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Sample records for neural pathways immunocytochemical

  1. Immunocytochemical characterisation of neural stem-progenitor cells from green terror cichlid Aequidens rivulatus.

    Science.gov (United States)

    Wen, C M; Chen, M M; Nan, F H; Wang, C S

    2017-01-01

    In this study, cultures of neural stem-progenitor cells (NSPC) from the brain of green terror cichlid Aequidens rivulatus were established and various NSPCs were demonstrated using immunocytochemistry. All of the NSPCs expressed brain lipid-binding protein, dopamine- and cAMP-regulated neuronal phosphoprotein 32 (DARPP-32), oligodendrocyte transcription factor 2, paired box 6 and sex determining region Y-box 2. The intensity and localisation of these proteins, however, varied among the different NSPCs. Despite being intermediate cells, NSPCs can be divided into radial glial cells, oligodendrocyte progenitor cells (OPC) and neuroblasts by expressing the astrocyte marker glial fibrillary acidic protein (GFAP), OPC marker A2B5 and neuronal markers, including acetyl-tubulin, βIII-tubulin, microtubule-associated protein 2 and neurofilament protein. Nevertheless, astrocytes were polymorphic and were the most dominant cells in the NSPC cultures. By using Matrigel, radial glia exhibiting a long GFAP(+) or DARPP-32(+) fibre and neurons exhibiting a significant acetyl-tubulin(+) process were obtained. The results confirmed that NSPCs obtained from A. rivulatus brains can proliferate and differentiate into neurons in vitro. Clonal culture can be useful for further studying the distinct NSPCs. © 2016 The Fisheries Society of the British Isles.

  2. 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

  3. Vergence Neural Pathways: A Systematic Narrative Literature Review.

    Science.gov (United States)

    Searle, Annabelle; Rowe, Fiona J

    2016-10-01

    Research in the neural pathway for vergence is less understood in comparison to the other four visual eye movements. The aim of this study was to review the literature on vergence neural pathways and associated disorders. A review of previous published literature though to March 2016 was conducted. Intracranial pathologies that affect entire neural functioning were found to cause convergence insufficiencies. In contrast, pathologies with a more localised intracranial lesion cause more specific vergence disorders. There is debate as to the potential presence of a "divergence centre." Detailed information on the divergence pathway is lacking and warrants further research.

  4. Dopamine system: Manager of neural pathways

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    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.

  5. Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

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    Damelio, F.; Gibbs, M. A.; Mehler, W. R.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

  6. Neural pathways for visual speech perception.

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    Bernstein, Lynne E; Liebenthal, Einat

    2014-01-01

    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 of 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.

  7. 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.

  8. Neural pathways for visual speech perception

    Science.gov (United States)

    Bernstein, Lynne E.; Liebenthal, Einat

    2014-01-01

    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 of 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. PMID:25520611

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

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    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.

  10. Impact of a Solution for the Study of Neural Pathways in Morphophysiology III

    OpenAIRE

    José Manuel Ruiz Medina; Alicia Ríos Carbonell; Gisela Trevín Fernández; Elnis Quiala Ballester; Vivian Santoya Varela

    2013-01-01

    Background: current conditions for teaching Morphophysiology subject and awareness of the historical difficulties that students face in understanding the morphological and functional characteristics of neural pathways require a solution. Objective: to create a set of means in order to provide a practical resource for the study of the morphological and functional characteristics of the neural pathways and to assess the impact of its implementation in Morphophysiology III teaching. Methods: we ...

  11. 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.

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

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    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.

  13. Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma

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    Joshua J. Breunig

    2015-07-01

    Full Text Available As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.

  14. Gustatory neural pathways revealed by genetic tracing from taste receptor cells.

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    Matsumoto, Ichiro

    2013-01-01

    Taste receptor cells encounter chemicals in foods and transmit this information to the gustatory neurons, which convey it further to the gustatory relay nuclei in the lower brainstem. Characterizing neurons involved in the transmission of gustatory information in the peripheral and central nervous systems helps us better understand how we perceive and discriminate tastes. However, it is difficult to anatomically identify them. Using cell-type-specific promoters/enhancers and a transneuronal tracer, we generated transgenic mice to visualize neurons in the gustatory neural pathways. We observed the tracer in the neurons of cranial sensory ganglia and the nucleus of the solitary tract in the medulla where gustatory neurons project. The tracer was also distributed in the reticular formation and several motor nuclei in the medulla that have not been recognized as gustatory ascending pathways. These transgenic mice revealed gustatory relay neurons in the known gustatory ascending pathway and an unexpected, thus presumably novel, neural circuit of gustatory system.

  15. Neural Pathway of Renovative and Innovative Products Appreciation

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    Huang, Furong; Chiu, Chiyue; Luo, Jing

    2016-12-01

    According to the level of change an invention makes on existing things and how it overrides people’s mental schemas on established categories, new inventions can be classified into two groups: incremental inventions (i.e., renovations), which make minor improvements on existing designs, and radical inventions (i.e., innovations), which make major developments that enable people to do things they have never been able to do before. Although innovation and renovation are two fundamentally different types of creation that feature new changes ranging from those in product development to those in large scale social changes, and people tend to report higher subjective preferences for incremental inventions compared to radical inventions, the cognitive brain mechanisms underlying the mental representation of these two types of inventions remains unknown. Through the use of innovative and renovative designs as materials, we found that relative to non-creative designs, creative (renovative &innovative) designs enhanced memory or association-related activation in the right parahippocampus. In particular, innovations evoked more activation in the conceptual pathway for representing objects than did renovations, whereas renovations evoked more activation in the motor pathway than innovations. These results suggest that operating experiences may provide advantages for understanding and appreciating creative designs.

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

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    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.

  17. Reduction in neural performance following recovery from anoxic stress is mimicked by AMPK pathway activation.

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    Tomas G A Money

    Full Text Available Nervous systems are energetically expensive to operate and maintain. Both synaptic and action potential signalling require a significant investment to maintain ion homeostasis. We have investigated the tuning of neural performance following a brief period of anoxia in a well-characterized visual pathway in the locust, the LGMD/DCMD looming motion-sensitive circuit. We hypothesised that the energetic cost of signalling can be dynamically modified by cellular mechanisms in response to metabolic stress. We examined whether recovery from anoxia resulted in a decrease in excitability of the electrophysiological properties in the DCMD neuron. We further examined the effect of these modifications on behavioural output. We show that recovery from anoxia affects metabolic rate, flight steering behaviour, and action potential properties. The effects of anoxia on action potentials can be mimicked by activation of the AMPK metabolic pathway. We suggest this is evidence of a coordinated cellular mechanism to reduce neural energetic demand following an anoxic stress. Together, this represents a dynamically-regulated means to link the energetic demands of neural signaling with the environmental constraints faced by the whole animal.

  18. Suitability of tissue prints for immunocytochemical diagnosis of mammary cancer.

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    Surowiak, P; Dziegiel, P; Zabel, M; Zasławski, R

    2001-01-01

    The present study was aimed at evaluating suitability of tissue prints for immunocytochemical evaluation of mammary cancer cells. The prints, originating from 30 cases of mammary cancer were studied using immunocytochemical reactions with monoclonal antibodies against estrogen and progesterone receptors, metallothionein (MT), P-glycoprotein and cytokeratins (clone LP34). Expression of individual antigens was assessed using the scale in which intensity of the colour reaction and percentage of positive cells were taken into account. The obtained results did not differ qualitatively or quantitatively from those obtained in paraffin sections. The studies have shown that tissue prints can be used for reliable immunocytochemical evaluation of expression of various proteins in mammary cancer cells.

  19. AAV-mediated Anterograde Transsynaptic Tagging: Mapping Input-Defined Functional Neural Pathways for Defense Behavior

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    Zingg, Brian; Chou, Xiao-lin; Zhang, Zheng-gang; Mesik, Lukas; Liang, Feixue; Tao, Huizhong Whit; Zhang, Li I.

