine-dependent Neurogenesis

    Directory of Open Access Journals (Sweden)

    Eric eSAMARUT

    2016-03-01

    Full Text Available How is the initial set of neurons correctly established during the development of the vertebrate central nervous system? In the embryo, glycine and GABA are depolarizing due the immature chloride gradient, which is only reversed to become hyperpolarizing later in post-natal development. We previously showed that glycine regulates neurogenesis via paracrine signalling that promotes calcium transients in neural stem cells (NSCs and their differentiation into interneurons within the spinal cord of the zebrafish embryo. However, the subjacent molecular mechanisms are not yet understood. Our previous work suggests that early neuronal progenitors were not differentiating correctly in the developing spinal cord. As a result, we aimed at identifying the downstream molecular mechanisms involved specifically in NSCs during glycine-dependent embryonic neurogenesis. Using a gfap:GFP transgenic line, we successfully purified NSCs by fluorescence-activated cell sorting (FACS from whole zebrafish embryos and in embryos in which the glycine receptor was knocked down. The strength of this approach is that it focused on the NSC population while tackling the biological issue in an in vivo context in whole zebrafish embryos. After sequencing the transcriptome by RNA-sequencing, we analyzed the genes whose expression was changed upon disruption of glycine signalling and we confirmed the differential expression by independent RTqPCR assay. While over a thousand genes showed altered expression levels, through pathway analysis we identified 14 top candidate genes belonging to five different canonical signalling pathways (signalling by calcium, TGF-beta, sonic hedgehog, Wnt and p53-related apoptosis that are likely to mediate the promotion of neurogenesis by glycine.

  19. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion

    Directory of Open Access Journals (Sweden)

    Michael Polanco

    2016-06-01

    Full Text Available The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  20. NEURAL PAIN PATHWAY TRACING OF RABBIT ISCHEMIC HEART BY DOUBLE-RETROGRADE NEUROTRACING

    Directory of Open Access Journals (Sweden)

    Theodorus Dapamede

    2015-01-01

    Full Text Available Background. Myocardial ischaemia occurs due to inadequate supply of oxygen to fulfill the myocardial tissue oxygen demand. This leads to angina pectoris or referred pain, whichhappens because of the inability of the brain to distinguish the visceral afferent inputs from the somatic afferent inputs since they run along a common pathway via the dorsal root ganglia. Aims. This study aims to distinguish specific areas of the rabbit heart that are projected to specific dorsal root ganglia, which then associates to its specific dermatomes. Methods. A double-retrograde neurotracing method was used, with True Blue and Nuclear Yellow as the neurotracers. Rabbits were divided into 3 groups, which the first and second groups were ligated at the left anterior descending artery and at the left circumflex artery, respectively.The third group acted as the control group, without ligation.True blue was injected at ischaemic sites following ligation. Nuclear yellowwas injected at the skin, dermatomes T1-T4. Dorsal root ganglia levels T1-T4 were then examined for both neurotracers at 3 days post injection. Results. There is significant association between the site of ligation to the projection of the neurotracers at specific dorsal root ganglia (p<0.05. The first group showed high tendency to be projected to T2 and the second group showed a high tendency to project to T1. Conclusion. This study shows that the rabbit heart can be specifically projected neuronally to specific dorsal root ganglia, following coronary artery ligation.

  1. The task novelty paradox: Flexible control of inflexible neural pathways during rapid instructed task learning.

    Science.gov (United States)

    Cole, Michael W; Braver, Todd S; Meiran, Nachshon

    2017-10-01

    Rapid instructed task learning (RITL) is one of the most remarkable human abilities, when considered from both computational and evolutionary perspectives. A key feature of RITL is that it enables new goals to be immediately pursued (and shared) following formation of task representations. Although RITL is a form of cognitive control that engenders immense flexibility, it also seems to produce inflexible activation of action plans in inappropriate contexts. We argue that this "prepared reflex" effect arises because RITL is implemented in the brain via a "flexible hub" mechanism, in which top-down influences from the frontoparietal control network reroute pathways among procedure-implementing brain areas (e.g., perceptual and motor areas). Specifically, we suggest that RITL-based proactive control - the preparatory biasing of task-relevant functional network routes - results in inflexible associative processing, demanding compensation in the form of increased reactive (in-the-moment) control. Thus, RITL produces a computational trade-off, in which the top-down influences of flexible hubs increase overall cognitive flexibility, but at the cost of temporally localized inflexibility (the prepared reflex effect). Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mei, E-mail: limeihit@163.com [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing (China); Zhang, Dong-Qing; Wang, Xiang-Zhen [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Xu, Tie-Jun, E-mail: xztjxu@163.com [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing (China)

    2011-08-12

    Highlights: {yields} The NR2B component of the NMDARs is important for the NSPC proliferation. {yields} pCaMKIV and pCREB exist in NSPCs. {yields} The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

  3. Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway

    Directory of Open Access Journals (Sweden)

    Lü He-Zuo

    2009-10-01

    Full Text Available Abstract Background Neural precursor cells (NPCs are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs are prominent components of the extracellular matrix (ECM in the central nervous system (CNS and are assumed to play important roles in controlling neuronal differentiation and development. Results In the present study, we demonstrated that CSPGs were constitutively expressed on the NPCs isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to abolish the function of endogenous CSPGs on NPCs, it induced a series of biological responses including the proliferation, differentiation and migration of NPCs, indicating that CSPGs may play a critical role in NPC development and differentiation. Finally, we provided evidence suggesting that integrin signaling pathway may be involved in the effects of CSPGs on NPCs. Conclusion The present study investigating the influence and mechanisms of CSPGs on the differentiation and migration of NPCs should help us to understand the basic biology of NPCs during CNS development and provide new insights into developing new strategies for the treatment of the neurological disorders in the CNS.

  4. Computations Underlying Social Hierarchy Learning: Distinct Neural Mechanisms for Updating and Representing Self-Relevant Information.

    Science.gov (United States)

    Kumaran, Dharshan; Banino, Andrea; Blundell, Charles; Hassabis, Demis; Dayan, Peter

    2016-12-07

    Knowledge about social hierarchies organizes human behavior, yet we understand little about the underlying computations. Here we show that a Bayesian inference scheme, which tracks the power of individuals, better captures behavioral and neural data compared with a reinforcement learning model inspired by rating systems used in games such as chess. We provide evidence that the medial prefrontal cortex (MPFC) selectively mediates the updating of knowledge about one's own hierarchy, as opposed to that of another individual, a process that underpinned successful performance and involved functional interactions with the amygdala and hippocampus. In contrast, we observed domain-general coding of rank in the amygdala and hippocampus, even when the task did not require it. Our findings reveal the computations underlying a core aspect of social cognition and provide new evidence that self-relevant information may indeed be afforded a unique representational status in the brain. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Modulating conscious movement intention by noninvasive brain stimulation and the underlying neural mechanisms.

    Science.gov (United States)

    Douglas, Zachary H; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M; He, Biyu J

    2015-05-06

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60-70 ms earlier. Slow brain waves recorded ∼2-3 s before movement onset, as well as hundreds of milliseconds after movement onset, independently correlated with the modulation of conscious intention by brain stimulation. These brain activities together accounted for 81% of interindividual variability in the modulation of movement intention by brain stimulation. A computational model using coupled leaky integrator units with biophysically plausible assumptions about the effect of tDCS captured the effects of stimulation on both neural activity and behavior. These results reveal a temporally extended brain process underlying conscious movement intention that spans seconds around movement commencement. Copyright © 2015 Douglas et al.

  6. Memory consolidation reconfigures neural pathways involved in the suppression of emotional memories.

    Science.gov (United States)

    Liu, Yunzhe; Lin, Wanjun; Liu, Chao; Luo, Yuejia; Wu, Jianhui; Bayley, Peter J; Qin, Shaozheng

    2016-11-29

    The ability to suppress unwanted emotional memories is crucial for human mental health. Through consolidation over time, emotional memories often become resistant to change. However, how consolidation impacts the effectiveness of emotional memory suppression is still unknown. Using event-related fMRI while concurrently recording skin conductance, we investigated the neurobiological processes underlying the suppression of aversive memories before and after overnight consolidation. Here we report that consolidated aversive memories retain their emotional reactivity and become more resistant to suppression. Suppression of consolidated memories involves higher prefrontal engagement, and less concomitant hippocampal and amygdala disengagement. In parallel, we show a shift away from hippocampal-dependent representational patterns to distributed neocortical representational patterns in the suppression of aversive memories after consolidation. These findings demonstrate rapid changes in emotional memory organization with overnight consolidation, and suggest possible neurobiological bases underlying the resistance to suppression of emotional memories in affective disorders.

  7. BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

    Science.gov (United States)

    Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

    2016-10-01

    Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

  8. Involvement of the flagellar assembly pathway in Vibrio alginolyticus adhesion under environmental stresses

    Directory of Open Access Journals (Sweden)

    Lu eWang

    2015-08-01

    Full Text Available Adhesion is an important virulence factor of Vibrio alginolyticus. This factor may be affected by environment conditions; however, its molecular mechanism remains unclear. In our previous research, adhesion tender models were obtained by culturing V. alginolyticus under stresses such as Cu2+, Pb2+, Hg2+, and low pH. With high-throughput sequencing and bioinformatics analysis, we found that all of these stress treatments significantly affected the flagellar assembly pathway, which may play an important role in V. alginolyticus adhesion. Therefore, we hypothesized that the environmental stresses of the flagellar assembly pathway may be one way in which environment conditions affect adhesion. To verify our hypothesis, a bioinformatics analysis, QPCR, RNAi, in vitro adhesion assay and motility assay were performed. Our results indicated that 1 the flagellar assembly pathway was sensitive to environmental stresses, 2 the flagellar assembly pathway played an important role in V. alginolyticus adhesion, and 3 motility is not the only way in which the flagellar assembly pathway affects adhesion.

  9. Involvement of cyclic AMP-mediated pathway in neural release of noradrenaline in canine isolated mesenteric artery and vein.

    Science.gov (United States)

    Mutafova-Yambolieva, Violeta N; Smyth, Lisa; Bobalova, Janette

    2003-01-01

    artery. The increasing effect of ISO (10 microM) was inhibited with either propranolol (1 microM) or the adenylyl cyclase (AC) inhibitor [9-(tetrahydro-2'-furyl)adenine] (SQ 22,536, 100 microM) in both blood vessels. The ISO effect was inhibited by the PKA inhibitor 14-22 amide (PKI(14-22)), 1 microM, in the artery but not in vein. The enhancing effect of FSK was inhibited by pretreatment of the tissue with SQ 22,536, 100 microM, or the PKA inhibitors PKI(14-22), 1 microM, and 4-cyano-3-methylisoquinoline, 50 nM. However, the inhibitors alone did not significantly change the EFS-evoked overflow of NA in both blood vessels. Activation of AC-cAMP-PKA pathway appears to play a role in modulating NA release at higher stimulation frequencies as might be expected during stress, strenuous exercise, or hemorrhage. The AC-cAMP pathway plays a more pronounced role in the autonomic neural control of mesenteric veins than of the corresponding arteries, whereas the PKA contribution is more distinct in the arteries.

  10. The insula: a critical neural substrate for craving and drug seeking under conflict and risk

    Science.gov (United States)

    Naqvi, Nasir H.; Gaznick, Natassia; Tranel, Daniel; Bechara, Antoine

    2014-01-01

    Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking—the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments. PMID:24690001

  11. Neural and computational processes underlying dynamic changes in self-esteem

    Science.gov (United States)

    Rutledge, Robb B; Moutoussis, Michael; Dolan, Raymond J

    2017-01-01

    Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an ‘interpersonal vulnerability’ dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability. PMID:29061228

  12. Feline Neural Progenitor Cells I: Long-Term Expansion under Defined Culture Conditions

    Directory of Open Access Journals (Sweden)

    Jing Yang

    2012-01-01

    Full Text Available Neural progenitor cells (NPCs of feline origin (cNPCs have demonstrated utility in transplantation experiments, yet are difficult to grow in culture beyond the 1 month time frame. Here we use an enriched, serum-free base medium (Ultraculture and report the successful long-term propagation of these cells. Primary cultures were derived from fetal brain tissue and passaged in DMEM/F12-based or Ultraculture-based proliferation media, both in the presence of EGF + bFGF. Cells in standard DMEM/F12-based medium ceased to proliferate by 1-month, whereas the cells in the Ultraculture-based medium continued to grow for at least 5 months (end of study with no evidence of senescence. The Ultraculture-based cultures expressed lower levels of progenitor and lineage-associated markers under proliferation conditions but retained multipotency as evidenced by the ability to differentiate into neurons and glia following growth factor removal in the presence of FBS. Importantly, later passage cNPCs did not develop chromosomal aberrations.

  13. Ear Detection under Uncontrolled Conditions with Multiple Scale Faster Region-Based Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2017-04-01

    Full Text Available Ear detection is an important step in ear recognition approaches. Most existing ear detection techniques are based on manually designing features or shallow learning algorithms. However, researchers found that the pose variation, occlusion, and imaging conditions provide a great challenge to the traditional ear detection methods under uncontrolled conditions. This paper proposes an efficient technique involving Multiple Scale Faster Region-based Convolutional Neural Networks (Faster R-CNN to detect ears from 2D profile images in natural images automatically. Firstly, three regions of different scales are detected to infer the information about the ear location context within the image. Then an ear region filtering approach is proposed to extract the correct ear region and eliminate the false positives automatically. In an experiment with a test set of 200 web images (with variable photographic conditions, 98% of ears were accurately detected. Experiments were likewise conducted on the Collection J2 of University of Notre Dame Biometrics Database (UND-J2 and University of Beira Interior Ear dataset (UBEAR, which contain large occlusion, scale, and pose variations. Detection rates of 100% and 98.22%, respectively, demonstrate the effectiveness of the proposed approach.

  14. The insula: a critical neural substrate for craving and drug seeking under conflict and risk.

    Science.gov (United States)

    Naqvi, Nasir H; Gaznick, Natassia; Tranel, Daniel; Bechara, Antoine

    2014-05-01

    Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking-the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments. © 2014 New York Academy of Sciences.

  15. Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

    Science.gov (United States)

    Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

    2014-01-01

    Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

  16. Unified neural field theory of brain dynamics underlying oscillations in Parkinson's disease and generalized epilepsies.

    Science.gov (United States)

    Müller, E J; van Albada, S J; Kim, J W; Robinson, P A

    2017-09-07

    The mechanisms underlying pathologically synchronized neural oscillations in Parkinson's disease (PD) and generalized epilepsies are explored in parallel via a physiologically-based neural field model of the corticothalamic-basal ganglia (CTBG) system. The basal ganglia (BG) are approximated as a single effective population and their roles in the modulation of oscillatory dynamics of the corticothalamic (CT) system and vice versa are analyzed. In addition to normal EEG rhythms, enhanced activity around 4 Hz and 20 Hz exists in the model, consistent with the characteristic frequencies observed in PD. These rhythms result from resonances in loops formed between the BG and CT populations, analogous to those that underlie epileptic oscillations in a previous CT model, and which are still present in the combined CTBG system. Dopamine depletion is argued to weaken the dampening of these loop resonances in PD, and network connections then explain the significant coherence observed between BG, thalamic, and cortical population activity around 4-8 Hz and 20 Hz. Parallels between the afferent and efferent connection sites of the thalamic reticular nucleus (TRN) and BG predict low dopamine to correspond to a reduced likelihood of tonic-clonic (grand mal) seizures, which agrees with experimental findings. Furthermore, the model predicts an increased likelihood of absence (petit mal) seizure resulting from pathologically low dopamine levels in accordance with experimental observations. Suppression of absence seizure activity is demonstrated when afferent and efferent BG connections to the CT system are strengthened, which is consistent with other CTBG modeling studies. The BG are demonstrated to have a suppressive effect on activity of the CTBG system near tonic-clonic seizure states, which provides insight into the reported efficacy of current treatments in BG circuits. Sleep states of the TRN are also found to suppress pathological PD activity in accordance with

  17. Vasculogenesis and angiogenesis initiation under normoxic conditions through Wnt/β-catenin pathway in gliomas.

    Science.gov (United States)

    Vallée, Alexandre; Guillevin, Rémy; Vallée, Jean-Noël

    2018-01-26

    The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas. Wnt-induced epidermal growth factor receptor/phosphatidylinositol 3-kinase (PI3K)/Akt signaling, Wnt-induced signal transducers and activators of transcription 3 (STAT3) signaling, and Wnt/β-catenin target gene transduction (c-Myc) can activate HIF-1α in a hypoxia-independent manner. The PI3K/Akt/mammalian target of rapamycin pathway activates HIF-1α through eukaryotic translation initiation factor 4E-binding protein 1 and STAT3. The β-catenin/T-cell factor 4 complex directly binds to STAT3 and activates HIF-1α, which up-regulates the Wnt/β-catenin target genes cyclin D1 and c-Myc in a positive feedback loop. Phosphorylated STAT3 by interleukin-6 or leukemia inhibitory factor activates HIF-1α even under normoxic conditions. The activation of the Wnt/β-catenin pathway induces, via the Wnt target genes c-Myc and cyclin D1 or via HIF-1α, gene transactivation encoding aerobic glycolysis enzymes, such as glucose transporter, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase 1 and lactate dehydrogenase-A, leading to lactate production, as the primary alternative of ATP, at all oxygen levels, even in normoxic conditions. Lactate released by glioma cells via the monocarboxylate lactate transporter-1 up-regulated by HIF-1α and lactate anion activates HIF-1α in normoxic endothelial cells by

  18. Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China.

    Science.gov (United States)

    Fang, Yulian; Zhang, Ruiping; Zhi, Xiufang; Zhao, Linsheng; Cao, Lirong; Wang, Yizheng; Cai, Chunquan

    2018-04-01

    Neural tube defects (NTDs) are one of the most prevalent and the most severe congenital malformations worldwide. Studies have confirmed that folic acid supplementation could effectively reduce NTDs risk, but the genetic mechanism remains unclear. In this study, we explored association of single nucleotide polymorphisms (SNP) within folate metabolic pathway genes with NTDs in Han population of Northern China. We performed a case-control study to compare genotype and allele distributions of SNPs in 152 patients with NTDs and 169 controls. A total of 16 SNPs within five genes were genotyped by the Sequenom MassARRAY assay. Our results indicated that three SNPs associated significantly with NTDs (P<0.05). For rs2236225 within MTHFD1, children with allele A or genotype AA had a high NTDs risk (OR=1.500, 95%CI=1.061~2.120; OR=2.862, 95%CI=1.022~8.015, respectively). For rs1801133 within MTHFR, NTDs risk markedly increased in patients with allele T or genotype TT (OR=1.552, 95%CI=1.130~2.131; OR=2.344, 95%CI=1.233~4.457, respectively). For rs1801394 within MTRR, children carrying allele G and genotype GG had a higher NTDs risk (OR=1.533, 95%CI=1.102~2.188; OR=2.355, 95%CI=1.044~5.312, respectively). Our results suggest that rs2236225 of MTHFD1 gene, rs1801133 of MTHFR gene and rs1801394 of MTRR gene were associated with NTDs in Han population of Northern China.

  19. Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway.

    Science.gov (United States)

    Jiang, Huili; Zhang, Xuhui; Wang, Yu; Zhang, Huimin; Li, Jing; Yang, Xinjing; Zhao, Bingcong; Zhang, Chuntao; Yu, Miao; Xu, Mingmin; Yu, Qiuyun; Liang, Xingchen; Li, Xiang; Shi, Peng; Bao, Tuya

    2017-01-01

    Protein kinase A (PKA)/cAMP response element-binding (CREB) protein signaling pathway, contributing to impaired neurogenesis parallel to depressive-like behaviors, has been identified as the crucial factor involved in the antidepressant response of acupuncture. However, the molecular mechanisms associated with antidepressant response of acupuncture, neurogenesis, and depressive-like behaviors ameliorating remain unexplored. The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor H89 in in vivo experiments. Our results indicated that the expression of hippocampal PKA- α and p-CREB was significantly downregulated by chronic unpredicted mild stress (CUMS) procedures. Importantly, acupuncture reversed the downregulation of PKA- α and p-CREB. The expression of PKA- α was upregulated by fluoxetine, but not p-CREB. No significant difference was found between Acu and FLX groups on the expression of PKA- α and p-CREB. Interestingly, H89 inhibited the effects of acupuncture or fluoxetine on upregulating the expression of p-CREB, but not PKA- α . There was no significant difference in expression of CREB among the groups. Conclusively, our findings further support the hypothesis that acupuncture could ameliorate depressive-like behaviors by regulating PKA/CREB signaling pathway, which might be mainly mediated by regulating the phosphorylation level of CREB.

  20. Photodegradation of malachite green under simulated and natural irradiation: Kinetics, products, and pathways

    Energy Technology Data Exchange (ETDEWEB)

    Yong, Li [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Zhanqi, Gao [State Environmental Protection Key Laboratory of Monitoring and Analysis for Organic Pollutants in Surface Water, Jiangsu Provincial Environmental Monitoring Center, Nanjing 210036 (China); Yuefei, Ji [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Xiaobin, Hu [School of Life Science, Huzhou University, Huzhou 313000 (China); Cheng, Sun, E-mail: envidean@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Shaogui, Yang; Lianhong, Wang; Qingeng, Wang; Die, Fang [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China)

    2015-03-21

    Highlights: • Photofate of malachite green was studied under simulated and natural irradiation. • Favorable conditions for degradation were optimized by the orthogonal array design. • Main ROS for the decomposition were determined by free radical quenchers. • Fifty-three products were determined by LC–MS and GC–MS. • Pathways were proposed with the aid of theoretical calculation. - Abstract: In this work photodegradation rates and pathways of malachite green were studied under simulated and solar irradiation with the goal of assessing the potential of photolysis as a removal mechanism in real aquatic environment. Factors influencing the photodegradation process were investigated, including pH, humic acid, Fe{sup 2+}, Ca{sup 2+}, HCO{sub 3}{sup −}, and NO{sub 3}{sup −}, of which favorable conditions were optimized by the orthogonal array design under simulated sunlight irradiation in the presence of dissolved oxygen. The degradation processes of malachite green conformed to pseudo first-order kinetics and their degradation rate constants were between 0.0062 and 0.4012 h{sup −1}. Under solar irradiation, the decolorization efficiency of most tests can reach almost 100%, and relatively thorough mineralization could be observed. Forty degradation products were detected by liquid chromatography–mass spectrometry, and thirteen small molecular products were identified by gas chromatography–mass spectrometry. Based on the analyses of the degradation products and calculation of the frontier electron density, the pathways were proposed: decomposition of conjugated structure, N-demethylation reactions, hydroxyl addition reactions, the removal of benzene ring, and the ring-opening reaction. This study has provided a reference, both for photodegradation of malachite green and future safety applications and predictions of decontamination of related triphenylmethane dyes under real conditions.

  1. Metabolic responses and pathway changes of mammalian cells under different culture conditions with media supplementations.

    Science.gov (United States)

    Park, Seo-Young; Reimonn, Thomas M; Agarabi, Cyrus D; Brorson, Kurt A; Yoon, Seongkyu

    2018-02-21

    Amino acids and glucose consumption, cell growth and monoclonal antibody (mAb) production in mammalian cell culture are key considerations during upstream process and particularly media optimization. Understanding the interrelations and the relevant cellular physiology will provide insight for setting strategy of robust and effective mAb production. The aim of this study was to further our understanding of nutrient consumption metabolism, since this could have significant impact on enhancing mAb titer, cell proliferation, designing feeding strategies, and development of feed media. The nutrient consumption pattern, mAb concentration, and cell growth were analyzed in three sets of cell cultures with media supplementation of glucose, methionine, threonine, tryptophan, and tyrosine. The amino acids metabolism and its impact on cell growth and mAb production during the batch and fed-batch culture were closely analyzed. It was shown that the phenylalanine, tyrosine and tryptophan biosynthesis pathways were significantly altered under different culture conditions with different media. These changes were more apparent in the fed-batch process in which higher mAb titer was observed due to the metabolic changes than mAb titer in the batch process. The pathway analysis approach was well utilized for evaluating the impact on the relevant pathways involved under different cell culture conditions to improve cell growth and mAb titer. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

  2. Proteomic analysis of Brucella suis under oxygen deficiency reveals flexibility in adaptive expression of various pathways.

    Science.gov (United States)

    Al Dahouk, Sascha; Loisel-Meyer, Séverine; Scholz, Holger C; Tomaso, Herbert; Kersten, Michael; Harder, Alois; Neubauer, Heinrich; Köhler, Stephan; Jubier-Maurin, Véronique

    2009-06-01

    Low oxygen tension was proposed to be one of the environmental parameters characteristic of the patho-physiological conditions of natural infections by Brucella suis. We previously showed that various respiratory pathways may be used by B. suis in response to microaerobiosis and anaerobiosis. Here, we compare the whole proteome of B. suis exposed to such low-oxygenated conditions to that obtained from bacteria grown under ambient air using 2-D DIGE. Data showed that the reduction of basal metabolism was in line with low or absence of growth of B. suis. Under both microaerobiosis and anaerobiosis, glycolysis and denitrification were favored. In addition, fatty acid oxidation and possibly citrate fermentation could also contribute to energy production sufficient for survival under anaerobiosis. When oxygen availability changed and became limiting, basic metabolic processes were still functional and variability of respiratory pathways was observed to a degree unexpected for a strictly aerobic microorganism. This highly flexible respiration probably constitutes an advantage for the survival of Brucella under the restricted oxygenation conditions encountered within host tissue.

  3. Optimal processing pathway selection for microalgae-based biorefinery under uncertainty

    DEFF Research Database (Denmark)

    Rizwan, Muhammad; Zaman, Muhammad; Lee, Jay H.

    2015-01-01

    to the sMINLP problem determines the processing technologies, material flows, and product portfolio that are optimal with respect to all the sampled scenarios. The developed framework is implemented and tested on a specific case study. The optimal processing pathways selected with and without......We propose a systematic framework for the selection of optimal processing pathways for a microalgaebased biorefinery under techno-economic uncertainty. The proposed framework promotes robust decision making by taking into account the uncertainties that arise due to inconsistencies among...... and shortage in the available technical information. A stochastic mixed integer nonlinear programming (sMINLP) problem is formulated for determining the optimal biorefinery configurations based on a superstructure model where parameter uncertainties are modeled and included as sampled scenarios. The solution...

  4. Metabolic pathways for lipid synthesis under nitrogen stress in Chlamydomonas and Nannochloropsis.

    Science.gov (United States)

    Banerjee, Avik; Maiti, Subodh K; Guria, Chandan; Banerjee, Chiranjib

    2017-01-01

    Microalgae are currently being considered as a clean, sustainable and renewable energy source. Enzymes that catalyse the metabolic pathways for biofuel production are specific and require strict regulation and co-ordination. Thorough knowledge of these key enzymes along with their regulatory molecules is essential to enable rational metabolic engineering, to drive the metabolic flux towards the desired metabolites of importance. This paper reviews two key enzymes that play their role in production of bio-oil: DGAT (acyl-CoA:diacylglycerol acyltransferase) and PDAT (phospholipid:diacylglycerol acyltransferase). It also deals with the transcription factors that control the enzymes while cell undergoes a metabolic shift under stress. The paper also discusses the association of other enzymes and pathways that provide substrates and precursors for oil accumulation. Finally a futuristic solution has been proposed about a synthetic algal cell platform that would be committed towards biofuel synthesis.

  5. Quantification of vapor intrusion pathways into a slab-on-ground building under varying environmental conditions.

    Science.gov (United States)

    Patterson, Bradley M; Davis, Greg B

    2009-02-01

    Potential hydrocarbon-vapor intrusion pathways into a building through a concrete slab-on-ground were investigated and quantified under a variety of environmental conditions to elucidate the potential mechanisms for indoor air contamination. Vapor discharge from the uncovered open ground soil adjacent to the building and subsequent advection into the building was unlikely due to the low soil-gas concentrations at the edge of the building as a result of aerobic biodegradation of hydrocarbon vapors. When the building's interior was under ambient pressure, a flux of vapors into the building due to molecular diffusion of vapors through the building's concrete slab (cyclohexane 11 and methylcyclohexane 31 mg m(-2) concrete slab day(-1)) and short-term (up to 8 h) cyclical pressure-driven advection of vapors through an artificial crack (cyclohexane 4.2 x 10(3) and methylcyclohexane 1.2 x 10(4) mg m(-2) cracks day(-1)) was observed. The average subslab vapor concentration under the center of the building was 25,000 microg L(-1). Based on the measured building's interiorvapor concentrations and the building's air exchange rate of 0.66 h(-1), diffusion of vapors through the concrete slab was the dominantvapor intrusion pathway and cyclical pressure exchanges resulted in a near zero advective flux. When the building's interior was under a reduced pressure (-12 Pa), advective transport through cracks or gaps in the concrete slab (cyclohexane 340 and methylcyclohexane 1100 mg m(-2) cracks day(-1)) was the dominant vapor intrusion pathway.

  6. Decision making under uncertainty in a spiking neural network model of the basal ganglia.

    Science.gov (United States)

    Héricé, Charlotte; Khalil, Radwa; Moftah, Marie; Boraud, Thomas; Guthrie, Martin; Garenne, André

    2016-12-01

    The mechanisms of decision-making and action selection are generally thought to be under the control of parallel cortico-subcortical loops connecting back to distinct areas of cortex through the basal ganglia and processing motor, cognitive and limbic modalities of decision-making. We have used these properties to develop and extend a connectionist model at a spiking neuron level based on a previous rate model approach. This model is demonstrated on decision-making tasks that have been studied in primates and the electrophysiology interpreted to show that the decision is made in two steps. To model this, we have used two parallel loops, each of which performs decision-making based on interactions between positive and negative feedback pathways. This model is able to perform two-level decision-making as in primates. We show here that, before learning, synaptic noise is sufficient to drive the decision-making process and that, after learning, the decision is based on the choice that has proven most likely to be rewarded. The model is then submitted to lesion tests, reversal learning and extinction protocols. We show that, under these conditions, it behaves in a consistent manner and provides predictions in accordance with observed experimental data.

  7. Neural network underlying ictal pouting ("chapeau de gendarme") in frontal lobe epilepsy.

    Science.gov (United States)

    Souirti, Zouhayr; Landré, Elisabeth; Mellerio, Charles; Devaux, Bertrand; Chassoux, Francine

    2014-08-01

    In order to determine the anatomical neural network underlying ictal pouting (IP), with the mouth turned down like a "chapeau de gendarme", in frontal lobe epilepsy (FLE), we reviewed the video-EEG recordings of 36 patients with FLE who became seizure-free after surgery. We selected the cases presenting IP, defined as a symmetrical and sustained (>5s) lowering of labial commissures with contraction of chin, mimicking an expression of fear, disgust, or menace. Ictal pouting was identified in 11 patients (8 males; 16-48 years old). We analyzed the clinical semiology, imaging, and electrophysiological data associated with IP, including FDG-PET in 10 and SEEG in 9 cases. In 37 analyzed seizures (2-7/patient), IP was an early symptom, occurring during the first 10s in 9 cases. The main associated features consisted of fear, anguish, vegetative disturbances, behavioral disorders (sudden agitation, insults, and fighting), tonic posturing, and complex motor activities. The epileptogenic zone assessed by SEEG involved the mesial frontal areas, especially the anterior cingulate cortex (ACC) in 8 patients, whereas lateral frontal onset with an early spread to the ACC was seen in the other patient. Ictal pouting associated with emotional changes and hypermotor behavior had high localizing value for rostroventral "affective" ACC, whereas less intense facial expressions were related to the dorsal "cognitive" ACC. Fluorodeoxyglucose positron emission tomography demonstrated the involvement of both the ACC and lateral cortex including the anterior insula in all cases. We propose that IP is sustained by reciprocal mesial and lateral frontal interactions involved in emotional and cognitive processes, in which the ACC plays a pivotal role. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Neural correlates of erotic stimulation under different levels of female sexual hormones.

    Directory of Open Access Journals (Sweden)

    Birgit Abler

    Full Text Available Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12, and a different group of females (nC group; N = 12 not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation, activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual

  9. Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo

    2009-09-01

    Full Text Available The alpha-isoform of calcium/calmodulin-dependent protein kinase II (α-CaMKII is expressed abundantly in the forebrain and is considered to have an essential role in synaptic plasticity and cognitive function. Previously, we reported that mice heterozygous for a null mutation of α-CaMKII (α-CaMKII+/- have profoundly dysregulated behaviors including a severe working memory deficit, which is an endophenotype of schizophrenia and other psychiatric disorders. In addition, we found that almost all the neurons in the dentate gyrus (DG of the mutant mice failed to mature at molecular, morphological and electrophysiological levels. In the present study, to identify the brain substrates of the working memory deficit in the mutant mice, we examined the expression of the immediate early genes (IEGs, c-Fos and Arc, in the brain after a working memory version of the eight-arm radial maze test. c-Fos expression was abolished almost completely in the DG and was reduced significantly in neurons in the CA1 and CA3 areas of the hippocampus, central amygdala, and medial prefrontal cortex (mPFC. However, c-Fos expression was intact in the entorhinal and visual cortices. Immunohistochemical studies using arc promoter driven dVenus transgenic mice demonstrated that arc gene activation after the working memory task occurred in mature, but not immature neurons in the DG of wild-type mice. These results suggest crucial insights for the neural circuits underlying spatial mnemonic processing during a working memory task and suggest the involvement of α-CaMKII in the proper maturation and integration of DG neurons into these circuits.

  10. Signaling pathway underlying the octopaminergic modulation of myogenic contraction in the cricket lateral oviduct.

    Science.gov (United States)

    Tamashiro, Hirotake; Yoshino, Masami

    2014-12-01

    Octopamine (OA), a biogenic monoamine, is a neurotransmitter and neuromodulator in invertebrates. Here, we report the effect of OA on the spontaneous rhythmic contractions (SRCs) of the lateral oviduct of the cricket Gryllus bimaculatus and the possible signaling pathway involved. Application of OA increased both the frequency and amplitude of SRCs in a dose-dependent manner. The effect of OA was inhibited by subsequent application of the OA receptor antagonist epinastine, indicating that the action of OA is mediated by OA receptor. To investigate the predominant signaling pathway underlying the action of OA, we first examined a possible involvement of the cAMP/cAMP-dependent protein kinase A (PKA) signaling pathway. Application of the membrane-permeable cAMP analog 8-Br-cAMP had little effect on SRCs and the effect of OA was not influenced by subsequent application of the PKA inhibitor H89, indicating that the cAMP/PKA signaling pathway is not the predominant pathway in the action of OA. Next, we examined a possible involvement of the second messenger inositol 1,4,5-trisphosphate in the action of OA. The effect of OA on SRCs was inhibited by subsequent application of the phosphoinositide-specific phospholipase C (PLC) inhibitor U73122, indicating that the PLC pathway is involved in the action of OA. The OA-induced increase in the frequency of SRCs was inhibited by pretreatment of the cell with the ryanodine receptor antagonist tetracaine but was not significantly affected by the IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB). On the other hand, the OA-induced increase in the amplitude of SRCs was inhibited by pretreatment of the cells with 2-APB but was not significantly affected by tetracaine. Taken together, these results suggest that the OA-induced excitatory effect on SRCs is mediated by the PLC signaling pathway: Ca2+ release from IP3 receptors may contribute to the modulation of the amplitude of SRCs, whereas Ca2+ release from ryanodine

  11. ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway.

    Science.gov (United States)

    Zhao, Yang; Hu, Xingbin; Liu, Yajing; Dong, Shumin; Wen, Zhaowei; He, Wanming; Zhang, Shuyi; Huang, Qiong; Shi, Min

    2017-04-13

    Cancer cells are frequently confronted with metabolic stress in tumor microenvironments due to their rapid growth and limited nutrient supply. Metabolic stress induces cell death through ROS-induced apoptosis. However, cancer cells can adapt to it by altering the metabolic pathways. AMPK and AKT are two primary effectors in response to metabolic stress: AMPK acts as an energy-sensing factor which rewires metabolism and maintains redox balance. AKT broadly promotes energy production in the nutrient abundance milieu, but the role of AKT under metabolic stress is in dispute. Recent studies show that AMPK and AKT display antagonistic roles under metabolic stress. Metabolic stress-induced ROS signaling lies in the hub between metabolic reprogramming and redox homeostasis. Here, we highlight the cross-talk between AMPK and AKT and their regulation on ROS production and elimination, which summarizes the mechanism of cancer cell adaptability under ROS stress and suggests potential options for cancer therapeutics.

  12. Prospero-related homeobox 1 (Prox1 at the crossroads of diverse pathways during adult neural fate specification

    Directory of Open Access Journals (Sweden)

    Athanasios eStergiopoulos

    2015-01-01

    Full Text Available Over the last decades, adult neurogenesis in the central nervous system (CNS has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation versus differentiation decisions of NSCs, promoting cell cycle exit and neuronal differentiation, while inhibits astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs, differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  13. Neural mechanisms underlying subsequent memory for personal beliefs:An fMRI study.

    Science.gov (United States)

    Wing, Erik A; Iyengar, Vijeth; Hess, Thomas M; LaBar, Kevin S; Huettel, Scott A; Cabeza, Roberto

    2018-04-01

    Many fMRI studies have examined the neural mechanisms supporting emotional memory for stimuli that generate emotion rather automatically (e.g., a picture of a dangerous animal or of appetizing food). However, far fewer studies have examined how memory is influenced by emotion related to social and political issues (e.g., a proposal for large changes in taxation policy), which clearly vary across individuals. In order to investigate the neural substrates of affective and mnemonic processes associated with personal opinions, we employed an fMRI task wherein participants rated the intensity of agreement/disagreement to sociopolitical belief statements paired with neural face pictures. Following the rating phase, participants performed an associative recognition test in which they distinguished identical versus recombined face-statement pairs. The study yielded three main findings: behaviorally, the intensity of agreement ratings was linked to greater subjective emotional arousal as well as enhanced high-confidence subsequent memory. Neurally, statements that elicited strong (vs. weak) agreement or disagreement were associated with greater activation of the amygdala. Finally, a subsequent memory analysis showed that the behavioral memory advantage for statements generating stronger ratings was dependent on the medial prefrontal cortex (mPFC). Together, these results both underscore consistencies in neural systems supporting emotional arousal and suggest a modulation of arousal-related encoding mechanisms when emotion is contingent on referencing personal beliefs.

  14. Catalyst-free activation of peroxides under visible LED light irradiation through photoexcitation pathway

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yaowen [Department of Environmental Engineering, Wuhan University, Wuhan, 430079 (China); Shenzhen Research Institute of Wuhan University, Shenzhen, 518057 (China); Li, Yixi; Yao, Linyu; Li, Simiao; Liu, Jin [Department of Environmental Engineering, Wuhan University, Wuhan, 430079 (China); Zhang, Hui, E-mail: eeng@whu.edu.cn [Department of Environmental Engineering, Wuhan University, Wuhan, 430079 (China); Shenzhen Research Institute of Wuhan University, Shenzhen, 518057 (China)

    2017-05-05

    Highlights: • Persulfate could decolorize Rhodamine B (RhB) directly via non-radical reactions. • LED lamps emitting white light were utilized as the visible light source. • Dyes could activate peroxides through photoexcitation pathway. • Decolorization of dyes and production of radicals were achieved simultaneously. • The catalyst-free peroxide/dye/Vis process was effective in a broad pH range. - Abstract: Catalysts are known to activate peroxides to generate active radicals (i.e., hydroxyl radical (·OH) and sulfate radical (SO{sub 4}·{sup −})) under certain conditions, but the activation of peroxides in the absence of catalysts under visible light irradiation has been rarely reported. This work demonstrates a catalyst-free activation of peroxides for the generation of ·OH and/or SO{sub 4}·{sup −} through photoexcited electron transfer from organic dyes to peroxides under visible LED light irradiation, where Rhodamine B (RhB) and Eosin Y (EY) were selected as model dyes. The formation of ·OH and/or SO{sub 4}·{sup −} in the reactions and the electron transfer from the excited dyes to peroxides were validated via electron paramagnetic resonance (EPR), photoluminescence (PL) spectra and cyclic voltammetry (CV). The performance of the peroxide/dye/Vis process was demonstrated to be altered depending on the target substrate. Meanwhile, the peroxide/dye/Vis process was effective for simultaneous decolorization of dyes and production of active radicals under neutral even or basic conditions. The findings of this study clarified a novel photoexcitation pathway for catalyst-free activation of peroxides under visible light irradiation, which could avoid the secondary metal ion (dissolved or leached) pollution from the metal-based catalysts and expand the application range of the peroxide-based catalytic process.