    2017-01-01

    To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of specific 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 report that adeno-associated virus (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drove Cre-dependent transgene expression in selected postsynaptic neuronal targets, and thus allowed the tracing and functional manipulation of axonal projections from the latter input-defined neuronal population. Application of this tool in superior colliculus (SC) revealed that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drove flight and freezing, two different types of defense behavior, respectively. Such anterograde transsynaptic tagging is thus useful for forward screening of distinct functional neural pathways embedded in complex brain circuits. PMID:27989459

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

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    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.

  1. Physiological evidence of neural pathways involved in reflexogenic penile erection in the rat.

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    Rampin, O; Giuliano, F; Dompeyre, P; Rousseau, J P

    1994-10-24

    To elucidate neural pathways responsible for the occurrence of reflexogenic erections, the response of the corpus cavernosum to electrical stimulation of the dorsal nerve of the penis (DNP) was measured in anesthetized, acutely spinalized rats. Stimulation elicited a dramatic increase in intracavernous pressure (ICP). ICP response was decreased by 70% after sectioning the pelvic nerve homolaterally to the stimulated DNP and abolished after bilateral section. ICP response was not impaired by curarization, but its latency was lengthened. Thus we physiologically evidenced a reflex loop independent from supraspinal centers between DNP and the pelvic nerve supporting penile reflexogenic erection.

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

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    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.

  3. Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis.

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    Wang, Linlin; Lin, Shanshan; Zhang, Ji; Tian, Tian; Jin, Lei; Ren, Aiguo

    2017-02-01

    Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.

  4. Nutrient pathways and neural tube defects: a semi-Bayesian hierarchical analysis.

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    Carmichael, Suzan L; Witte, John S; Shaw, Gary M

    2009-01-01

    We used conventional and hierarchical logistic regression to examine the association of neural tube defects (NTDs) with intake of 26 nutrients that contribute to the mechanistic pathways of methylation, glycemic control, and oxidative stress, all of which have been implicated in NTD etiology. The hierarchical approach produces more plausible, more stable estimates than the conventional approach, while adjusting for potential confounding by other nutrients. Analyses included 386 cases and 408 nonmalformed controls with complete data on nutrients and potential confounders (race/ethnicity, education, obesity, and intake of vitamin supplements) from a population-based case-control study of deliveries in California from 1989 to 1991. Nutrients were specified as continuous, and their units were standardized to have a mean of zero and standard deviation (SD) of 1 for comparability of units across pathways. ORs reflect a 1-SD increase in the corresponding nutrient. Among women who took vitamin supplements, semi-Bayesian hierarchical modeling results suggested no associations between nutrient intake and NTDs. Among women who did not take supplements, both conventional and hierarchical models (HM) suggested an inverse association between lutein intake and NTD risk (HM odds ratio [OR] = 0.6; 95% confidence interval = 0.5-0.9) and a positive association with sucrose (HM OR 1.4; 1.1-1.8) and glycemic index (HM OR 1.3; 1.0-1.6). Our findings for lutein, glycemic index, and sucrose suggest that further study of NTDs and the glycemic control and oxidative stress pathways is warranted.

  5. 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.

  6. A DSP for sensing the bladder volume through afferent neural pathways.

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    Mendez, Arnaldo; Belghith, Abrar; Sawan, Mohamad

    2014-08-01

    In this paper, we present a digital signal processor (DSP) capable of monitoring the urinary bladder volume through afferent neural pathways. The DSP carries out real-time detection and can discriminate extracellular action potentials, also known as on-the-fly spike sorting. Next, the DSP performs a decoding method to estimate either three qualitative levels of fullness or the bladder volume value, depending on the selected output mode. The proposed DSP was tested using both realistic synthetic signals with a known ground-truth, and real signals from bladder afferent nerves recorded during acute experiments with animal models. The spike sorting processing circuit yielded an average accuracy of 92% using signals with highly correlated spike waveforms and low signal-to-noise ratios. The volume estimation circuits, tested with real signals, reproduced accuracies achieved by offline simulations in Matlab, i.e., 94% and 97% for quantitative and qualitative estimations, respectively. To assess feasibility, the DSP was deployed in the Actel FPGA Igloo AGL1000V2, which showed a power consumption of 0.5 mW and a latency of 2.1 ms at a 333 kHz core frequency. These performance results demonstrate that an implantable bladder sensor that perform the detection, discrimination and decoding of afferent neural activity is feasible.

  7. FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells.

    Science.gov (United States)

    Yeo, Hyeonju; Lyssiotis, Costas A; Zhang, Yuqing; Ying, Haoqiang; Asara, John M; Cantley, Lewis C; Paik, Ji-Hye

    2013-10-02

    Forkhead Box O (FoxO) transcription factors act in adult stem cells to preserve their regenerative potential. Previously, we reported that FoxO maintains the long-term proliferative capacity of neural stem/progenitor cells (NPCs), and that this occurs, in part, through the maintenance of redox homeostasis. Herein, we demonstrate that among the FoxO3-regulated genes in NPCs are a host of enzymes in central carbon metabolism that act to combat reactive oxygen species (ROS) by directing the flow of glucose and glutamine carbon into defined metabolic pathways. Characterization of the metabolic circuit observed upon loss of FoxO3 revealed a drop in glutaminolysis and filling of the tricarboxylic acid (TCA) cycle. Additionally, we found that glucose uptake, glucose metabolism and oxidative pentose phosphate pathway activity were similarly repressed in the absence of FoxO3. Finally, we demonstrate that impaired glucose and glutamine metabolism compromises the proliferative potential of NPCs and that this is exacerbated following FoxO3 loss. Collectively, our findings show that a FoxO3-dependent metabolic programme supports redox balance and the neurogenic potential of NPCs.

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

    Science.gov (United States)

    Duric, Vanja; Duman, Ronald S

    2013-01-01

    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.

  9. Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Michael Fatt

    2015-12-01

    Full Text Available The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs. Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways.

  10. Two neural streams, one voice: pathways for theme and variation in the songbird brain.

    Science.gov (United States)

    Bertram, R; Daou, A; Hyson, R L; Johnson, F; Wu, W

    2014-09-26

    Birdsong offers a unique model system to understand how a developing brain - once given a set of purely acoustic targets - teaches itself the vocal-tract gestures necessary to imitate those sounds. Like human infants, to juvenile male zebra finches (Taeniopygia guttata) falls the burden of initiating the vocal-motor learning of adult sounds. In both species, adult caregivers provide only a set of sounds to be imitated, with little or no information about the vocal-tract gestures used to produce the sounds. Here, we focus on the central control of birdsong and review the recent discovery that zebra finch song is under dual premotor control. Distinct forebrain pathways for structured (theme) and unstructured (variation) singing not only raise new questions about mechanisms of sensory-motor integration, but also provide a fascinating new research opportunity. A cortical locus for a motor memory of the learned song is now firmly established, meaning that anatomical, physiological, and computational approaches are poised to reveal the neural mechanisms used by the brain to compose the songs of birds. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Nrf2/ARE Pathway Involved in Oxidative Stress Induced by Paraquat in Human Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tingting Dou

    2016-01-01

    Full Text Available Compelling evidences have shown that diverse environmental insults arising during early life can either directly lead to a reduction in the number of dopaminergic neurons or cause an increased susceptibility to neurons degeneration with subsequent environmental insults or with aging alone. Oxidative stress is considered the main effect of neurotoxins exposure. In this study, we investigated the oxidative stress effect of Paraquat (PQ on immortalized human embryonic neural progenitor cells by treating them with various concentrations of PQ. We show that PQ can decrease the activity of SOD and CAT but increase MDA and LDH level. Furthermore, the activities of Cyc and caspase-9 were found increased significantly at 10 μM of PQ treatment. The cytoplasmic Nrf2 protein expressions were upregulated at 10 μM but fell back at 100 μM. The nuclear Nrf2 protein expressions were upregulated as well as the downstream mRNA expressions of HO-1 and NQO1 in a dose-dependent manner. In addition, the proteins expression of PKC and CKII was also increased significantly even at 1 μM. The results suggested that Nrf2/ARE pathway is involved in mild to moderate PQ-induced oxidative stress which is evident from dampened Nrf2 activity and low expression of antioxidant genes in PQ induced oxidative damage.