  15. The neural basis of loss aversion in decision-making under risk.

    Science.gov (United States)

    Tom, Sabrina M; Fox, Craig R; Trepel, Christopher; Poldrack, Russell A

    2007-01-26

    People typically exhibit greater sensitivity to losses than to equivalent gains when making decisions. We investigated neural correlates of loss aversion while individuals decided whether to accept or reject gambles that offered a 50/50 chance of gaining or losing money. A broad set of areas (including midbrain dopaminergic regions and their targets) showed increasing activity as potential gains increased. Potential losses were represented by decreasing activity in several of these same gain-sensitive areas. Finally, individual differences in behavioral loss aversion were predicted by a measure of neural loss aversion in several regions, including the ventral striatum and prefrontal cortex.

  16. Neural network modeling to evaluate the dynamic flow stress of high strength armor steels under high strain rate compression

    Directory of Open Access Journals (Sweden)

    Ravindranadh Bobbili

    2014-12-01

    Full Text Available An artificial neural network (ANN constitutive model is developed for high strength armor steel tempered at 500 °C, 600 °C and 650 °C based on high strain rate data generated from split Hopkinson pressure bar (SHPB experiments. A new neural network configuration consisting of both training and validation is effectively employed to predict flow stress. Tempering temperature, strain rate and strain are considered as inputs, whereas flow stress is taken as output of the neural network. A comparative study on Johnson–Cook (J–C model and neural network model is performed. It was observed that the developed neural network model could predict flow stress under various strain rates and tempering temperatures. The experimental stress–strain data obtained from high strain rate compression tests using SHPB, over a range of tempering temperatures (500–650 °C, strains (0.05–0.2 and strain rates (1000–5500/s are employed to formulate J–C model to predict the high strain rate deformation behavior of high strength armor steels. The J-C model and the back-propagation ANN model were developed to predict the high strain rate deformation behavior of high strength armor steel and their predictability is evaluated in terms of correlation coefficient (R and average absolute relative error (AARE. R and AARE for the J–C model are found to be 0.7461 and 27.624%, respectively, while R and AARE for the ANN model are 0.9995 and 2.58%, respectively. It was observed that the predictions by ANN model are in consistence with the experimental data for all tempering temperatures.

  17. Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural differentiation through cross-talk between the specific RONS cascade and Trk/Ras/ERK signaling pathway.

    Science.gov (United States)

    Jang, Ja-Young; Hong, Young June; Lim, Junsup; Choi, Jin Sung; Choi, Eun Ha; Kang, Seongman; Rhim, Hyangshuk

    2018-02-01

    Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O 2 - ) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by O 2 - dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Imaging Neuronal Populations in Behaving Rodents: Paradigms for Studying Neural Circuits Underlying Behavior in the Mammalian Cortex

    Science.gov (United States)

    Andermann, Mark L.; Keck, Tara; Xu, Ning-Long; Ziv, Yaniv

    2013-01-01

    Understanding the neural correlates of behavior in the mammalian cortex requires measurements of activity in awake, behaving animals. Rodents have emerged as a powerful model for dissecting the cortical circuits underlying behavior attributable to the convergence of several methods. Genetically encoded calcium indicators combined with viral-mediated or transgenic tools enable chronic monitoring of calcium signals in neuronal populations and subcellular structures of identified cell types. Stable one- and two-photon imaging of neuronal activity in awake, behaving animals is now possible using new behavioral paradigms in head-fixed animals, or using novel miniature head-mounted microscopes in freely moving animals. This mini-symposium will highlight recent applications of these methods for studying sensorimotor integration, decision making, learning, and memory in cortical and subcortical brain areas. We will outline future prospects and challenges for identifying the neural underpinnings of task-dependent behavior using cellular imaging in rodents. PMID:24198355

  19. Photodegradation of gemfibrozil in aqueous solution under UV irradiation: kinetics, mechanism, toxicity, and degradation pathways.

    Science.gov (United States)

    Ma, Jingshuai; Lv, Wenying; Chen, Ping; Lu, Yida; Wang, Fengliang; Li, Fuhua; Yao, Kun; Liu, Guoguang

    2016-07-01

    The lipid regulator gemfibrozil (GEM) has been reported to be persistent in conventional wastewater treatment plants. This study investigated the photolytic behavior, toxicity of intermediate products, and degradation pathways of GEM in aqueous solutions under UV irradiation. The results demonstrated that the photodegradation of GEM followed pseudo-first-order kinetics, and the pseudo-first-order rate constant was decreased markedly with increasing initial concentrations of GEM and initial pH. The photodegradation of GEM included direct photolysis via (3)GEM(*) and self-sensitization via ROS, where the contribution rates of degradation were 0.52, 90.05, and 8.38 % for ·OH, (1)O2, and (3)GEM(*), respectively. Singlet oxygen ((1)O2) was evidenced by the molecular probe compound, furfuryl alcohol (FFA), and was identified as the primary reactive species in the photolytic process. The steady-state concentrations of (1)O2 increased from (0.324 ± 0.014) × 10(-12) to (1.021 ± 0.040) × 10(-12) mol L(-1), as the initial concentrations of GEM were increased from 5 to 20 mg L(-1). The second-order rate constant for the reaction of GEM with (1)O2 was calculated to be 2.55 × 10(6) M(-1) s(-1). The primary transformation products were identified using HPLC-MS/MS, and possible photodegradation pathways were proposed by hydroxylation, aldehydes reactions, as well as the cleavage of ether side chains. The toxicity of phototransformation product evaluation revealed that photolysis potentially provides a critical pathway for GEM toxicity reduction in potable water and wastewater treatment facilities.

  20. Proteomics and bioinformatics analysis reveal underlying pathways of infection associated histologic chorioamnionitis in pPROM.

    Science.gov (United States)

    Tambor, V; Kacerovsky, M; Lenco, J; Bhat, G; Menon, R

    2013-02-01

    The presence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) is associated with adverse neonatal outcomes in pregnancies complicated by preterm prelabor rupture of membranes (pPROM). Therefore, there is an urgent need to identify new biomarkers revealing these conditions. The objective of this study is to identify possible biomarkers and their underlying biofunctions in pPROM pregnancies with and without MIAC and HCA. A total of 72 women with pPROM were recruited. Only women with both MIAC and HCA (n = 19) and all women without these complications (n = 19) having the same range of gestational ages at sampling were included in the study. Samples of amniotic fluid were obtained by transabdominal amniocentesis, processed and analyzed using quantitative shotgun proteomics. Ingenuity pathway analysis was used to identify molecular networks that involve altered proteins. Network interaction identified by ingenuity pathway analysis revealed immunological disease and the inflammatory response as the top functions and disease associated with pPROM in the presence of MIAC and HCA. The proteins involved in these pathways were significantly altered between the groups with and without the presence of both MIAC and HCA. Proteins involved included histones H3, H4, H2B, cathelicidin antimicrobial peptide, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, peptidoglycan recognition protein-1 and neutrophil defensin 1, all of which were found to be up-regulated in the presence of MIAC and HCA. Bioinformatic analysis of proteomics data allowed us to project likely biomolecular pathology resulting in pPROM complicated by MIAC and HCA. As inflammation is not a homogeneous phenomenon, we provide evidence for oxidative-stress-associated DNA damage and biomarkers of reactive oxygen species generation as factors associated with inflammation and proteolysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Cortical Neural Synchronization Underlies Primary Visual Consciousness of Qualia: Evidence from Event-Related Potentials

    OpenAIRE

    Babiloni, Claudio; Marzano, Nicola; Soricelli, Andrea; Cordone, Susanna; Mill?n-Calenti, Jos? Carlos; Del Percio, Claudio; Buj?n, Ana

    2016-01-01

    This article reviews three experiments on event-related potentials (ERPs) testing the hypothesis that primary visual consciousness (stimulus self-report) is related to enhanced cortical neural synchronization as a function of stimulus features. ERP peak latency and sources were compared between “seen” trials and “not seen” trials, respectively related and unrelated to the primary visual consciousness. Three salient features of visual stimuli were considered (visuospatial, emotional face expre...

  2. Anger under Control: Neural Correlates of Frustration as a Function of Trait Aggression

    OpenAIRE

    Pawliczek, Christina M.; Derntl, Birgit; Kellermann, Thilo; Gur, Ruben C.; Schneider, Frank; Habel, Ute

    2013-01-01

    Antisocial behavior and aggression are prominent symptoms in several psychiatric disorders including antisocial personality disorder. An established precursor to aggression is a frustrating event, which can elicit anger or exasperation, thereby prompting aggressive responses. While some studies have investigated the neural correlates of frustration and aggression, examination of their relation to trait aggression in healthy populations are rare. Based on a screening of 550 males, we formed tw...

  3. Strong geomagnetic activity forecast by neural networks under dominant southern orientation of the interplanetary magnetic field

    Czech Academy of Sciences Publication Activity Database

    Valach, F.; Bochníček, Josef; Hejda, Pavel; Revallo, M.

    2014-01-01

    Roč. 53, č. 4 (2014), s. 589-598 ISSN 0273-1177 R&D Projects: GA AV ČR(CZ) IAA300120608; GA MŠk OC09070 Institutional support: RVO:67985530 Keywords : geomagnetic activity * interplanetary magnetic field * artificial neural network * ejection of coronal mass * X-ray flares Subject RIV: DE - Earth Magnetism, Geodesy, Geography Impact factor: 1.358, year: 2014

  4. Engagement of neural circuits underlying 2D spatial navigation in a rodent virtual reality system

    OpenAIRE

    Aronov, Dmitriy; Tank, David W.

    2014-01-01

    Virtual reality (VR) enables precise control of an animal’s environment and otherwise impossible experimental manipulations. Neural activity in navigating rodents has been studied on virtual linear tracks. However, the spatial navigation system’s engagement in complete two-dimensional environments has not been shown. We describe a VR setup for rats, including control software and a large-scale electrophysiology system, which supports 2D navigation by allowing animals to rotate and walk in any...

  5. Neural Systems Underlying Perceptual Adjustment to Non-Standard Speech Tokens.

    Science.gov (United States)

    Myers, Emily B; Mesite, Laura M

    2014-10-01

    It has long been noted that listeners use top-down information from context to guide perception of speech sounds. A recent line of work employing a phenomenon termed 'perceptual learning for speech' shows that listeners use top-down information to not only resolve the identity of perceptually ambiguous speech sounds, but also to adjust perceptual boundaries in subsequent processing of speech from the same talker. Even so, the neural mechanisms that underlie this process are not well understood. Of particular interest is whether this type of adjustment comes about because of a retuning of sensitivities to phonetic category structure early in the neural processing stream or whether the boundary shift results from decision-related or attentional mechanisms further downstream. In the current study, neural activation was measured using fMRI as participants categorized speech sounds that were perceptually shifted as a result of exposure to these sounds in lexically-unambiguous contexts. Sensitivity to lexically-mediated shifts in phonetic categorization emerged in right hemisphere frontal and middle temporal regions, suggesting that the perceptual learning for speech phenomenon relies on the adjustment of perceptual criteria downstream from primary auditory cortex. By the end of the session, this same sensitivity was seen in left superior temporal areas, which suggests that a rapidly-adapting system may be accompanied by more slowly evolving shifts in regions of the brain related to phonetic processing.

  6. Neural mechanisms underlying sound-induced visual motion perception: An fMRI study.

    Science.gov (United States)

    Hidaka, Souta; Higuchi, Satomi; Teramoto, Wataru; Sugita, Yoichi

    2017-07-01

    Studies of crossmodal interactions in motion perception have reported activation in several brain areas, including those related to motion processing and/or sensory association, in response to multimodal (e.g., visual and auditory) stimuli that were both in motion. Recent studies have demonstrated that sounds can trigger illusory visual apparent motion to static visual stimuli (sound-induced visual motion: SIVM): A visual stimulus blinking at a fixed location is perceived to be moving laterally when an alternating left-right sound is also present. Here, we investigated brain activity related to the perception of SIVM using a 7T functional magnetic resonance imaging technique. Specifically, we focused on the patterns of neural activities in SIVM and visually induced visual apparent motion (VIVM). We observed shared activations in the middle occipital area (V5/hMT), which is thought to be involved in visual motion processing, for SIVM and VIVM. Moreover, as compared to VIVM, SIVM resulted in greater activation in the superior temporal area and dominant functional connectivity between the V5/hMT area and the areas related to auditory and crossmodal motion processing. These findings indicate that similar but partially different neural mechanisms could be involved in auditory-induced and visually-induced motion perception, and neural signals in auditory, visual, and, crossmodal motion processing areas closely and directly interact in the perception of SIVM. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Fractionating the neural correlates of individual working memory components underlying arithmetic problem solving skills in children.

    Science.gov (United States)

    Metcalfe, Arron W S; Ashkenazi, Sarit; Rosenberg-Lee, Miriam; Menon, Vinod

    2013-10-01

    Baddeley and Hitch's multi-component working memory (WM) model has played an enduring and influential role in our understanding of cognitive abilities. Very little is known, however, about the neural basis of this multi-component WM model and the differential role each component plays in mediating arithmetic problem solving abilities in children. Here, we investigate the neural basis of the central executive (CE), phonological (PL) and visuo-spatial (VS) components of WM during a demanding mental arithmetic task in 7-9 year old children (N=74). The VS component was the strongest predictor of math ability in children and was associated with increased arithmetic complexity-related responses in left dorsolateral and right ventrolateral prefrontal cortices as well as bilateral intra-parietal sulcus and supramarginal gyrus in posterior parietal cortex. Critically, VS, CE and PL abilities were associated with largely distinct patterns of brain response. Overlap between VS and CE components was observed in left supramarginal gyrus and no overlap was observed between VS and PL components. Our findings point to a central role of visuo-spatial WM during arithmetic problem-solving in young grade-school children and highlight the usefulness of the multi-component Baddeley and Hitch WM model in fractionating the neural correlates of arithmetic problem solving during development. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. In vivo temporal property of GABAergic neural transmission in collateral feed-forward inhibition system of hippocampal-prefrontal pathway.

    Science.gov (United States)

    Takita, Masatoshi; Kuramochi, Masahito; Izaki, Yoshinori; Ohtomi, Michiko

    2007-05-30

    Anatomical evidence suggests that rat CA1 hippocampal afferents collaterally innervate excitatory projecting pyramidal neurons and inhibitory interneurons, creating a disynaptic, feed-forward inhibition microcircuit in the medial prefrontal cortex (mPFC). We investigated the temporal relationship between the frequency of paired synaptic transmission and gamma-aminobutyric acid (GABA)ergic receptor-mediated modulation of the microcircuit in vivo under urethane anesthesia. Local perfusions of a GABAa antagonist (-)-bicuculline into the mPFC via microdialysis resulted in a statistically significant disinhibitory effect on intrinsic GABA action, increasing the first and second mPFC responses following hippocampal paired stimulation at interstimulus intervals of 100-200 ms, but not those at 25-50 ms. This (-)-bicuculline-induced disinhibition was compensated by the GABAa agonist muscimol, which itself did not attenuate the intrinsic oscillation of the local field potentials. The perfusion of a sub-minimal concentration of GABAb agonist (R)-baclofen slightly enhanced the synaptic transmission, regardless of the interstimulus interval. In addition to the tonic control by spontaneous fast-spiking GABAergic neurons, it is clear the sequential transmission of the hippocampal-mPFC pathway can phasically drive the collateral feed-forward inhibition system through activation of a GABAa receptor, bringing an active signal filter to the various types of impulse trains that enter the mPFC from the hippocampus in vivo.

  9. Cortical Neural Synchronization Underlies Primary Visual Consciousness of Qualia: Evidence from Event-Related Potentials.

    Science.gov (United States)

    Babiloni, Claudio; Marzano, Nicola; Soricelli, Andrea; Cordone, Susanna; Millán-Calenti, José Carlos; Del Percio, Claudio; Buján, Ana

    2016-01-01

    This article reviews three experiments on event-related potentials (ERPs) testing the hypothesis that primary visual consciousness (stimulus self-report) is related to enhanced cortical neural synchronization as a function of stimulus features. ERP peak latency and sources were compared between "seen" trials and "not seen" trials, respectively related and unrelated to the primary visual consciousness. Three salient features of visual stimuli were considered (visuospatial, emotional face expression, and written words). Results showed the typical visual ERP components in both "seen" and "not seen" trials. There was no statistical difference in the ERP peak latencies between the "seen" and "not seen" trials, suggesting a similar timing of the cortical neural synchronization regardless the primary visual consciousness. In contrast, ERP sources showed differences between "seen" and "not seen" trials. For the visuospatial stimuli, the primary consciousness was related to higher activity in dorsal occipital and parietal sources at about 400 ms post-stimulus. For the emotional face expressions, there was greater activity in parietal and frontal sources at about 180 ms post-stimulus. For the written letters, there was higher activity in occipital, parietal and temporal sources at about 230 ms post-stimulus. These results hint that primary visual consciousness is associated with an enhanced cortical neural synchronization having entirely different spatiotemporal characteristics as a function of the features of the visual stimuli and possibly, the relative qualia (i.e., visuospatial, face expression, and words). In this framework, the dorsal visual stream may be synchronized in association with the primary consciousness of visuospatial and emotional face contents. Analogously, both dorsal and ventral visual streams may be synchronized in association with the primary consciousness of linguistic contents. In this line of reasoning, the ensemble of the cortical neural networks

  10. Induction of alternative respiratory pathway involves nitric oxide, hydrogen peroxide and ethylene under salt stress.

    Science.gov (United States)

    Wang, Huahua; Huang, Junjun; Bi, Yurong

    2010-12-01

    Alternative respiratory pathway (AP) plays an important role in plant thermogenesis, fruit ripening and responses to environmental stresses. AP may participate in the adaptation to salt stress since salt stress increased the activity of the AP. Recently, new evidence revealed that ethylene and hydrogen peroxide (H(2)O(2)) are involved in the salt-induced increase of the AP, which plays an important role in salt tolerance in Arabidopsis callus, and ethylene may be acting downstream of H(2)O(2). Recent observations also indicated both ethylene and nitric oxide (NO) act as signaling molecules in responses to salt stress, and ethylene may be a part of the downstream signal molecular in NO action. In this addendum, a hypothetical model for NO function in regulation of H(2)O(2)- and ethylene-mediated induction of AP under salt stress is presented.

  11. Dynamic changes in the inner ear function and vestibular neural pathway related to the progression of labyrinthine infarction in patient with an anterior inferior cerebellar artery infarction.

    Science.gov (United States)

    Kim, Duk Rim; Lee, Hyo-Jeong; Kim, Hyung-Jong; Hong, Sung Kwang

    2011-12-01

    To describe changes in the inner ear function and the vestibular neural pathway according to the progression of a labyrinthine infarction in a patient with an anterior inferior cerebellar artery (AICA) infarction. A 58-year-old woman with hypertension who presented with isolated inner ear symptoms similar to those of endolymphatic hydrops but finally progressed to an AICA infarction. Serial neurotologic testing according to progression to an AICA infarction and antiplatelet therapy. Radiologic findings and neurotologic parameters, including pure tone audiogram thresholds, spontaneous nystagmus, summating potentials/action potentials on electrocochleography, interaural amplitude difference on the vestibular-evoked myogenic potential test, canal paresis and fixation index on the bithermal caloric test, and gain on oculomotor tests. Our patient initially presented with sudden hearing loss and was diagnosed with an acute AICA infarction on a follow up MRI. Dynamic change in neurotologic testing was observed during disease progression. The vertigo and motion intolerance improved gradually after antiplatelet therapy. Changes in the clinical profile, which were documented during a transition from isolated labyrinthine ischemia to an AICA infarction, suggest that sensitivity to an ischemic injury is variable in different components of the labyrinthine organs in addition to providing a new insight into the response of vestibular neural pathway to ischemic injury.

  12. Neural Correlates of Choking Under Pressure: Athletes High in Sports Anxiety Monitor Errors More When Performance Is Being Evaluated.

    Science.gov (United States)

    Masaki, Hiroaki; Maruo, Yuya; Meyer, Alexandria; Hajcak, Greg

    2017-01-01

    We investigated the relationship between performance-related anxiety and the neural response to errors. Using the sport anxiety scale, we selected university athletes high in sports anxiety and low in sports anxiety. The two groups performed a spatial Stroop task while their performance was being evaluated by an experimenter and also during a control (i.e., no evaluation) condition. The error-related negativity was significantly larger during the evaluation than control condition among athletes who reported high performance-related anxiety. These results suggest that performance evaluation may make errors particularly aversive or salient for individuals who fail to perform well under pressure.

  13. Exponential synchronization of delayed neutral-type neural networks with Lévy noise under non-Lipschitz condition

    Science.gov (United States)

    Ma, Shuo; Kang, Yanmei

    2018-04-01

    In this paper, the exponential synchronization of stochastic neutral-type neural networks with time-varying delay and Lévy noise under non-Lipschitz condition is investigated for the first time. Using the general Itô's formula and the nonnegative semi-martingale convergence theorem, we derive general sufficient conditions of two kinds of exponential synchronization for the drive system and the response system with adaptive control. Numerical examples are presented to verify the effectiveness of the proposed criteria.

  14. Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance

    DEFF Research Database (Denmark)

    Campos, Lia S; Leone, Dino P; Relvas, Joao B

    2004-01-01

    , signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control...

  15. Robust Finite-Time Stabilization of Fractional-Order Neural Networks With Discontinuous and Continuous Activation Functions Under Uncertainty.

    Science.gov (United States)

    Ding, Zhixia; Zeng, Zhigang; Wang, Leimin

    2017-03-10

    This paper is concerned with robust finite-time stabilization for a class of fractional-order neural networks (FNNs) with two types of activation functions (i.e., discontinuous and continuous activation function) under uncertainty. It is worth noting that there exist few results about FNNs with discontinuous activation functions, which is mainly because classical solutions and theories of differential equations cannot be applied in this case. Especially, there is no relevant finite-time stabilization research for such system, and this paper makes up for the gap. The existence of global solution under the framework of Filippov for such system is guaranteed by limiting discontinuous activation functions. According to set-valued analysis and Kakutani's fixed point theorem, we obtain the existence of equilibrium point. In particular, based on differential inclusion theory and fractional Lyapunov stability theory, several new sufficient conditions are given to ensure finite-time stabilization via a novel discontinuous controller, and the upper bound of the settling time for stabilization is estimated. In addition, we analyze the finite-time stabilization of FNNs with Lipschitz-continuous activation functions under uncertainty. The results of this paper improve corresponding ones of integer-order neural networks with discontinuous and continuous activation functions. Finally, three numerical examples are given to show the effectiveness of the theoretical results.

  16. Temporal neural mechanisms underlying conscious access to different levels of facial stimulus contents.

    Science.gov (United States)

    Hsu, Shen-Mou; Yang, Yu-Fang

    2018-04-01

    An important issue facing the empirical study of consciousness concerns how the contents of incoming stimuli gain access to conscious processing. According to classic theories, facial stimuli are processed in a hierarchical manner. However, it remains unclear how the brain determines which level of stimulus content is consciously accessible when facing an incoming facial stimulus. Accordingly, with a magnetoencephalography technique, this study aims to investigate the temporal dynamics of the neural mechanism mediating which level of stimulus content is consciously accessible. Participants were instructed to view masked target faces at threshold so that, according to behavioral responses, their perceptual awareness alternated from consciously accessing facial identity in some trials to being able to consciously access facial configuration features but not facial identity in other trials. Conscious access at these two levels of facial contents were associated with a series of differential neural events. Before target presentation, different patterns of phase angle adjustment were observed between the two types of conscious access. This effect was followed by stronger phase clustering for awareness of facial identity immediately during stimulus presentation. After target onset, conscious access to facial identity, as opposed to facial configural features, was able to elicit more robust late positivity. In conclusion, we suggest that the stages of neural events, ranging from prestimulus to stimulus-related activities, may operate in combination to determine which level of stimulus contents is consciously accessed. Conscious access may thus be better construed as comprising various forms that depend on the level of stimulus contents accessed. NEW & NOTEWORTHY The present study investigates how the brain determines which level of stimulus contents is consciously accessible when facing an incoming facial stimulus. Using magnetoencephalography, we show that prestimulus

  17. Modulation of neural circuits underlying temporal production by facial expressions of pain.

    Directory of Open Access Journals (Sweden)

    Daniela Ballotta

    Full Text Available According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a whether observation of facial expressions of pain interferes with time production; and b the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1 the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2 the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.

  18. Neural systems underlying aversive conditioning in humans with primary and secondary reinforcers

    Directory of Open Access Journals (Sweden)

    Mauricio R Delgado

    2011-05-01

    Full Text Available Money is a secondary reinforcer commonly used across a range of disciplines in experimental paradigms investigating reward learning and decision-making. The effectiveness of monetary reinforcers during aversive learning and its neural basis, however, remains a topic of debate. Specifically, it is unclear if the initial acquisition of aversive representations of monetary losses depends on similar neural systems as more traditional aversive conditioning that involves primary reinforcers. This study contrasts the efficacy of a biologically defined primary reinforcer (shock and a socially defined secondary reinforcer (money during aversive learning and its associated neural circuitry. During a two-part experiment, participants first played a gambling game where wins and losses were based on performance to gain an experimental bank. Participants were then exposed to two separate aversive conditioning sessions. In one session, a primary reinforcer (mild shock served as an unconditioned stimulus (US and was paired with one of two colored squares, the conditioned stimuli (CS+ and CS-, respectively. In another session, a secondary reinforcer (loss of money served as the US and was paired with one of two different CS. Skin conductance responses were greater for CS+ compared to CS- trials irrespective of type of reinforcer. Neuroimaging results revealed that the striatum, a region typically linked with reward-related processing, was found to be involved in the acquisition of aversive conditioned response irrespective of reinforcer type. In contrast, the amygdala was involved during aversive conditioning with primary reinforcers, as suggested by both an exploratory fMRI analysis and a follow-up case study with a patient with bilateral amygdala damage. Taken together, these results suggest that learning about potential monetary losses may depend on reinforcement learning related systems, rather than on typical structures involved in more biologically based

  19. Effect of abacus training on executive function development and underlying neural correlates in Chinese children.

    Science.gov (United States)

    Wang, Chunjie; Weng, Jian; Yao, Yuan; Dong, Shanshan; Liu, Yuqiu; Chen, Feiyan

    2017-10-01

    Executive function (EF) refers to a set of cognitive abilities involved in self-regulated behavior. Given the critical role of EF in cognition, strategies for improving EF have attracted intensive attention in recent years. Previous studies have explored the effects of abacus-based mental calculation (AMC) training on several cognitive abilities. However, it remains unclear whether AMC training affects EF and its neural correlates. In this study, participants were randomly assigned to AMC or control groups upon starting primary school. The AMC group received 2 h AMC training every week, while the control group did not have any abacus experience. Neural activity during an EF task was examined using functional MRI for both groups in their 4 th and 6 th grades. Our results showed that the AMC group performed better and faster than the control group in both grades. They also had lower activation in the frontoparietal reigons than the control group in the 6 th grade. From the 4 th to the 6 th grade, the AMC group showed activation decreases in the frontoparietal regions, while the control group exhibited an opposite pattern. Furthermore, voxel-wise regression analyses revealed that better performance was associated with lower task-relevant brain activity in the AMC group but associated with greater task-relevant brain activity in the control group. These results suggest that long-term AMC training, with calculation ability as its original target, may improve EF and enhance neural efficiency of the frontoparietal regions during development. Hum Brain Mapp 38:5234-5249, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Modulation of neural circuits underlying temporal production by facial expressions of pain

    Science.gov (United States)

    Lui, Fausta; Porro, Carlo Adolfo; Nichelli, Paolo Frigio; Benuzzi, Francesca

    2018-01-01

    According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems. PMID:29447256

  1. Global wheat production potentials and management flexibility under the representative concentration pathways

    Science.gov (United States)

    Balkovic, Juraj; van der Velde, Marijn; Skalsky, Rastislav; Xiong, Wei; Folberth, Christian; Khabarov, Nikolay; Smirnov, Alexey

    2014-05-01

    Global wheat production is strongly linked with food security as wheat is one of the main sources of human nutrition. Increasing or stabilizing wheat yields in response to climate change is therefore imperative. To do so will require agricultural management interventions that have different levels of flexibility at regional level. Climate change is expected to worsen wheat growing conditions in many places and thus negatively impact on future management opportunities for sustainable intensification. We quantified, in a spatially explicit manner, global wheat yield developments under the envelope of Representative Concentration Pathways (RCP 2.6, 4.5, 6.0 and 8.5) under current and alternative fertilization and irrigation management to estimate future flexibility to cope with climate change impacts. A large-scale implementation of the EPIC model was integrated with the most recent information on global wheat cultivation currently available, and it was used to simulate regional and global wheat yields and production under historical climate and the RCP-driven and bias-corrected HadGEM2-ES climate projections. Fertilization and irrigation management scenarios were designed to project actual and exploitable (under current irrigation infrastructure) yields as well as the climate- and water-limited yield potentials. With current nutrient and water management, and across all RCPs, the global wheat production at the end of the century decreased from 50 to 100 Mt - with RCP2.6 having the lowest and RCP8.5 the highest impact. Despite the decrease in global wheat production potential on current cropland, the exploitable and climatic production gap of respectively 350 and 580 Mt indicates a considerable flexibility to counteract negative climate change impacts across all RCPs. Agricultural management could increase global wheat production by approximately 30% through intensified fertilization and 50% through improved fertilization and extended irrigation if nutrients or water

  2. Assessing carbon dioxide removal through global and regional ocean alkalinization under high and low emission pathways

    Directory of Open Access Journals (Sweden)

    A. Lenton

    2018-04-01

    Full Text Available Atmospheric carbon dioxide (CO2 levels continue to rise, increasing the risk of severe impacts on the Earth system, and on the ecosystem services that it provides. Artificial ocean alkalinization (AOA is capable of reducing atmospheric CO2 concentrations and surface warming and addressing ocean acidification. Here, we simulate global and regional responses to alkalinity (ALK addition (0.25 PmolALK yr−1 over the period 2020–2100 using the CSIRO-Mk3L-COAL Earth System Model, under high (Representative Concentration Pathway 8.5; RCP8.5 and low (RCP2.6 emissions. While regionally there are large changes in alkalinity associated with locations of AOA, globally we see only a very weak dependence on where and when AOA is applied. On a global scale, while we see that under RCP2.6 the carbon uptake associated with AOA is only ∼ 60 % of the total, under RCP8.5 the relative changes in temperature are larger, as are the changes in pH (140 % and aragonite saturation state (170 %. The simulations reveal AOA is more effective under lower emissions, therefore the higher the emissions the more AOA is required to achieve the same reduction in global warming and ocean acidification. Finally, our simulated AOA for 2020–2100 in the RCP2.6 scenario is capable of offsetting warming and ameliorating ocean acidification increases at the global scale, but with highly variable regional responses.

  3. Adaptation Pathway of Low Impact Development Planning under Climate Change for a Sustainable Rural Community

    Science.gov (United States)

    Chen, P. Y.; Tung, C. P.

    2016-12-01

    The study focuses on developing the methodology of adaptation pathway for storm water management in a community scale. Following previous results on adaptation procedures including problem and goal setup, current risk assessment and analysis, future risk assessment and analysis, and adaptation options identification and evaluation, the study aims at analyzing adaptation pathway planning and implementation, namely the fifth step, for applying low impact development (LID). Based on the efficacy analyses of the feasible adaptation options, an adaptation pathway map can be build. Each pathway is a combination of the adaptation measures arranged in certain order. The developed adaptation pathway map visualizes the relative effectiveness and the connection of the adaptation measures. In addition, the tipping points of the system can be clearly identified and the triggers can be defined accordingly. There are multiple choices of pathways in an adaptation pathway map, which can be referred as pathway candidates. To ensure the applicability and operability, the methodology of adaptation pathway analysis is applied to a case study. Required information for developing an adaptation pathway map includes the scores of the adaptation options on the criteria, namely the effects, costs, immediacy, and side effect. Feasible adaptation options for the design case are dredging, pipeline expansion, pumping station, LID and detention pond. By ranking the options according to the criteria, LID is found dominating dredging and pumping station in this case. The information of the pathway candidates can be further used by the stakeholders to select the most suitable and promising pathway.

  4. Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

    Directory of Open Access Journals (Sweden)

    Emilie Rouaud

    2010-02-01

    Full Text Available An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-Methyl-D-Aspartate receptors (NMDA-R by its agonist D-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous D-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of D-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of D-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the D-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

  5. Violence exposure and neural systems underlying working memory for emotional stimuli in youth.

    Science.gov (United States)

    Jenness, Jessica L; Rosen, Maya L; Sambrook, Kelly A; Dennison, Meg J; Lambert, Hilary K; Sheridan, Margaret A; McLaughlin, Katie A

    2017-11-16

    Violence exposure during childhood is common and associated with poor cognitive and academic functioning. However, little is known about how violence exposure influences cognitive processes that might contribute to these disparities, such as working memory, or their neural underpinnings, particularly for cognitive processes that occur in emotionally salient contexts. We address this gap in a sample of 54 participants aged 8 to 19 years (50% female), half with exposure to interpersonal violence. Participants completed a delayed match to sample task for emotional faces while undergoing functional magnetic resonance imaging scanning. Violence-exposed youth performed worse than controls on happy and neutral, but not angry, trials. In whole-brain analysis, violence-exposed youth had reduced activation in the left middle frontal gyrus and right intraparietal sulcus during encoding and the left superior temporal sulcus and temporal-parietal junction during retrieval compared to control youth. Reduced activation in the left middle frontal gyrus during encoding and the left superior temporal sulcus during retrieval mediated the association between violence exposure and task performance. Violence exposure influences the frontoparietal network that supports working memory as well as regions involved in facial processing during working memory for emotional stimuli. Reduced neural recruitment in these regions may explain atypical patterns of cognitive processing seen among violence-exposed youth, particularly within emotional contexts.

  6. Identifying temporal and causal contributions of neural processes underlying the Implicit Association Test (IAT

    Directory of Open Access Journals (Sweden)

    Chad Edward Forbes

    2012-11-01

    Full Text Available The Implicit Association Test (IAT is a popular behavioral measure that assesses the associative strength between outgroup members and stereotypical and counterstereotypical traits. Less is known, however, about the degree to which the IAT reflects automatic processing. Two studies examined automatic processing contributions to a gender-IAT using a data driven, social neuroscience approach. Performance on congruent (e.g., categorizing male names with synonyms of strength and incongruent (e.g., categorizing female names with synonyms of strength IAT blocks were separately analyzed using EEG (event-related potentials, or ERPs, and coherence; Study 1 and lesion (Study 2 methodologies. Compared to incongruent blocks, performance on congruent IAT blocks was associated with more positive ERPs that manifested in frontal and occipital regions at automatic processing speeds, occipital regions at more controlled processing speeds and was compromised by volume loss in the anterior temporal lobe, insula and medial PFC. Performance on incongruent blocks was associated with volume loss in supplementary motor areas, cingulate gyrus and a region in medial PFC similar to that found for congruent blocks. Greater coherence was found between frontal and occipital regions to the extent individuals exhibited more bias. This suggests there are separable neural contributions to congruent and incongruent blocks of the IAT but there is also a surprising amount of overlap. Given the temporal and regional neural distinctions, these results provide converging evidence that stereotypic associative strength assessed by the IAT indexes automatic processing to a degree.

  7. Neural mechanisms underlying contextual dependency of subjective values: converging evidence from monkeys and humans.

    Science.gov (United States)

    Abitbol, Raphaëlle; Lebreton, Maël; Hollard, Guillaume; Richmond, Barry J; Bouret, Sébastien; Pessiglione, Mathias

    2015-02-04

    A major challenge for decision theory is to account for the instability of expressed preferences across time and context. Such variability could arise from specific properties of the brain system used to assign subjective values. Growing evidence has identified the ventromedial prefrontal cortex (VMPFC) as a key node of the human brain valuation system. Here, we first replicate this observation with an fMRI study in humans showing that subjective values of painting pictures, as expressed in explicit pleasantness ratings, are specifically encoded in the VMPFC. We then establish a bridge with monkey electrophysiology, by comparing single-unit activity evoked by visual cues between the VMPFC and the orbitofrontal cortex. At the neural population level, expected reward magnitude was only encoded in the VMPFC, which also reflected subjective cue values, as expressed in Pavlovian appetitive responses. In addition, we demonstrate in both species that the additive effect of prestimulus activity on evoked activity has a significant impact on subjective values. In monkeys, the factor dominating prestimulus VMPFC activity was trial number, which likely indexed variations in internal dispositions related to fatigue or satiety. In humans, prestimulus VMPFC activity was externally manipulated through changes in the musical context, which induced a systematic bias in subjective values. Thus, the apparent stochasticity of preferences might relate to the VMPFC automatically aggregating the values of contextual features, which would bias subsequent valuation because of temporal autocorrelation in neural activity. Copyright © 2015 the authors 0270-6474/15/352308-13$15.00/0.

  8. Tuning to the significant: neural and genetic processes underlying affective enhancement of visual perception and memory.

    Science.gov (United States)

    Markovic, Jelena; Anderson, Adam K; Todd, Rebecca M

    2014-02-01

    Emotionally arousing events reach awareness more easily and evoke greater visual cortex activation than more mundane events. Recent studies have shown that they are also perceived more vividly and that emotionally enhanced perceptual vividness predicts memory vividness. We propose that affect-biased attention (ABA) - selective attention to emotionally salient events - is an endogenous attentional system tuned by an individual's history of reward and punishment. We present the Biased Attention via Norepinephrine (BANE) model, which unifies genetic, neuromodulatory, neural and behavioural evidence to account for ABA. We review evidence supporting BANE's proposal that a key mechanism of ABA is locus coeruleus-norepinephrine (LC-NE) activity, which interacts with activity in hubs of affective salience networks to modulate visual cortex activation and heighten the subjective vividness of emotionally salient stimuli. We further review literature on biased competition and look at initial evidence for its potential as a neural mechanism behind ABA. We also review evidence supporting the role of the LC-NE system as a driving force of ABA. Finally, we review individual differences in ABA and memory including differences in sensitivity to stimulus category and valence. We focus on differences arising from a variant of the ADRA2b gene, which codes for the alpha2b adrenoreceptor as a way of investigating influences of NE availability on ABA in humans. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

    Science.gov (United States)

    Moreno-López, Laura; Manktelow, Anne E; Sahakian, Barbara J; Menon, David K; Stamatakis, Emmanuel A

    2017-02-01

    Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  10. Bad and worse: neural systems underlying reappraisal of high- and low-intensity negative emotions.