  12. 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.

  13. 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.

  14. The alexithymic brain: the neural pathways linking alexithymia to physical disorders

    Directory of Open Access Journals (Sweden)

    Kano Michiko

    2013-01-01

    Full Text Available Abstract Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The

  15. With a little help from my friends: androgens tap BDNF signaling pathways to alter neural circuits.

    Science.gov (United States)

    Ottem, E N; Bailey, D J; Jordan, C L; Breedlove, S M

    2013-06-03

    Gonadal androgens are critical for the development and maintenance of sexually dimorphic regions of the male nervous system, which is critical for male-specific behavior and physiological functioning. In rodents, the motoneurons of the spinal nucleus of the bulbocavernosus (SNB) provide a useful example of a neural system dependent on androgen. Unless rescued by perinatal androgens, the SNB motoneurons will undergo apoptotic cell death. In adulthood, SNB motoneurons remain dependent on androgen, as castration leads to somal atrophy and dendritic retraction. In a second vertebrate model, the zebra finch, androgens are critical for the development of several brain nuclei involved in song production in males. Androgen deprivation during a critical period during postnatal development disrupts song acquisition and dimorphic size-associated nuclei. Mechanisms by which androgens exert masculinizing effects in each model system remain elusive. Recent studies suggest that brain-derived neurotrophic factor (BDNF) may play a role in androgen-dependent masculinization and maintenance of both SNB motoneurons and song nuclei of birds. This review aims to summarize studies demonstrating that BDNF signaling via its tyrosine receptor kinase (TrkB) receptor may work cooperatively with androgens to maintain somal and dendritic morphology of SNB motoneurons. We further describe studies that suggest the cellular origin of BDNF is of particular importance in androgen-dependent regulation of SNB motoneurons. We review evidence that androgens and BDNF may synergistically influence song development and plasticity in bird species. Finally, we provide hypothetical models of mechanisms that may underlie androgen- and BDNF-dependent signaling pathways. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. 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.

  17. Immunocytochemical detection of emerin within the nuclear matrix.

    Science.gov (United States)

    Squarzoni, S; Sabatelli, P; Ognibene, A; Toniolo, D; Cartegni, L; Cobianchi, F; Petrini, S; Merlini, L; Maraldi, N M

    1998-06-01

    Emerin, the protein whose production is altered in the X-linked form of Emery-Dreifuss muscular distrophy, has been hypothesized to be associated with the nuclear matrix on the basis of biochemical studies. In addition, immunocytochemical data reported its localization at the nuclear periphery, on the nuclear lamina, in sections of several normal tissues. We investigated the association of emerin with the nuclear matrix, by using cultured cells (SaOS-2, MG63 and HeLa-S3) and their in situ extracted matrix as a model, and immunocytochemical methods, both at the light and electron microscope level. Our results show a normal presence of emerin in the cultured cells and the specific persistence of emerin on the lamina of the in situ extracted nuclear matrix. This suggests a tight binding between emerin and the nuclear lamina independently from the interactions between the C-terminal hydrophobic domain of the protein and the inner nuclear membrane.

  18. 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.

  19. 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.

  20. 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.

  1. A neural circuit model of emotional learning using two pathways with different granularity and speed of information processing.

    Science.gov (United States)

    Murakoshi, Kazushi; Saito, Mayuko

    2009-02-01

    We propose a neural circuit model of emotional learning using two pathways with different granularity and speed of information processing. In order to derive a precise time process, we utilized a spiking model neuron proposed by Izhikevich and spike-timing-dependent synaptic plasticity (STDP) of both excitatory and inhibitory synapses. We conducted computer simulations to evaluate the proposed model. We demonstrate some aspects of emotional learning from the perspective of the time process. The agreement of the results with the previous behavioral experiments suggests that the structure and learning process of the proposed model are appropriate.

  2. Cytochemical and immunocytochemical characterization of Yoshida ascites sarcoma cells.

    Science.gov (United States)

    Nicotina, P A; Ruggeri, P; Ferlazzo, G; Fimiani, V

    1991-01-01

    Some cytochemical and immunocytochemical investigations were carried out on actively growing Yoshida ascites sarcoma cells. These cells displayed an intense granular alpha-naphthylacetate esterase (ANAE) staining while the alpha-naphthylbutyrate esterase (ANBE) reaction was in part fluoride-sensitive and marked particularly in the large-size malignant cells. Acid phosphatase as well as peroxidase activities were not detected. The lack of immunoreactive lysozyme and alpha 1-antitrypsin suggested a poor differentiation of the above-mentioned tumor cells, but fibronectin and S-100 protein where highly expressed, as in tumors arising from the mononuclear phagocyte system.

  3. The ROCK/GGTase Pathway Are Essential to the Proliferation and Differentiation of Neural Stem Cells Mediated by Simvastatin.

    Science.gov (United States)

    Zhang, Chan; Wu, Jian-Min; Liao, Min; Wang, Jun-Ling; Xu, Chao-Jin

    2016-12-01

    Simvastatin, a lipophilic and fermentation-derived natural statin, is reported to treat neurological disorders, such as traumatic brain injury, Parkinson's disease (PD), Alzheimer disease (AD), etc. Recently, research also indicated that simvastatin could promote regeneration in the dentate gyrus of adult mice by Wnt/β-catenin signaling (Robin et al. in Stem Cell Reports 2:9-17, 2014). However, the effect and mechanisms by which simvastatin may affect the neural stem cells (NSCs; from the embryonic day 14.5 (E14.5) SD rat brain) are not fully understood. Here, we investigated the effects of different doses of simvastatin on the survival, proliferation, differentiation, migration, and cell cycle of NSCs as well as underlying intracellular signaling pathways. The results showed that simvastatin not only inhibits the proliferation of NSCs but also enhances the βIII-tubulin(+) neuron differentiation rate. Additionally, we find that simvastatin could also promote NSC migration and induce cell cycle arrest at M2 phrase. All these effects of simvastatin on NSCs were mimicked with an inhibitor of Rho kinase (ROCK) and a specific inhibitor of geranylgeranyl transferase (GGTase). In conclusion, these data indicate that simvastatin could promote neurogenesis of neural stem cells, and these effects were mediated through the ROCK/GGTase pathway.

  4. 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

    important for cognitive function. However, the neural substrates involved in these effects remain elusive. Here we identify cortically projecting cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain (BF) as important targets for alpha(7) nAChR activation...

  5. 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…

  6. 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…

  7. [Retinoic acid signal pathway regulation of zebra fish tooth development through manipulation of the differentiation of neural crest].

    Science.gov (United States)

    Liu, Xin; Huang, Xing; Xu, Zhiyun; Yang, Deqin

    2016-04-01

    To investigate the mechanism of retinoic acid (RA) signal in dental evolution, RA is used to explore the influence of the mechanism on neural crest's migration during the early stage of zebra fish embryos. We divided embryos of wild type and transgenic line zebra fish into three groups. 1 x 10(-7) to 6 x 10(-7) mol x L(-1) RA and 1 x 10(-7) mo x L(-1) 4-diethylaminobenzaldehyde (DEAB) were added into egg water at 24 hpf for 9 h. Dimethyl sulfoxid (DMSO) with the concentration was used as control group. Then, antisense probes of dlx2a, dlx2b, and barxl were formulated to perform whole-mount in situ hybridization to check the expressions of the genes in 48 hpf to 72 hpf embryos. We observed fluorescence of transgenic line in 4 dpf embryos. We obtained three mRNA probes successfully. Compared with DMSO control group, a low concentration (1 x 10(-7) mol x L(-1)) of RA could up-regulate the expression of mRNA (barx1, dlx2a) in neural crest. Obvious migration trend was observed toward the pharyngeal arch in which teeth adhered. Transgenic fish had spreading fluorescence tendency in pharyngeal arch. However, a high concentration (4 x 10(-7) mol x L(-1)) of RA malformed the embryos and killed them after treatment. One third of the embryos of middle concentration (3 x 10(-7) mo x L(-1)) exhibited delayed development. DEAB resulted in neural crest dysplasia. The expression of barxl and dlx2a were suppressed, and the appearance of dlx2b in tooth was delayed. RA signal pathway can regulate the progenitors of tooth by controlling the growth of the neural crest and manipulating tooth development

  8. A dual immunocytochemical assay for oestrogen and epidermal growth factor receptors in tumour cell lines

    NARCIS (Netherlands)

    A.K. Sharma (Anisha K.); J.H. Horgan; R.L. McClelland (Robyn); A.G. Douglas-Jones (A.); T. van Agthoven (Ton); L.C.J. Dorssers (Lambert); R.I. Nicholson (R.)

    1994-01-01

    textabstractA new dual immunocytochemical assay for oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) has been developed. It has been tested in a variety of conditions using cell culture lines and the results correlate well with those obtained from single immunocytochemical assays.

  9. Immunocytochemical localization of osteocalcin in developing rat teeth.

    Science.gov (United States)

    Gorter de Vries, I; Quartier, E; Boute, P; Wisse, E; Coomans, D

    1987-03-01

    Osteocalcin was purified by gel chromatography from a crude extract obtained after decalcification of rat incisors. The apparent molecular weight, as determined by 5-15% SDS-polyacrylamide gel electrophoresis, was 18,000, and amino acid analysis revealed 60 gamma-carboxyglutamic acid residues per 1000. Antisera against osteocalcin, raised in rabbits, reacted specifically with osteocalcin when investigated by immuno-electroblotting of dentin crude extract. 4-micron cryosections of formaldehyde-fixed tooth germs showed positive immunocytochemical staining for osteocalcin in dentin and odontoblasts. The staining of the mantle dentin at the coronal sides of the tooth germs was more intense than that of the adjacent circumpulpal dentin, while the odontoblasts involved in the formation of mantle dentin showed stronger immunoreactivity than did odontoblasts involved in circumpulpal dentin formation. This marked difference was not observed on the root sides of the tooth germs. In 1-micron cryosections, osteocalcin immunoreactivity was found evenly distributed throughout the entire cell body, with the exception of the Golgi region, which was less intensely stained, while the nucleus and the cell process were negative. The positive staining reaction with anti-osteocalcin antiserum was found in dentin from the very onset of its formation in the fetus. In conclusion, our results demonstrate the presence of osteocalcin in odontoblasts and dentin. Its immunocytochemical localization may be compatible with a distinct role in early dentinogenesis.

  10. Desmoplastic small round cell tumour: Cytological and immunocytochemical features

    Directory of Open Access Journals (Sweden)

    Filho Adhemar

    2005-01-01

    Full Text Available Abstract Background Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive neoplasm. The cytological diagnosis of these tumors can be difficult because they show morphological features quite similar to other small round blue cells tumors. We described four cases of DSRCT with cytological sampling: one obtained by fine needle aspiration biopsy (FNAB and three from serous effusions. The corresponding immunocytochemical panel was also reviewed. Methods Papanicolaou stained samples from FNAB and effusions were morphologically described. Immunoreaction with WT1 antibody was performed in all cytological samples. An immunohistochemical panel including the following antibodies was performed in the corresponding biopsies: 34BE12, AE1/AE3, Chromogranin A, CK20, CK7, CK8, Desmin, EMA, NSE, Vimentin and WT1. Results The smears showed high cellularity with minor size alteration. Nuclei were round to oval, some of them with inconspicuous nucleoli. Tumor cells are clustered, showing rosette-like feature. Tumor cells in effusions and FNA were positive to WT1 in 3 of 4 cytology specimens (2 out 3 effusions and one FNA. Immunohistochemical reactions for vimentin, NSE, AE1/AE3 and WT1 were positive in all cases in tissue sections. Conclusion The use of an adjunct immunocytochemical panel coupled with the cytomorphological characteristics allows the diagnosis of DSRCT in cytological specimens.

  11. Physiological and immunocytochemical evidence that glutamatergic neurotransmission is involved in the activation of arm autotomy in the featherstar Antedon mediterranea (Echinodermata: Crinoidea).

    Science.gov (United States)

    Wilkie, I C; Barbaglio, A; Maclaren, W M; Carnevali, M D Candia

    2010-06-15

    The crinoid echinoderm Antedon mediterranea autotomises its arms at specialised skeletal joints known as syzygies that occur at regular intervals along the length of each arm. Detachment is achieved through the nervously mediated destabilisation of ligament fibres at a particular syzygy. The aim of this investigation was to identify neurotransmitters that are involved in the autotomy response. Physiological experiments were conducted on isolated preparations of syzygial joints, which can be induced to undergo autotomy-like fracture by applying stimulatory agents such as elevated [K(+)](o). Initial experiments with elevated [K(+)](o) showed that the autotomy threshold (the minimum amount of stimulation required to provoke autotomy) is lowest in syzygies at the arm base and rises distally. Of a range of neurotransmitter agonists tested, only l-glutamate invoked syzygial destabilisation, as did its analogues l-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate, but not l-(+)-2-amino-4-phosphonobutyrate (l-AP4) or N-methyl-d-aspartate (NMDA). The implication that l-glutamate stimulates syzygial fracture through AMPA/kainate-like receptors was supported by the finding that the action of l-glutamate was inhibited by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Acetylcholine depressed the response of syzygial preparations to l-glutamate, suggesting a possible mechanism by which the autotomy threshold could be varied constitutively and facultatively. An immunocytochemical method employing a polyclonal antibody against l-glutamate conjugated to glutaraldehyde revealed l-glutamate-like immunoreactivity in all components of the putative neural pathway controlling the autotomy reflex, including the epidermis, brachial nerve, syzygial nerves and cellular elements close to the syzygial ligaments. We conclude that it is highly probable that l-glutamate acts as an excitatory neurotransmitter in the activation of

  12. HHF35, a muscle-actin-specific monoclonal antibody. I. Immunocytochemical and biochemical characterization.

    Science.gov (United States)

    Tsukada, T; Tippens, D; Gordon, D; Ross, R; Gown, A M

    1987-01-01

    A monoclonal antibody to muscle cell actin isotypes was produced and characterized. Immunocytochemical analysis of methanol-Carnoy's-fixed, paraffin-embedded human tissue revealed that this antibody, termed HHF35, reacts with skeletal muscle cells, cardiac muscle cells, smooth muscle cells, pericytes, and myoepithelial cells, but is nonreactive with endothelial, epithelial, neural, or connective tissue cells. When assayed by indirect immunofluorescence, HHF35 reacts with microfilament bundles from various cultured mammalian smooth muscle cells, but does not react with cultured human dermal fibroblasts or various epithelial tumor cell lines. In one-dimensional gel electrophoresis immunoblot experiments this antibody detects a 42-kd polypeptide from tissue extracts of uterus, ileum, aorta, diaphragm, and heart and extract from smooth muscle cells. The antibody also reacts with a comigrating 42-kd band of highly purified rabbit skeletal muscle actin. HHF35 is nonreactive on immunoblots of extracts from all tested nonmuscle cell extracts. Immunoelectrophoresis followed by immunoblotting performed in the presence of urea and reducing agents reveals recognition of the alpha isoelectrophoretic variant of actin from skeletal, cardiac, and smooth muscle sources and of the gamma variant from smooth muscle sources. Because HHF35 reacts with virtually all muscle cells, it will be useful as a marker for muscle and muscle-derived cells.