    Science.gov (United States)

    Silvers, Jennifer A; Weber, Jochen; Wager, Tor D; Ochsner, Kevin N

    2015-02-01

    One of the most effective strategies for regulating emotional responses is cognitive reappraisal. While prior work has made great strides in characterizing reappraisal's neural mechanisms and behavioral outcomes, the key issue of how regulation varies as a function of emotional intensity remains unaddressed. We compared the behavioral and neural correlates of reappraisal of high- and low-intensity emotional responses using functional magnetic resonance imaging (fMRI). We found that successful reappraisal of both high- and low-intensity emotions depends upon recruitment of dorsomedial (dmPFC) as well as left dorsolateral (dlPFC) and ventrolateral (vlPFC) prefrontal cortex. However, reappraisal of high-intensity emotions more strongly activated left dlPFC, and in addition, activated right lateral and dorsomedial PFC regions not recruited by low-intensity reappraisal. No brain regions were more strongly recruited during reappraisal of low when compared with high-intensity emotions. Taken together, these results suggest that reappraisal of high-intensity emotion requires greater cognitive resources as evidenced by quantitative and qualitative differences in prefrontal recruitment. These data have implications for understanding how and when specific PFC systems are needed to regulate different types of emotional responses. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. Gender Differences in Behavioral and Neural Responses to Unfairness Under Social Pressure.

    Science.gov (United States)

    Zheng, Li; Ning, Reipeng; Li, Lin; Wei, Chunli; Cheng, Xuemei; Zhou, Chu; Guo, Xiuyan

    2017-10-18

    Numerous studies have revealed the key role of social pressure on individuals' decision-making processes. However, the impact of social pressure on unfairness-related decision-making processes remains unclear. In the present study, we investigated how social pressure modulated men's and women's responses in an ultimatum game. Twenty women and eighteen men played the ultimatum game as responders in the scanner, where fair and unfair offers were tendered by proposers acting alone (low pressure) or by proposers endorsed by three supporters (high pressure). Results showed that men rejected more, whereas women accepted more unfair offers in the high versus low pressure context. Neurally, pregenual anterior cingulate cortex activation in women positively predicted their acceptance rate difference between contexts. In men, stronger right anterior insula activation and increased connectivity between right anterior insula and dorsal anterior cingulate cortex were observed when they receiving unfair offers in the high than low pressure context. Furthermore, more bilateral anterior insula and left dorsolateral prefrontal cortex activations were found when men rejected (relative to accepted) unfair offers in the high than low pressure context. These findings highlighted gender differences in the modulation of behavioral and neural responses to unfairness by social pressure.

  12. Neural dynamics underlying attentional orienting to auditory representations in short-term memory.

    Science.gov (United States)

    Backer, Kristina C; Binns, Malcolm A; Alain, Claude

    2015-01-21

    Sounds are ephemeral. Thus, coherent auditory perception depends on "hearing" back in time: retrospectively attending that which was lost externally but preserved in short-term memory (STM). Current theories of auditory attention assume that sound features are integrated into a perceptual object, that multiple objects can coexist in STM, and that attention can be deployed to an object in STM. Recording electroencephalography from humans, we tested these assumptions, elucidating feature-general and feature-specific neural correlates of auditory attention to STM. Alpha/beta oscillations and frontal and posterior event-related potentials indexed feature-general top-down attentional control to one of several coexisting auditory representations in STM. Particularly, task performance during attentional orienting was correlated with alpha/low-beta desynchronization (i.e., power suppression). However, attention to one feature could occur without simultaneous processing of the second feature of the representation. Therefore, auditory attention to memory relies on both feature-specific and feature-general neural dynamics. Copyright © 2015 the authors 0270-6474/15/351307-12$15.00/0.

  13. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms.

    Science.gov (United States)

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-E; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs' appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers' attention from different fields and many studies have validated MMORPGs' positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers' overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas.

  14. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

    Science.gov (United States)

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers’ overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas. PMID:28303097

  15. Prediction of composite fatigue life under variable amplitude loading using artificial neural network trained by genetic algorithm

    Science.gov (United States)

    Rohman, Muhamad Nur; Hidayat, Mas Irfan P.; Purniawan, Agung

    2018-04-01

    Neural networks (NN) have been widely used in application of fatigue life prediction. In the use of fatigue life prediction for polymeric-base composite, development of NN model is necessary with respect to the limited fatigue data and applicable to be used to predict the fatigue life under varying stress amplitudes in the different stress ratios. In the present paper, Multilayer-Perceptrons (MLP) model of neural network is developed, and Genetic Algorithm was employed to optimize the respective weights of NN for prediction of polymeric-base composite materials under variable amplitude loading. From the simulation result obtained with two different composite systems, named E-glass fabrics/epoxy (layups [(±45)/(0)2]S), and E-glass/polyester (layups [90/0/±45/0]S), NN model were trained with fatigue data from two different stress ratios, which represent limited fatigue data, can be used to predict another four and seven stress ratios respectively, with high accuracy of fatigue life prediction. The accuracy of NN prediction were quantified with the small value of mean square error (MSE). When using 33% from the total fatigue data for training, the NN model able to produce high accuracy for all stress ratios. When using less fatigue data during training (22% from the total fatigue data), the NN model still able to produce high coefficient of determination between the prediction result compared with obtained by experiment.

  16. Thermodynamic pathways to melting, ablation, and solidification in absorbing solids under pulsed laser irradiation

    International Nuclear Information System (INIS)

    Lorazo, Patrick; Lewis, Laurent J.; Meunier, Michel

    2006-01-01

    The thermodynamic pathways involved in laser irradiation of absorbing solids are investigated in silicon for pulse durations of 500 fs and 100 ps. This is achieved by accounting for carrier and atom dynamics within a combined Monte Carlo and molecular-dynamics scheme and simultaneously tracking the time evolution of the irradiated material in ρ-T-P space. Our simulations reveal thermal changes in long-range order and state of aggregation driven, in most cases, by nonequilibrium states of rapidly heated or promptly cooled matter. Under femtosecond irradiation near the ablation threshold, the system is originally pulled to a near-critical state following rapid ( -12 s) disordering of the mechanically unstable crystal and isochoric heating of the resulting metallic liquid. The latter is then adiabatically cooled to the liquid-vapor regime where phase explosion of the subcritical, superheated melt is initiated by a direct conversion of translational, mechanical energy into surface energy on a ∼10 -12 -10 -11 s time scale. At higher fluences, matter removal involves, instead, the fragmentation of an initially homogeneous fluid subjected to large strain rates upon rapid, supercritical expansion in vacuum. Under picosecond irradiation, homogeneous and, at later times, heterogeneous melting of the superheated solid are followed by nonisochoric heating of the molten metal. In this case, the subcritical liquid material is subsequently cooled onto the binodal by thermal conduction and explosive boiling does not take place; as a result, ablation is associated with a ''trivial'' fragmentation process, i.e., the relatively slow expansion and dissociation into liquid droplets of supercritical matter near thermodynamic equilibrium. This implies a liquid-vapor equilibration time of ∼10 -11 -10 -10 s and heating along the binodal under nanosecond irradiation. Solidification of the nonablated, supercooled molten material is eventually observed on a ∼10 -11 -10 -9 s time scale

  17. Variants in TNIP1, a regulator of the NF-kB pathway, found in two patients with neural tube defects.

    Science.gov (United States)

    Francesca, La Carpia; Claudia, Rendeli; Molinario, Clelia; Annamaria, Milillo; Chiara, Farroni; Natalia, Cannelli; Emanuele, Ausili; Valentina, Paolucci; Giovanni, Neri; Costantino, Romagnoli; Eugenio, Sangiorgi; Fiorella, Gurrieri

    2016-06-01

    Neural tube defects (NTDs) occur in 1:1000 births. The etiology is complex, with the influence of environmental and genetic factors. Environmental factors, such as folate deficiency, diabetes, or hypoxia strongly contribute to the occurrence of NTD. Also, there is a strong genetic contribution to NTD, as highlighted by the number of genes so far identified in several different developmental pathways usually altered in NTD. Each gene identified so far accounts for a small percentage of all NTD cases, indicating a very high heterogeneity. Exome sequencing was performed in seven sporadic patients with severe mielomeningocele. Novel coding variants shared by two or more patients were selected for further analysis. We identified in two unrelated patients two different variants in TNIP1, a gene not previously involved in NTD whose main role is downregulation of the NF-kB pathway. One variant, c.1089T>G (p.Phe363Leu), is de novo, whereas the c.1781C>T (p.Pro594Leu) is absent in the mother, but could not be tested in the father, as he was unavailable. The latter variant is a very rare variant in the ExAC database. These findings suggest that TNIP1 is a new potential predisposing gene to spina bifida (SB) and its pathway needs to be investigated in human NTD in order to confirm its role and to plan appropriate counseling to families.

  18. The proliferation of amplifying neural progenitor cells is impaired in the aging brain and restored by the mTOR pathway activation.

    Science.gov (United States)

    Romine, Jennifer; Gao, Xiang; Xu, Xiao-Ming; So, Kwok Fai; Chen, Jinhui

    2015-04-01

    A decrease in neurogenesis in the aged brain has been correlated with cognitive decline. The molecular signaling that regulates age-related decline in neurogenesis is still not fully understood. We found that different subtypes of neural stem cells (NSCs) in the hippocampus were differentially impaired by aging. The quiescent NSCs decreased slowly, although the active NSCs exhibited a sharp and dramatic decline from the ages of 6-9 months and became more quiescent at an early stage during the aging process. The activity of the mammalian target of rapamycin (mTOR) signal pathway is compromised in the NSCs of the aged brain. Activating the mTOR signaling pathway increased NSC proliferation and promoted neurogenesis in aged mice. In contrast, inhibiting the mTOR signaling pathway decreased NSCs proliferation. These results indicate that an age-associated decline in neurogenesis is mainly because of the reduction in proliferation of active NSCs, at least partially because of the compromise in the mTOR signaling activity. Stimulating the mTOR signaling revitalizes the NSCs, restores their proliferation, and enhances neurogenesis in the hippocampus of the aged brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

    Full Text Available Our previous studies indicated that transcription factor Brn-4 is upregulated in the surgically denervated hippocampus in vivo, promoting neuronal differentiation of hippocampal neural stem cells (NSCs in vitro. The molecules mediating Brn-4 upregulation in the denervated hippocampus remain unknown. In this study we examined the levels of insulin-like growth factor-1 (IGF-1 in hippocampus following denervation. Surgical denervation led to a significant increase in IGF-1 expression in vivo. We also report that IGF-1 treatment on NSCs in vitro led to a marked acceleration of Brn-4 expression and cell differentiation down neuronal pathways. The promotion effects were blocked by PI3K-specific inhibitor (LY294002, but not MAPK inhibitor (PD98059; levels of phospho-Akt were increased by IGF-1 treatment. In addition, inhibition of IGF-1 receptor (AG1024 and mTOR (rapamycin both attenuated the increased expression of Brn-4 induced by IGF-1. Together, the results demonstrated that upregulation of IGF-1 induced by hippocampal denervation injury leads to activation of the PI3K/Akt signaling pathway, which in turn gives rise to upregulation of the Brn-4 and subsequent stem cell differentiation down neuronal pathways.

  20. Evoked EMG-based torque prediction under muscle fatigue in implanted neural stimulation

    Science.gov (United States)

    Hayashibe, Mitsuhiro; Zhang, Qin; Guiraud, David; Fattal, Charles

    2011-10-01

    In patients with complete spinal cord injury, fatigue occurs rapidly and there is no proprioceptive feedback regarding the current muscle condition. Therefore, it is essential to monitor the muscle state and assess the expected muscle response to improve the current FES system toward adaptive force/torque control in the presence of muscle fatigue. Our team implanted neural and epimysial electrodes in a complete paraplegic patient in 1999. We carried out a case study, in the specific case of implanted stimulation, in order to verify the corresponding torque prediction based on stimulus evoked EMG (eEMG) when muscle fatigue is occurring during electrical stimulation. Indeed, in implanted stimulation, the relationship between stimulation parameters and output torques is more stable than external stimulation in which the electrode location strongly affects the quality of the recruitment. Thus, the assumption that changes in the stimulation-torque relationship would be mainly due to muscle fatigue can be made reasonably. The eEMG was proved to be correlated to the generated torque during the continuous stimulation while the frequency of eEMG also decreased during fatigue. The median frequency showed a similar variation trend to the mean absolute value of eEMG. Torque prediction during fatigue-inducing tests was performed based on eEMG in model cross-validation where the model was identified using recruitment test data. The torque prediction, apart from the potentiation period, showed acceptable tracking performances that would enable us to perform adaptive closed-loop control through implanted neural stimulation in the future.

  1. Neural Mechanisms Underlying Affective Theory of Mind in Violent Antisocial Personality Disorder and/or Schizophrenia.

    Science.gov (United States)

    Schiffer, Boris; Pawliczek, Christina; Müller, Bernhard W; Wiltfang, Jens; Brüne, Martin; Forsting, Michael; Gizewski, Elke R; Leygraf, Norbert; Hodgins, Sheilagh

    2017-10-21

    Among violent offenders with schizophrenia, there are 2 sub-groups, one with and one without, conduct disorder (CD) and antisocial personality disorder (ASPD), who differ as to treatment response and alterations of brain structure. The present study aimed to determine whether the 2 groups also differ in Theory of Mind and neural activations subsuming this task. Five groups of men were compared: 3 groups of violent offenders-schizophrenia plus CD/ASPD, schizophrenia with no history of antisocial behavior prior to illness onset, and CD/ASPD with no severe mental illness-and 2 groups of non-offenders, one with schizophrenia and one without (H). Participants completed diagnostic interviews, the Psychopathy Checklist Screening Version Interview, the Interpersonal Reactivity Index, authorized access to clinical and criminal files, and underwent functional magnetic resonance imaging while completing an adapted version of the Reading-the-Mind-in-the-Eyes Task (RMET). Relative to H, nonviolent and violent men with schizophrenia and not CD/ASPD performed more poorly on the RMET, while violent offenders with CD/ASPD, both those with and without schizophrenia, performed similarly. The 2 groups of violent offenders with CD/ASPD, both those with and without schizophrenia, relative to the other groups, displayed higher levels of activation in a network of prefrontal and temporal-parietal regions and reduced activation in the amygdala. Relative to men without CD/ASPD, both groups of violent offenders with CD/ASPD displayed a distinct pattern of neural responses during emotional/mental state attribution pointing to distinct and comparatively successful processing of social information. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Estimation of lost circulation amount occurs during under balanced drilling using drilling data and neural network

    Directory of Open Access Journals (Sweden)

    Pouria Behnoud far

    2017-09-01

    Full Text Available Lost circulation can cause an increase in time and cost of operation. Pipe sticking, formation damage and uncontrolled flow of oil and gas may be consequences of lost circulation. Dealing with this problem is a key factor to conduct a successful drilling operation. Estimation of lost circulation amount is necessary to find a solution. Lost circulation is influenced by different parameters such as mud weight, pump pressure, depth etc. Mud weight, pump pressure and flow rate of mud should be designed to prevent induced fractures and have the least amount of lost circulation. Artificial neural network is useful to find the relations of parameters with lost circulation. Genetic algorithm is applied on the achieved relations to determine the optimum mud weight, pump pressure, and flow rate. In an Iranian oil field, daily drilling reports of wells which are drilled using UBD technique are studied. Asmari formation is the most important oil reservoir of the studied field and UBD is used only in this interval. Three wells with the most, moderate and without lost circulation are chosen. In this article, the effect of mud weight, depth, pump pressure and flow rate of pump on lost circulation in UBD of Asmari formation in one of the Southwest Iranian fields is studied using drilling data and artificial neural network. In addition, the amount of lost circulation is predicted precisely with respect to two of the studied parameters using the presented correlations and the optimum mud weight, pump pressure and flow rate are calculated to minimize the lost circulation amount.

  3. "NeuroStem Chip": a novel highly specialized tool to study neural differentiation pathways in human stem cells

    Directory of Open Access Journals (Sweden)

    Li Jia-Yi

    2007-02-01

    Full Text Available Abstract Background Human stem cells are viewed as a possible source of neurons for a cell-based therapy of neurodegenerative disorders, such as Parkinson's disease. Several protocols that generate different types of neurons from human stem cells (hSCs have been developed. Nevertheless, the cellular mechanisms that underlie the development of neurons in vitro as they are subjected to the specific differentiation protocols are often poorly understood. Results We have designed a focused DNA (oligonucleotide-based large-scale microarray platform (named "NeuroStem Chip" and used it to study gene expression patterns in hSCs as they differentiate into neurons. We have selected genes that are relevant to cells (i being stem cells, (ii becoming neurons, and (iii being neurons. The NeuroStem Chip has over 1,300 pre-selected gene targets and multiple controls spotted in quadruplicates (~46,000 spots total. In this study, we present the NeuroStem Chip in detail and describe the special advantages it offers to the fields of experimental neurology and stem cell biology. To illustrate the utility of NeuroStem Chip platform, we have characterized an undifferentiated population of pluripotent human embryonic stem cells (hESCs, cell line SA02. In addition, we have performed a comparative gene expression analysis of those cells versus a heterogeneous population of hESC-derived cells committed towards neuronal/dopaminergic differentiation pathway by co-culturing with PA6 stromal cells for 16 days and containing a few tyrosine hydroxylase-positive dopaminergic neurons. Conclusion We characterized the gene expression profiles of undifferentiated and dopaminergic lineage-committed hESC-derived cells using a highly focused custom microarray platform (NeuroStem Chip that can become an important research tool in human stem cell biology. We propose that the areas of application for NeuroStem microarray platform could be the following: (i characterization of the

  4. Energy dissipation pathways in Photosystem 2 of the diatom, Phaeodactylum tricornutum, under high-light conditions.

    Science.gov (United States)

    Kuzminov, Fedor I; Gorbunov, Maxim Y

    2016-02-01

    To prevent photooxidative damage under supraoptimal light, photosynthetic organisms evolved mechanisms to thermally dissipate excess absorbed energy, known as non-photochemical quenching (NPQ). Here we quantify NPQ-induced alterations in light-harvesting processes and photochemical reactions in Photosystem 2 (PS2) in the pennate diatom Phaeodactylum tricornutum. Using a combination of picosecond lifetime analysis and variable fluorescence technique, we examined the dynamics of NPQ activation upon transition from dark to high light. Our analysis revealed that NPQ activation starts with a 2-3-fold increase in the rate constant of non-radiative charge recombination in the reaction center (RC); however, this increase is compensated with a proportional increase in the rate constant of back reactions. The resulting alterations in photochemical processes in PS2 RC do not contribute directly to quenching of antenna excitons by the RC, but favor non-radiative dissipation pathways within the RC, reducing the yields of spin conversion of the RC chlorophyll to the triplet state. The NPQ-induced changes in the RC are followed by a gradual ~ 2.5-fold increase in the yields of thermal dissipation in light-harvesting complexes. Our data suggest that thermal dissipation in light-harvesting complexes is the major sink for NPQ; RCs are not directly involved in the NPQ process, but could contribute to photoprotection via reduction in the probability of (3)Chl formation.

  5. Shedding Light on the Mechanisms Underlying Health Disparities Through Community Participatory Methods: The Stress Pathway

    Science.gov (United States)

    Schetter, Christine Dunkel; Schafer, Peter; Lanzi, Robin Gaines; Clark-Kauffman, Elizabeth; Raju, Tonse N. K.; Hillemeier, Marianne M.

    2015-01-01

    Health disparities are large and persistent gaps in the rates of disease and death between racial/ethnic and socioeconomic status subgroups in the population. Stress is a major pathway hypothesized to explain such disparities. The Eunice Kennedy Shriver National Institute of Child Health and Human Development formed a community/research collaborative—the Community Child Health Network—to investigate disparities in maternal and child health in five high-risk communities. Using community participation methods, we enrolled a large cohort of African American/Black, Latino/Hispanic, and non-Hispanic/White mothers and fathers of newborns at the time of birth and followed them over 2 years. A majority had household incomes near or below the federal poverty level. Home interviews yielded detailed information regarding multiple types of stress such as major life events and many forms of chronic stress including racism. Several forms of stress varied markedly by racial/ethnic group and income, with decreasing stress as income increased among Caucasians but not among African Americans; other forms of stress varied by race/ethnicity or poverty alone. We conclude that greater sophistication in studying the many forms of stress and community partnership is necessary to uncover the mechanisms underlying health disparities in poor and ethnic-minority families and to implement community health interventions. PMID:26173227

  6. B1-B2 phase transition mechanism and pathway of PbS under pressure

    Science.gov (United States)

    Adeleke, Adebayo A.; Yao, Yansun

    2018-03-01

    Experimental studies at finite Pressure-Temperature (P-T) conditions and a theoretical study at 0 K of the phase transition in lead sulphide (PbS) have been inconclusive. Many studies that have been done to understand structural transformation in PbS can broadly be classified into two main ideological streams—one with Pnma and another with Cmcm orthorhombic intermediate phase. To foster better understanding of this phenomenon, we present the result of the first-principles study of phase transition in PbS at finite temperature. We employed the particle swarm-intelligence optimization algorithm for the 0 K structure search and first-principles metadynamics simulations to study the phase transition pathway of PbS from the ambient pressure, 0 K Fm-3m structure to the high-pressure Pm-3m phase under experimentally achievable P-T conditions. Significantly, our calculation shows that both streams are achievable under specific P-T conditions. We further uncover new tetragonal and monoclinic structures of PbS with space group P21/c and I41/amd, respectively. We propose the P21/c and I41/amd as a precursor phase to the Pnma and Cmcm phases, respectively. We investigated the stability of the new structures and found them to be dynamically stable at their stability pressure range. Electronic structure calculations reveal that both P21/c and I41/amd phases are semiconducting with direct and indirect bandgap energies of 0.69(5) eV and 0.97(3) eV, respectively. In general, both P21/c and I41/amd phases were found to be energetically competitive with their respective orthorhombic successors.

  7. The TCA Pathway is an Important Player in the Regulatory Network Governing Vibrio alginolyticus Adhesion Under Adversity.

    Science.gov (United States)

    Huang, Lixing; Huang, Li; Yan, Qingpi; Qin, Yingxue; Ma, Ying; Lin, Mao; Xu, Xiaojin; Zheng, Jiang

    2016-01-01

    Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway) might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, quantitative Real-Time PCR (qPCR), RNAi, and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity, and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that (1) the TCA pathway plays a key role in V. alginolyticus adhesion: (2) the TCA pathway is sensitive to environmental stresses.

  8. The TCA pathway is an important player in the regulatory network governing Vibrio alginolyticus adhesion under adversity

    Directory of Open Access Journals (Sweden)

    Lixing eHuang

    2016-02-01

    Full Text Available Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, qPCR, RNAi and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that 1 the TCA pathway plays a key role in V. alginolyticus adhesion: 2 the TCA pathway is sensitive to environmental stresses.

  9. 3D seismic detection of shallow faults and fluid migration pathways offshore Southern Costa Rica: Application of neural-network meta-attributes

    Science.gov (United States)

    Kluesner, J. W.; Silver, E. A.; Nale, S. M.; Bangs, N. L.; McIntosh, K. D.

    2013-12-01

    We employ a seismic meta-attribute workflow to detect and analyze probable faults and fluid-pathways in 3D within the sedimentary section offshore Southern Costa Rica. During the CRISP seismic survey in 2011 we collected an 11 x 55 km grid of 3D seismic reflection data and high-resolvability EM122 multibeam data, with coverage extending from the incoming plate to the outer-shelf. We mapped numerous seafloor seep indicators, with distributions ranging from the lower-slope to ~15 km landward of the shelf break [Kluesner et al., 2013, G3, doi:10.1002/ggge.20058; Silver et al., this meeting]. We used the OpendTect software package to calculate meta-attribute volumes from the 3D seismic data in order to detect and visualize seismic discontinuities in 3D. This methodology consists of dip-steered filtering to pre-condition the data, followed by combining a set of advanced dip-steered seismic attributes into a single object probability attribute using a user-trained neural-network pattern-recognition algorithm. The parameters of the advanced seismic attributes are set for optimal detection of the desired geologic discontinuity (e.g. faults or fluid-pathways). The product is a measure of probability for the desired target that ranges between 0 and 1, with 1 representing the highest probability. Within the sedimentary section of the CRISP survey the results indicate focused fluid-migration pathways along dense networks of intersecting normal faults with approximately N-S and E-W trends. This pattern extends from the middle slope to the outer-shelf region. Dense clusters of fluid-migration pathways are located above basement highs and deeply rooted reverse faults [see Bangs et al., this meeting], including a dense zone of fluid-pathways imaged below IODP Site U1413. In addition, fault intersections frequently show an increased signal of fluid-migration and these zones may act as major conduits for fluid-flow through the sedimentary cover. Imaged fluid pathways root into high

  10. The dominant acetate degradation pathway/methanogenic composition in full-scale anaerobic digesters operating under different ammonia levels

    DEFF Research Database (Denmark)

    Fotidis, Ioannis; Karakashev, Dimitar Borisov; Angelidaki, Irini

    2014-01-01

    Ammonia is a major environmental factor influencing biomethanation in full-scale anaerobic digesters. In this study, the effect of different ammonia levels on methanogenic pathways and methanogenic community composition of full-scale biogas plants was investigated. Eight full-scale digesters...... operating under different ammonia levels were sampled, and the residual biogas production was followed in fed-batch reactors. Acetate, labelled in the methyl group, was used to determine the methanogenic pathway by following the 14CH4 and 14CO2 production. Fluorescence in situ hybridisation was used...... to determine the methanogenic communities’ composition. Results obtained clearly demonstrated that syntrophic acetate oxidation coupled with hydrogenotrophic methanogenesis was the dominant pathway in all digesters with high ammonia levels (2.8–4.57 g NH4 +-N L−1), while acetoclastic methanogenic pathway...

  11. [Calculation of soil water erosion modulus based on RUSLE and its assessment under support of artificial neural network].

    Science.gov (United States)

    Li, Yuhuan; Wang, Jing; Zhang, Jixian

    2006-06-01

    With Hengshan County of Shanxi Province in the North Loess Plateau as an example, and by using ETM + and remote sensing data and RUSLE module, this paper quantitatively derived the soil and water loss in loess hilly region based on "3S" technology, and assessed the derivation results under the support of artificial neural network. The results showed that the annual average erosion modulus of Hengshan County was 103.23 t x hm(-2), and the gross erosion loss per year was 4. 38 x 10(7) t. The erosion was increased from northwest to southeast, and varied significantly with topographic position. A slight erosion or no erosion happened in walled basin, flat-headed mountain ridges and sandy area, which always suffered from dropping erosion, while strip erosion often happened on the upslope of mountain ridge and mountaintop flat. Moderate rill erosion always occurred on the middle and down slope of mountain ridge and mountaintop flat, and weighty rushing erosion occurred on the steep ravine and brink. The RUSLE model and artificial neural network technique were feasible and could be propagandized for drainage areas control and preserved practice.

  12. Neural correlates and network connectivity underlying narrative production and comprehension: a combined fMRI and PET study.

    Science.gov (United States)

    AbdulSabur, Nuria Y; Xu, Yisheng; Liu, Siyuan; Chow, Ho Ming; Baxter, Miranda; Carson, Jessica; Braun, Allen R

    2014-08-01

    The neural correlates of narrative production and comprehension remain poorly understood. Here, using positron emission tomography (PET), functional magnetic resonance imaging (fMRI), contrast and functional network connectivity analyses we comprehensively characterize the neural mechanisms underlying these complex behaviors. Eighteen healthy subjects told and listened to fictional stories during scanning. In addition to traditional language areas (e.g., left inferior frontal and posterior middle temporal gyri), both narrative production and comprehension engaged regions associated with mentalizing and situation model construction (e.g., dorsomedial prefrontal cortex, precuneus and inferior parietal lobules) as well as neocortical premotor areas, such as the pre-supplementary motor area and left dorsal premotor cortex. Narrative comprehension alone showed marked bilaterality, activating right hemisphere homologs of perisylvian language areas. Narrative production remained predominantly left lateralized, uniquely activating executive and motor-related regions essential to language formulation and articulation. Connectivity analyses revealed strong associations between language areas and the superior and middle temporal gyri during both tasks. However, only during storytelling were these same language-related regions connected to cortical and subcortical motor regions. In contrast, during story comprehension alone, they were strongly linked to regions supporting mentalizing. Thus, when employed in a more complex, ecologically-valid context, language production and comprehension show both overlapping and idiosyncratic patterns of activation and functional connectivity. Importantly, in each case the language system is integrated with regions that support other cognitive and sensorimotor domains. Copyright © 2014. Published by Elsevier Ltd.

  13. Projected changes of the southwest Australian wave climate under two atmospheric greenhouse gas concentration pathways

    Science.gov (United States)

    Wandres, Moritz; Pattiaratchi, Charitha; Hemer, Mark A.

    2017-09-01

    Incident wave energy flux is responsible for sediment transport and coastal erosion in wave-dominated regions such as the southwestern Australian (SWA) coastal zone. To evaluate future wave climates under increased greenhouse gas concentration scenarios, past studies have forced global wave simulations with wind data sourced from global climate model (GCM) simulations. However, due to the generally coarse spatial resolution of global climate and wave simulations, the effects of changing offshore wave conditions and sea level rise on the nearshore wave climate are still relatively unknown. To address this gap of knowledge, we investigated the projected SWA offshore, shelf, and nearshore wave climate under two potential future greenhouse gas concentration trajectories (representative concentration pathways RCP4.5 and RCP8.5). This was achieved by downscaling an ensemble of global wave simulations, forced with winds from GCMs participating in the Coupled Model Inter-comparison Project (CMIP5), into two regional domains, using the Simulating WAves Nearshore (SWAN) wave model. The wave climate is modeled for a historical 20-year time slice (1986-2005) and a projected future 20-year time-slice (2081-2100) for both scenarios. Furthermore, we compare these scenarios to the effects of considering sea-level rise (SLR) alone (stationary wave climate), and to the effects of combined SLR and projected wind-wave change. Results indicated that the SWA shelf and nearshore wave climate is more sensitive to changes in offshore mean wave direction than offshore wave heights. Nearshore, wave energy flux was projected to increase by ∼10% in exposed areas and decrease by ∼10% in sheltered areas under both climate scenarios due to a change in wave directions, compared to an overall increase of 2-4% in offshore wave heights. With SLR, the annual mean wave energy flux was projected to increase by up to 20% in shallow water (climates, since the coastal wave climate is more responsive to

  14. Modulation of calcium-induced cell death in human neural stem cells by the novel peptidylarginine deiminase-AIF pathway.

    Science.gov (United States)

    U, Kin Pong; Subramanian, Venkataraman; Nicholas, Antony P; Thompson, Paul R; Ferretti, Patrizia

    2014-06-01

    PADs (peptidylarginine deiminases) are calcium-dependent enzymes that change protein-bound arginine to citrulline (citrullination/deimination) affecting protein conformation and function. PAD up-regulation following chick spinal cord injury has been linked to extensive tissue damage and loss of regenerative capability. Having found that human neural stem cells (hNSCs) expressed PAD2 and PAD3, we studied PAD function in these cells and investigated PAD3 as a potential target for neuroprotection by mimicking calcium-induced secondary injury responses. We show that PAD3, rather than PAD2 is a modulator of cell growth/death and that PAD activity is not associated with caspase-3-dependent cell death, but is required for AIF (apoptosis inducing factor)-mediated apoptosis. PAD inhibition prevents association of PAD3 with AIF and AIF cleavage required for its translocation to the nucleus. Finally, PAD inhibition also hinders calcium-induced cytoskeleton disassembly and association of PAD3 with vimentin, that we show to be associated also with AIF; together this suggests that PAD-dependent cytoskeleton disassembly may play a role in AIF translocation to the nucleus. This is the first study highlighting a role of PAD activity in balancing hNSC survival/death, identifying PAD3 as an important upstream regulator of calcium-induced apoptosis, which could be targeted to reduce neural loss, and shedding light on the mechanisms involved. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  15. What ethologically based models have taught us about the neural systems underlying fear and anxiety

    Directory of Open Access Journals (Sweden)

    N.S. Canteras

    2012-04-01

    Full Text Available Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

  16. Engagement of neural circuits underlying 2D spatial navigation in a rodent virtual reality system

    Science.gov (United States)

    Aronov, Dmitriy; Tank, David W.

    2015-01-01

    SUMMARY Virtual reality (VR) enables precise control of an animal’s environment and otherwise impossible experimental manipulations. Neural activity in navigating rodents has been studied on virtual linear tracks. However, the spatial navigation system’s engagement in complete two-dimensional environments has not been shown. We describe a VR setup for rats, including control software and a large-scale electrophysiology system, which supports 2D navigation by allowing animals to rotate and walk in any direction. The entorhinal-hippocampal circuit, including place cells, grid cells, head direction cells and border cells, showed 2D activity patterns in VR similar to those in the real world. Hippocampal neurons exhibited various remapping responses to changes in the appearance or the shape of the virtual environment, including a novel form in which a VR-induced cue conflict caused remapping to lock to geometry rather than salient cues. These results suggest a general-purpose tool for novel types of experimental manipulations in navigating rats. PMID:25374363

  17. Artificial neural networks based estimation of optical parameters by diffuse reflectance imaging under in vitro conditions

    Directory of Open Access Journals (Sweden)

    Mahmut Ozan Gökkan

    2017-01-01

    Full Text Available Optical parameters (properties of tissue-mimicking phantoms are determined through noninvasive optical imaging. Objective of this study is to decompose obtained diffuse reflectance into these optical properties such as absorption and scattering coefficients. To do so, transmission spectroscopy is firstly used to measure the coefficients via an experimental setup. Next, the optical properties of each characterized phantom are input for Monte Carlo (MC simulations to get diffuse reflectance. Also, a surface image for each single phantom with its known optical properties is obliquely captured due to reflectance-based geometrical setup using CMOS camera that is positioned at 5∘ angle to the phantoms. For the illumination of light, a laser light source at 633nm wavelength is preferred, because optical properties of different components in a biological tissue on that wavelength are nonoverlapped. During in vitro measurements, we prepared 30 different mixture samples adding clinoleic intravenous lipid emulsion (CILE and evans blue (EB dye into a distilled water. Finally, all obtained diffuse reflectance values are used to estimate the optical coefficients by artificial neural networks (ANNs in inverse modeling. For a biological tissue it is found that the simulated and measured values in our results are in good agreement.

  18. Neural mechanisms underlying valence inferences to sound: The role of the right angular gyrus.

    Science.gov (United States)

    Bravo, Fernando; Cross, Ian; Hawkins, Sarah; Gonzalez, Nadia; Docampo, Jorge; Bruno, Claudio; Stamatakis, Emmanuel Andreas

    2017-07-28

    We frequently infer others' intentions based on non-verbal auditory cues. Although the brain underpinnings of social cognition have been extensively studied, no empirical work has yet examined the impact of musical structure manipulation on the neural processing of emotional valence during mental state inferences. We used a novel sound-based theory-of-mind paradigm in which participants categorized stimuli of different sensory dissonance level in terms of positive/negative valence. Whilst consistent with previous studies which propose facilitated encoding of consonances, our results demonstrated that distinct levels of consonance/dissonance elicited differential influences on the right angular gyrus, an area implicated in mental state attribution and attention reorienting processes. Functional and effective connectivity analyses further showed that consonances modulated a specific inhibitory interaction from associative memory to mental state attribution substrates. Following evidence suggesting that individuals with autism may process social affective cues differently, we assessed the relationship between participants' task performance and self-reported autistic traits in clinically typical adults. Higher scores on the social cognition scales of the AQ were associated with deficits in recognising positive valence in consonant sound cues. These findings are discussed with respect to Bayesian perspectives on autistic perception, which highlight a functional failure to optimize precision in relation to prior beliefs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Neural oscillatory mechanisms during novel grammar learning underlying language analytical abilities.

    Science.gov (United States)

    Kepinska, Olga; Pereda, Ernesto; Caspers, Johanneke; Schiller, Niels O

    2017-12-01

    The goal of the present study was to investigate the initial phases of novel grammar learning on a neural level, concentrating on mechanisms responsible for individual variability between learners. Two groups of participants, one with high and one with average language analytical abilities, performed an Artificial Grammar Learning (AGL) task consisting of learning and test phases. During the task, EEG signals from 32 cap-mounted electrodes were recorded and epochs corresponding to the learning phases were analysed. We investigated spectral power modulations over time, and functional connectivity patterns by means of a bivariate, frequency-specific index of phase synchronization termed Phase Locking Value (PLV). Behavioural data showed learning effects in both groups, with a steeper learning curve and higher ultimate attainment for the highly skilled learners. Moreover, we established that cortical connectivity patterns and profiles of spectral power modulations over time differentiated L2 learners with various levels of language analytical abilities. Over the course of the task, the learning process seemed to be driven by whole-brain functional connectivity between neuronal assemblies achieved by means of communication in the beta band frequency. On a shorter time-scale, increasing proficiency on the AGL task appeared to be supported by stronger local synchronisation within the right hemisphere regions. Finally, we observed that the highly skilled learners might have exerted less mental effort, or reduced attention for the task at hand once the learning was achieved, as evidenced by the higher alpha band power. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Neural computations underlying arbitration between model-based and model-free learning

    Science.gov (United States)

    Lee, Sang Wan; Shimojo, Shinsuke; O’Doherty, John P.

    2014-01-01

    SUMMARY There is accumulating neural evidence to support the existence of two distinct systems for guiding action-selection in the brain, a deliberative “model-based” and a reflexive “model-free” system. However, little is known about how the brain determines which of these systems controls behavior at one moment in time. We provide evidence for an arbitration mechanism that allocates the degree of control over behavior by model-based and model-free systems as a function of the reliability of their respective predictions. We show that inferior lateral prefrontal and frontopolar cortex encode both reliability signals and the output of a comparison between those signals, implicating these regions in the arbitration process. Moreover, connectivity between these regions and model-free valuation areas is negatively modulated by the degree of model-based control in the arbitrator, suggesting that arbitration may work through modulation of the model-free valuation system when the arbitrator deems that the model-based system should drive behavior. PMID:24507199

  1. Neural correlates of exemplar novelty processing under different spatial attention conditions.

    Science.gov (United States)

    Stoppel, Christian Michael; Boehler, Carsten Nicolas; Strumpf, Hendrik; Heinze, Hans-Jochen; Hopf, Jens Max; Düzel, Emrah; Schoenfeld, Mircea Ariel

    2009-11-01

    The detection of novel events and their identification is a basic prerequisite in a rapidly changing environment. Recently, the processing of novelty has been shown to rely on the hippocampus and to be associated with activity in reward-related areas. The present study investigated the influence of spatial attention on neural processing of novel relative to frequently presented standard and target stimuli. Never-before-seen Mandelbrot-fractals absent of semantic content were employed as stimulus material. Consistent with current theories, novelty activated a widespread network of brain areas including the hippocampus. No activity, however, could be observed in reward-related areas with the novel stimuli absent of a semantic meaning employed here. In the perceptual part of the novelty-processing network a region in the lingual gyrus was found to specifically process novel events when they occurred outside the focus of spatial attention. These findings indicate that the initial detection of unexpected novel events generally occurs in specialized perceptual areas within the ventral visual stream, whereas activation of reward-related areas appears to be restricted to events that do possess a semantic content indicative of the biological relevance of the stimulus.