  13. Lymphovascular and neural regulation of metastasis: Shared tumour signalling pathways and novel therapeutic approaches

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    Le, C.P.; Karnezis, T.; Achen, M. G.; Stacker, S.A.; Sloan, E.K.

    2014-01-01

    The progression of cancer is supported by a wide variety of non-neoplastic cell types which make up the tumour stroma, including immune cells, endothelial cells, cancer-associated fibroblasts and nerve fibres. These host cells contribute molecular signals that enhance primary tumour growth and provide physical avenues for metastatic dissemination. This article provides an overview of the role of blood vessels, lymphatic vessels and nerve fibres in the tumour microenvironment, and highlights the interconnected molecular signalling pathways that control their development and activation in cancer. Further the review highlights the known pharmacological agents which target these pathways and discusses the potential therapeutic uses of drugs that target angiogenesis, lymphangiogenesis and stress response pathways in the different stages of cancer care. PMID:24267548

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

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    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.

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

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    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

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    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. Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide

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    Bruno P. Carreira

    2012-02-01

    Full Text Available Nitric oxide (NO is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP and the cGMP-dependent kinase (PKG are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ were used. We observed that long-term exposure to the NO donor (24 h, NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.

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

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    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

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

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    Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K

    2014-01-01

    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 vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting 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.

  20. Variances handling method of clinical pathways based on T-S fuzzy neural networks with novel hybrid learning algorithm.

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    Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Ye, Yan; Yao, Yang

    2012-06-01

    Clinical pathways' variances present complex, fuzzy, uncertain and high-risk characteristics. They could cause complicating diseases or even endanger patients' life if not handled effectively. In order to improve the accuracy and efficiency of variances handling by Takagi-Sugeno (T-S) fuzzy neural networks (FNNs), a new variances handling method for clinical pathways (CPs) is proposed in this study, which is based on T-S FNNs with novel hybrid learning algorithm. And the optimal structure and parameters can be achieved simultaneously by integrating the random cooperative decomposing particle swarm optimization algorithm (RCDPSO) and discrete binary version of PSO (DPSO) algorithm. Finally, a case study on liver poisoning of osteosarcoma preoperative chemotherapy CP is used to validate the proposed method. The result demonstrates that T-S FNNs based on the proposed algorithm achieves superior performances in efficiency, precision, and generalization ability to standard T-S FNNs, Mamdani FNNs and T-S FNNs based on other algorithms (CPSO and PSO) for variances handling of CPs.

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

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    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 extreme capsule) may be altered in individuals with autism. These pathways may also provide targets for experimental treatments to facilitate communication skills in autism. We propose that music-based interventions (e.g., auditory–motor mapping training) would take advantage of the musical strengths of these children, and are likely to engage, and possibly strengthen, the connections between frontal and temporal regions bilaterally. Such treatments have important clinical potential in facilitating expressive language in nonverbal children with autism. PMID:21197137

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

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    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...

  3. 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.

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

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    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.

  5. Valproic acid inhibits neural progenitor cell death by activation of NF-κB signaling pathway and up-regulation of Bcl-XL

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    Han Seol

    2011-07-01

    Full Text Available Abstract Background At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis. Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs. Methods Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C. diluted with normal saline at E12. To analyze the cell death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression level of proteins was investigated by Western blot and immunocytochemical assays. The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL gene promoter and NF-κB p65 was investigated by ChIP assay. Results In this study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed that VPA protects cultured NPCs from cell death after growth factor withdrawal both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The protective effect of prenatally injected VPA was also observed in E16 embryonic brain. Treatment of VPA decreased the level of IκBα and increased the nuclear translocation of NF-κB, which subsequently enhanced expression of anti-apoptotic protein Bcl-XL. Conclusion To the best of our knowledge, this is the first report to indicate the reduced death of NPCs by VPA at developmentally

  6. Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation

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    Rich, Brendan A.; Carver, Frederick W.; Holroyd, Tom; Rosen, Heather R.; Mendoza, Jennifer K.; Cornwell, Brian R.; Fox, Nathan A.; Pine, Daniel S.; Coppola, Richard; Leibenluft, Ellen

    2011-01-01

    Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyperarousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8–17. Magnetoencephalography (MEG) examined neuronal activity (4–50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability. PMID:21561628

  7. Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation.

    Science.gov (United States)

    Rich, Brendan A; Carver, Frederick W; Holroyd, Tom; Rosen, Heather R; Mendoza, Jennifer K; Cornwell, Brian R; Fox, Nathan A; Pine, Daniel S; Coppola, Richard; Leibenluft, Ellen

    2011-10-01

    Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8-17. Magnetoencephalography (MEG) examined neuronal activity (4-50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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    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

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

    Science.gov (United States)

    Poon, Chi-Sang; Young, Daniel L

    2006-08-08

    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, nonassociative fear and anxiety

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

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    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.

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

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    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.

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

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    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.

  13. Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care.

    Science.gov (United States)

    Murgatroyd, Christopher A; Peña, Catherine J; Podda, Giovanni; Nestler, Eric J; Nephew, Benjamin C

    2015-08-01

    Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. AICAR induces astroglial differentiation of neural stem cells via activating the JAK/STAT3 pathway independently of AMP-activated protein kinase.

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    Zang, Yi; Yu, Li-Fang; Pang, Tao; Fang, Lei-Ping; Feng, Xu; Wen, Tie-Qiao; Nan, Fa-Jun; Feng, Lin-Yin; Li, Jia

    2008-03-07

    Neural stem cell differentiation and the determination of lineage decision between neuronal and glial fates have important implications in the study of developmental, pathological, and regenerative processes. Although small molecule chemicals with the ability to control neural stem cell fate are considered extremely useful tools in this field, few were reported. AICAR is an adenosine analog and extensively used to activate AMP-activated protein kinase (AMPK), a metabolic "fuel gauge" of the biological system. In the present study, we found an unrecognized astrogliogenic activity of AICAR on not only immortalized neural stem cell line C17.2 (C17.2-NSC), but also primary neural stem cells (NSCs) derived from post-natal (P0) rat hippocampus (P0-NSC) and embryonic day 14 (E14) rat embryonic cortex (E14-NSC). However, another AMPK activator, Metformin, did not alter either the C17.2-NSC or E14-NSC undifferentiated state although both Metformin and AICAR can activate the AMPK pathway in NSC. Furthermore, overexpression of dominant-negative mutants of AMPK in C17.2-NSC was unable to block the gliogenic effects of AICAR. We also found AICAR could activate the Janus kinase (JAK) STAT3 pathway in both C17.2-NSC and E14-NSC but Metformin fails. JAK inhibitor I abolished the gliogenic effects of AICAR. Taken together, these results suggest that the astroglial differentiation effect of AICAR on neural stem cells was acting independently of AMPK and that the JAK-STAT3 pathway is essential for the gliogenic effect of AICAR.

  15. Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway

    DEFF Research Database (Denmark)

    Kolkova, K; Novitskaya, V; Pedersen, N

    2000-01-01

    The signal transduction pathways associated with neural cell adhesion molecule (NCAM)-induced neuritogenesis are only partially characterized. We here demonstrate that NCAM-induced neurite outgrowth depends on activation of p59(fyn), focal adhesion kinase (FAK), phospholipase Cgamma (PLCgamma......), protein kinase C (PKC), and the Ras-mitogen-activated protein (MAP) kinase pathway. This was done using a coculture system consisting of PC12-E2 cells grown on fibroblasts, with or without NCAM expression, allowing NCAM-NCAM interactions resulting in neurite outgrowth. PC12-E2 cells were transiently...... propose a model of NCAM signaling involving two pathways: NCAM-Ras-MAP kinase and NCAM-FGF receptor-PLCgamma-PKC, and we propose that PKC serves as the link between the two pathways activating Raf and thereby creating the sustained activity of the MAP kinases necessary for neuronal differentiation....