  2. Reduced Fidelity of Neural Representation Underlies Episodic Memory Decline in Normal Aging.

    Science.gov (United States)

    Zheng, Li; Gao, Zhiyao; Xiao, Xiaoqian; Ye, Zhifang; Chen, Chuansheng; Xue, Gui

    2017-06-07

    Emerging studies have emphasized the importance of the fidelity of cortical representation in forming enduring episodic memory. No study, however, has examined whether there are age-related reductions in representation fidelity that can explain memory declines in normal aging. Using functional MRI and multivariate pattern analysis, we found that older adults showed reduced representation fidelity in the visual cortex, which accounted for their decreased memory performance even after controlling for the contribution of reduced activation level. This reduced fidelity was specifically due to older adults' poorer item-specific representation, not due to their lower activation level and variance, greater variability in neuro-vascular coupling, or decreased selectivity of categorical representation (i.e., dedifferentiation). Older adults also showed an enhanced subsequent memory effect in the prefrontal cortex based on activation level, and their prefrontal activation was associated with greater fidelity of representation in the visual cortex and better memory performance. The fidelity of cortical representation thus may serve as a promising neural index for better mechanistic understanding of the memory declines and its compensation in normal aging. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Modeling root length density of field grown potatoes under different irrigation strategies and soil textures using artificial neural networks

    DEFF Research Database (Denmark)

    Ahmadi, Seyed Hamid; Sepaskhah, Ali Reza; Andersen, Mathias Neumann

    2014-01-01

    Root length density (RLD) is a highly wanted parameter for use in crop growth modeling but difficult to measure under field conditions. Therefore, artificial neural networks (ANNs) were implemented to predict the RLD of field grown potatoes that were subject to three irrigation strategies and three...... soil textures with different soil water status and soil densities. The objectives of the study were to test whether soil textural information, soil water status, and soil density might be used by ANN to simulate RLD at harvest. In the study 63 data pairs were divided into data sets of training (80......) of the eight input variables: soil layer intervals (D), percentages of sand (Sa), silt (Si), and clay (Cl), bulk density of soil layers (Bd), weighted soil moisture deficit during the irrigation strategies period (SMD), geometric mean particle size diameter (dg), and geometric standard deviation (σg...

  4. A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

    Science.gov (United States)

    Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

    2015-04-29

    Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

  5. Neural mechanisms underlying catastrophic failure in human-machine interaction during aerial navigation

    Science.gov (United States)

    Saproo, Sameer; Shih, Victor; Jangraw, David C.; Sajda, Paul

    2016-12-01

    Objective. We investigated the neural correlates of workload buildup in a fine visuomotor task called the boundary avoidance task (BAT). The BAT has been known to induce naturally occurring failures of human-machine coupling in high performance aircraft that can potentially lead to a crash—these failures are termed pilot induced oscillations (PIOs). Approach. We recorded EEG and pupillometry data from human subjects engaged in a flight BAT simulated within a virtual 3D environment. Main results. We find that workload buildup in a BAT can be successfully decoded from oscillatory features in the electroencephalogram (EEG). Information in delta, theta, alpha, beta, and gamma spectral bands of the EEG all contribute to successful decoding, however gamma band activity with a lateralized somatosensory topography has the highest contribution, while theta band activity with a fronto-central topography has the most robust contribution in terms of real-world usability. We show that the output of the spectral decoder can be used to predict PIO susceptibility. We also find that workload buildup in the task induces pupil dilation, the magnitude of which is significantly correlated with the magnitude of the decoded EEG signals. These results suggest that PIOs may result from the dysregulation of cortical networks such as the locus coeruleus (LC)—anterior cingulate cortex (ACC) circuit. Significance. Our findings may generalize to similar control failures in other cases of tight man-machine coupling where gains and latencies in the control system must be inferred and compensated for by the human operators. A closed-loop intervention using neurophysiological decoding of workload buildup that targets the LC-ACC circuit may positively impact operator performance in such situations.

  6. Neural substrates of cognitive control under the belief of getting neurofeedback training

    Directory of Open Access Journals (Sweden)

    Manuel eNinaus

    2013-12-01

    Full Text Available Learning to modulate one’s own brain activity is the fundament of neurofeedback (NF applications. Besides the neural networks directly involved in the generation and modulation of the neurophysiological parameter being specifically trained, more general determinants of NF efficacy such as self-referential processes and cognitive control have been frequently disregarded. Nonetheless, deeper insight into these cognitive mechanisms and their neuronal underpinnings sheds light on various open NF related questions concerning individual differences, brain-computer interface (BCI illiteracy as well as a more general model of NF learning. In this context, we investigated the neuronal substrate of these more general regulatory mechanisms that are engaged when participants believe that they are receiving NF. Twenty healthy participants (40-63 years, 10 female performed a sham NF paradigm during fMRI scanning. All participants were novices to NF-experiments and were instructed to voluntarily modulate their own brain activity based on a visual display of moving color bars. However, the bar depicted a recording and not the actual brain activity of participants. Reports collected at the end of the experiment indicate that participants were unaware of the sham feedback. In comparison to a passive watching condition, bilateral insula, anterior cingulate cortex and supplementary motor and dorsomedial and lateral prefrontal area were activated when participants actively tried to control the bar. In contrast, when merely watching moving bars, increased activation in the left angular gyrus was observed. These results show that the intention to control a moving bar is sufficient to engage a broad frontoparietal and cingulo-opercular network involved in cognitive control. The results of the present study indicate that tasks such as those generally employed in NF training recruit the neuronal correlates of cognitive control even when only sham NF is presented.

  7. Neural substrates of cognitive control under the belief of getting neurofeedback training.

    Science.gov (United States)

    Ninaus, Manuel; Kober, Silvia E; Witte, Matthias; Koschutnig, Karl; Stangl, Matthias; Neuper, Christa; Wood, Guilherme

    2013-01-01

    Learning to modulate one's own brain activity is the fundament of neurofeedback (NF) applications. Besides the neural networks directly involved in the generation and modulation of the neurophysiological parameter being specifically trained, more general determinants of NF efficacy such as self-referential processes and cognitive control have been frequently disregarded. Nonetheless, deeper insight into these cognitive mechanisms and their neuronal underpinnings sheds light on various open NF related questions concerning individual differences, brain-computer interface (BCI) illiteracy as well as a more general model of NF learning. In this context, we investigated the neuronal substrate of these more general regulatory mechanisms that are engaged when participants believe that they are receiving NF. Twenty healthy participants (40-63 years, 10 female) performed a sham NF paradigm during fMRI scanning. All participants were novices to NF-experiments and were instructed to voluntarily modulate their own brain activity based on a visual display of moving color bars. However, the bar depicted a recording and not the actual brain activity of participants. Reports collected at the end of the experiment indicate that participants were unaware of the sham feedback. In comparison to a passive watching condition, bilateral insula, anterior cingulate cortex and supplementary motor and dorsomedial and lateral prefrontal areas were activated when participants actively tried to control the bar. In contrast, when merely watching moving bars, increased activation in the left angular gyrus was observed. These results show that the intention to control a moving bar is sufficient to engage a broad frontoparietal and cingulo-opercular network involved in cognitive control. The results of the present study indicate that tasks such as those generally employed in NF training recruit the neuronal correlates of cognitive control even when only sham NF is presented.

  8. Revisiting the Neural Basis of Acquired Amusia: Lesion Patterns and Structural Changes Underlying Amusia Recovery

    Science.gov (United States)

    Sihvonen, Aleksi J.; Ripollés, Pablo; Rodríguez-Fornells, Antoni; Soinila, Seppo; Särkämö, Teppo

    2017-01-01

    Although, acquired amusia is a common deficit following stroke, relatively little is still known about its precise neural basis, let alone to its recovery. Recently, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study which revealed a right lateralized lesion pattern, and longitudinal gray matter volume (GMV) and white matter volume (WMV) changes that were specifically associated with acquired amusia after stroke. In the present study, using a larger sample of stroke patients (N = 90), we aimed to replicate and extend the previous structural findings as well as to determine the lesion patterns and volumetric changes associated with amusia recovery. Structural MRIs were acquired at acute and 6-month post-stroke stages. Music perception was behaviorally assessed at acute and 3-month post-stroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Using these scores, the patients were classified as non-amusic, recovered amusic, and non-recovered amusic. The results of the acute stage VLSM analyses and the longitudinal VBM analyses converged to show that more severe and persistent (non-recovered) amusia was associated with an extensive pattern of lesions and GMV/WMV decrease in right temporal, frontal, parietal, striatal, and limbic areas. In contrast, less severe and transient (recovered) amusia was linked to lesions specifically in left inferior frontal gyrus as well as to a GMV decrease in right parietal areas. Separate continuous analyses of MBEA Scale and Rhythm scores showed extensively overlapping lesion pattern in right temporal, frontal, and subcortical structures as well as in the right insula. Interestingly, the recovered pitch amusia was related to smaller GMV decreases in the temporoparietal junction whereas the recovered rhythm amusia was associated to smaller GMV decreases in the inferior temporal pole. Overall, the results provide a more comprehensive picture of the lesions

  9. Revisiting the Neural Basis of Acquired Amusia: Lesion Patterns and Structural Changes Underlying Amusia Recovery

    Directory of Open Access Journals (Sweden)

    Aleksi J. Sihvonen

    2017-07-01

    Full Text Available Although, acquired amusia is a common deficit following stroke, relatively little is still known about its precise neural basis, let alone to its recovery. Recently, we performed a voxel-based lesion-symptom mapping (VLSM and morphometry (VBM study which revealed a right lateralized lesion pattern, and longitudinal gray matter volume (GMV and white matter volume (WMV changes that were specifically associated with acquired amusia after stroke. In the present study, using a larger sample of stroke patients (N = 90, we aimed to replicate and extend the previous structural findings as well as to determine the lesion patterns and volumetric changes associated with amusia recovery. Structural MRIs were acquired at acute and 6-month post-stroke stages. Music perception was behaviorally assessed at acute and 3-month post-stroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA. Using these scores, the patients were classified as non-amusic, recovered amusic, and non-recovered amusic. The results of the acute stage VLSM analyses and the longitudinal VBM analyses converged to show that more severe and persistent (non-recovered amusia was associated with an extensive pattern of lesions and GMV/WMV decrease in right temporal, frontal, parietal, striatal, and limbic areas. In contrast, less severe and transient (recovered amusia was linked to lesions specifically in left inferior frontal gyrus as well as to a GMV decrease in right parietal areas. Separate continuous analyses of MBEA Scale and Rhythm scores showed extensively overlapping lesion pattern in right temporal, frontal, and subcortical structures as well as in the right insula. Interestingly, the recovered pitch amusia was related to smaller GMV decreases in the temporoparietal junction whereas the recovered rhythm amusia was associated to smaller GMV decreases in the inferior temporal pole. Overall, the results provide a more comprehensive picture of

  10. Revisiting the Neural Basis of Acquired Amusia: Lesion Patterns and Structural Changes Underlying Amusia Recovery.

    Science.gov (United States)

    Sihvonen, Aleksi J; Ripollés, Pablo; Rodríguez-Fornells, Antoni; Soinila, Seppo; Särkämö, Teppo

    2017-01-01

    Although, acquired amusia is a common deficit following stroke, relatively little is still known about its precise neural basis, let alone to its recovery. Recently, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study which revealed a right lateralized lesion pattern, and longitudinal gray matter volume (GMV) and white matter volume (WMV) changes that were specifically associated with acquired amusia after stroke. In the present study, using a larger sample of stroke patients ( N = 90), we aimed to replicate and extend the previous structural findings as well as to determine the lesion patterns and volumetric changes associated with amusia recovery. Structural MRIs were acquired at acute and 6-month post-stroke stages. Music perception was behaviorally assessed at acute and 3-month post-stroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Using these scores, the patients were classified as non-amusic, recovered amusic, and non-recovered amusic. The results of the acute stage VLSM analyses and the longitudinal VBM analyses converged to show that more severe and persistent (non-recovered) amusia was associated with an extensive pattern of lesions and GMV/WMV decrease in right temporal, frontal, parietal, striatal, and limbic areas. In contrast, less severe and transient (recovered) amusia was linked to lesions specifically in left inferior frontal gyrus as well as to a GMV decrease in right parietal areas. Separate continuous analyses of MBEA Scale and Rhythm scores showed extensively overlapping lesion pattern in right temporal, frontal, and subcortical structures as well as in the right insula. Interestingly, the recovered pitch amusia was related to smaller GMV decreases in the temporoparietal junction whereas the recovered rhythm amusia was associated to smaller GMV decreases in the inferior temporal pole. Overall, the results provide a more comprehensive picture of the lesions

  11. Automated probabilistic reconstruction of white-matter pathways in health and disease using an atlas of the underlying anatomy

    Directory of Open Access Journals (Sweden)

    Anastasia eYendiki

    2011-10-01

    Full Text Available We have developed a method for automated probabilistic reconstruction of a set of major white-matter pathways from diffusion-weighted MR images. Our method is called TRACULA (TRActs Constrained by UnderLying Anatomy and utilizes prior information on the anatomy of the pathways from a set of training subjects. By incorporating this prior knowledge in the reconstruction procedure, our method obviates the need for manual interaction with the tract solutions at a later stage and thus facilitates the application of tractography to large studies. In this paper we illustrate the application of the method on data from a schizophrenia study and investigate whether the inclusion of both patients and healthy subjects in the training set affects our ability to reconstruct the pathways reliably. We show that, since our method does not constrain the exact spatial location or shape of the pathways but only their trajectory relative to the surrounding anatomical structures, a set a of healthy training subjects can be used to reconstruct the pathways accurately in patients as well as in controls.

  12. BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic NeuronsIn Vivoand in Human Induced Pluripotent and Neural Stem Cells.

    Science.gov (United States)

    Jovanovic, Vukasin M; Salti, Ahmad; Tilleman, Hadas; Zega, Ksenija; Jukic, Marin M; Zou, Hongyan; Friedel, Roland H; Prakash, Nilima; Blaess, Sandra; Edenhofer, Frank; Brodski, Claude

    2018-02-14

    The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, which are currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown. Here, we report that BMP5/7-deficient mice ( Bmp5 -/- ; Bmp7 -/- ) lack mDA neurons due to reduced neurogenesis in the mDA progenitor domain. As molecular mechanisms accounting for these alterations in Bmp5 -/- ; Bmp7 -/- mutants, we have identified expression changes of the BMP/SMAD target genes MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog). Conditionally inactivating SMAD1 in neural stem cells of mice in vivo ( Smad1 Nes ) hampered the differentiation of progenitor cells into mDA neurons by preventing cell cycle exit, especially of TH + SOX6 + (tyrosine hydroxylase, SRY-box 6) and TH + GIRK2 + (potassium voltage-gated channel subfamily-J member-6) substantia nigra neurons. BMP5/7 robustly increased the in vitro differentiation of human induced pluripotent stem cells and induced neural stem cells to mDA neurons by up to threefold. In conclusion, we have identified BMP/SMAD signaling as a novel critical pathway orchestrating essential steps of mammalian mDA neurogenesis in vivo that balances progenitor proliferation and differentiation. Moreover, we demonstrate the potential of BMPs to improve the generation of stem-cell-derived mDA neurons in vitro , highlighting the importance of sequential BMP/SMAD inhibition and activation in this process. SIGNIFICANCE STATEMENT We identify bone morphogenetic protein (BMP)/SMAD signaling as a novel essential pathway regulating the development of mammalian midbrain dopaminergic (mDA) neurons

  13. Bearing Fault Diagnosis under Variable Speed Using Convolutional Neural Networks and the Stochastic Diagonal Levenberg-Marquardt Algorithm

    Directory of Open Access Journals (Sweden)

    Viet Tra

    2017-12-01

    Full Text Available This paper presents a novel method for diagnosing incipient bearing defects under variable operating speeds using convolutional neural networks (CNNs trained via the stochastic diagonal Levenberg-Marquardt (S-DLM algorithm. The CNNs utilize the spectral energy maps (SEMs of the acoustic emission (AE signals as inputs and automatically learn the optimal features, which yield the best discriminative models for diagnosing incipient bearing defects under variable operating speeds. The SEMs are two-dimensional maps that show the distribution of energy across different bands of the AE spectrum. It is hypothesized that the variation of a bearing’s speed would not alter the overall shape of the AE spectrum rather, it may only scale and translate it. Thus, at different speeds, the same defect would yield SEMs that are scaled and shifted versions of each other. This hypothesis is confirmed by the experimental results, where CNNs trained using the S-DLM algorithm yield significantly better diagnostic performance under variable operating speeds compared to existing methods. In this work, the performance of different training algorithms is also evaluated to select the best training algorithm for the CNNs. The proposed method is used to diagnose both single and compound defects at six different operating speeds.

  14. What's the gist? The influence of schemas on the neural correlates underlying true and false memories.

    Science.gov (United States)

    Webb, Christina E; Turney, Indira C; Dennis, Nancy A

    2016-12-01

    The current study used a novel scene paradigm to investigate the role of encoding schemas on memory. Specifically, the study examined the influence of a strong encoding schema on retrieval of both schematic and non-schematic information, as well as false memories for information associated with the schema. Additionally, the separate roles of recollection and familiarity in both veridical and false memory retrieval were examined. The study identified several novel results. First, while many common neural regions mediated both schematic and non-schematic retrieval success, schematic recollection exhibited greater activation in visual cortex and hippocampus, regions commonly shown to mediate detailed retrieval. More effortful cognitive control regions in the prefrontal and parietal cortices, on the other hand, supported non-schematic recollection, while lateral temporal cortices supported familiarity-based retrieval of non-schematic items. Second, both true and false recollection, as well as familiarity, were mediated by activity in left middle temporal gyrus, a region associated with semantic processing and retrieval of schematic gist. Moreover, activity in this region was greater for both false recollection and false familiarity, suggesting a greater reliance on lateral temporal cortices for retrieval of illusory memories, irrespective of memory strength. Consistent with previous false memory studies, visual cortex showed increased activity for true compared to false recollection, suggesting that visual cortices are critical for distinguishing between previously viewed targets and related lures at retrieval. Additionally, the absence of common visual activity between true and false retrieval suggests that, unlike previous studies utilizing visual stimuli, when false memories are predicated on schematic gist and not perceptual overlap, there is little reliance on visual processes during false memory retrieval. Finally, the medial temporal lobe exhibited an

  15. Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats.

    Science.gov (United States)

    Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

    2018-02-01

    Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10 th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.

  16. Neural Mechanisms Underlying Social Intelligence and Their Relationship with the Performance of Sales Managers

    NARCIS (Netherlands)

    R.C. Dietvorst (Roeland)

    2010-01-01

    textabstractIdentifying the drivers of salespeople’s performance, strategies and moral behavior have been under the scrutiny of marketing scholars for many years. The functioning of the drivers of salespeople’s behaviors rests on processes going on in the minds of salespeople. However, research to

  17. Artificial neural network for prediction of the area under the disease progress curve of tomato late blight

    Directory of Open Access Journals (Sweden)

    Daniel Pedrosa Alves

    Full Text Available ABSTRACT: Artificial neural networks (ANN are computational models inspired by the neural systems of living beings capable of learning from examples and using them to solve problems such as non-linear prediction, and pattern recognition, in addition to several other applications. In this study, ANN were used to predict the value of the area under the disease progress curve (AUDPC for the tomato late blight pathosystem. The AUDPC is widely used by epidemiologic studies of polycyclic diseases, especially those regarding quantitative resistance of genotypes. However, a series of six evaluations over time is necessary to obtain the final area value for this pathosystem. This study aimed to investigate the utilization of ANN to construct an AUDPC in the tomato late blight pathosystem, using a reduced number of severity evaluations. For this, four independent experiments were performed giving a total of 1836 plants infected with Phytophthora infestans pathogen. They were assessed every three days, comprised six opportunities and AUDPC calculations were performed by the conventional method. After the ANN were created it was possible to predict the AUDPC with correlations of 0.97 and 0.84 when compared to conventional methods, using 50 % and 67 % of the genotype evaluations, respectively. When using the ANN created in an experiment to predict the AUDPC of the other experiments the average correlation was 0.94, with two evaluations, 0.96, with three evaluations, between the predicted values of the ANN and they were observed in six evaluations. We present in this study a new paradigm for the use of AUDPC information in tomato experiments faced with P. infestans. This new proposed paradigm might be adapted to different pathosystems.

  18. Modulating Conscious Movement Intention by Noninvasive Brain Stimulation and the Underlying Neural Mechanisms

    OpenAIRE

    Douglas, Zachary H.; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M.; He, Biyu J.

    2015-01-01

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60–70 ms earlier. Slow brain waves recorded ∼2–...

  19. Cannabinoid inhibition of guinea-pig intestinal peristalsis via inhibition of excitatory and activation of inhibitory neural pathways.

    Science.gov (United States)

    Heinemann, A; Shahbazian, A; Holzer, P

    1999-09-01

    Since activation of cannabinoid CB1 receptors inhibits gastrointestinal transit in the mouse, this study analyzed the action of the cannabinoid receptor agonist methanandamide on distension-induced propulsive motility. Peristalsis in luminally perfused segments of the guinea-pig isolated ileum was elicited by a rise of the intraluminal pressure. The pressure threshold at which peristaltic contractions were triggered was used to quantify drug effects. Methanandamide (0.1-3 microM) inhibited peristalsis as deduced from a concentration-related increase in the peristaltic pressure threshold, an action that was prevented by the CB1 receptor antagonist SR141716A (1 microM) per se, which had no effect on peristalsis. The distension-induced ascending reflex contraction of the circular muscle was likewise depressed by methanandamide in a SR141716A-sensitive manner, whereas indomethacin-induced phasic contractions of the circular muscle were left unchanged by methanandamide. The anti-peristaltic action of methanandamide was inhibited by apamin (0.5 microM), attenuated by N-nitro-L-arginine methyl ester (300 microM) and left unaltered by suramin (300 microM), pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (150 microM) and naloxone (0.5 microM). It is concluded that methanandamide depresses intestinal peristalsis via activation of CB1 receptors on enteric neurons, which results in blockade of excitatory motor pathways and facilitation of inhibitory pathways operating via apamin-sensitive K+ channels and nitric oxide.

  20. Artificial neural networks for control of a grid-connected rectifier/inverter under disturbance, dynamic and power converter switching conditions.

    Science.gov (United States)

    Li, Shuhui; Fairbank, Michael; Johnson, Cameron; Wunsch, Donald C; Alonso, Eduardo; Proaño, Julio L

    2014-04-01

    Three-phase grid-connected converters are widely used in renewable and electric power system applications. Traditionally, grid-connected converters are controlled with standard decoupled d-q vector control mechanisms. However, recent studies indicate that such mechanisms show limitations in their applicability to dynamic systems. This paper investigates how to mitigate such restrictions using a neural network to control a grid-connected rectifier/inverter. The neural network implements a dynamic programming algorithm and is trained by using back-propagation through time. To enhance performance and stability under disturbance, additional strategies are adopted, including the use of integrals of error signals to the network inputs and the introduction of grid disturbance voltage to the outputs of a well-trained network. The performance of the neural-network controller is studied under typical vector control conditions and compared against conventional vector control methods, which demonstrates that the neural vector control strategy proposed in this paper is effective. Even in dynamic and power converter switching environments, the neural vector controller shows strong ability to trace rapidly changing reference commands, tolerate system disturbances, and satisfy control requirements for a faulted power system.

  1. The neural correlates of subjective utility of monetary outcome and probability weight in economic and in motor decision under risk

    Science.gov (United States)

    Wu, Shih-Wei; Delgado, Mauricio R.; Maloney, Laurence T.

    2011-01-01

    In decision under risk, people choose between lotteries that contain a list of potential outcomes paired with their probabilities of occurrence. We previously developed a method for translating such lotteries to mathematically equivalent motor lotteries. The probability of each outcome in a motor lottery is determined by the subject’s noise in executing a movement. In this study, we used functional magnetic resonance imaging in humans to compare the neural correlates of monetary outcome and probability in classical lottery tasks where information about probability was explicitly communicated to the subjects and in mathematically equivalent motor lottery tasks where probability was implicit in the subjects’ own motor noise. We found that activity in the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC) quantitatively represent the subjective utility of monetary outcome in both tasks. For probability, we found that the mPFC significantly tracked the distortion of such information in both tasks. Specifically, activity in mPFC represents probability information but not the physical properties of the stimuli correlated with this information. Together, the results demonstrate that mPFC represents probability from two distinct forms of decision under risk. PMID:21677166

  2. Contrast negation differentiates visual pathways underlying dynamic and invariant facial processing.

    Science.gov (United States)

    Pallett, Pamela M; Meng, Ming

    2013-12-16

    Bruce and Young (1986) proposed a model for face processing that begins with structural encoding, followed by a split into two processing streams: one for the dynamic aspects of the face (e.g., facial expressions of emotion) and the other for the invariant aspects of the face (e.g., gender, identity). Yet how this is accomplished remains unclear. Here, we took a psychophysical approach using contrast negation to test the Bruce and Young model. Previous research suggests that contrast negation impairs processing of invariant features (e.g., gender) but not dynamic features (e.g., expression). In our first experiment, participants discriminated differences in gender and facial expressions of emotion in upright, inverted, and contrast-negated faces. Results revealed a profound impairment for contrast-negated gender discrimination, whereas expression discrimination remained relatively robust to contrast negation. To test whether this differential effect occurs during perceptual encoding, we conducted three additional experiments in which we measured aftereffects following upright, inverted, or contrast-negated face adaptation for the same discrimination task as in the first experiment. Results showed a mild impairment with contrast negation during perceptual encoding for both gender and expression, followed by a marked gender-specific deficit during contrast-negated face discrimination. Taken together, our results suggest that there are shared neural mechanisms during perceptual encoding, and at least partially separate neural mechanisms during recognition and decision making for dynamic and invariant facial-feature processing.

  3. Bioinformatic dissecting of TP53 regulation pathway underlying butyrate-induced histone modification in epigenetic regulation

    Science.gov (United States)

    Butyrate affects cell proliferation, differentiation and motility. Butyrate inhibits histone deacetylase (HDAC) activities and induces cell cycle arrest and apoptosis. TP53 is one of the most active upstream regulators discovered by IPA in our RNA sequencing data set. The TP53 signaling pathway pl...

  4. Pathways and Mechanisms Underlying the Photophysics and Photochemistry of Riboflavin induced cornea crosslinking

    DEFF Research Database (Denmark)

    Breitenbach, Thomas; Ogilby, Peter Remsen

    In this talk, we will describe general pathways involved in the photophysics of a photosensitized process, which can lead to crosslinking due to light excitation of Riboflavin in the cornea. Furthermore, we will elucidate different aspects of reactions that can produce crosslinks, with respect...

  5. A View of the Neural Representation of Second Language Syntax through Artificial Language Learning under Implicit Contexts of Exposure

    Science.gov (United States)

    Morgan-Short, Kara; Deng, ZhiZhou; Brill-Schuetz, Katherine A.; Faretta- Stutenberg, Mandy; Wong, Patrick C. M.; Wong, Francis C. K.

    2015-01-01

    The current study aims to make an initial neuroimaging contribution to central implicit-explicit issues in second language (L2) acquisition by considering how implicit and explicit contexts mediate the neural representation of L2. Focusing on implicit contexts, the study employs a longitudinal design to examine the neural representation of L2…

  6. Neural and psychophysiological correlates of human performance under stress and high mental workload.

    Science.gov (United States)

    Mandrick, Kevin; Peysakhovich, Vsevolod; Rémy, Florence; Lepron, Evelyne; Causse, Mickaël

    2016-12-01

    In our anxiogenic and stressful world, the maintenance of an optimal cognitive performance is a constant challenge. It is particularly true in complex working environments (e.g. flight deck, air traffic control tower), where individuals have sometimes to cope with a high mental workload and stressful situations. Several models (i.e. processing efficiency theory, cognitive-energetical framework) have attempted to provide a conceptual basis on how human performance is modulated by high workload and stress/anxiety. These models predict that stress can reduce human cognitive efficiency, even in the absence of a visible impact on the task performance. Performance may be protected under stress thanks to compensatory effort, but only at the expense of a cognitive cost. Yet, the psychophysiological cost of this regulation remains unclear. We designed two experiments involving pupil diameter, cardiovascular and prefrontal oxygenation measurements. Participants performed the Toulouse N-back Task that intensively engaged both working memory and mental calculation processes under the threat (or not) of unpredictable aversive sounds. The results revealed that higher task difficulty (higher n level) degraded the performance and induced an increased tonic pupil diameter, heart rate and activity in the lateral prefrontal cortex, and a decreased phasic pupil response and heart rate variability. Importantly, the condition of stress did not impact the performance, but at the expense of a psychophysiological cost as demonstrated by lower phasic pupil response, and greater heart rate and prefrontal activity. Prefrontal cortex seems to be a central region for mitigating the influence of stress because it subserves crucial functions (e.g. inhibition, working memory) that can promote the engagement of coping strategies. Overall, findings confirmed the psychophysiological cost of both mental effort and stress. Stress likely triggered increased motivation and the recruitment of additional

  7. 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.

  8. Revealing the Neural Mechanisms Underlying the Beneficial Effects of Tai Chi: A Neuroimaging Perspective.

    Science.gov (United States)

    Yu, Angus P; Tam, Bjorn T; Lai, Christopher W; Yu, Doris S; Woo, Jean; Chung, Ka-Fai; Hui, Stanley S; Liu, Justina Y; Wei, Gao X; Siu, Parco M

    2018-01-01

    Tai Chi Chuan (TCC), a traditional Chinese martial art, is well-documented to result in beneficial consequences in physical and mental health. TCC is regarded as a mind-body exercise that is comprised of physical exercise and meditation. Favorable effects of TCC on body balance, gait, bone mineral density, metabolic parameters, anxiety, depression, cognitive function, and sleep have been previously reported. However, the underlying mechanisms explaining the effects of TCC remain largely unclear. Recently, advances in neuroimaging technology have offered new investigative opportunities to reveal the effects of TCC on anatomical morphologies and neurological activities in different regions of the brain. These neuroimaging findings have provided new clues for revealing the mechanisms behind the observed effects of TCC. In this review paper, we discussed the possible effects of TCC-induced modulation of brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity on health. Moreover, we identified possible links between the alterations in brain and beneficial effects of TCC, such as improved motor functions, pain perception, metabolic profile, cognitive functions, mental health and sleep quality. This paper aimed to stimulate further mechanistic neuroimaging studies in TCC and its effects on brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity, which ultimately lead to a better understanding of the mechanisms responsible for the beneficial effects of TCC on human health.

  9. Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature.

    Directory of Open Access Journals (Sweden)

    Ti Zhang

    Full Text Available BACKGROUND: Neural Tube Defects (NTDs are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996-2011 and performed a comprehensive meta-analysis to provide empirical evidence on the association. METHODS AND FINDINGS: We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls, MTHFR A1298C (22 studies; 2602 cases, 4070 controls, MTR A2756G (9 studies; 843 cases, 1006 controls, MTRR A66G (8 studies; 703 cases, 1572 controls, and RFC-1 A80G (4 studies; 1107 cases, 1585 controls. We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07-1.42 and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24-1.92. However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models. CONCLUSIONS: Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.

  10. Spinocerebellar ataxia: miRNAs expose biological pathways underlying pervasive Purkinje cell degeneration.

    Science.gov (United States)

    van der Stijl, Rogier; Withoff, Sebo; Verbeek, Dineke S

    2017-12-01

    Recent work has demonstrated the importance of miRNAs in the pathogenesis of various brain disorders including the neurodegenerative disorder spinocerebellar ataxia (SCA). This review focuses on the role of miRNAs in the shared pathogenesis of the different SCA types. We examine the novel findings of a recent cell-type-specific RNA-sequencing study in mouse brain and discuss how the identification of Purkinje-cell-enriched miRNAs highlights biological pathways that expose the mechanisms behind pervasive Purkinje cell degeneration in SCA. These key pathways are likely to contain targets for therapeutic development and represent potential candidate genes for genetically unsolved SCAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left–right patterning

    OpenAIRE

    McDowell, Gary; Rajadurai, Suvithan; Levin, Michael

    2016-01-01

    Consistent left–right (LR) asymmetry is a fundamental aspect of the bodyplan across phyla, and errors of laterality form an important class of human birth defects. Its molecular underpinning was first discovered as a sequential pathway of left- and right-sided gene expression that controlled positioning of the heart and visceral organs. Recent data have revised this picture in two important ways. First, the physical origin of chirality has been identified; cytoskeletal dynamics underlie the a...

  12. ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway

    OpenAIRE

    Zhao, Yang; Hu, Xingbin; Liu, Yajing; Dong, Shumin; Wen, Zhaowei; He, Wanming; Zhang, Shuyi; Huang, Qiong; Shi, Min

    2017-01-01

    Cancer cells are frequently confronted with metabolic stress in tumor microenvironments due to their rapid growth and limited nutrient supply. Metabolic stress induces cell death through ROS-induced apoptosis. However, cancer cells can adapt to it by altering the metabolic pathways. AMPK and AKT are two primary effectors in response to metabolic stress: AMPK acts as an energy-sensing factor which rewires metabolism and maintains redox balance. AKT broadly promotes energy production in the nut...

  13. The impact of pain-related fear on neural pathways of pain modulation in chronic low back pain

    Directory of Open Access Journals (Sweden)

    Michael Lukas Meier

    2017-06-01

    Discussion:. Our findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP.

  14. Sensory neural pathways revisited to unravel the temporal dynamics of the Simon effect : A model-based cognitive neuroscience approach

    NARCIS (Netherlands)

    Salzer, Yael; de Hollander, Gilles; Forstmann, Birte U

    2017-01-01

    The Simon task is one of the most prominent interference tasks and has been extensively studied in experimental psychology and cognitive neuroscience. Despite years of research, the underlying mechanism driving the phenomenon and its temporal dynamics are still disputed. Within the framework of the

  15. Identification of key processes underlying cancer phenotypes using biologic pathway analysis.

    Directory of Open Access Journals (Sweden)

    Sol Efroni

    2007-05-01

    Full Text Available Cancer is recognized to be a family of gene-based diseases whose causes are to be found in disruptions of basic biologic processes. An increasingly deep catalogue of canonical networks details the specific molecular interaction of genes and their products. However, mapping of disease phenotypes to alterations of these networks of interactions is accomplished indirectly and non-systematically. Here we objectively identify pathways associated with malignancy, staging, and outcome in cancer through application of an analytic approach that systematically evaluates differences in the activity and consistency of interactions within canonical biologic processes. Using large collections of publicly accessible genome-wide gene expression, we identify small, common sets of pathways - Trka Receptor, Apoptosis response to DNA Damage, Ceramide, Telomerase, CD40L and Calcineurin - whose differences robustly distinguish diverse tumor types from corresponding normal samples, predict tumor grade, and distinguish phenotypes such as estrogen receptor status and p53 mutation state. Pathways identified through this analysis perform as well or better than phenotypes used in the original studies in predicting cancer outcome. This approach provides a means to use genome-wide characterizations to map key biological processes to important clinical features in disease.

  16. Graphene oxide and reduced graphene oxide induced neural pheochromocytoma-derived PC12 cell lines apoptosis and cell cycle alterations via the ERK signaling pathways.

    Science.gov (United States)

    Kang, Yiyuan; Liu, Jia; Wu, Junrong; Yin, Qian; Liang, Huimin; Chen, Aijie; Shao, Longquan

    2017-01-01

    Given the novel applications of graphene materials in biomedical and electronics industry, the health hazards of these particles have attracted extensive worldwide attention. Although many studies have been performed on graphene material-induced toxic effects, toxicological data for the effect of graphene materials on the nervous system are lacking. In this study, we focused on the biological effects of graphene oxide (GO) and reduced graphene oxide (rGO) materials on PC12 cells, a type of traditional neural cell line. We found that GO and rGO exerted significant toxic effects on PC12 cells in a dose- and time-dependent manner. Moreover, apoptosis appeared to be a response to toxicity. A potent increase in the number of PC12 cells at G0/G1 phase after GO and rGO exposure was detected by cell cycle analysis. We found that phosphorylation levels of ERK signaling molecules, which are related to cell cycle regulation and apoptosis, were significantly altered after GO and rGO exposure. In conclusion, our results show that GO has more potent toxic effects than rGO and that apoptosis and cell cycle arrest are the main toxicity responses to GO and rGO treatments, which are likely due to ERK pathway regulation.

  17. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    Science.gov (United States)

    Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Mixed Stimulus-Induced Mode Selection in Neural Activity Driven by High and Low Frequency Current under Electromagnetic Radiation

    Directory of Open Access Journals (Sweden)

    Lulu Lu

    2017-01-01

    Full Text Available The electrical activities of neurons are dependent on the complex electrophysiological condition in neuronal system, the three-variable Hindmarsh-Rose (HR neuron model is improved to describe the dynamical behaviors of neuronal activities with electromagnetic induction being considered, and the mode transition of electrical activities in neuron is detected when external electromagnetic radiation is imposed on the neuron. In this paper, different types of electrical stimulus impended with a high-low frequency current are imposed on new HR neuron model, and mixed stimulus-induced mode selection in neural activity is discussed in detail. It is found that mode selection of electrical activities stimulated by high-low frequency current, which also changes the excitability of neuron, can be triggered owing to adding the Gaussian white noise. Meanwhile, the mode selection of the neuron electrical activity is much dependent on the amplitude B of the high frequency current under the same noise intensity, and the high frequency response is selected preferentially by applying appropriate parameters and noise intensity. Our results provide insights into the transmission of complex signals in nerve system, which is valuable in engineering prospective applications such as information encoding.

  19. Neural mechanisms underlying the effects of face-based affective signals on memory for faces: a tentative model

    Science.gov (United States)

    Tsukiura, Takashi

    2012-01-01

    In our daily lives, we form some impressions of other people. Although those impressions are affected by many factors, face-based affective signals such as facial expression, facial attractiveness, or trustworthiness are important. Previous psychological studies have demonstrated the impact of facial impressions on remembering other people, but little is known about the neural mechanisms underlying this psychological process. The purpose of this article is to review recent functional MRI (fMRI) studies to investigate the effects of face-based affective signals including facial expression, facial attractiveness, and trustworthiness on memory for faces, and to propose a tentative concept for understanding this affective-cognitive interaction. On the basis of the aforementioned research, three brain regions are potentially involved in the processing of face-based affective signals. The first candidate is the amygdala, where activity is generally modulated by both affectively positive and negative signals from faces. Activity in the orbitofrontal cortex (OFC), as the second candidate, increases as a function of perceived positive signals from faces; whereas activity in the insular cortex, as the third candidate, reflects a function of face-based negative signals. In addition, neuroscientific studies have reported that the three regions are functionally connected to the memory-related hippocampal regions. These findings suggest that the effects of face-based affective signals on memory for faces could be modulated by interactions between the regions associated with the processing of face-based affective signals and the hippocampus as a memory-related region. PMID:22837740

  20. Modelling the release of volatile fission product cesium from CANDU fuel under severe accident conditions using artificial neural networks

    International Nuclear Information System (INIS)

    Andrews, W.S.; Lewis, B.J.; Cox, D.S.

    1997-01-01

    An artificial neural network (ANN) model has been developed to predict the release of volatile fission products from CANDU fuel under severe accident conditions. The model was based on data for the release Of 134 Cs measured during three annealing experiments (Hot Cell Experiments 1 and 2, or HCE- 1, HCE-2 and Metallurgical Cell Experiment 1, or MCE- 1) at Chalk River Laboratories. These experiments were comprised of a total of 30 separate tests. The ANN established a correlation among 14 separate input variables and predicted the cumulative fractional release for a set of 386 data points drawn from 29 tests to a normalized error, E n , of 0.104 and an average absolute error, E abs , of 0.064. Predictions for a blind validation set (test HCE2-CM6) had an E n of 0.064 and an E abs of 0.054. A methodology is presented for deploying the ANN model by providing the connection weights. Finally, the performance of an ANN model was compared to a fuel oxidation model developed by Lewis et al. and to the U.S. Nuclear Regulatory Commission's CORSOR-M. (author)

  1. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

    Science.gov (United States)

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results and confirmation with additional research and ongoing rodent and human studies of KB220Z, is required. PMID:25526228

  2. Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells.

    Science.gov (United States)

    Najem, Dema; Bamji-Mirza, Michelle; Yang, Ze; Zhang, Wandong

    2016-06-01

    Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) toxicity, tau pathology, insulin resistance, neuroinflammation, and dysregulation of cholesterol homeostasis, all of which play roles in neurodegeneration. Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes. In this study, we investigated possible relationships among insulin signaling and cholesterol biosynthesis, along with the effects of Aβ42 on these pathways in vitro. We found that neuroblastoma 2a (N2a) cells transfected with the human gene encoding amyloid-β protein precursor (AβPP) (N2a-AβPP) produced Aβ and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment, and by increased phosphorylation of insulin receptor subunit-1 at serine 612 (p-IRS-S612) as compared to parental N2a cells. Treatment of human neuroblastoma SH-SY5Y cells with Aβ42 also increased p-IRS-S612, suggesting that Aβ42 is responsible for insulin resistance. The insulin resistance was alleviated when N2a-AβPP cells were treated with higher insulin concentrations. Insulin increased Aβ release from N2a-AβPP cells, by which it may promote Aβ clearance. Insulin increased cholesterol-synthesis gene expression in SH-SY5Y and N2a cells, including 24-dehydrocholesterol reductase (DHCR24) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) through sterol-regulatory element-binding protein-2 (SREBP2). While Aβ42-treated SH-SY5Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses, they also showed down-regulation of neuro-protective/anti-inflammatory DHCR24. These results suggest that Aβ42 may cause insulin resistance, activate JNK for c-Jun phosphorylation, and lead to dysregulation of cholesterol homeostasis, and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote A

  3. Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms.

    Directory of Open Access Journals (Sweden)

    Jonas Kalderstam

    Full Text Available We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart, which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do.

  4. Up-regulation of abscisic acid signaling pathway facilitates aphid xylem absorption and osmoregulation under drought stress

    Science.gov (United States)

    Guo, Huijuan; Sun, Yucheng; Peng, Xinhong; Wang, Qinyang; Harris, Marvin; Ge, Feng

    2016-01-01

    The activation of the abscisic acid (ABA) signaling pathway reduces water loss from plants challenged by drought stress. The effect of drought-induced ABA signaling on the defense and nutrition allocation of plants is largely unknown. We postulated that these changes can affect herbivorous insects. We studied the effects of drought on different feeding stages of pea aphids in the wild-type A17 of Medicago truncatula and ABA signaling pathway mutant sta-1. We examined the impact of drought on plant water status, induced plant defense signaling via the abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) pathways, and on the host nutritional quality in terms of leaf free amino acid content. During the penetration phase of aphid feeding, drought decreased epidermis/mesophyll resistance but increased mesophyll/phloem resistance of A17 but not sta-1 plants. Quantification of transcripts associated with ABA, JA and SA signaling indicated that the drought-induced up-regulation of ABA signaling decreased the SA-dependent defense but increased the JA-dependent defense in A17 plants. During the phloem-feeding phase, drought had little effect on the amino acid concentrations and the associated aphid phloem-feeding parameters in both plant genotypes. In the xylem absorption stage, drought decreased xylem absorption time of aphids in both genotypes because of decreased water potential. Nevertheless, the activation of the ABA signaling pathway increased water-use efficiency of A17 plants by decreasing the stomatal aperture and transpiration rate. In contrast, the water potential of sta-1 plants (unable to close stomata) was too low to support xylem absorption activity of aphids; the aphids on sta-1 plants had the highest hemolymph osmolarity and lowest abundance under drought conditions. Taken together this study illustrates the significance of cross-talk between biotic-abiotic signaling pathways in plant-aphid interaction, and reveals the mechanisms leading to alter

  5. Metabolic flux of the oxidative pentose phosphate pathway under low light conditions in Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Ueda, Kentaro; Nakajima, Tsubasa; Yoshikawa, Katsunori; Toya, Yoshihiro; Matsuda, Fumio; Shimizu, Hiroshi

    2018-02-27

    The role of the oxidative pentose phosphate pathway (oxPPP) in Synechocystis sp. PCC 6803 under mixotrophic conditions was investigated by 13 C metabolic flux analysis. Cells were cultured under low (10 μmol m -2  s -1 ) and high light intensities (100 μmol m -2  s -1 ) in the presence of glucose. The flux of CO 2 fixation by ribulose bisphosphate carboxylase/oxygenase under the high light condition was approximately 3-fold higher than that under the low light condition. Although no flux of the oxPPP was observed under the high light condition, flux of 0.08-0.19 mmol gDCW -1  h -1 in the oxPPP was observed under the low light condition. The balance between the consumption and production of NADPH suggested that approximately 10% of the total NADPH production was generated by the oxPPP under the low light condition. The growth phenotype of a mutant with deleted zwf, which encodes glucose-6-phosphate dehydrogenase in the oxPPP, was compared to that of the parental strain under low and high light conditions. Growth of the Δzwf mutant nearly stopped during the late growth phase under the low light condition, whereas the growth rates of the two strains were identical under the high light condition. These results indicate that NADPH production in the oxPPP is essential for anabolism under low light conditions. The oxPPP appears to play an important role in producing NADPH from glucose and ATP to compensate for NADPH shortage under low light conditions. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. Carbon Fluxes between Primary Metabolism and Phenolic Pathway in Plant Tissues under Stress

    Directory of Open Access Journals (Sweden)

    Sofia Caretto

    2015-11-01

    Full Text Available Higher plants synthesize an amazing diversity of phenolic secondary metabolites. Phenolics are defined secondary metabolites or natural products because, originally, they were considered not essential for plant growth and development. Plant phenolics, like other natural compounds, provide the plant with specific adaptations to changing environmental conditions and, therefore, they are essential for plant defense mechanisms. Plant defensive traits are costly for plants due to the energy drain from growth toward defensive metabolite production. Being limited with environmental resources, plants have to decide how allocate these resources to various competing functions. This decision brings about trade-offs, i.e., promoting some functions by neglecting others as an inverse relationship. Many studies have been carried out in order to link an evaluation of plant performance (in terms of growth rate with levels of defense-related metabolites. Available results suggest that environmental stresses and stress-induced phenolics could be linked by a transduction pathway that involves: (i the proline redox cycle; (ii the stimulated oxidative pentose phosphate pathway; and, in turn, (iii the reduced growth of plant tissues.

  7. Carbon Fluxes between Primary Metabolism and Phenolic Pathway in Plant Tissues under Stress

    Science.gov (United States)

    Caretto, Sofia; Linsalata, Vito; Colella, Giovanni; Mita, Giovanni; Lattanzio, Vincenzo

    2015-01-01

    Higher plants synthesize an amazing diversity of phenolic secondary metabolites. Phenolics are defined secondary metabolites or natural products because, originally, they were considered not essential for plant growth and development. Plant phenolics, like other natural compounds, provide the plant with specific adaptations to changing environmental conditions and, therefore, they are essential for plant defense mechanisms. Plant defensive traits are costly for plants due to the energy drain from growth toward defensive metabolite production. Being limited with environmental resources, plants have to decide how allocate these resources to various competing functions. This decision brings about trade-offs, i.e., promoting some functions by neglecting others as an inverse relationship. Many studies have been carried out in order to link an evaluation of plant performance (in terms of growth rate) with levels of defense-related metabolites. Available results suggest that environmental stresses and stress-induced phenolics could be linked by a transduction pathway that involves: (i) the proline redox cycle; (ii) the stimulated oxidative pentose phosphate pathway; and, in turn, (iii) the reduced growth of plant tissues. PMID:26556338

  8. Spectrin-based pathways underlying electrical and mechanical dysfunction in cardiac disease.

    Science.gov (United States)

    Unudurthi, Sathya D; Greer-Short, Amara; Patel, Nehal; Nassal, Drew; Hund, Thomas J

    2018-01-01

    In the heart, pathways that transduce extracellular environmental cues (e.g. mechanical force, inflammatory stress) into electrical and/or chemical signals at the cellular level are critical for the organ-level response to chronic biomechanical/neurohumoral stress. Specifically, a diverse array of membrane-bound receptors and stretch-activated proteins converge on a network of intracellular signaling cascades that control gene expression, protein translation, degradation and/or regulation. These cellular reprogramming events ultimately lead to changes in cell excitability, growth, proliferation, and/or survival. Areas covered: The actin/spectrin cytoskeleton has emerged as having important roles in not only providing structural support for organelle function but also in serving as a signaling 'superhighway,' linking signaling events at/near the membrane to distal cellular domains (e.g. nucleus, mitochondria). Furthermore, recent work suggests that the integrity of the actin/spectrin cytoskeleton is critical for canonical signaling of pathways involved in cellular response to stress. This review discusses these emerging roles for spectrin and consider implications for heart function and disease. Expert commentary: Despite growth in our understanding of the broader roles for spectrins in cardiac myocytes and other metazoan cells, there remain important unanswered questions, the answers to which may point the way to new therapies for human cardiac disease patients.

  9. Quantitative analysis of neurotransmitter pathways under steady state conditions - a perspective.

    Science.gov (United States)

    Cooper, Arthur J L

    2013-11-18

    In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti carried out a mathematical analysis of neurotransmitter pathways in brain, modeling compartmental nitrogen flux among several major participants - ammonia, glutamine, glutamate, GABA, and selected amino acids. This analysis is important because cerebral nitrogen metabolism is perturbed in many diseases, including liver disease and inborn errors of the urea cycle. These diseases result in an elevation of blood ammonia, which is neurotoxic. Here, a brief description is provided of the discovery of cerebral metabolic compartmentation of nitrogen metabolism - a key feature of cerebral glutamate-glutamine and GABA-glutamine cycles. The work of Somersalo and Calvetti is discussed as a model for future studies of normal and pathological cerebral ammonia metabolism.

  10. Quantitative Analysis of Neurotransmitter Pathways under Steady State Conditions – A Perspective

    Directory of Open Access Journals (Sweden)

    Arthur Joseph Cooper

    2013-11-01

    Full Text Available In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti carried out a mathematical analysis of neurotransmitter pathways in brain, modeling compartmental nitrogen flux among several major participants – ammonia, glutamine, glutamate, GABA and selected amino acids. This analysis is important because cerebral nitrogen metabolism is perturbed in many diseases, including liver disease and inborn errors of the urea cycle. These diseases result in an elevation of blood ammonia, which is neurotoxic. Here, a brief description is provided of the discovery of cerebral metabolic compartmentation of nitrogen metabolism – a key feature of cerebral glutamate-glutamine and GABA-glutamine cycles. The work of Somersalo and Calvetti is discussed as a model for future studies of normal and pathological cerebral ammonia metabolism.

  11. Synthesis of Optimal Processing Pathway for Microalgae-based Biorefinery under Uncertainty

    DEFF Research Database (Denmark)

    Rizwan, Muhammad; Lee, Jay H.; Gani, Rafiqul

    2015-01-01

    MINLP) problem is formulated for determining the optimal biorefinery structure under given parameter uncertainties modelled as sampled scenarios. The solution to the sMINLP problem determines the optimal decisions with respect to processing technologies, material flows, and product portfolio in the presence...... decision making, we propose a systematic framework for the synthesis and optimal design of microalgae-based processing network under uncertainty. By incorporating major uncertainties into the biorefinery superstructure model we developed previously, a stochastic mixed integer nonlinear programming (s...

  12. Multifractal analysis of information processing in hippocampal neural ensembles during working memory under Δ⁹-tetrahydrocannabinol administration.

    Science.gov (United States)

    Fetterhoff, Dustin; Opris, Ioan; Simpson, Sean L; Deadwyler, Sam A; Hampson, Robert E; Kraft, Robert A

    2015-04-15

    Multifractal analysis quantifies the time-scale-invariant properties in data by describing the structure of variability over time. By applying this analysis to hippocampal interspike interval sequences recorded during performance of a working memory task, a measure of long-range temporal correlations and multifractal dynamics can reveal single neuron correlates of information processing. Wavelet leaders-based multifractal analysis (WLMA) was applied to hippocampal interspike intervals recorded during a working memory task. WLMA can be used to identify neurons likely to exhibit information processing relevant to operation of brain-computer interfaces and nonlinear neuronal models. Neurons involved in memory processing ("Functional Cell Types" or FCTs) showed a greater degree of multifractal firing properties than neurons without task-relevant firing characteristics. In addition, previously unidentified FCTs were revealed because multifractal analysis suggested further functional classification. The cannabinoid type-1 receptor (CB1R) partial agonist, tetrahydrocannabinol (THC), selectively reduced multifractal dynamics in FCT neurons compared to non-FCT neurons. WLMA is an objective tool for quantifying the memory-correlated complexity represented by FCTs that reveals additional information compared to classification of FCTs using traditional z-scores to identify neuronal correlates of behavioral events. z-Score-based FCT classification provides limited information about the dynamical range of neuronal activity characterized by WLMA. Increased complexity, as measured with multifractal analysis, may be a marker of functional involvement in memory processing. The level of multifractal attributes can be used to differentially emphasize neural signals to improve computational models and algorithms underlying brain-computer interfaces. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Artificial Neural Network Modelling of Photodegradation in Suspension of Manganese Doped Zinc Oxide Nanoparticles under Visible-Light Irradiation

    Directory of Open Access Journals (Sweden)

    Yadollah Abdollahi

    2014-01-01

    Full Text Available The artificial neural network (ANN modeling of m-cresol photodegradation was carried out for determination of the optimum and importance values of the effective variables to achieve the maximum efficiency. The photodegradation was carried out in the suspension of synthesized manganese doped ZnO nanoparticles under visible-light irradiation. The input considered effective variables of the photodegradation were irradiation time, pH, photocatalyst amount, and concentration of m-cresol while the efficiency was the only response as output. The performed experiments were designed into three data sets such as training, testing, and validation that were randomly splitted by the software’s option. To obtain the optimum topologies, ANN was trained by quick propagation (QP, Incremental Back Propagation (IBP, Batch Back Propagation (BBP, and Levenberg-Marquardt (LM algorithms for testing data set. The topologies were determined by the indicator of minimized root mean squared error (RMSE for each algorithm. According to the indicator, the QP-4-8-1, IBP-4-15-1, BBP-4-6-1, and LM-4-10-1 were selected as the optimized topologies. Among the topologies, QP-4-8-1 has presented the minimum RMSE and absolute average deviation as well as maximum R-squared. Therefore, QP-4-8-1 was selected as final model for validation test and navigation of the process. The model was used for determination of the optimum values of the effective variables by a few three-dimensional plots. The optimum points of the variables were confirmed by further validated experiments. Moreover, the model predicted the relative importance of the variables which showed none of them was neglectable in this work.

  14. Water scarcity under various socio-economic pathways and its potential effects on food production in the Yellow River basin

    Science.gov (United States)

    Yin, Yuanyuan; Tang, Qiuhong; Liu, Xingcai; Zhang, Xuejun

    2017-02-01

    Increasing population and socio-economic development have put great pressure on water resources of the Yellow River (YR) basin. The anticipated climate and socio-economic changes may further increase water stress. Many studies have investigated the changes in renewable water resources under various climate change scenarios, but few have considered the joint pressure from both climate change and socio-economic development. In this study, we assess water scarcity under various socio-economic pathways with emphasis on the impact of water scarcity on food production. The water demands in the 21st century are estimated based on the newly developed shared socio-economic pathways (SSPs) and renewable water supply is estimated using the climate projections under the Representative Concentration Pathway (RCP) 8.5 scenario. The assessment predicts that the renewable water resources would decrease slightly then increase. The domestic and industrial water withdrawals are projected to increase in the next a few decades and then remain at the high level or decrease slightly during the 21st century. The increase in water withdrawals will put the middle and lower reaches in a condition of severe water scarcity beginning in the next a few decades. If 40 % of the renewable water resources were used to sustain ecosystems, a portion of irrigated land would have to be converted to rain-fed agriculture, which would lead to a 2-11 % reduction in food production. This study highlights the links between water, food and ecosystems in a changing environment and suggests that trade-offs should be considered when developing regional adaptation strategies.

  15. Neural substrates underlying reconcentration for the preparation of an appropriate cognitive state to prevent future mistakes: a functional magnetic resonance imaging study

    Science.gov (United States)

    Miura, Naoki; Nozawa, Takayuki; Takahashi, Makoto; Yokoyama, Ryoichi; Sasaki, Yukako; Sakaki, Kohei; Kawashima, Ryuta

    2015-01-01

    The ability to reconcentrate on the present situation by recognizing one’s own recent errors is a cognitive mechanism that is crucial for safe and appropriate behavior in a particular situation. However, an individual may not be able to adequately perform a subsequent task even if he/she recognize his/her own error; thus, it is hypothesized that the neural mechanisms underlying the reconcentration process are different from the neural substrates supporting error recognition. The present study performed a functional magnetic resonance imaging (fMRI) analysis to explore the neural substrates associated with reconcentration related to achieving an appropriate cognitive state, and to dissociate these brain regions from the neural substrates involved in recognizing one’s own mistake. This study included 44 healthy volunteers who completed an experimental procedure that was based on the Eriksen flanker task and included feedback regarding the results of the current trial. The hemodynamic response induced by each instance of feedback was modeled using a combination of the successes and failures of the current and subsequent trials in order to identify the neural substrates underlying the ability to reconcentrate for the next situation and to dissociate them from those involved in recognizing current errors. The fMRI findings revealed significant and specific activation in the dorsal aspect of the medial prefrontal cortex (MFC) when participants successfully reconcentrated on the task after recognizing their own error based on feedback. Additionally, this specific activation was clearly dissociated from the activation foci that occurred during error recognition. These findings indicate that the dorsal aspect of the MFC may be a distinct functional region that specifically supports the reconcentration process and that is associated with the prevention of successive errors when a human subject recognizes his/her own mistake. Furthermore, it is likely that this

  16. Linking sea level rise and socioeconomic indicators under the Shared Socioeconomic Pathways

    Science.gov (United States)

    Nauels, Alexander; Rogelj, Joeri; Schleussner, Carl-Friedrich; Meinshausen, Malte; Mengel, Matthias

    2017-11-01

    In order to assess future sea level rise and its societal impacts, we need to study climate change pathways combined with different scenarios of socioeconomic development. Here, we present sea level rise (SLR) projections for the Shared Socioeconomic Pathway (SSP) storylines and different year-2100 radiative forcing targets (FTs). Future SLR is estimated with a comprehensive SLR emulator that accounts for Antarctic rapid discharge from hydrofracturing and ice cliff instability. Across all baseline scenario realizations (no dedicated climate mitigation), we find 2100 median SLR relative to 1986-2005 of 89 cm (likely range: 57-130 cm) for SSP1, 105 cm (73-150 cm) for SSP2, 105 cm (75-147 cm) for SSP3, 93 cm (63-133 cm) for SSP4, and 132 cm (95-189 cm) for SSP5. The 2100 sea level responses for combined SSP-FT scenarios are dominated by the mitigation targets and yield median estimates of 52 cm (34-75 cm) for FT 2.6 Wm-2, 62 cm (40-96 cm) for FT 3.4 Wm-2, 75 cm (47-113 cm) for FT 4.5 Wm-2, and 91 cm (61-132 cm) for FT 6.0 Wm-2. Average 2081-2100 annual SLR rates are 5 mm yr-1 and 19 mm yr-1 for FT 2.6 Wm-2 and the baseline scenarios, respectively. Our model setup allows linking scenario-specific emission and socioeconomic indicators to projected SLR. We find that 2100 median SSP SLR projections could be limited to around 50 cm if 2050 cumulative CO2 emissions since pre-industrial stay below 850 GtC, with a global coal phase-out nearly completed by that time. For SSP mitigation scenarios, a 2050 carbon price of 100 US2005 tCO2 -1 would correspond to a median 2100 SLR of around 65 cm. Our results confirm that rapid and early emission reductions are essential for limiting 2100 SLR.

  17. [Mechanistic modelling allows to assess pathways of DNA lesion interactions underlying chromosome aberration formation].

    Science.gov (United States)

    Eĭdel'man, Iu A; Slanina, S V; Sal'nikov, I V; Andreev, S G

    2012-12-01

    The knowledge of radiation-induced chromosomal aberration (CA) mechanisms is required in many fields of radiation genetics, radiation biology, biodosimetry, etc. However, these mechanisms are yet to be quantitatively characterised. One of the reasons is that the relationships between primary lesions of DNA/chromatin/chromosomes and dose-response curves for CA are unknown because the pathways of lesion interactions in an interphase nucleus are currently inaccessible for direct experimental observation. This article aims for the comparative analysis of two principally different scenarios of formation of simple and complex interchromosomal exchange aberrations: by lesion interactions at chromosome territories' surface vs. in the whole space of the nucleus. The analysis was based on quantitative mechanistic modelling of different levels of structures and processes involved in CA formation: chromosome structure in an interphase nucleus, induction, repair and interactions of DNA lesions. It was shown that the restricted diffusion of chromosomal loci, predicted by computational modelling of chromosome organization, results in lesion interactions in the whole space of the nucleus being impossible. At the same time, predicted features of subchromosomal dynamics agrees well with in vivo observations and does not contradict the mechanism of CA formation at the surface of chromosome territories. On the other hand, the "surface mechanism" of CA formation, despite having certain qualities, proved to be insufficient to explain high frequency of complex exchange aberrations observed by mFISH technique. The alternative mechanism, CA formation on nuclear centres is expected to be sufficient to explain frequent complex exchanges.

  18. Flower abscission in Vitis vinifera L. triggered by gibberellic acid and shade discloses differences in the underlying metabolic pathways

    Directory of Open Access Journals (Sweden)

    Sara eDomingos

    2015-06-01

    Full Text Available Understanding abscission is both a biological and an agronomic challenge. Flower abscission induced independently by shade and gibberellic acid (GAc sprays was monitored in grapevine (Vitis vinifera L. growing under a soilless greenhouse system during two seasonal growing conditions, in an early and late production cycle. Physiological and metabolic changes triggered by each of the two distinct stimuli were determined. Environmental conditions exerted a significant effect on fruit set as showed by the higher natural drop rate recorded in the late production cycle with respect to the early cycle. Shade and GAc treatments increased the percentage of flower drop compared to the control, and at a similar degree, during the late production cycle. The reduction of leaf gas exchanges under shade conditions was not observed in GAc treated vines. The metabolic profile assessed in samples collected during the late cycle differently affected primary and secondary metabolisms and showed that most of the treatment-resulting variations occurred in opposite trends in inflorescences unbalanced in either hormonal or energy deficit abscission-inducing signals. Particularly concerning carbohydrates metabolism, sucrose, glucose, tricarboxylic acid (TCA metabolites and intermediates of the raffinose family oligosaccharides pathway were lower in shaded and higher in GAc samples. Altered oxidative stress remediation mechanisms and indolacetic acid (IAA concentration were identified as abscission signatures common to both stimuli. According to the global analysis performed, we report that grape flower abscission mechanisms triggered by GAc application and C-starvation are not based on the same metabolic pathways.

  19. Different routes, same pathways: Molecular mechanisms under silver ion and nanoparticle exposures in the soil sentinel Eisenia fetida

    International Nuclear Information System (INIS)

    Novo, Marta; Lahive, Elma; Díez-Ortiz, María; Matzke, Marianne; Morgan, Andrew J.; Spurgeon, David J.; Svendsen, Claus; Kille, Peter

    2015-01-01

    Use of nanotechnology products is increasing; with silver (Ag) nanoparticles particularly widely used. A key uncertainty surrounding the risk assessment of AgNPs is whether their effects are driven through the same mechanism of action that underlies the toxic effects of Ag ions. We present the first full transcriptome study of the effects of Ag ions and NPs in an ecotoxicological model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses indicated similar mechanisms for both silver forms with toxicity being exerted through pathways related to ribosome function, sugar and protein metabolism, molecular stress, disruption of energy production and histones. The main difference seen between Ag ions and NPs was associated with potential toxicokinetic effects related to cellular internalisation and communication, with pathways related to endocytosis and cilia being significantly enriched. These results point to a common final toxicodynamic response, but initial internalisation driven by different exposure routes and toxicokinetic mechanisms. - Highlights: • Molecular effects underlying Ag ions and NPs exposure were studied in Eisenia fetida. • Full transcriptomic study of a genetically characterised lineage. • NPs and ions presented a similar toxicodynamic response. • Internalisation of the two Ag forms by different toxicokinetic mechanisms. - Transcriptomic analyses after exposure of earthworms to silver NPs or ions showed a final common toxicodynamic response, but internalisation by different toxicokinetic mechanisms

  20. Gridded population projections for the coastal zone under the Shared Socioeconomic Pathways

    Science.gov (United States)

    Merkens, Jan-Ludolf; Reimann, Lena; Hinkel, Jochen; Vafeidis, Athanasios T.

    2016-10-01

    Existing quantifications of the Shared Socioeconomic Pathways (SSP) used for climate impact assessment do not account for subnational population dynamics such as coastward-migration that can be critical for coastal impact assessment. This paper extends the SSPs by developing spatial projections of global coastal population distribution for the five basic SSPs. Based on a series of coastal migration drivers we develop coastal narratives for each SSP. These narratives account for differences in coastal and inland population developments in urban and rural areas. To spatially distribute population, we use the International Institute for Applied Systems Analysis (IIASA) national population and urbanisation projections and employ country-specific growth rates, which differ for coastal and inland as well as for urban and rural regions, to project coastal population for each SSP. These rates are derived from spatial analysis of historical population data and adjusted for each SSP based on the coastal narratives. Our results show that, compared to the year 2000 (638 million), the population living in the Low Elevated Coastal Zone (LECZ) increases by 58% to 71% until 2050 and exceeds one billion in all SSPs. By the end of the 21st century, global coastal population declines to 830-907 million in all SSPs except for SSP3, where coastal population growth continues and reaches 1.184 billion. Overall, the population living in the LECZ is higher by 85 to 239 million compared to the original IIASA projections. Asia expects the highest absolute growth (238-303 million), Africa the highest relative growth (153% to 218%). Our results highlight regions where high coastal population growth is expected and will therefore face an increased exposure to coastal flooding.

  1. Exploring critical pathways for urban water management to identify robust strategies under deep uncertainties.

    Science.gov (United States)

    Urich, Christian; Rauch, Wolfgang

    2014-12-01

    Long-term projections for key drivers needed in urban water infrastructure planning such as climate change, population growth, and socio-economic changes are deeply uncertain. Traditional planning approaches heavily rely on these projections, which, if a projection stays unfulfilled, can lead to problematic infrastructure decisions causing high operational costs and/or lock-in effects. New approaches based on exploratory modelling take a fundamentally different view. Aim of these is, to identify an adaptation strategy that performs well under many future scenarios, instead of optimising a strategy for a handful. However, a modelling tool to support strategic planning to test the implication of adaptation strategies under deeply uncertain conditions for urban water management does not exist yet. This paper presents a first step towards a new generation of such strategic planning tools, by combing innovative modelling tools, which coevolve the urban environment and urban water infrastructure under many different future scenarios, with robust decision making. The developed approach is applied to the city of Innsbruck, Austria, which is spatially explicitly evolved 20 years into the future under 1000 scenarios to test the robustness of different adaptation strategies. Key findings of this paper show that: (1) Such an approach can be used to successfully identify parameter ranges of key drivers in which a desired performance criterion is not fulfilled, which is an important indicator for the robustness of an adaptation strategy; and (2) Analysis of the rich dataset gives new insights into the adaptive responses of agents to key drivers in the urban system by modifying a strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Development of a signal-analysis algorithm for the ZEUS transition-radiation detector under application of a neural network

    International Nuclear Information System (INIS)

    Wollschlaeger, U.

    1992-07-01

    The aim of this thesis consisted in the development of a procedure for the analysis of the data of the transition-radiation detector at ZEUS. For this a neural network was applied and first studied, which results concerning the separation power between electron an pions can be reached by this procedure. It was shown that neural nets yield within the error limits as well results as standard algorithms (total charge, cluster analysis). At an electron efficiency of 90% pion contaminations in the range 1%-2% were reached. Furthermore it could be confirmed that neural networks can be considered for the here present application field as robust in relatively insensitive against external perturbations. For the application in the experiment beside the separation power also the time-behaviour is of importance. The requirement to keep dead-times small didn't allow the application of standard method. By a simulation the time availabel for the signal analysis was estimated. For the testing of the processing time in a neural network subsequently the corresponding algorithm was implemented into an assembler code for the digital signal processor DSP56001. (orig./HSI) [de

  3. 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

  4. Normative data on development of neural and behavioral mechanisms underlying attention orienting toward social-emotional stimuli: an exploratory study.

    Science.gov (United States)

    Lindstrom, Kara M; Guyer, Amanda E; Mogg, Karin; Bradley, Brendan P; Fox, Nathan A; Ernst, Monique; Nelson, Eric E; Leibenluft, Ellen; Britton, Jennifer C; Monk, Christopher S; Pine, Daniel S; Bar-Haim, Yair

    2009-10-06

    The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. We examined age-related correlations in attention-orienting biases to positive and negative face emotions in a healthy sample (N=37; 9-40 years old) using functional magnetic resonance imaging and a dot-probe task. The dot-probe task in an fMRI setting yields both behavioral and neural indices of attention biases towards or away from an emotional cue (happy or angry face). In the full sample, angry-face attention bias scores did not correlate with age, and age did not correlate with brain activation to angry faces. However, age did positively correlate with attention bias towards happy faces; age also negatively correlated with left cuneus and left caudate activation to a happy bias fMRI contrast. Secondary analyses suggested age-related changes in attention bias to happy faces. The tendency in younger children to direct attention away from happy faces (relative to neutral faces) was diminished in the older age groups, in tandem with increasing neural deactivation. Implications for future work on developmental changes in attention-emotion processing are discussed.

  5. Extra- and intracellular signaling pathways under red blood cell aggregation and deformability changes.

    Science.gov (United States)

    Muravyov, Alexei V; Tikhomirova, Irina A; Maimistova, Alla A; Bulaeva, Svetlana V

    2009-01-01

    Exposure of red blood cells (RBCs) to catecholamines (epinephrine, phenylephrine, an agonist of alpha1-adrenergic receptors, clonidine, an agonist of alpha2-adrenergic receptors and isoproterenol, an agonist of beta-adrenergic receptors) led to change in the RBC microrheological properties. When forskolin (10 microM), an AC stimulator was added to RBC suspension, the RBC deformability (RBCD) was increased by 17% (pRBCA) was significantly decreased under these conditions (pRBCA reduction effect was found under cell incubation with pentoxifylline and inhibitor PDE1-vinpocetine. On the whole RBCA reduction averaged 36% (pRBCA, whereas red cell deformability was changed insignificantly. At the same time Ca2+ entry blocking into the red cells by verapamil or its chelating in medium by EGTA led to significant RBCA decrease and deformability rise (pRBCA decrease was mainly associated with an activation of the adenylyl-cyclase-cAMP system, while the red cell deformability was closely associated with Ca2+ control mechanisms.

  6. Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

    DEFF Research Database (Denmark)

    Strom, C.C.; Kruhoffer, M.; Knudsen, S.

    2004-01-01

    Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic...... gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved...... in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61...

  7. Subsurface flow pathway dynamics in the active layer of coupled permafrost-hydrogeological systems under seasonal and annual temperature variability.

    Science.gov (United States)

    Frampton, Andrew

    2017-04-01

    There is a need for improved understanding of the mechanisms controlling subsurface solute transport in the active layer in order to better understand permafrost-hydrological-carbon feedbacks, in particular with regards to how dissolved carbon is transported in coupled surface and subsurface terrestrial arctic water systems under climate change. Studying solute transport in arctic systems is also relevant in the context of anthropogenic pollution which may increase due to increased activity in cold region environments. In this contribution subsurface solute transport subject to ground surface warming causing permafrost thaw and active layer change is studied using a physically based model of coupled cryotic and hydrogeological flow processes combined with a particle tracking method. Changes in subsurface water flows and solute transport travel times are analysed for different modelled geological configurations during a 100-year warming period. Results show that for all simulated cases, the minimum and mean travel times increase non-linearly with warming irrespective of geological configuration and heterogeneity structure. The timing of the start of increase in travel time depends on heterogeneity structure, combined with the rate of permafrost degradation that also depends on material thermal and hydrogeological properties. These travel time changes are shown to depend on combined warming effects of increase in pathway length due to deepening of the active layer, reduced transport velocities due to a shift from horizontal saturated groundwater flow near the surface to vertical water percolation deeper into the subsurface, and pathway length increase and temporary immobilization caused by cryosuction-induced seasonal freeze cycles. The impact these change mechanisms have on solute and dissolved substance transport is further analysed by integrating pathway analysis with a Lagrangian approach, incorporating considerations for both dissolved organic and inorganic

  8. Can agricultural groundwater economies collapse? An inquiry into the pathways of four groundwater economies under threat

    Science.gov (United States)

    Petit, Olivier; Kuper, Marcel; López-Gunn, Elena; Rinaudo, Jean-Daniel; Daoudi, Ali; Lejars, Caroline

    2017-09-01

    The aim of this paper is to investigate the notion of collapse of agricultural groundwater economies using the adaptive-cycle analytical framework. This framework was applied to four case studies in southern Europe and North Africa to question and discuss the dynamics of agricultural groundwater economies. In two case studies (Saiss in Morocco and Clain basin in France), the imminent physical or socio-economic collapse was a major concern for stakeholders and the early signs of collapse led to re-organization of the groundwater economy. In the other two cases (Biskra in Algeria and Almeria in Spain), collapse was either not yet a concern or had been temporarily resolved through increased efficiency and access to additional water resources. This comparative analysis shows the importance of taking the early signs of collapse into account. These signs can be either related to resource depletion or to environmental and socio-economic impacts. Beyond these four case studies, the large number of groundwater economies under threat in (semi-)arid areas should present a warning regarding their possible collapse. Collapse can have severe and irreversible consequences in some cases, but it can also mean new opportunities and changes.

  9. Rupturing the hemi-fission intermediate in membrane fission under tension: Reaction coordinates, kinetic pathways, and free-energy barriers

    Science.gov (United States)

    Zhang, Guojie; Müller, Marcus

    2017-08-01

    Membrane fission is a fundamental process in cells, involved inter alia in endocytosis, intracellular trafficking, and virus infection. Its underlying molecular mechanism, however, is only incompletely understood. Recently, experiments and computer simulation studies have revealed that dynamin-mediated membrane fission is a two-step process that proceeds via a metastable hemi-fission intermediate (or wormlike micelle) formed by dynamin's constriction. Importantly, this hemi-fission intermediate is remarkably metastable, i.e., its subsequent rupture that completes the fission process does not occur spontaneously but requires additional, external effects, e.g., dynamin's (unknown) conformational changes or membrane tension. Using simulations of a coarse-grained, implicit-solvent model of lipid membranes, we investigate the molecular mechanism of rupturing the hemi-fission intermediate, such as its pathway, the concomitant transition states, and barriers, as well as the role of membrane tension. The membrane tension is controlled by the chemical potential of the lipids, and the free-energy landscape as a function of two reaction coordinates is obtained by grand canonical Wang-Landau sampling. Our results show that, in the course of rupturing, the hemi-fission intermediate undergoes a "thinning → local pinching → rupture/fission" pathway, with a bottle-neck-shaped cylindrical micelle as a transition state. Although an increase of membrane tension facilitates the fission process by reducing the corresponding free-energy barrier, for biologically relevant tensions, the free-energy barriers still significantly exceed the thermal energy scale kBT.

  10. HIV-1-infected and immune-activated macrophages induce astrocytic differentiation of human cortical neural progenitor cells via the STAT3 pathway.

    Directory of Open Access Journals (Sweden)

    Hui Peng

    Full Text Available Diminished adult neurogenesis is considered a potential mechanism in the pathogenesis of HIV-1-associated dementia (HAD. In HAD, HIV-1-infected and immune-activated brain mononuclear phagocytes (MP; perivascular macrophages and microglia drive central nervous system (CNS inflammation and may alter normal neurogenesis. We previously demonstrated HIV-1-infected and lipopolysaccharide (LPS activated monocyte-derived macrophages (MDM inhibit human neural progenitor cell (NPC neurogenesis, while enhancing astrogliogenesis through the secretion of the inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α, in vitro and in vivo. Here we further test the hypothesis that HIV-1-infected/activated MDM promote NPC astrogliogenesis via activation of the transcription factor signal transducer and activator of transcription 3 (STAT3, a critical factor for astrogliogenesis. Our results show that LPS-activated MDM-conditioned medium (LPS-MCM and HIV-infected/LPS-activated MDM-conditioned medium (LPS+HIV-MCM induced Janus kinase 1 (Jak1 and STAT3 activation. Induction of the Jak-STAT3 activation correlated with increased glia fibrillary acidic protein (GFAP expression, demonstrating an induction of astrogliogenesis. Moreover, STAT3-targeting siRNA (siSTAT3 decreased MCM-induced STAT3 activation and NPC astrogliogenesis. Furthermore, inflammatory cytokines (including IL-6, IL-1β and TNF-α produced by LPS-activated and/or HIV-1-infected MDM may contribute to MCM-induced STAT3 activation and astrocytic differentiation. These observations were confirmed in severe combined immunodeficient (SCID mice with HIV-1 encephalitis (HIVE. In HIVE mice, siRNA control (without target sequence, sicon pre-transfected NPCs injected with HIV-1-infected MDM showed more astrocytic differentiation and less neuronal differentiation of NPCs as compared to NPC injection alone. siSTAT3 abrogated HIV-1-infected MDM-induced astrogliogenesis of injected NPCs. Collectively, these

  11. Experiences of pathways, outcomes and choice after severe traumatic brain injury under no-fault versus fault-based motor accident insurance.

    Science.gov (United States)

    Harrington, Rosamund; Foster, Michele; Fleming, Jennifer

    2015-01-01

    To explore experiences of pathways, outcomes and choice after motor vehicle accident (MVA) acquired severe traumatic brain injury (sTBI) under fault-based vs no-fault motor accident insurance (MAI). In-depth qualitative interviews with 10 adults with sTBI and 17 family members examined experiences of pathways, outcomes and choice and how these were shaped by both compensable status and interactions with service providers and service funders under a no-fault and a fault-based MAI scheme. Participants were sampled to provide variation in compensable status, injury severity, time post-injury and metropolitan vs regional residency. Interviews were recorded, transcribed and thematically analysed to identify dominant themes under each scheme. Dominant themes emerging under the no-fault scheme included: (a) rehabilitation-focused pathways; (b) a sense of security; and (c) bounded choices. Dominant themes under the fault-based scheme included: (a) resource-rationed pathways; (b) pressured lives; and (c) unknown choices. Participants under the no-fault scheme experienced superior access to specialist rehabilitation services, greater surety of support and more choice over how rehabilitation and life-time care needs were met. This study provides valuable insights into individual experiences under fault-based vs no-fault MAI. Implications for an injury insurance scheme design to optimize pathways, outcomes and choice after sTBI are discussed.