  16. [Selective ablation of certain neural pathways by gene transfer using viral vectors: analysis of primate basal ganglia functions by using immunotoxin-mediated tract targeting].

    Science.gov (United States)

    Takada, Masahiko

    2013-06-01

    Using a neuron-specific retrograde gene-transfer vector based on the lentivirus, we established immunotoxin (IT)-mediated tract targeting in the primate brain; this technique allows ablation of a neuronal population constituting a certain pathway. Here, we introduce a recent study on selective removal of the cortico-subthalamic "hyperdirect" pathway. Together with the direct and indirect pathways, the hyperdirect pathway plays a crucial role in motor information processing in the basal ganglia. This pathway links the motor-related areas of the frontal lobe directly to the subthalamic nucleus (STN) without relay at the striatum. After electrical stimulation of the motor-related areas, such as the supplementary motor area (SMA), triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually detected in the internal segment of the globus pallidus (GPi). Several lines of evidence suggest that the early excitation may be derived from the hyperdirect pathway. We injected the lentiviral vector expressing human interleukin-2 receptor α-subunit into the monkey STN. IT was then injected into the SMA. We recorded GPi neuron responses to SMA stimulation. We found that the early excitation was reduced neither with the inhibition nor with the late excitation. The spontaneous firing rate and pattern of GPi neurons remained unchanged. This indicated that IT-mediated tract targeting successfully and selectively eliminated the hyperdirect pathway from the basal ganglia circuitry without affecting the spontaneous activity of STN neurons. This electrophysiological finding was confirmed using anatomical data obtained from retrograde and anterograde neural tracings. The present results show that the cortically driven early excitation in GPi neurons is mediated by the hyperdirect pathway. The IT-mediated tract targeting technique will provide us with novel strategies for elucidating various neural network functions.

  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 (O2-) 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 O2- 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. Immunocytochemical localization of muscarinic acetylcholine receptors in the rat endocrine pancreas

    NARCIS (Netherlands)

    Zee, E.A. van der; Buwalda, B.; Strubbe, J.H.; Strosberg, A.D.; Luiten, P.G.M.

    Immunocytochemical application of the antimuscarinic acetylcholine receptor antibody M35 to pancreas tissue revealed the target areas for the parasympathetic nervous system. Immunoreactivity in the endocrine pancreas was much higher than that in the exocrine part. Moreover, the endocrine cells at

  19. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    Science.gov (United States)

    Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

  20. Development of quality control preparations for immunocytochemical assessment of urokinase-type plasminogen activator.

    Science.gov (United States)

    de Witte, H; van den Hurk, M; Sweep, F; Benraad, T; Geurts-Moespot, A; Ruiter, D; Verhofstad, A

    2001-09-01

    Quality control of immunochemical and/or immunocytochemical analyses warrants constant reproducibility and reliability of assay performance. In this respect, stable reference preparations containing known quantities of the components to be assessed may serve purposes in the quality assessment of antigen expression levels, including those of the plasminogen activation system. Quality control preparations for the immunocytochemical assessment of urokinase-type plasminogen activator (uPA) were developed using different combinations of cultured cell lines (BLM and IF6), each expressing immunochemically well-defined (by enzyme-linked immunosorbent assay[ELISA]) amounts of the respective component. Cytospins and frozen sections cut from sucrose/Tissue-Tek blocks containing these cell lines demonstrated stable and homogeneous expression of uPA. An excellent correlation was found between the immunocytochemical staining results and the data obtained by ELISA. Because these cell lines are available in practically unlimited quantities, large numbers of nearly identical quality control preparations can be made over a long period of time. Therefore, the incorporation of (combinations of) cell lines in cytospins or sucrose/Tissue-Tek blocks represents a simple model system in establishing quality control preparations for immunocytochemical assessment of components of the plasminogen activator system.

  1. 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

  2. Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

    Science.gov (United States)

    Huang, Yan; Bornstein, Michael M; Lambrichts, Ivo; Yu, Hai-Yang; Politis, Constantinus; Jacobs, Reinhilde

    2017-01-01

    Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal mechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma (PRP) therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field. Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and (pre-)clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of injured peripheral nerves around dental implants is discussed. PMID:28282030

  3. Immunocytochemical and ultrastructural characterization of endocrine cells and nerves in the intestine of Rana temporaria.

    Science.gov (United States)

    Valverde, E; Díaz de Rada, O; Burrell, M A; Rovira, J; Sesma, P

    1993-08-01

    Endocrine cells have been identified in the intestine of the frog Rana temporaria after application of the Grimelius and Masson-Fontana techniques. These endocrine cells were examined using immunocytochemical techniques on paraffin and semithin sections for light microscopy. After testing 19 antisera, 12 immunoreactivities were identified. Numerous serotonin-, somatostatin- and GLP-1-immunoreactive cells; a moderate number of PYY-, glucagon-, VIP-, gastrin/CCK-immunoreactive cells and few human PP-, bombesin-, substance P- and neurotensin-immunoreactive cells were found. VIP- and met-enkephalin were identified in nerve fibers of the muscular layer. Using semithin-thin sections five types of endocrine cells (serotonin-, somatostatin-, gastrin/CCK-, glucagon- and bombesin-immunoreactive cells) have been characterized according to their immunocytochemical reaction and the ultrastructure of the secretory granules.

  4. 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.

  5. 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.

  6. The cytoskeleton of chondrocytes of Sepia officinalis (Mollusca, Cephalopoda): an immunocytochemical study

    OpenAIRE

    F Leone; A Bairati; L Vitellaro-Zuccarello

    2009-01-01

    Our previous electron microscope study showed that chondrocytes from cephalopod cartilage possess a highly developed cytoskeleton and numerous cytoplasmic processes that ramify extensively through the tissue. We have now carried out a light microscope immunocytochemical study of chondrocytes from the orbital cartilage of Sepia officinalis to obtain indications as to the nature of the cytoskeletal components. We found clear positivity to antibodies against mammalian tubulin, vimentin, GFAP, an...

  7. 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.

  8. 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.

  9. Immunocytochemical study of canine lymphomas and its correlation with exposure to tobacco smoke

    Directory of Open Access Journals (Sweden)

    K. C. Pinello

    2017-11-01

    Full Text Available Aim: Canine lymphoma is one of the most common canine neoplasms, but little is known regarding the effects of exposure to tobacco smoke on their biologic behavior. As cytology is the most frequent diagnostic method of canine lymphoma, the aims of this study were to perform an immunocytochemical study of canine lymphomas, including subtyping and cell proliferation analysis, and to establish their correlation with tobacco smoke exposure. Materials and Methods: A total of 23 dogs diagnosed with lymphoma were subjected to careful fine-needle biopsies of enlarged lymph nodes. The smears were air-dried, fixed with cold acetone, and immunocytochemically stained using CD3, PAX5, and Ki-67. Owners were requested to complete an epidemiologic questionnaire. Results: According to the updated Kiel classification, 65% were B-cell lymphomas - three low grade (LG and 12 high grade (HG and 35% were T-cell - two LG and six HG. Thirteen tumors presented high Ki67 indexes (>40% (11 HG and 2 LG, two revealed moderate ones (20-40% (1 HG and 1 LG, and three had low indexes (≤20% (1 HG and 2 LG. Both a significant positive correlation and a significant linear-by-linear association (p=0.018 were observed between high Ki67 indexes and smoking owners (r=0.753, p=0.002 as well as with the number of smokers in the household (r=0.641, p=0.001. Moreover, the mean percentage of Ki67+ cells from the group of "smoker owners" was statically higher (p=0.011 than that from the "non-smoker owners." Conclusion: The results suggest that cytological diagnosis of canine lymphomas benefits from being complemented with immunocytochemical studies that include subtyping and assessment of proliferative activity, both contributing for the prognosis and therapeutic planning. Furthermore, exposure to tobacco smoke seems to be related to the biological behavior of canine lymphomas.

  10. 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.

  11. Immunocytochemical Localization of Prunasin Hydrolase and Mandelonitrile Lyase in Stems and Leaves of Prunus serotina.

    Science.gov (United States)

    Swain, E.; Poulton, J. E.

    1994-12-01

    In macerates of black cherry (Prunus serotina Ehrh.) leaves and stems, (R)-prunasin is catabolized to HCN, benzaldehyde, and D-glucose by the sequential action of prunasin hydrolase (EC 3.2.1.21) and (R)-(+)-mandelonitrile lyase (EC 4.1.2.10). Immuno-cytochemical techniques have shown that within these organs prunasin hydrolase occurs within the vacuoles of phloem parenchyma cells. In arborescent leaves, mandelonitrile lyase was also located in phloem parenchyma vacuoles, but comparison of serial sections revealed that these two degradative enzymes are usually localized within different cells.

  12. Immunocytochemical studies on the naupliar nervous system of Balanus improvisus (Crustacea, Cirripedia, Thecostraca)

    DEFF Research Database (Denmark)

    Semmler, Henrike; Wanninger, Andreas; Høeg, Jens T

    2008-01-01

    revealed a circumoesophageal neuropil ring with nerves extending to the first and second antennae and to the mandibles, all features typical for Crustacea. In addition, RFamidergic structures are present in the region of the thoraco-abdomen. A pair of posterior nerves and a pair of lateral nerves run...... neurons in the protocerebrum, along the circumoesophageal connectives and in the mandibular ganglion stain only for serotonin. Due to the almost complete absence of comparable data on the neuroanatomy of early (naupliar) stages in other Crustacea, we include immunocytochemical data on the larvae...

  13. Burst firing in a motion-sensitive neural pathway correlates with expansion properties of looming objects that evoke avoidance behaviours

    Directory of Open Access Journals (Sweden)

    Glyn Allan McMillan

    2015-12-01

    Full Text Available The locust visual system contains a well-defined motion-sensitive pathway that transfers visual input to motor centers involved in predator evasion and collision avoidance. One interneuron in this pathway, the descending contralateral movement detector (DCMD, is typically described as using rate coding; edge expansion of approaching objects causes an increased rate of neuronal firing that peaks after a certain retinal threshold angle is exceeded. However, evidence of intrinsic DCMD bursting properties combined with observable oscillations in mean firing rates and tight clustering of spikes in raw traces, suggest that bursting may be important for motion detection. Sensory neuron bursting provides important timing information about dynamic stimuli in many model systems, yet no studies have rigorously investigated if bursting occurs in the locust DCMD during object approach. We presented repetitions of 30 looming stimuli known to generate behavioural responses to each of 20 locusts in order to identify and quantify putative bursting activity in the DCMD. Overall, we found a bimodal distribution of inter-spike intervals (ISI with peaks of more frequent and shorter ISIs occurring from 1-8 ms and longer less frequent ISIs occurring from 40-50 ms. Subsequent analysis identified bursts and isolated single spikes from the responses. Bursting frequency increased in the latter phase of an approach and peaked at the time of collision, while isolated spiking was predominant during the beginning of stimulus approach. We also found that the majority of inter-burst intervals occurred at 40-50 ms (or 20-25 bursts/s. Bursting also occurred across varied stimulus parameters and suggests that burst timing may be a key component of looming detection. Our findings suggest that the DCMD uses two modes of coding to transmit information about looming stimuli and that these modes change dynamically with a changing stimulus at a behaviourally-relevant time.

  14. Burst Firing in a Motion-Sensitive Neural Pathway Correlates with Expansion Properties of Looming Objects that Evoke Avoidance Behaviors.

    Science.gov (United States)

    McMillan, Glyn A; Gray, John R

    2015-01-01

    The locust visual system contains a well-defined motion-sensitive pathway that transfers visual input to motor centers involved in predator evasion and collision avoidance. One interneuron in this pathway, the descending contralateral movement detector (DCMD), is typically described as using rate coding; edge expansion of approaching objects causes an increased rate of neuronal firing that peaks after a certain retinal threshold angle is exceeded. However, evidence of intrinsic DCMD bursting properties combined with observable oscillations in mean firing rates and tight clustering of spikes in raw traces, suggest that bursting may be important for motion detection. Sensory neuron bursting provides important timing information about dynamic stimuli in many model systems, yet no studies have rigorously investigated if bursting occurs in the locust DCMD during object approach. We presented repetitions of 30 looming stimuli known to generate behavioral responses to each of 20 locusts in order to identify and quantify putative bursting activity in the DCMD. Overall, we found a bimodal distribution of inter-spike intervals (ISI) with peaks of more frequent and shorter ISIs occurring from 1-8 ms and longer less frequent ISIs occurring from 40-50 ms. Subsequent analysis identified bursts and isolated single spikes from the responses. Bursting frequency increased in the latter phase of an approach and peaked at the time of collision, while isolated spiking was predominant during the beginning of stimulus approach. We also found that the majority of inter-burst intervals (IBIs) occurred at 40-50 ms (or 20-25 bursts/s). Bursting also occurred across varied stimulus parameters and suggests that burst timing may be a key component of looming detection. Our findings suggest that the DCMD uses two modes of coding to transmit information about looming stimuli and that these modes change dynamically with a changing stimulus at a behaviorally-relevant time.

  15. 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.

  16. Immunohistochemical and immunocytochemical findings associated with Marek's disease virus in naturally infected laying hens.

    Science.gov (United States)

    Yavuz, O; Erer, H

    2017-09-14

    We compared immunohistochemical (IHC) staining of tissue sections of liver, kidney, spleen, lung, proventriculus, sciatic nerve, bursa of Fabricius, brain, heart, intestine and skin; immunocytochemical (ICC) staining of peripheral blood samples and touch preparations of liver, spleen and kidney of laying hens naturally infected with Marek's disease (MD) virus. We used one hundred and fifty 5-17-week-old commercial hens. IHC and ICC staining were performed using polymer-based techniques. IHC staining exhibited mostly free immunopositive reactions in tumor cells and in the cytoplasm of the parenchymal cells of liver, kidney, spleen and bursa of Fabricius. In the sciatic nerve, severe reactions were observed in the cytoplasm of plasma and MD cells in the lymphoproliferative areas. Pronounced staining was found in the lymphoid cells in the medulla of intrafollicular regions in the bursa of Fabricius. Although immunostaining was observed in the liver and spleen touch preparations, there was no staining in the kidneys and peripheral blood cell samples. The presence of virus in the tissue and peripheral blood samples and in touch preparations was compared immunohistochemically and immunocytochemically. IHC and ICC techniques were helpful for diagnosis of MD. Peripheral blood samples are inappropriate for field conditions and natural infections.

  17. Interaction of Notch signaling modulator Numb with α-Adaptin regulates endocytosis of Notch pathway components and cell fate determination of neural stem cells.

    Science.gov (United States)

    Song, Yan; Lu, Bingwei

    2012-05-18

    The ability to balance self-renewal and differentiation is a hallmark of stem cells. In Drosophila neural stem cells (NSCs), Numb/Notch (N) signaling plays a key role in this process. However, the molecular and cellular mechanisms underlying Numb function in a stem cell setting remain poorly defined. Here we show that α-Adaptin (α-Ada), a subunit of the endocytic AP-2 complex, interacts with Numb through a new mode of interaction to regulate NSC homeostasis. In α-ada mutants, N pathway component Sanpodo and the N receptor itself exhibited altered trafficking, and N signaling was up-regulated in the intermediate progenitors of type II NSC lineages, leading to their transformation into ectopic NSCs. Surprisingly, although the Ear domain of α-Ada interacts with the C terminus of Numb and is important for α-Ada function in the sensory organ precursor lineage, it was dispensable in the NSCs. Instead, α-Ada could regulate Sanpodo, N trafficking, and NSC homeostasis by interacting with Numb through new domains in both proteins previously not known to mediate their interaction. This interaction could be bypassed when α-Ada was directly fused to the phospho-tyrosine binding domain of Numb. Our results identify a critical role for the AP-2-mediated endocytosis in regulating NSC behavior and reveal a new mechanism by which Numb regulates NSC behavior through N. These findings are likely to have important implications for cancer biology.