  12. Effect of ERK1/2 signal pathway on the expression of OPG/RANKL in cementoblasts under stress stimulation

    Directory of Open Access Journals (Sweden)

    Feng-xue YANG

    2015-01-01

    Full Text Available Objective To explore the effect of extracellular signal regulated kinase (ERK1/2 on the expression of osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL in cementoblasts under mechanical tensile stress stimulation. Methods Using Flexcell FX4000T tension loading system and the ERK1/2-specific inhibitor PD98059, cementoblasts OCCM30 were randomly divided into four groups: group A (without loading and inhibitor, group B (without loading but inhibitor, group C (loading but without inhibitor, and group D (with both loading and inhibitor. The phosphorylation level of ERK1/2 was measured by Western blotting after 5, 15, 30 and 60min loading. OPG and RANKL mRNA were analyzed with fluorescent quantitative RT-PCR after 12h loading. Results Mechanical tensile stress activated ERK1/2 signal pathway of group C rapidly, and the P-ERK1/2 levels were significantly higher in group C than in group A at 5, 15 and 30min (P<0.05, then the P-ERK1/2 level of group C resumed to similar level of group A at 60min. The P-ERK levels of group B and D were significantly reduced by inhibitor PD98059. Tension stress up-regulated the expression of RANKL mRNA, and down-regulated the expression of OPG mRNA in OCCM30, the RANKL/OPG ratio increased after tension loading. With PD98059, the expression of RANKL mRNA decreased, that of OPG mRNA increased, and the RANKL/OPG ratio decreased (P<0.05. Conclusion ERK1/2 may be a signal transduction pathway for the regulation of OPG and RANKL expression after tension stress loading, but it is not the only one of activation pathways, and there may be other common signal pathways involved in the regulation of OPG and RANKL expression. DOI: 10.11855/j.issn.0577-7402.2014.12.03

  13. Modeling the photochemical transformation of nitrobenzene under conditions relevant to sunlit surface waters: Reaction pathways and formation of intermediates.

    Science.gov (United States)

    Vione, Davide; De Laurentiis, Elisa; Berto, Silvia; Minero, Claudio; Hatipoglu, Arzu; Cinar, Zekiye

    2016-02-01

    Nitrobenzene (NB) would undergo photodegradation in sunlit surface waters, mainly by direct photolysis and triplet-sensitized oxidation, with a secondary role of the *OH reaction. Its photochemical half-life time would range from a few days to a couple of months under fair-weather summertime irradiation, depending on water chemistry and depth. NB phototransformation gives phenol and the three nitrophenol isomers, in different yields depending on the considered pathway. The minor *OH role in degradation would make NB unsuitable as *OH probe in irradiated natural water samples, but the selectivity towards *OH could be increased by monitoring the formation of phenol from NB+*OH. The relevant reaction would proceed through ipso-addition of *OH on the carbon atom bearing the nitro-group, forming a pre-reactive complex that would evolve into a transition state (and then into a radical addition intermediate) with very low activation energy barrier. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. iTRAQ-based quantitative proteomic analysis reveals new metabolic pathways of wheat seedling growth under hydrogen peroxide stress.

    Science.gov (United States)

    Ge, Pei; Hao, Pengchao; Cao, Min; Guo, Guangfang; Lv, Dongwen; Subburaj, Saminathan; Li, Xiaohui; Yan, Xing; Xiao, Jitian; Ma, Wujun; Yan, Yueming

    2013-10-01

    As an abundant ROS, hydrogen peroxide (H2 O2 ) plays pivotal roles in plant growth and development. In this work, we conducted for the first time an iTRAQ-based quantitative proteomic analysis of wheat seedling growth under different exogenous H2 O2 treatments. The growth of seedlings and roots was significantly restrained by increased H2 O2 concentration stress. Malondialdehyde, soluble sugar, and proline contents as well as peroxidase activity increased with increasing H2 O2 levels. A total of 3,425 proteins were identified by iTRAQ, of which 157 showed differential expression and 44 were newly identified H2 O2 -responsive proteins. H2 O2 -responsive proteins were mainly involved in stress/defense/detoxification, signal transduction, and carbohydrate metabolism. It is clear that up-regulated expression of signal transduction and stress/defence/detoxification-related proteins under H2 O2 stress, such as plasma membrane intrinsic protein 1, fasciclin-like arabinogalactan protein, and superoxide dismutase, could contribute to H2 O2 tolerance of wheat seedlings. Increased gluconeogenesis (phosphoenol-pyruvate carboxykinase) and decreased pyruvate kinase proteins are potentially related to the higher H2 O2 tolerance of wheat seedlings. A metabolic pathway of wheat seedling growth under H2 O2 stress is presented. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

    Science.gov (United States)

    Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

    2017-09-28

    Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Agnete Kirkeby

    2012-06-01

    Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

  17. Neural electrical activity and neural network growth.

    Science.gov (United States)

    Gafarov, F M

    2018-02-09

    The development of central and peripheral neural system depends in part on the emergence of the correct functional connectivity in its input and output pathways. Now it is generally accepted that molecular factors guide neurons to establish a primary scaffold that undergoes activity-dependent refinement for building a fully functional circuit. However, a number of experimental results obtained recently shows that the neuronal electrical activity plays an important role in the establishing of initial interneuronal connections. Nevertheless, these processes are rather difficult to study experimentally, due to the absence of theoretical description and quantitative parameters for estimation of the neuronal activity influence on growth in neural networks. In this work we propose a general framework for a theoretical description of the activity-dependent neural network growth. The theoretical description incorporates a closed-loop growth model in which the neural activity can affect neurite outgrowth, which in turn can affect neural activity. We carried out the detailed quantitative analysis of spatiotemporal activity patterns and studied the relationship between individual cells and the network as a whole to explore the relationship between developing connectivity and activity patterns. The model, developed in this work will allow us to develop new experimental techniques for studying and quantifying the influence of the neuronal activity on growth processes in neural networks and may lead to a novel techniques for constructing large-scale neural networks by self-organization. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Quantitative Proteomic Analyses Identify ABA-related Proteins and Signal Pathways in Maize Leaves Under Drought Conditions

    Directory of Open Access Journals (Sweden)

    zhao Yulong

    2016-12-01

    Full Text Available Drought stress is one of major factors resulting in maize yield loss. The roles of abscisic acid (ABA have been widely studied in crops in response to drought stress. However, more attention is needed to identify key ABA-related proteins and also gain deeper molecular insights about drought stress in maize. Based on this need, the physiology and proteomics of the ABA-deficient maize mutant vp5 and its wild-type Vp5 under drought stress were examined and analyzed. Malondialdehyde content increased and quantum efficiency of photosystem II decreased under drought stress in both genotypes. However, the magnitude of the increase or decrease was significantly higher in vp5 than in Vp5. A total of 7051 proteins with overlapping expression patterns among three replicates in the two genotypes were identified by Multiplex run iTRAQ-based quantitative proteomic and liquid chromatography-tandem mass spectrometry methods, of which the expression of only 150 proteins (130 in Vp5, 27 in vp5 showed changes of at least 1.5-fold under drought stress. Among the 150 proteins, 67 and 60 proteins were up-regulated and down-regulated by drought stress in an ABA-dependent way, respectively. ABA was found to play active roles in regulating signaling pathways related to photosynthesis, oxidative phosphorylation (mainly related to ATP synthesis, and glutathione metabolism (involved in antioxidative reaction in the maize response to drought stress. Our results provide an extensive dataset of ABA-dependent, drought-regulated proteins in maize plants, which may help to elucidate the underlying mechanisms of ABA-enhanced tolerance to drought stress in maize.

  19. Mechanisms underlying the perifocal neuroprotective effect of the Nrf2–ARE signaling pathway after intracranial hemorrhage

    Directory of Open Access Journals (Sweden)

    Yin XP

    2015-11-01

    Full Text Available Xiao-ping Yin,1,2 Zhi-ying Chen,2 Jun Zhou,1 Dan Wu,1,3 Bing Bao2 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, People’s Republic of China; 3Department of Neurology, The Sixth Hospital of Wuhan, Wuhan, People’s Republic of China Background: It has been found that nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2–ARE signaling pathway plays a role in antioxidative response, anti-inflammatory response, and neuron-protection in intracerebral hemorrhage (ICH. The aim of this study is to explore mechanisms underlying the perifocal neuroprotective effect of the Nrf2–ARE signaling pathway after ICH.Methods: There were a total of 90 rats with basal ganglia hemorrhage, which were randomly divided into the following four groups: ICH (Sprague–Dawley rats with autologous femoral arterial blood injection into the basal ganglia, sulforaphane (SFN (SFN was intraperitoneally administered into rats, retinoic acid (RA (RA was intraperitoneally administered into rats, and dimethyl sulfoxide (the rats were treated with dimethyl sulfoxide. We observed the neurological score of the rats in the different groups, and collected brain tissues for immunofluorescence, Western blot, and reverse transcription polymerase chain reaction to detect expression of Nrf2, heme oxygenase (HO-1, nuclear factor-κB (NF-κB, and tumor necrosis factor-α (TNF-α.Results: The results indicated that neurological dysfunction of rats was significantly improved in the SFN group, and the expressions of Nrf2 and HO-1 in tissues surrounding the hemorrhage were increased. Also, the level of NF-κB and TNF-α were reduced compared to the ICH group. The RA group exhibited more severe neurological dysfunction and lower levels of Nrf2 and HO-1 than the SFN and ICH groups. Compared to the ICH group, the NF

  20. Photosensitized methyl paraben induces apoptosis via caspase dependent pathway under ambient UVB exposure in human skin cells.

    Science.gov (United States)

    Dubey, Divya; Chopra, Deepti; Singh, Jyoti; Srivastav, Ajeet K; Kumari, Smita; Verma, Ankit; Ray, Ratan Singh

    2017-10-01

    Methyl paraben (MP), is a widely used preservative in pharmaceutical, food and cosmetic products. Its molecular mechanism under ambient ultraviolet radiation is not well understood. We investigated photosensitizing mechanism of MP under ambient UVB (0.6 mW/cm 2 ) intensity. MP showed dose dependent decrease in cell viability of human keratinocyte cell line (HaCaT) by MTT and NRU assays. Study showed 40% reduction in antimicrobial activity of UVB irradiated MP through E. coli culture. Photosensitized MP (25 μg/ml) significantly enhanced lipid peroxidation, intracellular ROS generation and disrupted mitochondrial membrane integrity. MP induced loss of lysosomal membrane integrity and endoplasmic reticulum (ER) mediated stress evident from Ca +2 release. Phototoxicity of MP showed nuclear fragmentation, phosphatidylserine translocation, 30% tail DNA and micronuclei formation. Study showed mitochondria mediated apoptosis via upregulation of Bax, Apaf-1, Cytochrome C and Caspase-3. Upregulation of Caspase-12 (2 folds) specifically showed role of ER in apoptosis. Specific caspase inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis. Results indicate that photosensitive MP leads to oxidative stress mediated DNA damage and apoptosis through mitochondria and ER. MP causes deleterious effects and its long term exposure to human skin may promote skin diseases. Therefore, MP should be replaced by other photosafe preservatives for humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Crosstalk between adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism under red blood cell microrheological changes.

    Science.gov (United States)

    Muravyov, Alexei V; Tikhomirova, Irina A; Maimistova, Alla A; Bulaeva, Svetlana V; Zamishlayev, Andrey V; Batalova, Ekaterina A

    2010-01-01

    There are evidences that red blood cell (RBC) deformation and aggregation change under their incubation with catecholamines and it is connected with activation of intracellular signaling pathways. The present study was designed to explore the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism of RBCs together with their microrheological changes. The washed RBCs were resuspended in PBS. In each of the three research sessions RBC suspensions were divided into two aliquots: 1) control (without drug) and 2) with an appropriate drug. After cell incubation RBC deformability (RBCD) and aggregation (RBCA) were estimated. RBC incubation with catecholamines resulted in RBCD changes by 18-30%. RBCs incubation with forskolin facilitated an increase of RBCD by 17% (p RBCA; whereas red cell deformability was changed only slightly. On the other hand, Ca2+ entry blocking into the cells by verapamil has led to significant RBCA decrease and RBCD rise. The obtained results make us believe that RBCD change was closely associated with Ca2+ control mechanisms. An effect of Ca2+ concentration increase on RBC microrheology was removed, if it was preliminary added to incubation medium EGTA as Ca2+ chelator. It was found that all four PDE inhibitors: IBMX, vinpocetine, rolipram, pentoxifylline decreased RBCA significantly and, quite the contrary, they increased red cell deformability. Our data have shown that Ca2+ entry increase was accompanied by red cell aggregation rise, while adenylyl cyclase-cAMP system stimulation led to red cell deformability increase and its aggregation lowered. The crosstalk between two intracellular signaling systems is probably connected with phosphodiesterase activity.

  2. Combining ground-based and airborne EM through Artificial Neural Networks for modelling glacial till under saline groundwater conditions

    DEFF Research Database (Denmark)

    Gunnink, J.L.; Bosch, A.; Siemon, B.

    2012-01-01

    Airborne electromagnetic (AEM) methods supply data over large areas in a cost-effective way. We used ArtificialNeural Networks (ANN) to classify the geophysical signal into a meaningful geological parameter. By using examples of known relations between ground-based geophysical data (in this case ...... is acting as a layer that inhibits groundwater flow, due to its high clay-content, and is therefore an important layer in hydrogeological modelling and for predicting the effects of climate change on groundwater quantity and quality....

  3. Prediction of hydrogen concentration in nuclear power plant containment under severe accidents using cascaded fuzzy neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Geon Pil; Kim, Dong Yeong; Yoo, Kwae Hwan; Na, Man Gyun, E-mail: magyna@chosun.ac.kr

    2016-04-15

    Highlights: • We present a hydrogen-concentration prediction method in an NPP containment. • The cascaded fuzzy neural network (CFNN) is used in this prediction model. • The CFNN model is much better than the existing FNN model. • This prediction can help prevent severe accidents in NPP due to hydrogen explosion. - Abstract: Recently, severe accidents in nuclear power plants (NPPs) have attracted worldwide interest since the Fukushima accident. If the hydrogen concentration in an NPP containment is increased above 4% in atmospheric pressure, hydrogen combustion will likely occur. Therefore, the hydrogen concentration must be kept below 4%. This study presents the prediction of hydrogen concentration using cascaded fuzzy neural network (CFNN). The CFNN model repeatedly applies FNN modules that are serially connected. The CFNN model was developed using data on severe accidents in NPPs. The data were obtained by numerically simulating the accident scenarios using the MAAP4 code for optimized power reactor 1000 (OPR1000) because real severe accident data cannot be obtained from actual NPP accidents. The root-mean-square error level predicted by the CFNN model is below approximately 5%. It was confirmed that the CFNN model could accurately predict the hydrogen concentration in the containment. If NPP operators can predict the hydrogen concentration in the containment using the CFNN model, this prediction can assist them in preventing a hydrogen explosion.

  4. 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.

  5. Increased Thymic Cell Turnover under Boron Stress May Bypass TLR3/4 Pathway in African Ostrich.

    Science.gov (United States)

    Huang, Hai-bo; Xiao, Ke; Lu, Shun; Yang, Ke-li; Ansari, Abdur Rahman; Khaliq, Haseeb; Song, Hui; Zhong, Juming; Liu, Hua-zhen; Peng, Ke-mei

    2015-01-01

    Previous studies revealed that thymus is a targeted immune organ in malnutrition, and high-boron stress is harmful for immune organs. African ostrich is the living fossil of ancient birds and the food animals in modern life. There is no report about the effect of boron intake on thymus of ostrich. The purpose of present study was to evaluate the effect of excessive boron stress on ostrich thymus and the potential role of TLR3/4 signals in this process. Histological analysis demonstrated that long-term boron stress (640 mg/L for 90 days) did not disrupt ostrich thymic structure during postnatal development. However, the numbers of apoptotic cells showed an increased tendency, and the expression of autophagy and proliferation markers increased significantly in ostrich thymus after boron treatment. Next, we examined the expression of TLR3 and TLR4 with their downstream molecular in thymus under boron stress. Since ostrich genome was not available when we started the research, we first cloned ostrich TLR3 TLR4 cDNA from thymus. Ostrich TLR4 was close to white-throated Tinamou. Whole avian TLR4 codons were under purify selection during evolution, whereas 80 codons were under positive selection. TLR3 and TLR4 were expressed in ostrich thymus and bursa of fabricius as was revealed by quantitative real-time PCR (qRT-PCR). TLR4 expression increased with age but significantly decreased after boron treatment, whereas TLR3 expression showed the similar tendency. Their downstream molecular factors (IRF1, JNK, ERK, p38, IL-6 and IFN) did not change significantly in thymus, except that p100 was significantly increased under boron stress when analyzed by qRT-PCR or western blot. Taken together, these results suggest that ostrich thymus developed resistance against long-term excessive boron stress, possibly by accelerating intrathymic cell death and proliferation, which may bypass the TLR3/4 pathway. In addition, attenuated TLRs activity may explain the reduced inflammatory

  6. ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

    Science.gov (United States)

    Zheng, Shanqing; Liao, Sentai; Zou, Yuxiao; Qu, Zhi; Liu, Fan

    2014-01-01

    DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS), and this is notably true when Caenorhabditis elegans (C. elegans) is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

  7. Learning control of inverted pendulum system by neural network driven fuzzy reasoning: The learning function of NN-driven fuzzy reasoning under changes of reasoning environment

    Science.gov (United States)

    Hayashi, Isao; Nomura, Hiroyoshi; Wakami, Noboru

    1991-01-01

    Whereas conventional fuzzy reasonings are associated with tuning problems, which are lack of membership functions and inference rule designs, a neural network driven fuzzy reasoning (NDF) capable of determining membership functions by neural network is formulated. In the antecedent parts of the neural network driven fuzzy reasoning, the optimum membership function is determined by a neural network, while in the consequent parts, an amount of control for each rule is determined by other plural neural networks. By introducing an algorithm of neural network driven fuzzy reasoning, inference rules for making a pendulum stand up from its lowest suspended point are determined for verifying the usefulness of the algorithm.

  8. A global water scarcity assessment under Shared Socio-economic Pathways - Part 2: Water availability and scarcity

    Science.gov (United States)

    Hanasaki, N.; Fujimori, S.; Yamamoto, T.; Yoshikawa, S.; Masaki, Y.; Hijioka, Y.; Kainuma, M.; Kanamori, Y.; Masui, T.; Takahashi, K.; Kanae, S.

    2013-07-01

    A global water scarcity assessment for the 21st century was conducted under the latest socio-economic scenario for global change studies, namely Shared Socio-economic Pathways (SSPs). SSPs depict five global situations with substantially different socio-economic conditions. In the accompanying paper, a water use scenario compatible with the SSPs was developed. This scenario considers not only quantitative socio-economic factors such as population and electricity production but also qualitative ones such as the degree of technological change and overall environmental consciousness. In this paper, water availability and water scarcity were assessed using a global hydrological model called H08. H08 simulates both the natural water cycle and major human activities such as water abstraction and reservoir operation. It simulates water availability and use at daily time intervals at a spatial resolution of 0.5° × 0.5°. A series of global hydrological simulations were conducted under the SSPs, taking into account different climate policy options and the results of climate models. Water scarcity was assessed using an index termed the Cumulative Abstraction to Demand ratio, which is expressed as the accumulation of daily water abstraction from a river divided by the daily consumption-based potential water demand. This index can be used to express whether renewable water resources are available from rivers when required. The results suggested that by 2071-2100 the population living under severely water-stressed conditions for SSP1-5 will reach 2588-2793 × 106 (39-42% of total population), 3966-4298 × 106 (46-50%), 5334-5643 × 106 (52-55%), 3427-3786 × 106 (40-45%), 3164-3379 × 106 (46-49%) respectively, if climate policies are not adopted. Even in SSP1 (the scenario with least change in water use and climate) global water scarcity increases considerably, as compared to the present-day. This is mainly due to the growth in population and economic activity in developing

  9. Anatomy of the soul as reflected in the cerebral hemispheres: neural circuits underlying voluntary control of basic motivated behaviors.

    Science.gov (United States)

    Swanson, Larry W

    2005-12-05

    Understanding the principles of cerebral hemisphere neural network organization is essential for understanding the biological foundations of cognition and affect-thinking and feeling. A tripartite model of cerebral structure-function organization is reviewed, with attention focused on a behavior control system differentiation that mediates voluntary influences on three fundamental classes of goal-oriented behavior common to all animals. The model postulates just three cerebral divisions, one cortical and two nuclear (lateral or striatal, and medial or pallidal), that together generate a triple descending projection to the brainstem/cord motor system. This minimal circuit element is topographically organized and regionally differentiated, with the map of cortical areas serving as a basic starting point. Virtually all of the cerebral hemisphere projects on the upper brainstem behavior control column, atop the motor system hierarchy. The latter's rostral segment helps control ingestive (eating and drinking), defensive (fight or flight), and reproductive (sexual and parental) motivated behaviors, whereas its caudal segment helps control foraging or exploratory behavior to obtain or avoid specific goal objects associated with all classes of motivated behavior. (c) 2005 Wiley-Liss, Inc.

  10. Risk-taking and social exclusion in adolescence: Neural mechanisms underlying peer influences on decision-making

    Science.gov (United States)

    Peake, Shannon J.; Dishion, Thomas J.; Stormshak, Elizabeth A.; Moore, William E.; Pfeifer, Jennifer H.

    2013-01-01

    Social exclusion and risk-taking are both common experiences of concern in adolescence, yet little is known about how the two may be related at behavioral or neural levels. In this fMRI study, adolescents (N=27, 14 male, 14–17 years-old) completed a series of tasks in the scanner assessing risky decision-making before and after an episode of social exclusion. In this particular context, exclusion was associated with greater behavioral risk-taking among adolescents with low self-reported resistance to peer influence (RPI). When making risky decisions after social exclusion, adolescents who had lower RPI exhibited higher levels of activity in right temporoparietal junction (rTPJ), and this response in rTPJ was a significant mediator of the relationship between RPI and greater risk-taking after social exclusion. Lower RPI was also associated with lower levels of activity in lPFC during crashes following social exclusion, but unlike rTPJ this response in lPFC was not a significant mediator of the relationship between RPI and greater risk-taking after social exclusion. The results suggest that mentalizing and/or attentional mechanisms have a unique direct effect on adolescents’ vulnerability to peer influence on risk-taking. PMID:23707590

  11. The impact of emission and climate change on ozone in the United States under representative concentration pathways (RCPs

    Directory of Open Access Journals (Sweden)

    Y. Gao

    2013-09-01

    Full Text Available Dynamical downscaling was applied in this study to link the global climate-chemistry model Community Atmosphere Model (CAM-Chem with the regional models Weather Research and Forecasting (WRF Model and Community Multi-scale Air Quality (CMAQ. Two representative concentration pathway (RCP scenarios (RCP 4.5 and RCP 8.5 were used to evaluate the climate impact on ozone concentrations in the 2050s. From the CAM-Chem global simulation results, ozone concentrations in the lower to mid-troposphere (surface to ~300 hPa, from mid- to high latitudes in the Northern Hemisphere, decreases by the end of the 2050s (2057–2059 in RCP 4.5 compared to present (2001–2004, with the largest decrease of 4–10 ppbv occurring in the summer and the fall; and an increase as high as 10 ppbv in RCP 8.5 resulting from the increased methane emissions. From the regional model CMAQ simulation results, under the RCP 4.5 scenario (2057–2059, in the summer when photochemical reactions are the most active, the large ozone precursor emissions reduction leads to the greatest decrease of downscaled surface ozone concentrations compared to present (2001–2004, ranging from 6 to 10 ppbv. However, a few major cities show ozone increases of 3 to 7 ppbv due to weakened NO titration. Under the RCP 8.5 scenario, in winter, downscaled ozone concentrations increase across nearly the entire continental US in winter, ranging from 3 to 10 ppbv due to increased methane emissions. More intense heat waves are projected to occur by the end of the 2050s in RCP 8.5, leading to a 0.3 ppbv to 2.0 ppbv increase (statistically significant except in the Southeast of the mean maximum daily 8 h daily average (MDA8 ozone in nine climate regions in the US. Moreover, the upper 95% limit of MDA8 increase reaches 0.4 ppbv to 1.5 ppbv in RCP 4.5 and 0.6 ppbv to 3.2 ppbv in RCP 8.5. The magnitude differences of increase between RCP 4.5 and 8.5 also reflect that the increase of methane emissions may favor or

  12. ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

    Science.gov (United States)

    Winiarska, Katarzyna; Jarzyna, Robert; Dzik, Jolanta M; Jagielski, Adam K; Grabowski, Michal; Nowosielska, Agata; Focht, Dorota; Sierakowski, Bartosz

    2015-04-01

    The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has

  13. Transcriptome analysis and discovery of genes involved in immune pathways in large yellow croaker (Larimichthys crocea) under high stocking density stress.

    Science.gov (United States)

    Sun, Peng; Bao, Peibo; Tang, Baojun

    2017-09-01

    The large yellow croaker, Larimichthys crocea, is an economically important maricultured species in southeast China. Owing to the importance of stocking densities in commercial fish production, it is crucial to establish the physiological responses and molecular mechanisms that govern adaptation to crowding in order to optimize welfare and health. In the present study, an extensive immunity-related analysis was performed at the transcriptome level in L. crocea in response to crowding stress. Over 145 million high-quality reads were generated and de novo assembled into a final set of 40,123 unigenes. Gene Ontology and genome analyses revealed that molecular function, biological process, intracellular, ion binding, and cell process were the most highly enriched pathways among genes that were differentially expressed under stress. Among all of the pathways involved, 16 pathways were related to the immune system, among which the complement and coagulation cascades pathway was the most enriched for differentially expressed immunity-related genes, followed by the chemokine signaling pathway, toll-like receptor signaling pathway, and leukocyte transendothelial migration pathway. The consistently high expression of immune-related genes in the complement and coagulation cascades pathway (from 24 to 96 h after being subjected to stress) suggested its importance in both response to stress and resistance against bacterial invasion at an early stage. These results also demonstrated that crowding can significantly induce immunological responses in fish. However, long-term exposure to stress eventually impairs the defense capability in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Self vs. other: neural correlates underlying agent identification based on unimodal auditory information as revealed by electrotomography (sLORETA).

    Science.gov (United States)

    Justen, C; Herbert, C; Werner, K; Raab, M

    2014-02-14

    Recent neuroscientific studies have identified activity changes in an extensive cerebral network consisting of medial prefrontal cortex, precuneus, temporo-parietal junction, and temporal pole during the perception and identification of self- and other-generated stimuli. Because this network is supposed to be engaged in tasks which require agent identification, it has been labeled the evaluation network (e-network). The present study used self- versus other-generated movement sounds (long jumps) and electroencephalography (EEG) in order to unravel the neural dynamics of agent identification for complex auditory information. Participants (N=14) performed an auditory self-other identification task with EEG. Data was then subjected to a subsequent standardized low-resolution brain electromagnetic tomography (sLORETA) analysis (source localization analysis). Differences between conditions were assessed using t-statistics (corrected for multiple testing) on the normalized and log-transformed current density values of the sLORETA images. Three-dimensional sLORETA source localization analysis revealed cortical activations in brain regions mostly associated with the e-network, especially in the medial prefrontal cortex (bilaterally in the alpha-1-band and right-lateralized in the gamma-band) and the temporo-parietal junction (right hemisphere in the alpha-1-band). Taken together, the findings are partly consistent with previous functional neuroimaging studies investigating unimodal visual or multimodal agent identification tasks (cf. e-network) and extent them to the auditory domain. Cortical activations in brain regions of the e-network seem to have functional relevance, especially the significantly higher cortical activation in the right medial prefrontal cortex. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. [Glutamate signaling and neural plasticity].

    Science.gov (United States)

    Watanabe, Masahiko

    2013-07-01

    Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting

  16. Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats.

    Science.gov (United States)

    Wan, Feng; Bai, Hua-Jing; Liu, Jun-Qi; Tian, Mo; Wang, Yong-Xue; Niu, Xin; Si, Yin-Chu

    2016-01-01

    We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair.

  17. Diallyl trisufide protects against oxygen glucose deprivation -induced apoptosis by scavenging free radicals via the PI3K/Akt -mediated Nrf2/HO-1 signaling pathway in B35 neural cells.

    Science.gov (United States)

    Xu, Xian Hua; Li, Gai Li; Wang, Bing Ang; Qin, Yang; Bai, Shu Rong; Rong, Jian; Deng, Tao; Li, Qiang

    2015-07-21

    Oxidative stress contributes to development of ischemic brain damage. Many antioxidants have been proven effective in ameliorating cerebral ischemia injury by inhibiting oxidative stress. DATS, an organosulfuric component of garlic oil, exhibits antioxidative effects. In present study, we used OGD model to investigate the neuroprotective effects of DATS and the mechanisms related to these effects. B35 neural cells exposed to OGD caused a decrease in cell viability and increases in the percentage of apoptotic cells and the level of intracellular cleaved caspase-3, all of which were markedly attenuated by DATS. Further, DATS treatment significantly increased Nrf2 expression and nuclear translocation, upregulated downstream gene HO-1 and inhibited intracellular ROS and MDA generation, all of which were markedly attenuated in cells transfected with Nrf2-specific siRNA. In addition, inhibition of PI3K/Akt signaling by PI3K-specific siRNA not only decreased the expression level of Nrf2 and HO-1 proteins, but also diminished the antioxidative and neuroprotective effect of DATS. Taken together, these results indicate that DATS protects B35 neural cells against OGD-induced cell injury by inhibiting ROS production via upregulating the PI3K/Akt-mediated Nrf2 pathway, which further activates HO-1. Based on our results, DATS may be a potential candidate for intervention in hypoxic-ischemic brain injuries such as stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. What’s the Gist? The influence of schemas on the neural correlates underlying true and false memories

    Science.gov (United States)

    Webb, Christina E.; Turney, Indira C.; Dennis, Nancy A.

    2017-01-01

    The current study used a novel scene paradigm to investigate the role of encoding schemas on memory. Specifically, the study examined the influence of a strong encoding schema on retrieval of both schematic and non-schematic information, as well as false memories for information associated with the schema. Additionally, the separate roles of recollection and familiarity in both veridical and false memory retrieval were examined. The study identified several novel results. First, while many common neural regions mediated both schematic and non-schematic retrieval success, schematic recollection exhibited greater activation in visual cortex and hippocampus, regions commonly shown to mediate detailed retrieval. More effortful cognitive control regions in the prefrontal and parietal cortices, on the other hand, supported non-schematic recollection, while lateral temporal cortices supported familiarity-based retrieval of non-schematic items. Second, both true and false recollection, as well as familiarity, were mediated by activity in left middle temporal gyrus, a region associated with semantic processing and retrieval of schematic gist. Moreover, activity in this region was greater for both false recollection and false familiarity, suggesting a greater reliance on lateral temporal cortices for retrieval of illusory memories, irrespective of memory strength. Consistent with previous false memory studies, visual cortex showed increased activity for true compared to false recollection, suggesting that visual cortices are critical for distinguishing between previously viewed targets and related lures at retrieval. Additionally, the absence of common visual activity between true and false retrieval suggests that, unlike previous studies utilizing visual stimuli, when false memories are predicated on schematic gist and not perceptual overlap, there is little reliance on visual processes during false memory retrieval. Finally, the medial temporal lobe exhibited an

  19. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

    Directory of Open Access Journals (Sweden)

    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  20. Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage.

    Science.gov (United States)

    Lai, Ying-Jang

    2015-05-01

    Amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD). Moreover, it has been reported that oxidative stress is involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Recently, docosahexaenoic acid (DHA; C22:6) and eicosapentaenoic acid (EPA; C20:5n-3) have been reported to protect against AD. However, these omega-3 fatty acids are frequently obtained from fish oil and may contain heavy metals. In this study, we utilized Nannochloropsis oceanica to produce omega-3 fatty acid. We observed that when urea levels (nitrogen source) were lowered from 2 to 0.2 g/L in Nannochloropsis oceanica cultures, EPA production increased. Moreover, EPA in Nannochloropsis oceanica effectively promoted antioxidant activity to counter the Abeta-induced oxidative stress in Neuro-2A cells. These results indicate that Nannochloropsis oceanica may be potentially used as a therapeutic agent or as a functional food that promotes protection against AD.

  1. Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

    Science.gov (United States)

    Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

    2017-08-01

    The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

  2. YB-1 gene expression is kept constant during myocyte differentiation through replacement of different transcription factors and then falls gradually under the control of neural activity.

    Science.gov (United States)

    Kobayashi, Shunsuke; Tanaka, Toru; Moue, Masamitsu; Ohashi, Sachiyo; Nishikawa, Taishi

    2015-11-01

    We have previously reported that translation of acetylcholine receptor α-subunit (AChR α) mRNA in skeletal muscle cells is regulated by Y-box binding protein 1 (YB-1) in response to neural activity, and that in the postnatal mouse developmental changes in the amount of YB-1 mRNA are similar to those of AChR α mRNA, which is known to be regulated by myogenic transcription factors. Here, we examined transcriptional regulation of the YB-1 gene in mouse skeletal muscle and differentiating C2C12 myocytes. Although neither YB-1 nor AChR α was detected at either the mRNA or protein level in adult hind limb muscle, YB-1 expression was transiently activated in response to denervation of the sciatic nerve and completely paralleled that of AChR α, suggesting that these genes are regulated by the same transcription factors. However, during differentiation of C2C12 cells to myotubes, the level of YB-1 remained constant even though the level of AChR α increased markedly. Reporter gene, gel mobility shift and ChIP assays revealed that in the initial stage of myocyte differentiation, transcription of the YB-1 gene was regulated by E2F1 and Sp1, and was then gradually replaced under the control of both MyoD and myogenin through an E-box sequence in the proximal region of the YB-1 gene promoter. These results suggest that transcription factors for the YB-1 gene are exchanged during skeletal muscle cell differentiation, perhaps playing a role in translational control of mRNAs by YB-1 in both myotube formation and the response of skeletal muscle tissues to neural stimulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex

    Directory of Open Access Journals (Sweden)

    Ricardo eGómez-Nieto

    2014-07-01

    Full Text Available The acoustic startle reflex (ASR is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs, neurons in the caudal pontine reticular nucleus (PnC, and motoneurons in the medulla and spinal cord. It is well established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioural techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1. Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviourally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviours and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural

  4. Investigating category- and shape-selective neural processing in ventral and dorsal visual stream under interocular suppression.

    Science.gov (United States)

    Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido

    2015-01-01

    Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.

  5. Neural Control of the Lower Urinary Tract

    Science.gov (United States)

    de Groat, William C.; Griffiths, Derek; Yoshimura, Naoki

    2015-01-01

    This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed. PMID:25589273

  6. Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    2010-05-01

    Full Text Available New mechanisms that regulate neural stem cell (NSC expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers.Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.

  7. Co-combustion of sewage sludge and coffee grounds under increased O2/CO2atmospheres: Thermodynamic characteristics, kinetics and artificial neural network modeling.

    Science.gov (United States)

    Chen, Jiacong; Xie, Candie; Liu, Jingyong; He, Yao; Xie, Wuming; Zhang, Xiaochun; Chang, Kenlin; Kuo, Jiahong; Sun, Jian; Zheng, Li; Sun, Shuiyu; Buyukada, Musa; Evrendilek, Fatih

    2018-02-01

    (Co-)combustion characteristics of sewage sludge (SS), coffee grounds (CG) and their blends were quantified under increased O 2 /CO 2 atmosphere (21, 30, 40 and 60%) using a thermogravimetric analysis. Observed percentages of CG mass loss and its maximum were higher than those of SS. Under the same atmospheric O 2 concentration, both higher ignition and lower burnout temperatures occurred with the increased CG content. Results showed that ignition temperature and comprehensive combustion index for the blend of 60%SS-40%CG increased, whereas burnout temperature and co-combustion time decreased with the increased O 2 concentration. Artificial neural network was applied to predict mass loss percent as a function of gas mixing ratio, heating rate, and temperature, with a good agreement between the experimental and ANN-predicted values. Activation energy in response to the increased O 2 concentration was found to increase from 218.91 to 347.32 kJ·mol -1 and from 218.34 to 340.08 kJ·mol -1 according to the Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa methods, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Ultrastructural evidence for two-cell and three-cell neural pathways in the tentacle epidermis of the sea anemone Aiptasia pallida.

    Science.gov (United States)

    Westfall, Jane A; Elliott, Carol F; Carlin, Ryan W

    2002-01-01

    Sensory and ganglion cells in the tentacle epidermis of the sea anemone Aiptasia pallida were traced in serial transmission electron micrographs to their synaptic contacts on other cells. Sensory cell synapses were found on spirocytes, muscle cells, and ganglion cells. Ganglion cells, in turn, synapsed on sensory cells, spirocytes, muscle cells, and other neurons and formed en passant axo-axonal synapses. Axonal synapses on nematocytes and gland cells were not traced to their cells of origin, i.e., identified sensory or ganglion cells. Direct synaptic contacts of sensory cells with spirocytes and sensory cells with muscle cells suggest a local two-cell pathway for spirocyst discharge and muscle cell contraction, whereas interjection of a ganglion cell between the sensory and effector cells creates a local three-cell pathway. The network of ganglion cells and their processes allows for a through-conduction system that is interconnected by chemical synapses. Although the sea anemone nervous system is more complex than that of Hydra, it has similar two-cell and three-cell effector pathways that may function in local responses to tentacle contact with food. Copyright 2002 Wiley-Liss, Inc.

  9. A deep convolutional neural network with new training methods for bearing fault diagnosis under noisy environment and different working load

    Science.gov (United States)

    Zhang, Wei; Li, Chuanhao; Peng, Gaoliang; Chen, Yuanhang; Zhang, Zhujun

    2018-02-01

    In recent years, intelligent fault diagnosis algorithms using machine learning technique have achieved much success. However, due to the fact that in real world industrial applications, the working load is changing all the time and noise from the working environment is inevitable, degradation of the performance of intelligent fault diagnosis methods is very serious. In this paper, a new model based on deep learning is proposed to address the problem. Our contributions of include: First, we proposed an end-to-end method that takes raw temporal signals as inputs and thus doesn't need any time consuming denoising preprocessing. The model can achieve pretty high accuracy under noisy environment. Second, the model does not rely on any domain adaptation algorithm or require information of the target domain. It can achieve high accuracy when working load is changed. To understand the proposed model, we will visualize the learned features, and try to analyze the reasons behind the high performance of the model.

  10. Neural correlates of cue-unique outcome expectations under differential outcomes training: an fMRI study.

    Science.gov (United States)

    Mok, Leh Woon; Thomas, Kathleen M; Lungu, Ovidiu V; Overmier, J Bruce

    2009-04-10

    In conditional discriminative choice learning, one learns the relations between discriminative/cue stimuli, associated choices, and their outcomes. When each correct cue-choice occurrence is followed by a cue-unique trial outcome (differential outcomes, DO, procedure), learning is faster and more accurate than when all correct cue-choice occurrences are followed by a common outcome (CO procedure)--differential outcomes effect (DOE). Superior DO performance is theorized to be mediated by the additional learning of cue-unique outcome expectations that "enrich" the prospective code available over the delay between cue and choice. We anticipated that such learned expectations comprise representations of expected outcomes. Here, we conducted an event-related functional MR imaging (fMRI) analysis of healthy adults who trained concurrently in two difficult but similar perceptual discrimination tasks under DO and CO procedures, respectively, and displayed the DOE. Control participants performed related tasks that differentially biased them towards delay-period retrospection versus prospection. Indeed, when differential outcomes were sensory-perceptual events (visual vs. auditory), delay-period expectations were experienced as sensory-specific imagery of the respectively expected outcome content, generated by sensory-specific cortices. Visual-specific imagery additionally activated stimulus-specific representations in prefrontal, lateral and medial frontal, fusiform and cerebellar regions, whereas auditory-specific imagery recruited claustrum/insula. Posterior parietal cortex (PPC), BA 39, was non-modality specific in mediating delay-period cue-unique outcome expectations. Greater hippocampal involvement in retrospection than prospection contrasted against the PPC's role in prospection. Time course analyses of hippocampal versus PPC responses suggest the DOE derives from an earlier transition from retrospection to prospection, which taps into long-term associative memory

  11. What and Where in auditory sensory processing: A high-density electrical mapping study of distinct neural processes underlying sound object recognition and sound localization

    Directory of Open Access Journals (Sweden)

    Victoria M Leavitt

    2011-06-01

    Full Text Available Functionally distinct dorsal and ventral auditory pathways for sound localization (where and sound object recognition (what have been described in non-human primates. A handful of studies have explored differential processing within these streams in humans, with highly inconsistent findings. Stimuli employed have included simple tones, noise bursts and speech sounds, with simulated left-right spatial manipulations, and in some cases participants were not required to actively discriminate the stimuli. Our contention is that these paradigms were not well suited to dissociating processing within the two streams. Our aim here was to determine how early in processing we could find evidence for dissociable pathways using better titrated what and where task conditions. The use of more compelling tasks should allow us to amplify differential processing within the dorsal and ventral pathways. We employed high-density electrical mapping using a relatively large and environmentally realistic stimulus set (seven animal calls delivered from seven free-field spatial locations; with stimulus configuration identical across the where and what tasks. Topographic analysis revealed distinct dorsal and ventral auditory processing networks during the where and what tasks with the earliest point of divergence seen during the N1 component of the auditory evoked response, beginning at approximately 100 ms. While this difference occurred during the N1 timeframe, it was not a simple modulation of N1 amplitude as it displayed a wholly different topographic distribution to that of the N1. Global dissimilarity measures using topographic modulation analysis confirmed that this difference between tasks was driven by a shift in the underlying generator configuration. Minimum norm source reconstruction revealed distinct activations that corresponded well with activity within putative dorsal and ventral auditory structures.