  18. 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.

  19. 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

  20. 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

  1. Immunocytochemical localization and immunochemical characterization of an insulin-related peptide in the pancreas of the urodele amphibian, Ambystoma mexicanum

    DEFF Research Database (Denmark)

    Hansen, G N; Hansen, B L; Jørgensen, P N

    1989-01-01

    The pancreas of the axolotl, Ambystoma mexicanum, was investigated by immunocytochemical methods for the presence of immunoreactivity to a number of antisera raised against mammalian insulins. All anti-insulin antisera tested revealed substantial amounts of reaction products confined solely to th...

  2. Immunocytochemical analysis of the tumour suppressor protein (p53) in feline neoplasia.

    Science.gov (United States)

    Nasir, L; Krasner, H; Argyle, D J; Williams, A

    2000-07-03

    Detectable p53 immunostaining in neoplasia generally correlates with the presence of a mutation in the coding region of the p53 gene and may provide insights into the pathogenic mechanisms underlying tumourigenesis. p53 immunoreactivity was examined in 77 feline tumours, selected as a representative sample of 486 specimens submitted for diagnosis and analyzed to estimate the relative frequencies of feline neoplasias. Immunocytochemical staining demonstrated nuclear immunopositivity in 46% of the squamous cell carcinomas (SCCs), 50% of the osteosarcomas, 33% of the mammary carcinomas, 16% of the adenocarcinomas and 14% of the haemangiosarcomas. In contrast, none of the malignant lymphomas or fibrosarcomas examined showed p53 immunoreactivity. These data support a role for p53 aberrations in the pathogenesis of certain feline tumours.

  3. Lipid transfer proteins in Parietaria judaica L. pollen grains: immunocytochemical localization and function.

    Science.gov (United States)

    Vega-Maray, Ana M; Fernández-González, Delia; Valencia-Barrera, Rosa; Polo, Florentino; Seoane-Camba, Juan A; Sudrez-Cervera, Maria

    2004-09-01

    Parietariajudaica L. (Urticaceae) pollen is considered one of the most common causes of allergic respiratory symptoms in the Mediterranean area. The localization of lipid transfer proteins (LTPs) in P. judaica mature and hydrated-activated pollen grains was investigated applying a combination of transmission electron microscopy (TEM) with immunocytochemical methods. Our results show that the content of LTPs in P. judaica pollen grains changes during the process of hydration. The localization of judaica LTPs in the cytoplasm and in the lipid bodies associated with vacuoles demonstrated that LTPs represent primarily intracellular proteins. On the other hand, exposure of the pollen grains to germination medium induced the release of LTPs from the pollen grain. Thus, LTPs are cytoplasmic proteins that are secreted to become available for pollen-stigma interactions and probably induce the IgE antibody responses in allergic patients.

  4. Immunochemical and immunocytochemical studies of the crustacean vitellogenesis-inhibiting hormone (VIH).

    Science.gov (United States)

    Meusy, J J; Martin, G; Soyez, D; van Deijnen, J E; Gallo, J M

    1987-09-01

    Immunochemical investigations, using dot immunobinding assay (DIA) and enzyme-linked immunosorbent assay (ELISA), and immunocytochemical studies reveal the following new information about crustacean vitellogenesis-inhibiting hormone (VIH): (1) The structure of VIH is sufficiently different from that of the other sinus gland neuropeptides to allow a selective recognition of VIH by polyclonal antibodies. (2) From immunochemical criteria, VIH does not seem strictly species specific. The antisera raised against VIH of Homarus americanus cross-react with sinus gland extracts of Palaemonetes varians, Palaemon serratus, Macrobrachium rosenbergii, Carcinus maenas, and Porcellio dilatatus. (3) In the sinus gland of H. americanus, VIH immunoreactivity is localized mainly in electron-dense granules of medium size (110-185 nm in diameter) while, in P. dilatatus, the labeling is mostly on the largest granules (200-270 nm in diameter).

  5. The cytoskeleton of chondrocytes of Sepia officinalis (Mollusca, Cephalopoda: an immunocytochemical study

    Directory of Open Access Journals (Sweden)

    F Leone

    2009-06-01

    Full Text Available Our previous electron microscope study showed that chondrocytes from cephalopod cartilage possess a highly developed cytoskeleton and numerous cytoplasmic processes that ramify extensively through the tissue. We have now carried out a light microscope immunocytochemical study of chondrocytes from the orbital cartilage of Sepia officinalis to obtain indications as to the nature of the cytoskeletal components. We found clear positivity to antibodies against mammalian tubulin, vimentin, GFAP, and actin, but not keratin. The simultaneous presence of several cytoskeletal components is consistent with the hypothesis that cephalopod chondrocytes have the characteristics of both chondrocytes and osteocytes of vertebrates, which endow the tissue as a whole with some of the properties of vertebrate bone. We confirm, therefore, the presence in molluscs of the ubiquitous cytoskeletal proteins of metazoan cells that have remained highly conserved throughout phylogenetic evolution.

  6. Immunocytochemical study of argyrophil (Sevier Munger) endocrine cells of adult human pancreas.

    Science.gov (United States)

    Wilander, E; Lundqvist, M; Westermark, P; Grimelius, L

    1980-01-01

    Bouin-fixed tissues from non-diabetic adult human pancreata display an argyrophil reaction mainly in the periphery of the islets with the silver technique of Sevier-Munger. The nature of these argyrophil cells was examined after restaining by an indirect immunocytochemical method using antibodies against insulin, glucagon, somatostatin and pancreatic polypeptide. After this procedure the argyrophil cells were identified as glucagon (A-) cells and pancreatic polypeptide (PP-) cells, although the latter exhibited a weaker reaction. The insulin (B-) cells and somatostatin (D-) cells were unreactive. The results show that the Seiver-Munger stain is of equal value to the Grimelius silver nitrate stain in adult human pancreatic islets after fixation in Bouin's fluid.

  7. Intelligent ensemble T-S fuzzy neural networks with RCDPSO_DM optimization for effective handling of complex clinical pathway variances.

    Science.gov (United States)

    Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Yao, Yang

    2013-07-01

    Takagi-Sugeno (T-S) fuzzy neural networks (FNNs) can be used to handle complex, fuzzy, uncertain clinical pathway (CP) variances. However, there are many drawbacks, such as slow training rate, propensity to become trapped in a local minimum and poor ability to perform a global search. In order to improve overall performance of variance handling by T-S FNNs, a new CP variance handling method is proposed in this study. It is based on random cooperative decomposing particle swarm optimization with double mutation mechanism (RCDPSO_DM) for T-S FNNs. Moreover, the proposed integrated learning algorithm, combining the RCDPSO_DM algorithm with a Kalman filtering algorithm, is applied to optimize antecedent and consequent parameters of constructed T-S FNNs. Then, a multi-swarm cooperative immigrating particle swarm algorithm ensemble method is used for intelligent ensemble T-S FNNs with RCDPSO_DM optimization to further improve stability and accuracy of CP variance handling. Finally, two case studies on liver and kidney poisoning variances in osteosarcoma preoperative chemotherapy are used to validate the proposed method. The result demonstrates that intelligent ensemble T-S FNNs based on the RCDPSO_DM achieves superior performances, in terms of stability, efficiency, precision and generalizability, over PSO ensemble of all T-S FNNs with RCDPSO_DM optimization, single T-S FNNs with RCDPSO_DM optimization, standard