  12. Two major gate-keepers in the self-renewal of neural stem cells: Erk1/2 and PLCγ1 in FGFR signaling

    Directory of Open Access Journals (Sweden)

    Lee Jin-A

    2009-06-01

    Full Text Available Abstract Neural stem cells are undifferentiated precursor cells that proliferate, self-renew, and give rise to neuronal and glial lineages. Understanding the molecular mechanisms underlying their self-renewal is an important aspect in neural stem cell biology. The regulation mechanisms governing self-renewal of neural stem cells and the signaling pathways responsible for the proliferation and maintenance of adult stem cells remain largely unknown. In this issue of Molecular Brain [Ma DK et al. Molecular genetic analysis of FGFR1 signaling reveals distinct roles of MAPK and PLCγ1 activation for self-renewal of adult neural stem cells. Molecular Brain 2009, 2:16], characterized the different roles of MAPK and PLCγ1 in FGFR1 signaling in the self-renewal of neural stem cells. These novel findings provide insights into basic neural stem cell biology and clinical applications of potential stem-cell-based therapy.

  13. Secondary metabolites and phenylpropanoid pathway enzymes as influenced under supplemental ultraviolet-B radiation in Withania somnifera Dunal, an indigenous medicinal plant.

    Science.gov (United States)

    Takshak, Swabha; Agrawal, S B

    2014-11-01

    The present study aims to investigate the effects of supplemental ultraviolet B (3.6 kJ m(-2)day(-1) above ambient) radiation on secondary metabolites and phenylpropanoid pathway enzymes of Withania somnifera under field conditions at 40, 70, and 100 days after transplantation. Secondary metabolites' (alkaloids, anthocyanins, carotenoids, flavonoids, lignin, phytosterols, saponins, and tannins) concentrations were analysed at the end of the treatments. Activities of phenylalanine ammonia lyase (PAL), cinnamyl alcohol dehydrogenase (CAD), 4-coumarate-CoA ligase (4CL), chalcone-flavanone isomerase (CHI), and dihydroflavonol reductase (DFR) were also determined. In treated plants, secondary metabolite-concentrations generally increased (higher concentrations being recorded in roots compared to leaves). Anomalies were recorded for lycopene in roots and phytosterols in leaves (all sampling ages); β-carotene declined in leaves at third sampling age. s-UV-B-treated plants depicted decrease in withanolide A content with concomitant increase in withaferin A (two major alkaloids analysed by HPLC) compared to their respective controls. Phenylpropanoid pathway enzyme-activities increased in leaves and roots under s-UV-B treatment, the latter showing greater increase. The study concludes that s-UV-B is a potent factor in increasing the concentrations of secondary metabolites and their biosynthetic pathway enzymes in W. somnifera. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A Computational Analysis of Neural Mechanisms Underlying the Maturation of Multisensory Speech Integration in Neurotypical Children and Those on the Autism Spectrum

    Directory of Open Access Journals (Sweden)

    Cristiano Cuppini

    2017-10-01

    Full Text Available Failure to appropriately develop multisensory integration (MSI of audiovisual speech may affect a child's ability to attain optimal communication. Studies have shown protracted development of MSI into late-childhood and identified deficits in MSI in children with an autism spectrum disorder (ASD. Currently, the neural basis of acquisition of this ability is not well understood. Here, we developed a computational model informed by neurophysiology to analyze possible mechanisms underlying MSI maturation, and its delayed development in ASD. The model posits that strengthening of feedforward and cross-sensory connections, responsible for the alignment of auditory and visual speech sound representations in posterior superior temporal gyrus/sulcus, can explain behavioral data on the acquisition of MSI. This was simulated by a training phase during which the network was exposed to unisensory and multisensory stimuli, and projections were crafted by Hebbian rules of potentiation and depression. In its mature architecture, the network also reproduced the well-known multisensory McGurk speech effect. Deficits in audiovisual speech perception in ASD were well accounted for by fewer multisensory exposures, compatible with a lack of attention, but not by reduced synaptic connectivity or synaptic plasticity.

  15. AcconPred: Predicting Solvent Accessibility and Contact Number Simultaneously by a Multitask Learning Framework under the Conditional Neural Fields Model

    Directory of Open Access Journals (Sweden)

    Jianzhu Ma

    2015-01-01

    Full Text Available Motivation. The solvent accessibility of protein residues is one of the driving forces of protein folding, while the contact number of protein residues limits the possibilities of protein conformations. The de novo prediction of these properties from protein sequence is important for the study of protein structure and function. Although these two properties are certainly related with each other, it is challenging to exploit this dependency for the prediction. Method. We present a method AcconPred for predicting solvent accessibility and contact number simultaneously, which is based on a shared weight multitask learning framework under the CNF (conditional neural fields model. The multitask learning framework on a collection of related tasks provides more accurate prediction than the framework trained only on a single task. The CNF method not only models the complex relationship between the input features and the predicted labels, but also exploits the interdependency among adjacent labels. Results. Trained on 5729 monomeric soluble globular protein datasets, AcconPred could reach 0.68 three-state accuracy for solvent accessibility and 0.75 correlation for contact number. Tested on the 105 CASP11 domain datasets for solvent accessibility, AcconPred could reach 0.64 accuracy, which outperforms existing methods.

  16. Health assessment of future PM2.5 exposures from indoor, outdoor, and secondhand tobacco smoke concentrations under alternative policy pathways in Ulaanbaatar, Mongolia.

    Directory of Open Access Journals (Sweden)

    L Drew Hill

    Full Text Available Winter air pollution in Ulaanbaatar, Mongolia is among the worst in the world. The health impacts of policy decisions affecting air pollution exposures in Ulaanbaatar were modeled and evaluated under business as usual and two more-strict alternative emissions pathways through 2024. Previous studies have relied on either outdoor or indoor concentrations to assesses the health risks of air pollution, but the burden is really a function of total exposure. This study combined projections of indoor and outdoor concentrations of PM2.5 with population time-activity estimates to develop trajectories of total age-specific PM2.5 exposure for the Ulaanbaatar population. Indoor PM2.5 contributions from secondhand tobacco smoke (SHS were estimated in order to fill out total exposures, and changes in population and background disease were modeled. The health impacts were derived using integrated exposure-response curves from the Global Burden of Disease Study.Annual average population-weighted PM2.5 exposures at baseline (2014 were estimated at 59 μg/m3. These were dominated by exposures occurring indoors, influenced considerably by infiltrated outdoor pollution. Under current control policies, exposures increased slightly to 60 μg/m3 by 2024; under moderate emissions reductions and under a switch to clean technologies, exposures were reduced from baseline levels by 45% and 80%, respectively. The moderate improvement pathway decreased per capita annual disability-adjusted life year (DALY and death burdens by approximately 40%. A switch to clean fuels decreased per capita annual DALY and death burdens by about 85% by 2024 with the relative SHS contribution increasing substantially.This study demonstrates a way to combine estimated changes in total exposure, background disease and population levels, and exposure-response functions to project the health impacts of alternative policy pathways. The resulting burden analysis highlights the need for aggressive

  17. TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.

    Science.gov (United States)

    Bai, Xiao; Xi, Jie; Bi, Yanwen; Zhao, Xin; Bing, Weidong; Meng, Xiangbin; Liu, Yimin; Zhu, Zhonglai; Song, Guangmin

    2017-09-01

    The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor-α (TNF-α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF-κB pathway plays in this. In this study, we preconditioned MSCs with TNF-α ( TNF -α-PC MSCs) for 24 hrs and measured the activation of the IKK/NF-κB pathway. EdU and transwell assays were performed to assess proliferation and migration of TNF -α-PC MSCs. Apoptosis and migration of TNF -α- PC MSCs were evaluated in conditions of oxidative stress by analysis of the expression of Bcl-2 and CXCR4 proteins. TNF -α- PC MSCs were transplanted into a vein graft model, so that cell homing could be tracked, and endothelial apoptosis and IH of vein grafts were measured. The results demonstrated that TNF-α promotes proliferation and migration of MSCs. Furthermore, survival and migration of TNF -α- PC MSCs under oxidative stress were both enhanced. A greater number of MSCs migrated to the intima of vein grafts after preconditioning with TNF-α, and the formation of neointima was significantly reduced. These effects could be partially abolished by IKK XII (NF-κB inhibitor). All these results indicate that preconditioning with TNF-α can promote survival and migration of MSCs under oxidative stress via the NF-κB pathway and thus attenuate IH of vein grafts. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Neural networks

    International Nuclear Information System (INIS)

    Denby, Bruce; Lindsey, Clark; Lyons, Louis

    1992-01-01

    The 1980s saw a tremendous renewal of interest in 'neural' information processing systems, or 'artificial neural networks', among computer scientists and computational biologists studying cognition. Since then, the growth of interest in neural networks in high energy physics, fueled by the need for new information processing technologies for the next generation of high energy proton colliders, can only be described as explosive

  19. Microbial oil-degradation under mild hydrostatic pressure (10 MPa): which pathways are impacted in piezosensitive hydrocarbonoclastic bacteria?

    KAUST Repository

    Scoma, Alberto

    2016-03-29

    Oil spills represent an overwhelming carbon input to the marine environment that immediately impacts the sea surface ecosystem. Microbial communities degrading the oil fraction that eventually sinks to the seafloor must also deal with hydrostatic pressure, which linearly increases with depth. Piezosensitive hydrocarbonoclastic bacteria are ideal candidates to elucidate impaired pathways following oil spills at low depth. In the present paper, we tested two strains of the ubiquitous Alcanivorax genus, namely A. jadensis KS_339 and A. dieselolei KS_293, which is known to rapidly grow after oil spills. Strains were subjected to atmospheric and mild pressure (0.1, 5 and 10 MPa, corresponding to a depth of 0, 500 and 1000 m, respectively) providing n-dodecane as sole carbon source. Pressures equal to 5 and 10 MPa significantly lowered growth yields of both strains. However, in strain KS_293 grown at 10 MPa CO2 production per cell was not affected, cell integrity was preserved and PO43− uptake increased. Analysis of its transcriptome revealed that 95% of its genes were downregulated. Increased transcription involved protein synthesis, energy generation and respiration pathways. Interplay between these factors may play a key role in shaping the structure of microbial communities developed after oil spills at low depth and limit their bioremediation potential.

  20. Molecular hypotheses to explain the shared pathways and underlying pathobiological causes in catatonia and in catatonic presentations in neuropsychiatric disorders.

    Science.gov (United States)

    Peter-Ross, E M

    2018-04-01

    The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways). SNORD115 controls five genes CRHR1, PBRM1, TAF1, DPM2, and RALGPS1 as well as the alternative splicing of serotonin 2C receptor. SNORD115 abnormalities with varying downstream multigene involvement would account for catatonia across the life span within some subtypes of autism spectrum disorders, schizophrenia, bipolar and major depressive disorder, psychosis, genetic disorders, and in immune disorders such as anti-N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis as well as the susceptibility to the neuroleptic malignant syndrome (NMS) if environmentally triggered. Furthermore, SNORD115 genes may underlie a genetic vulnerability when environmental triggers result in excess serotonin producing the serotonin syndrome, a condition similar to NMS in which catatonia may occur. Dysfunction of SNORD115-PBRM1 connecting with SMARCA2 as well as other proven schizophrenia-associated genes might explain why traditionally catatonia has been classified with schizophrenia. SNORD115-TAF1 and SNORD-DPM2 dysfunction introduce possible clues to the parkinsonism and increased creatinine phosphokinase in NMS, while abnormalities of SNORD115-RALGPS1 suggest links to both anti

  1. TrpA1 Regulates Defecation of Food-Borne Pathogens under the Control of the Duox Pathway.

    Directory of Open Access Journals (Sweden)

    Eun Jo Du

    2016-01-01

    Full Text Available Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS, hypochlorous acid (HOCl in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A transcript spliced with exon10b (TrpA1(A10b that is present in a subset of midgut enteroendocrine cells (EECs is critical for uracil-dependent defecation. TRPA1(A10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A10a isoform. Consistent with TrpA1's role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A10b, thereby minimizing the chances that bacteria adapt to survive host defense systems.

  2. Characterization and expression patterns of key C4photosynthetic pathway genes in bread wheat (Triticum aestivum L.) under field conditions.

    Science.gov (United States)

    Bachir, Daoura Goudia; Saeed, Iqbal; Song, Quanhao; Linn, Tay Zar; Chen, Liang; Hu, Yin-Gang

    2017-06-01

    Wheat is a C 3 plant with relatively low photosynthetic efficiency and is a potential target for C 4 photosynthetic pathway engineering. Here we reported the characterization of four key C 4 pathway genes and assessed their expression patterns and enzymatic activities at three growth stages in flag leaves of 59 bread wheat genotypes. The C 4 -like genes homologous to PEPC, NADP-ME, MDH, and PPDK in maize were identified in the A, B, and D sub-genomes of bread wheat, located on the long arms of chromosomes 3 and 5 (TaPEPC), short arms of chromosomes 1 and 3 (TaNADP-ME), long arms of chromosomes 1 and 7 (TaMDH), and long arms of chromosome 1 (TaPPDK), respectively. All the four C 4 -like genes were expressed in the flag leaves at the three growth stages with considerable variations among the 59 bread wheat genotypes. Significant differences were observed between the photosynthesis rates (A) of wheat genotypes with higher expressions of TaPEPC_5, TaNADP-ME_1, and TaMDH_7 at heading and middle grain-filling stages and those with intermediate and low expressions. Our results also indicated that the four C 4 enzymes showed activity in the flag leaves and were obviously different among the 59 wheat genotypes. The activities of PEPcase and PPDK decreased at anthesis and slightly increased at grain-filling stage, while NADP-ME and MDH exhibited a decreasing trend at the three stages. The results of the current study could be very valuable and useful for wheat researchers in improving photosynthetic capacity of wheat. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-12-01

    How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

  4. Large-Scale microRNA Expression Profiling Identifies Putative Retinal miRNA-mRNA Signaling Pathways Underlying Form-Deprivation Myopia in Mice.

    Science.gov (United States)

    Tkatchenko, Andrei V; Luo, Xiaoyan; Tkatchenko, Tatiana V; Vaz, Candida; Tanavde, Vivek M; Maurer-Stroh, Sebastian; Zauscher, Stefan; Gonzalez, Pedro; Young, Terri L

    2016-01-01

    Development of myopia is associated with large-scale changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in the development of myopia is largely unknown. In this study, we explored myopia-associated miRNA expression profiles in the retina and sclera of C57Bl/6J mice with experimentally induced myopia using microarray technology. We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (p myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways. Our findings highlighted that changes in microRNA expression are involved in the regulation of refractive eye development and predicted how they may be involved in the development of myopia by regulating retinal gene expression.

  5. Large-Scale microRNA Expression Profiling Identifies Putative Retinal miRNA-mRNA Signaling Pathways Underlying Form-Deprivation Myopia in Mice.

    Directory of Open Access Journals (Sweden)

    Andrei V Tkatchenko

    Full Text Available Development of myopia is associated with large-scale changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in the development of myopia is largely unknown. In this study, we explored myopia-associated miRNA expression profiles in the retina and sclera of C57Bl/6J mice with experimentally induced myopia using microarray technology. We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (p < 0.000001, n = 12 of myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways. Our findings highlighted that changes in microRNA expression are involved in the regulation of refractive eye development and predicted how they may be involved in the development of myopia by regulating retinal gene expression.

  6. Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

    Science.gov (United States)

    Han, Xiaorui; Leng, Xiaoming; Zhao, Man; Wu, Mei; Chen, Amei; Hong, Guoju; Sun, Ping

    2017-12-22

    Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration. © 2017 The Author(s).

  7. Blood -brain barrier disruption was less under isoflurane than pentobarbital anesthesia via a PI3K/Akt pathway in early cerebral ischemia.

    Science.gov (United States)

    Chi, Oak Z; Mellender, Scott J; Kiss, Geza K; Liu, Xia; Weiss, Harvey R

    2017-05-01

    One of the important factors altering the degree of blood-brain barrier (BBB) disruption in cerebral ischemia is the anesthetic used. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been reported to be involved in modulating BBB permeability and in isoflurane induced neuroprotection. This study was performed to compare the degree of BBB disruption in focal cerebral ischemia under isoflurane vs pentobarbital anesthesia and to determine whether inhibition of PI3K/Akt would affect the disruption in the early stage of focal cerebral ischemia. Permanent middle cerebral artery (MCA) occlusion was performed in rats under 1.4% isoflurane or pentobarbital (50mg/kg i.p.) anesthesia with controlled ventilation. In half of each group LY294002, which is a PI3K/Akt inhibitor, was applied on the ischemic cortex immediately after MCA occlusion. After one hour of MCA occlusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid ( 14 C-AIB) was determined to quantify the degree of BBB disruption. MCA occlusion increased the K i both in the isoflurane and pentobarbital anesthetized rats. However, the value of K i was lower under isoflurane (11.5±6.0μL/g/min) than under pentobarbital (18.3±7.1μL/g/min) anesthesia. The K i of the contralateral cortex of the pentobarbital group was higher (+74%) than that of the isoflurane group. Application of LY294002 on the ischemic cortex increased the K i (+99%) only in the isoflurane group. The degree of BBB disruption by MCA occlusion was significantly lower under isoflurane than pentobarbital anesthesia in the early stage of cerebral ischemia. Our data demonstrated the importance of choice of anesthetics and suggest that PI3K/Akt signaling pathway plays a significant role in altering BBB disruption in cerebral ischemia during isoflurane but not during pentobarbital anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space--the roles of Brodmann areas 44 and 45.

    Science.gov (United States)

    Amunts, Katrin; Weiss, Peter H; Mohlberg, Hartmut; Pieperhoff, Peter; Eickhoff, Simon; Gurd, Jennifer M; Marshall, John C; Shah, Nadim J; Fink, Gereon R; Zilles, Karl

    2004-05-01

    We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Broca's speech region (Brodmann's areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

  9. A network pharmacology study of Chinese medicine QiShenYiQi to reveal its underlying multi-compound, multi-target, multi-pathway mode of action.

    Directory of Open Access Journals (Sweden)

    Xiang Li

    Full Text Available Chinese medicine is a complex system guided by traditional Chinese medicine (TCM theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine, QiShenYiQi (QSYQ, on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi, Salvia miltiorrhiza (Danshen, Panax notoginseng (Sanqi, and Dalbergia odorifera (Jiangxiang. Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction.

  10. Neural dynamics of phonological processing in the dorsal auditory stream.

    Science.gov (United States)

    Liebenthal, Einat; Sabri, Merav; Beardsley, Scott A; Mangalathu-Arumana, Jain; Desai, Anjali

    2013-09-25

    Neuroanatomical models hypothesize a role for the dorsal auditory pathway in phonological processing as a feedforward efferent system (Davis and Johnsrude, 2007; Rauschecker and Scott, 2009; Hickok et al., 2011). But the functional organization of the pathway, in terms of time course of interactions between auditory, somatosensory, and motor regions, and the hemispheric lateralization pattern is largely unknown. Here, ambiguous duplex syllables, with elements presented dichotically at varying interaural asynchronies, were used to parametrically modulate phonological processing and associated neural activity in the human dorsal auditory stream. Subjects performed syllable and chirp identification tasks, while event-related potentials and functional magnetic resonance images were concurrently collected. Joint independent component analysis was applied to fuse the neuroimaging data and study the neural dynamics of brain regions involved in phonological processing with high spatiotemporal resolution. Results revealed a highly interactive neural network associated with phonological processing, composed of functional fields in posterior temporal gyrus (pSTG), inferior parietal lobule (IPL), and ventral central sulcus (vCS) that were engaged early and almost simultaneously (at 80-100 ms), consistent with a direct influence of articulatory somatomotor areas on phonemic perception. Left hemispheric lateralization was observed 250 ms earlier in IPL and vCS than pSTG, suggesting that functional specialization of somatomotor (and not auditory) areas determined lateralization in the dorsal auditory pathway. The temporal dynamics of the dorsal auditory pathway described here offer a new understanding of its functional organization and demonstrate that temporal information is essential to resolve neural circuits underlying complex behaviors.

  11. Mapping of the Underlying Neural Mechanisms of Maintenance and Manipulation in Visuo-Spatial Working Memory Using An n-back Mental Rotation Task: A Functional Magnetic Resonance Imaging Study

    OpenAIRE

    Lamp, Gemma; Alexander, Bonnie; Laycock, Robin; Crewther, David P.; Crewther, Sheila G.

    2016-01-01

    Mapping of the underlying neural mechanisms of visuo-spatial working memory (WM) has been shown to consistently elicit activity in right hemisphere dominant fronto-parietal networks. However to date, the bulk of neuroimaging literature has focused largely on the maintenance aspect of visuo-spatial WM, with a scarcity of research into the aspects of WM involving manipulation of information. Thus, this study aimed to compare maintenance-only with maintenance and manipulation of visuo-spatial st...

  12. Invasion risk of the yellow crazy ant (Anoplolepis gracilipes under the Representative Concentration Pathways 8.5 climate change scenario in South Korea

    Directory of Open Access Journals (Sweden)

    Jae-Min Jung

    2017-12-01

    Full Text Available The yellow crazy ant (Anoplolepis gracilipes has destroyed local ecosystems in numerous countries, and their population sizes and distribution are likely to increase under global warming. To evaluate the risk of invasion by yellow crazy ant in South Korea, this study identified their potential habitats and predicted their future global distribution by modeling various climate change scenarios using CLIMEX software. Our modeling predicted that future climate conditions in South Korea will be favorable for the yellow crazy ant, and they could invade by the mid-21st century. We highlight the use of predictive algorithms to establish geographical areas with a high risk of yellow crazy ant invasion under Representative Concentration Pathways (RCP 8.5 climate scenarios. Keywords: Anoplolepis gracilipes, climate change scenario, CLIMEX, invasive species, yellow crazy ant

  13. Identification of genes from the ICE-CBF-COR pathway under cold stress inAegilops-Triticumcomposite group and the evolution analysis with those fromTriticeae.

    Science.gov (United States)

    Jin, Ya'nan; Zhai, Shanshan; Wang, Wenjia; Ding, Xihan; Guo, Zhifu; Bai, Liping; Wang, Shu

    2018-03-01

    Adverse environmental conditions limit various aspects of plant growth, productivity, and ecological distribution. To get more insights into the signaling pathways under low temperature, we identified 10 C-repeat binding factors ( CBFs ), 9 inducer of CBF expression ( ICEs ) and 10 cold-responsive ( CORs ) genes from Aegilops - Triticum composite group under cold stress. Conserved amino acids analysis revealed that all CBF, ICE, COR contained specific and typical functional domains. Phylogenetic analysis of CBF proteins from Triticeae showed that these CBF homologs were divided into 11 groups. CBFs from Triticum were found in every group, which shows that these CBFs generated prior to the divergence of the subfamilies of Triticeae . The evolutionary relationship among the ICE and COR proteins in Poaceae were divided into four groups with high multispecies specificity, respectively. Moreover, expression analysis revealed that mRNA accumulation was altered by cold treatment and the genes of three types involved in the ICE-CBF-COR signaling pathway were induced by cold stress. Together, the results make CBF , ICE , COR genes family in Triticeae more abundant, and provide a starting point for future studies on transcriptional regulatory network for improvement of chilling tolerance in crop.

  14. Redox Signaling and CBF-Responsive Pathway Are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    Science.gov (United States)

    Cheng, Fei; Lu, Junyang; Gao, Min; Shi, Kai; Kong, Qiusheng; Huang, Yuan; Bie, Zhilong

    2016-01-01

    Salicylic acid (SA) plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus). Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-α-aminooxy-β-phenylpropionic acid (AOPP) increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon. PMID:27777580

  15. Redox Signaling and CBF-Responsive Pathway are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    Directory of Open Access Journals (Sweden)

    Fei Cheng

    2016-10-01

    Full Text Available Salicylic acid (SA plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus. Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-ɑ-aminooxy-β-phenylpropionic acid (AOPP increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon.

  16. Activation of autophagy via Ca(2+)-dependent AMPK/mTOR pathway in rat notochordal cells is a cellular adaptation under hyperosmotic stress.

    Science.gov (United States)

    Jiang, Li-Bo; Cao, Lu; Yin, Xiao-Fan; Yasen, Miersalijiang; Yishake, Mumingjiang; Dong, Jian; Li, Xi-Lei

    2015-01-01

    Nucleus pulposus (NP) cells experience hyperosmotic stress in spinal discs; however, how these cells can survive in the hostile microenvironment remains unclear. Autophagy has been suggested to maintain cellular homeostasis under different stresses by degrading the cytoplasmic proteins and organelles. Here, we explored whether autophagy is a cellular adaptation in rat notochordal cells under hyperosmotic stress. Hyperosmotic stress was found to activate autophagy in a dose- and time-dependent manner. SQSTM1/P62 expression was decreased as the autophagy level increased. Transient Ca(2+) influx from intracellular stores and extracellular space was stimulated by hyperosmotic stress. Activation of AMPK and inhibition of p70S6K were observed under hyperosmotic conditions. However, intercellular Ca(2+) chelation inhibited the increase of LC3-II and partly reversed the decrease of p70S6K. Hyperosmotic stress decreased cell viability and promoted apoptosis. Inhibition of autophagy led to SQSTM1/P62 accumulation, reduced cell viability, and accelerated apoptosis in notochordal cells under this condition. These evidences suggest that autophagy induction via the Ca(2+)-dependent AMPK/mTOR pathway might occur as an adaptation mechanism for notochordal cells under hyperosmotic stress. Thus, activating autophagy might be a promising approach to improve viability of notochordal cells in intervertebral discs.

  17. Abscisic acid-induced nitric oxide and proline accumulation in independent pathways under water-deficit stress during seedling establishment in Medicago truncatula.

    Science.gov (United States)

    Planchet, Elisabeth; Verdu, Isabelle; Delahaie, Julien; Cukier, Caroline; Girard, Clément; Morère-Le Paven, Marie-Christine; Limami, Anis M

    2014-05-01

    Nitric oxide (NO) production and amino acid metabolism modulation, in particular abscisic acid (ABA)-dependent proline accumulation, are stimulated in planta by most abiotic stresses. However, the relationship between NO production and proline accumulation under abiotic stress is still poorly understood, especially in the early phases of plant development. To unravel this question, this work investigated the tight relationship between NO production and proline metabolism under water-deficit stress during seedling establishment. Endogenous nitrate reductase-dependent NO production in Medicago truncatula seedlings increased in a time-dependent manner after short-term water-deficit stress. This water-deficit-induced endogenous NO accumulation was mediated through a ABA-dependent pathway and accompanied by an inhibition of seed germination, a loss of water content, and a decrease in elongation of embryo axes. Interestingly, a treatment with a specific NO scavenger (cPTIO) alleviated these water-deficit detrimental effects. However, the content of total amino acids, in particular glutamate and proline, as well as the expression of genes encoding enzymes of synthesis and degradation of proline were not affected by cPTIO treatment under water-deficit stress. Under normal conditions, exogenous NO donor stimulated neither the expression of P5CS2 nor the proline content, as observed after PEG treatment. These results strongly suggest that the modulation of proline metabolism is independent of NO production under short-term water-deficit stress during seedling establishment.

  18. GXNOR-Net: Training deep neural networks with ternary weights and activations without full-precision memory under a unified discretization framework.

    Science.gov (United States)

    Deng, Lei; Jiao, Peng; Pei, Jing; Wu, Zhenzhi; Li, Guoqi

    2018-04-01

    Although deep neural networks (DNNs) are being a revolutionary power to open up the AI era, the notoriously huge hardware overhead has challenged their applications. Recently, several binary and ternary networks, in which the costly multiply-accumulate operations can be replaced by accumulations or even binary logic operations, make the on-chip training of DNNs quite promising. Therefore there is a pressing need to build an architecture that could subsume these networks under a unified framework that achieves both higher performance and less overhead. To this end, two fundamental issues are yet to be addressed. The first one is how to implement the back propagation when neuronal activations are discrete. The second one is how to remove the full-precision hidden weights in the training phase to break the bottlenecks of memory/computation consumption. To address the first issue, we present a multi-step neuronal activation discretization method and a derivative approximation technique that enable the implementing the back propagation algorithm on discrete DNNs. While for the second issue, we propose a discrete state transition (DST) methodology to constrain the weights in a discrete space without saving the hidden weights. Through this way, we build a unified framework that subsumes the binary or ternary networks as its special cases, and under which a heuristic algorithm is provided at the website https://github.com/AcrossV/Gated-XNOR. More particularly, we find that when both the weights and activations become ternary values, the DNNs can be reduced to sparse binary networks, termed as gated XNOR networks (GXNOR-Nets) since only the event of non-zero weight and non-zero activation enables the control gate to start the XNOR logic operations in the original binary networks. This promises the event-driven hardware design for efficient mobile intelligence. We achieve advanced performance compared with state-of-the-art algorithms. Furthermore, the computational sparsity

  19. Comprehensive analysis of tobacco pollen transcriptome unveils common pathways in polar cell expansion and underlying heterochronic shift during spermatogenesis

    Directory of Open Access Journals (Sweden)

    Hafidh Said

    2012-02-01

    Full Text Available Abstract Background Many flowering plants produce bicellular pollen. The two cells of the pollen grain are destined for separate fates in the male gametophyte, which provides a unique opportunity to study genetic interactions that govern guided single-cell polar expansion of the growing pollen tube and the coordinated control of germ cell division and sperm cell fate specification. We applied the Agilent 44 K tobacco gene chip to conduct the first transcriptomic analysis of the tobacco male gametophyte. In addition, we performed a comparative study of the Arabidopsis root-hair trichoblast transcriptome to evaluate genetic factors and common pathways involved in polarized cell-tip expansion. Results Progression of pollen grains from freshly dehisced anthers to pollen tubes 4 h after germination is accompanied with > 5,161 (14.9% gametophyte-specific expressed probes active in at least one of the developmental stages. In contrast, > 18,821 (54.4% probes were preferentially expressed in the sporophyte. Our comparative approach identified a subset of 104 pollen tube-expressed genes that overlap with root-hair trichoblasts. Reverse genetic analysis of selected candidates demonstrated that Cu/Zn superoxide dismutase 1 (CSD1, a WD-40 containing protein (BP130384, and Replication factor C1 (NtRFC1 are among the central regulators of pollen-tube tip growth. Extension of our analysis beyond the second haploid mitosis enabled identification of an opposing-dynamic accumulation of core regulators of cell proliferation and cell fate determinants in accordance with the progression of the germ cell cycle. Conclusions The current study provides a foundation to isolate conserved regulators of cell tip expansion and those that are unique for pollen tube growth to the female gametophyte. A transcriptomic data set is presented as a benchmark for future functional studies using developing pollen as a model. Our results demonstrated previously unknown functions of

  20. Comprehensive analysis of tobacco pollen transcriptome unveils common pathways in polar cell expansion and underlying heterochronic shift during spermatogenesis

    Science.gov (United States)

    2012-01-01

    Background Many flowering plants produce bicellular pollen. The two cells of the pollen grain are destined for separate fates in the male gametophyte, which provides a unique opportunity to study genetic interactions that govern guided single-cell polar expansion of the growing pollen tube and the coordinated control of germ cell division and sperm cell fate specification. We applied the Agilent 44 K tobacco gene chip to conduct the first transcriptomic analysis of the tobacco male gametophyte. In addition, we performed a comparative study of the Arabidopsis root-hair trichoblast transcriptome to evaluate genetic factors and common pathways involved in polarized cell-tip expansion. Results Progression of pollen grains from freshly dehisced anthers to pollen tubes 4 h after germination is accompanied with > 5,161 (14.9%) gametophyte-specific expressed probes active in at least one of the developmental stages. In contrast, > 18,821 (54.4%) probes were preferentially expressed in the sporophyte. Our comparative approach identified a subset of 104 pollen tube-expressed genes that overlap with root-hair trichoblasts. Reverse genetic analysis of selected candidates demonstrated that Cu/Zn superoxide dismutase 1 (CSD1), a WD-40 containing protein (BP130384), and Replication factor C1 (NtRFC1) are among the central regulators of pollen-tube tip growth. Extension of our analysis beyond the second haploid mitosis enabled identification of an opposing-dynamic accumulation of core regulators of cell proliferation and cell fate determinants in accordance with the progression of the germ cell cycle. Conclusions The current study provides a foundation to isolate conserved regulators of cell tip expansion and those that are unique for pollen tube growth to the female gametophyte. A transcriptomic data set is presented as a benchmark for future functional studies using developing pollen as a model. Our results demonstrated previously unknown functions of certain genes in pollen

  1. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

    Science.gov (United States)

    Phillips, Mary L; Swartz, Holly A.

    2014-01-01

    Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

  2. Neural engineering

    CERN Document Server

    2013-01-01

    Neural Engineering, 2nd Edition, contains reviews and discussions of contemporary and relevant topics by leading investigators in the field. It is intended to serve as a textbook at the graduate and advanced undergraduate level in a bioengineering curriculum. This principles and applications approach to neural engineering is essential reading for all academics, biomedical engineers, neuroscientists, neurophysiologists, and industry professionals wishing to take advantage of the latest and greatest in this emerging field.

  3. Climate change forecasting in a mountainous data scarce watershed using CMIP5 models under representative concentration pathways

    Science.gov (United States)

    Aghakhani Afshar, A.; Hasanzadeh, Y.; Besalatpour, A. A.; Pourreza-Bilondi, M.

    2017-07-01

    Hydrology cycle of river basins and available water resources in arid and semi-arid regions are highly affected by climate changes. In recent years, the increment of temperature due to excessive increased emission of greenhouse gases has led to an abnormality in the climate system of the earth. The main objective of this study is to survey the future climate changes in one of the biggest mountainous watersheds in northeast of Iran (i.e., Kashafrood). In this research, by considering the precipitation and temperature as two important climatic parameters in watersheds, 14 models evolved in the general circulation models (GCMs) of the newest generation in the Coupled Model Intercomparison Project Phase 5 (CMIP5) were used to forecast the future climate changes in the study area. For the historical period of 1992-2005, four evaluation criteria including Nash-Sutcliffe (NS), percent of bias (PBIAS), coefficient of determination ( R 2) and the ratio of the root-mean-square-error to the standard deviation of measured data (RSR) were used to compare the simulated observed data for assessing goodness-of-fit of the models. In the primary results, four climate models namely GFDL-ESM2G, IPSL-CM5A-MR, MIROC-ESM, and NorESM1-M were selected among the abovementioned 14 models due to their more prediction accuracies to the investigated evaluation criteria. Thereafter, climate changes of the future periods (near-century, 2006-2037; mid-century, 2037-2070; and late-century, 2070-2100) were investigated and compared by four representative concentration pathways (RCPs) of new emission scenarios of RCP2.6, RCP4.5, RCP6.0, and RCP8.5. In order to assess the trend of annual and seasonal changes of climatic components, Mann-Kendall non-parametric test (MK) was also employed. The results of Mann-Kendall test revealed that the precipitation has significant variable trends of both positive and negative alterations. Furthermore, the mean, maximum, and minimum temperature values had

  4. A Combined Proteomic and Transcriptomic Analysis on Sulfur Metabolism Pathways of Arabidopsis thaliana under Simulated Acid Rain

    Science.gov (United States)

    Wang, Wenhua; Simon, Martin; Wu, Feihua; Hu, Wenjun; Chen, Juan B.; Zheng, Hailei

    2014-01-01

    With rapid economic development, most regions in southern China have suffered acid rain (AR) pollution. In our study, we analyzed the changes in sulfur metabolism in Arabidopsis under simulated AR stress which provide one of the first case studies, in which the systematic responses in sulfur metabolism were characterized by high-throughput methods at different levels including proteomic, genomic and physiological approaches. Generally, we found that all of the processes related to sulfur metabolism responded to AR stress, including sulfur uptake, activation and also synthesis of sulfur-containing amino acid and other secondary metabolites. Finally, we provided a catalogue of the detected sulfur metabolic changes and reconstructed the coordinating network of their mutual influences. This study can help us to understand the mechanisms of plants to adapt to AR stress. PMID:24595051

  5. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  6. Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue factor pathway inhibitor under static and shear conditions in vitro.

    Directory of Open Access Journals (Sweden)

    Sara P Y Che

    Full Text Available Mammary tumors and malignant breast cancer cell lines over-express the coagulation factor, tissue factor (TF. High expression of TF is associated with a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI, the endogenous inhibitor of TF, is constitutively expressed on the endothelium. We hypothesized that TF-expressing tumor cells can bind to immobilized recombinant TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the adhesion of breast cancer cells to immobilized TFPI under static and shear conditions (0.35 - 1.3 dyn/cm2. We found that high-TF-expressing breast cancer cells, MDA-MB-231 (with a TF density of 460,000/cell, but not low TF-expressing MCF-7 (with a TF density of 1,400/cell, adhered to recombinant TFPI, under static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required activated factor VII (FVIIa, but not FX, and was inhibited by a factor VIIa-blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the TFPI-coating concentration, FVIIa concentration and shear stress, with no observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first study showing that TF-expressing tumor cells can be captured by immobilized TFPI, a ligand constitutively expressed on the endothelium, under low shear in vitro. Based on our results, we hypothesize that TFPI could be a novel ligand mediating the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under conditions of low shear during metastasis.

  7. The neural basis of emotions varies over time: different regions go with onset- and offset-bound processes underlying emotion intensity.

    Science.gov (United States)

    Résibois, Maxime; Verduyn, Philippe; Delaveau, Pauline; Rotgé, Jean-Yves; Kuppens, Peter; Van Mechelen, Iven; Fossati, Philippe

    2017-08-01

    According to theories of emotion dynamics, emotions unfold across two phases in which different types of processes come to the fore: emotion onset and emotion offset. Differences in onset-bound processes are reflected by the degree of explosiveness or steepness of the response at onset, and differences in offset-bound processes by the degree of accumulation or intensification of the subsequent response. Whether onset- and offset-bound processes have distinctive neural correlates and, hence, whether the neural basis of emotions varies over time, still remains unknown. In the present fMRI study, we address this question using a recently developed paradigm that allows to disentangle explosiveness and accumulation. Thirty-one participants were exposed to neutral and negative social feedback, and asked to reflect on its contents. Emotional intensity while reading and thinking about the feedback was measured with an intensity profile tracking approach. Using non-negative matrix factorization, the resulting profile data were decomposed in explosiveness and accumulation components, which were subsequently entered as continuous regressors of the BOLD response. It was found that the neural basis of emotion intensity shifts as emotions unfold over time with emotion explosiveness and accumulation having distinctive neural correlates. © The Author (2017). Published by Oxford University Press.

  8. Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

    Directory of Open Access Journals (Sweden)

    Ekaterini Blaveri

    2010-09-01

    Full Text Available The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

  9. Mechanical stress in abdominal aortic aneurysms using artificial neural networks

    OpenAIRE

    Soudah Prieto, Eduardo; Rodriguez, Jose; López González, Roberto

    2015-01-01

    Combination of numerical modeling and artificial intelligence (AI) in bioengineering processes are a promising pathway for the further development of bioengineering sciences. The objective of this work is to use Artificial Neural Networks (ANN) to reduce the long computational times needed in the analysis of shear stress in the Abdominal Aortic Aneurysm (AAA) by finite element methods (FEM). For that purpose two different neural networks are created. The first neural network (Mesh Neural Netw...

  10. Microarray and pathway analysis reveal distinct mechanisms underlying cannabinoid-mediated modulation of LPS-induced activation of BV-2 microglial cells.

    Directory of Open Access Journals (Sweden)

    Ana Juknat

    Full Text Available Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS to activate BV-2 microglial cells, we examined how Δ(9-tetrahydrocannabinol (THC, the major psychoactive component of marijuana, and cannabidiol (CBD the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC. From the 5338 transcripts that were differentially expressed across treatments, 400 transcripts were found to be upregulated by LPS, 502 by CBD+LPS and 424 by THC+LPS, while 145 were downregulated by LPS, 297 by CBD+LPS and 149 by THC+LPS, by 2-fold or more (p≤0.005. Results clearly link the effects of CBD and THC to inflammatory signaling pathways and identify new cannabinoid targets in the MAPK pathway (Dusp1, Dusp8, Dusp2, cell cycle related (Cdkn2b, Gadd45a as well as JAK/STAT regulatory molecules (Socs3, Cish, Stat1. The impact of CBD on LPS-stimulated gene expression was greater than that of THC. We attribute this difference to the fact that CBD highly upregulated several genes encoding negative regulators of both NFκB and AP-1 transcriptional activities, such as Trib3 and Dusp1 known to be modulated through Nrf2 activation. The CBD-specific expression profile reflected changes associated with oxidative stress and glutathione depletion via Trib3 and expression of ATF4 target genes. Furthermore, the CBD affected genes were shown to be controlled by nuclear factors usually involved in regulation of stress response and inflammation, mainly via Nrf2/Hmox1 axis and the Nrf2/ATF4-Trib3 pathway. These observations indicate that CBD, and less so THC, induce a cellular stress

  11. Radiation response of rodent neural precursor cells

    International Nuclear Information System (INIS)

    Limoli, C.L.; Fike, J.R.

    2003-01-01

    Full text: Therapeutic irradiation of the brain can cause cognitive dysfunction that is not treatable or well understood. Several lines of evidence from our laboratory suggest that radiation induced inhibition of neurogenesis in the hippocampus may be involved. To understand the mechanisms underlying these observations, we initiated studies using neural precursor cells isolated from the adult rat hippocampus. Cells were cultured exponentially and analyzed for acute (0-24h) and chronic (3-33 day) changes in apoptosis and oxidative stress following exposure to X-rays. Oxidative stress was measured using a dye sensitive to reactive oxygen species (ROS) and apoptosis was measured using annexin V binding; each endpoint was quantified by fluorescent automated cell sorting (FACS). Following exposure to X-rays, neural precursor cells exhibit a dose-responsive increase in the level of ROS and apoptosis over acute and chronic time frames. ROS and apoptosis were maximal at 12h, increasing 35 and 37% respectively over that of unirradiated controls. ROS and apoptosis peaked again at 24h, increasing 31 and 21% respectively over controls. Chronic levels of ROS and apoptosis were persistently elevated in a dose-dependent manner. ROS showed significant increases (34-180%) over a 3-4 week interval, while increases in apoptosis were less dramatic, rising 45% by week one before dropping to background. Irradiation of rat neural precursor cells was associated with an increase in p53 protein levels, and the activation of G1/S and G2/M checkpoints. These data suggest that the apoptotic and ROS responses may be tied to p53 dependent regulation of cell cycle control and stress activated pathways. We propose that oxidative stress plays a critical role in the radiation response of neural precursor cells, and discuss how this might contribute to the inhibition of neurogenesis and the cognitive impairment observed in the irradiated CNS

  12. The Impact of climate change on heat-related mortality in six major cities, South Korea, under representative concentration pathways (RCPs

    Directory of Open Access Journals (Sweden)

    Youngmin eKim

    2014-02-01

    Full Text Available Background: We aimed to quantify the excess mortality associated with increased temperature due to climate change in six major Korean cities under Representative Concentration Pathways (RCPs which are new emission scenarios designed for the fifth assessment report of the Intergovernmental Panel on Climate Change (IPCC. Methods: We first examined the association between daily mean temperature and mortality in each during the summertime (June to September from 2001 to 2008. This was done using a generalized linear Poisson model with adjustment for a long-term time trend, relative humidity, air pollutants, and day of the week. We then computed heat-related mortality attributable to future climate change using estimated mortality risks, projected future populations, and temperature increments for both future years 2041-2070 and 2071-2100 under RCP 4.5 and 8.5. We considered effects from added days with high temperatures over thresholds and shifted effects from high to higher temperature.Results: Estimated excess all-cause mortalities for six cities in Korea ranged from 500 (95% CI: 313-703 for 2041-2070 to 2,320 (95% CI: 1,430-3,281 deaths per year for 2071-2100 under two RCPs. Excess cardiovascular mortality was estimated to range from 192 (95% CI: 41-351 to 896 (95% CI: 185-1,694 deaths per year, covering about 38.5% of all-cause excess mortality. Increased rates of heat-related mortality were higher in cities located at relatively lower latitude than cities with higher latitude. Estimated excess mortality under RCP 8.5, a fossil fuel-intensive emission scenario, was more than twice as high compared with RCP 4.5, low to medium emission scenario.Conclusions: Excess mortality due to climate change is expected to be profound in the future showing spatial variation. Efforts to mitigate climate change can cause substantial health benefits via reducing heat-related mortality.

  13. Identification of putative RuBisCo activase (TaRca1 ˗ the catalytic chaperone regulating carbon assimilatory pathway in wheat (Triticum aestivum under the heat stress

    Directory of Open Access Journals (Sweden)

    RANJEET RANJAN KUMAR

    2016-07-01

    Full Text Available RuBisCo activase (Rca is a catalytic chaperone involved in modulating the activity of RuBisCo (key enzyme of photosynthetic pathway. Here, we identified eight novel transcripts from wheat through data mining predicted to be Rca and cloned a transcript of 1.4 kb from cv. HD2985, named as TaRca1 (GenBank acc. no. KC776912. Single copy number of TaRca1 was observed in wheat genome. Expression analysis in diverse wheat genotypes (HD2985, Halna, PBW621 and HD2329 showed very high relative expression of TaRca1 in Halna under control and HS-treated, as compared to other cultivars at different stages of growth. TaRca1 protein was predicted to be chloroplast-localized with numerous potential phosphorylation sites. Nothern blot analysis showed maximum accumulation of TaRca1 transcript in thermotolerant cv. during mealy-ripe stage, as compared to thermosusceptible. Decrease in the photosynthetic parameters was observed in all the cultivars, except PBW621 in response to HS. We observed significant increase in the Rca activity in all the cultivars under HS at different stages of growth. HS causes decrease in the RuBisCo activity; maximum reduction was observed during pollination stage in thermosusceptible cvs. as validated through immunoblotting. We observed uniform carbon distribution in different tissues of thermotolerant cvs., as compared to thermosusceptible. Similarly, tolerance level of leaf was observed maximum in Halna having high Rca activity under HS. A positive correlation was observed between the transcript and activity of TaRca1 in HS-treated Halna. Similarly, TaRca1 enzyme showed positive correlation with the activity of RuBisCo. There is, however, need to manipulate the thermal stability of TaRca1 enzyme through protein engineering for sustaining the photosynthetic rate under HS – a novel approach towards development of ‘climate-smart’ crop.

  14. Molecular and neural control of sexually dimorphic social behaviors.

    Science.gov (United States)

    Yang, Taehong; Shah, Nirao M

    2016-06-01

    Sexually reproducing animals exhibit sex differences in behavior. Sexual dimorphisms in mating, aggression, and parental care directly contribute to reproductive success of the individual and survival of progeny. In this review, we discuss recent advances in our understanding of the molecular and neural network mechanisms underlying these behaviors in mice. Notable advances include novel insights into the sensory control of social interactions and the identification of molecularly-specified neuronal populations in the brain that control mating, aggression, and parental behaviors. In the case of the latter, these advances mark a watershed because scientists can now focus on discrete neural pathways in an effort to understand how the brain encodes these fundamental social behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions.

    Science.gov (United States)

    Lipinski, Marta M; Hoffman, Greg; Ng, Aylwin; Zhou, Wen; Py, Bénédicte F; Hsu, Emily; Liu, Xuxin; Eisenberg, Jason; Liu, Jun; Blenis, John; Xavier, Ramnik J; Yuan, Junying

    2010-06-15

    Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer, and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions upregulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3, and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner. Copyright 2010 Elsevier Inc. All rights reserved.

  16. MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway[OPEN

    Science.gov (United States)

    Lee, Du-Hwa; Park, Seung Jun; Ahn, Chang Sook

    2017-01-01

    Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes (MRF1-MRF4) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway. PMID:29084871

  17. MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway.

    Science.gov (United States)

    Lee, Du-Hwa; Park, Seung Jun; Ahn, Chang Sook; Pai, Hyun-Sook

    2017-11-01

    Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes ( MRF1 - MRF4 ) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway. © 2017 American Society of Plant Biologists. All rights reserved.

  18. Utilising reinforcement learning to develop strategies for driving auditory neural implants.

    Science.gov (United States)

    Lee, Geoffrey W; Zambetta, Fabio; Li, Xiaodong; Paolini, Antonio G

    2016-08-01

    In this paper we propose a novel application of reinforcement learning to the area of auditory neural stimulation. We aim to develop a simulation environment which is based off real neurological responses to auditory and electrical stimulation in the cochlear nucleus (CN) and inferior colliculus (IC) of an animal model. Using this simulator we implement closed loop reinforcement learning algorithms to determine which methods are most effective at learning effective acoustic neural stimulation strategies. By recording a comprehensive set of acoustic frequency presentations and neural responses from a set of animals we created a large database of neural responses to acoustic stimulation. Extensive electrical stimulation in the CN and the recording of neural responses in the IC provides a mapping of how the auditory system responds to electrical stimuli. The combined dataset is used as the foundation for the simulator, which is used to implement and test learning algorithms. Reinforcement learning, utilising a modified n-Armed Bandit solution, is implemented to demonstrate the model's function. We show the ability to effectively learn stimulation patterns which mimic the cochlea's ability to covert acoustic frequencies to neural activity. Time taken to learn effective replication using neural stimulation takes less than 20 min under continuous testing. These results show the utility of reinforcement learning in the field of neural stimulation. These results can be coupled with existing sound processing technologies to develop new auditory prosthetics that are adaptable to the recipients current auditory pathway. The same process can theoretically be abstracted to other sensory and motor systems to develop similar electrical replication of neural signals.

  19. Utilising reinforcement learning to develop strategies for driving auditory neural implants

    Science.gov (United States)

    Lee, Geoffrey W.; Zambetta, Fabio; Li, Xiaodong; Paolini, Antonio G.

    2016-08-01

    Objective. In this paper we propose a novel application of reinforcement learning to the area of auditory neural stimulation. We aim to develop a simulation environment which is based off real neurological responses to auditory and electrical stimulation in the cochlear nucleus (CN) and inferior colliculus (IC) of an animal model. Using this simulator we implement closed loop reinforcement learning algorithms to determine which methods are most effective at learning effective acoustic neural stimulation strategies. Approach. By recording a comprehensive set of acoustic frequency presentations and neural responses from a set of animals we created a large database of neural responses to acoustic stimulation. Extensive electrical stimulation in the CN and the recording of neural responses in the IC provides a mapping of how the auditory system responds to electrical stimuli. The combined dataset is used as the foundation for the simulator, which is used to implement and test learning algorithms. Main results. Reinforcement learning, utilising a modified n-Armed Bandit solution, is implemented to demonstrate the model’s function. We show the ability to effectively learn stimulation patterns which mimic the cochlea’s ability to covert acoustic frequencies to neural activity. Time taken to learn effective replication using neural stimulation takes less than 20 min under continuous testing. Significance. These results show the utility of reinforcement learning in the field of neural stimulation. These results can be coupled with existing sound processing technologies to develop new auditory prosthetics that are adaptable to the recipients current auditory pathway. The same process can theoretically be abstracted to other sensory and motor systems to develop similar electrical replication of neural signals.

  20. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  1. Neural components of altruistic punishment

    Directory of Open Access Journals (Sweden)

    Emily eDu

    2015-02-01

    Full Text Available Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  2. Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation.

    Science.gov (United States)

    Zhang, Mingliang; Lin, Yuan-Hung; Sun, Yujiao Jennifer; Zhu, Saiyong; Zheng, Jiashun; Liu, Kai; Cao, Nan; Li, Ke; Huang, Yadong; Ding, Sheng

    2016-05-05

    Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small-molecule approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts toward a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study provides an effective chemical approach for generating neural stem cells from mouse fibroblasts and reveals mechanistic insights into underlying reprogramming processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Stochastic Spiking Neural Networks Enabled by Magnetic Tunnel Junctions: From Nontelegraphic to Telegraphic Switching Regimes

    Science.gov (United States)

    Liyanagedera, Chamika M.; Sengupta, Abhronil; Jaiswal, Akhilesh; Roy, Kaushik

    2017-12-01

    Stochastic spiking neural networks based on nanoelectronic spin devices can be a possible pathway to achieving "brainlike" compact and energy-efficient cognitive intelligence. The computational model attempt to exploit the intrinsic device stochasticity of nanoelectronic synaptic or neural components to perform learning or inference. However, there has been limited analysis on the scaling effect of stochastic spin devices and its impact on the operation of such stochastic networks at the system level. This work attempts to explore the design space and analyze the performance of nanomagnet-based stochastic neuromorphic computing architectures for magnets with different barrier heights. We illustrate how the underlying network architecture must be modified to account for the random telegraphic switching behavior displayed by magnets with low barrier heights as they are scaled into the superparamagnetic regime. We perform a device-to-system-level analysis on a deep neural-network architecture for a digit-recognition problem on the MNIST data set.

  4. Artificial neural network modelling

    CERN Document Server

    Samarasinghe, Sandhya

    2016-01-01

    This book covers theoretical aspects as well as recent innovative applications of Artificial Neural networks (ANNs) in natural, environmental, biological, social, industrial and automated systems. It presents recent results of ANNs in modelling small, large and complex systems under three categories, namely, 1) Networks, Structure Optimisation, Robustness and Stochasticity 2) Advances in Modelling Biological and Environmental Systems and 3) Advances in Modelling Social and Economic Systems. The book aims at serving undergraduates, postgraduates and researchers in ANN computational modelling. .

  5. Molecular characterization of the cold- and heat-induced Arabidopsis PXL1 gene and its potential role in transduction pathways under temperature fluctuations.

    Science.gov (United States)

    Jung, Chang Gyo; Hwang, Sun-Goo; Park, Yong Chan; Park, Hyeon Mi; Kim, Dong Sub; Park, Duck Hwan; Jang, Cheol Seong

    2015-03-15

    LRR-RLK (Leucine-Rich Repeat Receptor-Like Kinase) proteins are believed to play essential roles in cell-to-cell communication during various cellular processes including development, hormone perception, and abiotic stress responses. We isolated an LRR-RLK gene previously named Arabidopsis PHLOEM INTERCALATED WITH XYLEM-LIKE 1 (AtPXL1) and examined its expression patterns. AtPXL1 was highly induced by cold and heat stress, but not by drought. The fluorescence signal of 35S::AtPXL1-EGFP was closely localized to the plasma membrane. A yeast two-hybrid and bimolecular fluorescence complementation assay exhibited that AtPXL1 interacts with both proteins, A. thaliana histidine-rich dehydrin1 (AtHIRD1) and A. thaliana light-harvesting protein complex I (AtLHCA1). We found that AtPXL1 possesses autophosphorylation activity and phosphorylates AtHIRD1 and AtLHCA1 in an in vitro assay. Subsequently, we found that the knockout line (atpxl1) showed hypersensitive phenotypes when subjected to cold and heat during the germination stage, while the AtPXL1 overexpressing line as well as wild type plants showed high germination rates compared to the knockout plants. These results provide an insight into the molecular function of AtPXL1 in the regulation of signal transduction pathways under temperature fluctuations. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Effective Electron Transfer Pathway of the Ternary TiO2/RGO/Ag Nanocomposite with Enhanced Photocatalytic Activity under Visible Light

    Directory of Open Access Journals (Sweden)

    Hongwei Tian

    2017-05-01

    Full Text Available Mesoporous TiO2/reduced graphene oxide/Ag (TiO2/RGO/Ag ternary nanocomposite with an effective electron transfer pathway is obtained by an electrostatic self-assembly method and photo-assisted treatment. Compared with bare mesoporous TiO2 (MT and mesoporous TiO2/RGO (MTG, the ternary mesoporous TiO2/RGO/Ag (MTGA nanocomposite exhibited superior photocatalytic performance for the degradation of methylene blue (MB under visible light, and the degradation rate reached 0.017 min−1, which was 3.4-times higher than that of MTG. What is more, the degradation rate of MTGA nanocomposite after three cycle times is 91.2%, and the composition is unchanged. In addition, we found that the OH•, h+ and especially O2•− contribute to the high photocatalytic activity of MTGA for MB degradation. It is proposed that Ag nanoparticles can form the local surface plasmon resonance (LSPR to absorb the visible light and distract the electrons into MT, and RGO can accept the electrons from MT to accelerate the separation efficiency of photogenerated carriers. The establishment of MTGA ternary nanocomposite makes the three components act synergistically to enhance the photocatalytic performance.

  7. Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jie Chen

    2015-11-01

    Full Text Available Background/Aims: Mesenchymal stem cell (MSC based therapies may be useful for treating acute respiratory distress syndrome (ARDS, but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC and primary human small airway epithelial cells (SAEC were subjected to lipopolysaccharide (LPS with or without the presence of hUC-MSC-conditioned medium (CM. Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC. Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.

  8. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

    Full Text Available This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p. corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  9. FGF Signaling Transforms Non-neural Ectoderm into Neural Crest

    OpenAIRE

    Yardley, Nathan; García-Castro, Martín I.

    2012-01-01

    The neural crest arises at the border between the neural plate and the adjacent non-neural ectoderm. It has been suggested that both neural and non-neural ectoderm can contribute to the neural crest. Several studies have examined the molecular mechanisms that regulate neural crest induction in neuralized tissues or the neural plate border. Here, using the chick as a model system, we address the molecular mechanisms by which non-neural ectoderm generates neural crest. We report that in respons...

  10. Mapping of the Underlying Neural Mechanisms of Maintenance and Manipulation in Visuo-Spatial Working Memory Using An n-back Mental Rotation Task: A Functional Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Lamp, Gemma; Alexander, Bonnie; Laycock, Robin; Crewther, David P; Crewther, Sheila G

    2016-01-01

    Mapping of the underlying neural mechanisms of visuo-spatial working memory (WM) has been shown to consistently elicit activity in right hemisphere dominant fronto-parietal networks. However to date, the bulk of neuroimaging literature has focused largely on the maintenance aspect of visuo-spatial WM, with a scarcity of research into the aspects of WM involving manipulation of information. Thus, this study aimed to compare maintenance-only with maintenance and manipulation of visuo-spatial stimuli (3D cube shapes) utilizing a 1-back task while functional magnetic resonance imaging (fMRI) scans were acquired. Sixteen healthy participants (9 women, M = 23.94 years, SD = 2.49) were required to perform the 1-back task with or without mentally rotating the shapes 90° on a vertical axis. When no rotation was required (maintenance-only condition), a right hemispheric lateralization was revealed across fronto-parietal areas. However, when the task involved maintaining and manipulating the same stimuli through 90° rotation, activation was primarily seen in the bilateral parietal lobe and left fusiform gyrus. The findings confirm that the well-established right lateralized fronto-parietal networks are likely to underlie simple maintenance of visuo-spatial stimuli. The results also suggest that the added demand of manipulation of information maintained online appears to require further neural recruitment of functionally related areas. In particular mental rotation of visuospatial stimuli required bilateral parietal areas, and the left fusiform gyrus potentially to maintain a categorical or object representation. It can be concluded that WM is a complex neural process involving the interaction of an increasingly large network.

  11. Involvement of PKA-dependent upregulation of nNOS-CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats.

    Science.gov (United States)

    Wang, Dongmei; Ruan, Liqin; Hong, Yanguo; Chabot, Jean-Guy; Quirion, Rémi

    2013-01-01

    We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. An intrathecal administration of AM(22-52), but not the CGRP antagonist BIBN4096BS, abolished the CFA-induced increase of nNOS. Moreover, AM-induced increase of CGRP was inhibited by the nNOS inhibitors L-NAME and 7-nitroindazole in cultured ganglion explants. Addition of AM to ganglion cultures induced an increase in nNOS protein, which was attenuated by the PKA inhibitor H-89. Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Enhancement of the proline and nitric oxide synthetic pathway improves fermentation ability under multiple baking-associated stress conditions in industrial baker's yeast

    Science.gov (United States)

    2012-01-01

    plays an important role in baking-associated stress tolerance. Conclusions In this work, we clarified the importance of Put1- and Mpr1-mediated NO generation from proline to the baking-associated stress tolerance in industrial baker's yeast. We also demonstrated that baker's yeast that enhances the proline and NO synthetic pathway by expressing the Pro1-I150T and Mpr1-F65L variants showed improved fermentation ability under multiple baking-associated stress conditions. From a biotechnological perspective, the enhancement of proline and NO synthesis could be promising for breeding novel baker's yeast strains. PMID:22462683

  13. Enhancement of the proline and nitric oxide synthetic pathway improves fermentation ability under multiple baking-associated stress conditions in industrial baker's yeast

    Directory of Open Access Journals (Sweden)

    Sasano Yu

    2012-04-01

    generation and that increased NO plays an important role in baking-associated stress tolerance. Conclusions In this work, we clarified the importance of Put1- and Mpr1-mediated NO generation from proline to the baking-associated stress tolerance in industrial baker's yeast. We also demonstrated that baker's yeast that enhances the proline and NO synthetic pathway by expressing the Pro1-I150T and Mpr1-F65L variants showed improved fermentation ability under multiple baking-associated stress conditions. From a biotechnological perspective, the enhancement of proline and NO synthesis could be promising for breeding novel baker's yeast strains.

  14. Enhancement of the proline and nitric oxide synthetic pathway improves fermentation ability under multiple baking-associated stress conditions in industrial baker's yeast.

    Science.gov (United States)

    Sasano, Yu; Haitani, Yutaka; Hashida, Keisuke; Ohtsu, Iwao; Shima, Jun; Takagi, Hiroshi

    2012-04-01

    role in baking-associated stress tolerance. In this work, we clarified the importance of Put1- and Mpr1-mediated NO generation from proline to the baking-associated stress tolerance in industrial baker's yeast. We also demonstrated that baker's yeast that enhances the proline and NO synthetic pathway by expressing the Pro1-I150T and Mpr1-F65L variants showed improved fermentation ability under multiple baking-associated stress conditions. From a biotechnological perspective, the enhancement of proline and NO synthesis could be promising for breeding novel baker's yeast strains.

  15. Coxsackievirus A16 infection induces neural cell and non-neural cell apoptosis in vitro.

    Directory of Open Access Journals (Sweden)

    Zhaolong Li

    Full Text Available Coxsackievirus A16 (CA16 is one of the main causative pathogens of hand, foot and mouth disease (HFMD. Viral replication typically results in host cell apoptosis. Although CA16 infection has been reported to induce apoptosis in the human rhabdomyosarcoma (RD cell line, it remains unclear whether CA16 induces apoptosis in diverse cell types, especially neural cells which have important clinical significance. In the current study, CA16 infection was found to induce similar apoptotic responses in both neural cells and non-neural cells in vitro, including nuclear fragmentation, DNA fragmentation and phosphatidylserine translocation. CA16 generally is not known to lead to serious neurological symptoms in vivo. In order to further clarify the correlation between clinical symptoms and cell apoptosis, two CA16 strains from patients with different clinical features were investigated. The results showed that both CA16 strains with or without neurological symptoms in infected patients led to neural and muscle cell apoptosis. Furthermore, mechanistic studies showed that CA16 infection induced apoptosis through the same mechanism in both neural and non-neural cells, namely via activation of both the mitochondrial (intrinsic pathway-related caspase 9 protein and the Fas death receptor (extrinsic pathway-related caspase 8 protein. Understanding the mechanisms by which CA16 infection induces apoptosis in both neural and non-neural cells will facilitate a better understanding of CA16 pathogenesis.

  16. An adaptive recurrent neural-network controller using a stabilization matrix and predictive inputs to solve a tracking problem under disturbances.

    Science.gov (United States)

    Fairbank, Michael; Li, Shuhui; Fu, Xingang; Alonso, Eduardo; Wunsch, Donald

    2014-01-01

    We present a recurrent neural-network (RNN) controller designed to solve the tracking problem for control systems. We demonstrate that a major difficulty in training any RNN is the problem of exploding gradients, and we propose a solution to this in the case of tracking problems, by introducing a stabilization matrix and by using carefully constrained context units. This solution allows us to achieve consistently lower training errors, and hence allows us to more easily introduce adaptive capabilities. The resulting RNN is one that has been trained off-line to be rapidly adaptive to changing plant conditions and changing tracking targets. The case study we use is a renewable-energy generator application; that of producing an efficient controller for a three-phase grid-connected converter. The controller we produce can cope with the random variation of system parameters and fluctuating grid voltages. It produces tracking control with almost instantaneous response to changing reference states, and virtually zero oscillation. This compares very favorably to the classical proportional integrator (PI) controllers, which we show produce a much slower response and settling time. In addition, the RNN we propose exhibits better learning stability and convergence properties, and can exhibit faster adaptation, than has been achieved with adaptive critic designs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Review article: Autonomous neural inflammatory reflex and control of

    African Journals Online (AJOL)

    ... and neural autonomic pathway through vagus nerve monitor inflammatory status and coordinate appropriate host defences. Immunomodulatory stimulation of vagus nerve, acetylcholinesterase inhibitory mechanism and 7 nAChR receptor expressed on immune cells plays a role on autonomous neural inflammatory reflex.

  18. Robustness of RISMC Insights under Alternative Aleatory/Epistemic Uncertainty Classifications: Draft Report under the Risk-Informed Safety Margin Characterization (RISMC) Pathway of the DOE Light Water Reactor Sustainability Program

    Energy Technology Data Exchange (ETDEWEB)

    Unwin, Stephen D.; Eslinger, Paul W.; Johnson, Kenneth I.

    2012-09-20

    The Risk-Informed Safety Margin Characterization (RISMC) pathway is a set of activities defined under the U.S. Department of Energy (DOE) Light Water Reactor Sustainability Program. The overarching objective of RISMC is to support plant life-extension decision-making by providing a state-of-knowledge characterization of safety margins in key systems, structures, and components (SSCs). A technical challenge at the core of this effort is to establish the conceptual and technical feasibility of analyzing safety margin in a risk-informed way, which, unlike conventionally defined deterministic margin analysis, would be founded on probabilistic characterizations of uncertainty in SSC performance. In the context of probabilistic risk assessment (PRA) technology, there has arisen a general consensus about the distinctive roles of two types of uncertainty: aleatory and epistemic, where the former represents irreducible, random variability inherent in a system, whereas the latter represents a state of knowledge uncertainty on the part of the analyst about the system which is, in principle, reducible through further research. While there is often some ambiguity about how any one contributing uncertainty in an analysis should be classified, there has nevertheless emerged a broad consensus on the meanings of these uncertainty types in the PRA setting. However, while RISMC methodology shares some features with conventional PRA, it will nevertheless be a distinctive methodology set. Therefore, the paradigms for classification of uncertainty in the PRA setting may not fully port to the RISMC environment. Yet the notion of risk-informed margin is based on the characterization of uncertainty, and it is therefore critical to establish a common understanding of uncertainty in the RISMC setting.

  19. Neural Networks for Mindfulness and Emotion Suppression.

    Directory of Open Access Journals (Sweden)

    Hiroki Murakami

    Full Text Available Mindfulness, an attentive non-judgmental focus on "here and now" experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one's own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed.

  20. Integrating multiple vegetation indices via an artificial neural network model for estimating the leaf chlorophyll content of Spartina alterniflora under interspecies competition.

    Science.gov (United States)

    Liu, Pudong; Shi, Runhe; Zhang, Chao; Zeng, Yuyan; Wang, Jiapeng; Tao, Zhu; Gao, Wei

    2017-10-31

    The invasive species Spartina alterniflora and native species Phragmites australis display a significant co-occurrence zonation pattern and this co-exist region exerts most competitive situations between these two species, competing for the limited space, directly influencing the co-exist distribution in the future. However, these two species have different growth ratios in this area, which increase the difficulty to detect the distribution situation directly by remote sensing. As chlorophyll content is a key indicator of plant growth and physiological status, the objective of this study was to reduce the effect of interspecies competition when estimating Cab content; we evaluated 79 published representative indices to determine the optimal indices for estimating the chlorophyll a and b (Cab) content. After performing a sensitivity analysis for all 79 spectral indices, five spectral indices were selected and integrated using an artificial neural network (ANN) to estimate the Cab content of different competition ratios: the Gitelson ratio green index, the transformed chlorophyll absorption ratio index/optimized soil-adjusted vegetation index, the modified normalized difference vegetation index, the chlorophyll fluorescence index, and the Vogelmann chlorophyll index. The ANN method yielded better results (R 2  = 0.7110 and RMSE = 8.3829 μg cm -2 ) on average than the best single spectral index (R 2  = 0.6319 and RMSE = 9.3535 μg cm -2 ), representing an increase of 10.78% in R 2 and a decrease of 10.38% in RMSE. Our results indicated that integrating multiple vegetation indices with an ANN can alleviate the impact of interspecies competition and achieve higher estimation accuracy than the traditional approach using a single index.

  1. Bootstrap testing for cross-correlation under low firing activity.

    Science.gov (United States)

    González-Montoro, Aldana M; Cao, Ricardo; Espinosa, Nelson; Cudeiro, Javier; Mariño, Jorge

    2015-06-01

    A new cross-correlation synchrony index for neural activity is proposed. The index is based on the integration of the kernel estimation of the cross-correlation function. It is used to test for the dynamic synchronization levels of spontaneous neural activity under two induced brain states: sleep-like and awake-like. Two bootstrap resampling plans are proposed to approximate the distribution of the test statistics. The results of the first bootstrap method indicate that it is useful to discern significant differences in the synchronization dynamics of brain states characterized by a neural activity with low firing rate. The second bootstrap method is useful to unveil subtle differences in the synchronization levels of the awake-like state, depending on the activation pathway.

  2. Effect of resistance exercise under conditions of reduced blood insulin on AMPKα Ser485/491 inhibitory phosphorylation and AMPK pathway activation.

    Science.gov (United States)

    Kido, Kohei; Yokokawa, Takumi; Ato, Satoru; Sato, Koji; Fujita, Satoshi

    2017-08-01

    Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK α-subunit. Thus lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation. Based on previous findings, we hypothesized that the acute resistance exercise-induced AMPK pathway activation would be augmented by disruptions in insulin secretion through a decrease in AMPKα Ser485/491 inhibitory phosphorylation. To test the hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting β-cells. Three days postinjection, the right gastrocnemius muscle from STZ and control rats was subjected to resistance exercise by percutaneous electrical stimulation. Animals were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream pathways in the muscle tissue was analyzed by Western blotting and real-time PCR. Notably, STZ rats showed a significant decrease in basal Akt and AMPKα Ser485/491 phosphorylation, but substantial exercise-induced increases in both AMPKα Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were observed. Although no significant impact on resistance exercise-induced Akt pathway activation or glucose uptake was found, resistance exercise-induced peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 α (PGC-1α) gene expression was augmented by STZ treatment. Collectively, these data suggest that circulating insulin levels may regulate acute resistance exercise-induced AMPK pathway activation and AMPK-dependent gene expression relating to basal AMPKα Ser485/491 phosphorylation. Copyright © 2017

  3. Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells.

    Science.gov (United States)

    Spéder, Pauline; Brand, Andrea H

    2014-08-11

    Neural stem cells in the adult brain exist primarily in a quiescent state but are reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. Feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/insulin-like growth factor pathway in underlying neural stem cells and stimulating their growth and proliferation. Here we show that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behavior, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Copine1 regulates neural stem cell functions during brain development.

    Science.gov (United States)

    Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

    2018-01-01

    Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Acute intermittent hypoxia induced neural plasticity in respiratory motor control.

    Science.gov (United States)

    Xing, Tao; Fong, Angelina Y; Bautista, Tara G; Pilowsky, Paul M

    2013-09-01

    Respiratory neural networks can adapt to rapid environmental change or be altered over the long term by various inputs. The mechanisms that underlie the plasticity necessary for adaptive changes in breathing remain unclear. Acute intermittent hypoxia (AIH)-induced respiratory long-term facilitation (LTF) is one of the most extensively studied types of respiratory plasticity. Acute intermittent hypoxia-induced LTF is present in several respiratory motor outputs, innervating both pump muscles (i.e. diaphragm) and valve muscles (i.e. tongue, pharynx and larynx). Long-term facilitation is present in various species, including humans, and the expression of LTF is influenced by gender, age and genetics. Serotonin plays a key role in initiating and modulating plasticity at the level of respiratory motor neurons. Recently, multiple intracellular pathways have been elucidated that are capable of giving rise to respiratory LTF. These mainly activate the metabolic receptors coupled to Gq ('Q' pathway) and Gs ('S' pathway) proteins. Herein, we discuss AIH-induced respiratory LTF in animals and humans, as well as recent advances in our understanding of the synaptic and intracellular pathways underlying this form of plasticity. We also discuss the potential to use intermittent hypoxia to induce functional recovery following cervical spinal injury. © 2013 Wiley Publishing Asia Pty Ltd.

  6. Proteomic-based identification of multiple pathways underlying n-butylidenephthalide-induced apoptosis in LNCaP human prostate cancer cells.

    Science.gov (United States)

    Pang, Cheng-Yoong; Chiu, Sheng-Chun; Harn, Horng-Jyh; Zhai, Wei-Jun; Lin, Shinn-Zong; Yang, Hsueh-Hui

    2013-09-01

    Although numerous studies have shown the cancer-preventive properties of butylidenephthalide (BP), there is little report of BP affecting human prostate cancer cells. In the present study, proteomic-based approaches were used to elucidate the anticancer mechanism of BP in LNCaP human prostate cancer cells. BP treatment decreased the viability of LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which was correlated with G0/G1 phase cell cycle arrest. Increased cell cycle arrest was associated with a decrease in the level of CCND1, CDK2, and PCNA proteins and an increase in the level of CDKN2A, CDKN1A, and SFN proteins. Proteomic studies revealed that among 48 differentially expressed proteins, 25 proteins were down-regulated and 23 proteins were up-regulated and these proteins fall into one large protein protein interaction network. Among these proteins, FAS, AIFM1, BIK, CYCS, SFN, PPP2R1A, CALR, HSPA5, DDIT3, and ERN1 are apoptosis and endoplasmic reticulum (ER) stress associated proteins. Proteomic data suggested that multiple signaling pathways including FAS-dependent pathway, mitochondrial pathway, and ER stress pathway are involved in the apoptosis induced by BP. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Draxin, an axon guidance protein, affects chick trunk neural crest migration.

    Science.gov (United States)

    Su, Yuhong; Naser, Iftekhar B; Islam, Shahidul M; Zhang, Sanbing; Ahmed, Giasuddin; Chen, Sandy; Shinmyo, Yohei; Kawakami, Minoru; Yamamura, Ken-ichi; Tanaka, Hideaki

    2009-12-01

    The neural crest is a multipotent population of migratory cells that arises in the central nervous system and subsequently migrates along defined stereotypic pathways. In the present work, we analyzed the role of a repulsive axon guidance protein, draxin, in the migration of neural crest cells. Draxin is expressed in the roof plate of the chick trunk spinal cord and around the early migration pathway of neural crest cells. Draxin modulates chick neural crest cell migration in vitro by reducing the polarization of these cells. When exposed to draxin, the velocity of migrating neural crest cells was reduced, and the cells changed direction so frequently that the net migration distance was also reduced. Overexpression of draxin also caused some early migrating neural crest cells to change direction to the dorsolateral pathway in the chick trunk region, presumably due to draxin's inhibitory activity. These results demonstrate that draxin, an axon guidance protein, can also affect trunk neural crest migration in the chick embryo.

  8. The underlying mechanism of proinflammatory NF-κB activation by the mTORC2/Akt/IKKα pathway during skin aging.

    Science.gov (United States)

    Choi, Yeon Ja; Moon, Kyoung Mi; Chung, Ki Wung; Jeong, Ji Won; Park, Daeui; Kim, Dae Hyun; Yu, Byung Pal; Chung, Hae Young

    2016-08-16

    Mammalian target of rapamycin complex 2 (mTORC2), one of two different enzymatic complexes of mTOR, regulates a diverse set of substrates including Akt. mTOR pathway is one of well-known mediators of aging process, however, its role in skin aging has not been determined. Skin aging can be induced by physical age and ultraviolet (UV) irradiation which are intrinsic and extrinsic factors, respectively. Here, we report increased mTORC2 pathway in intrinsic and photo-induced skin aging, which is implicated in the activation of nuclear factor-κB (NF-κB). UVB-irradiated or aged mice skin revealed that mTORC2 activity and its component, rictor were significantly upregulated which in turn increased Akt activation and Akt-dependent IκB kinase α (IKKα) phosphorylation at Thr23 in vivo. We also confirmed that UVB induced the mTORC2/Akt/IKKα signaling pathway with HaCaT human normal keratinocytes. The increased mTORC2 signaling pathway during skin aging were associated to NF-κB activation. Suppression of mTORC2 activity by the treatment of a mTOR small inhibitor or knockdown of RICTOR partially rescued UVB-induced NF-κB activation through the downregulation of Akt/IKKα activity. Our data demonstrated the upregulation of mTORC2 pathway in intrinsic and photo-induced skin aging and its role in IKKα/NF-κB activation. These data not only expanded the functions of mTOR to skin aging but also revealed the therapeutic potential of inhibiting mTORC2 in ameliorating both intrinsic skin aging and photoaging.

  9. Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach

    Directory of Open Access Journals (Sweden)

    Alejo J Nevado-Holgado

    Full Text Available Alzheimer's disease (AD represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID drugs, and genome wide association studies (GWAS show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive.In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin. Gene expression signatures were derived for disease from both blood (n = 344 and post-mortem brain (n = 690, and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level.These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness. Keywords: Alzheimer's disease, NSAID, Inflammation, Fuzzy logic, Ribosome

  10. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary con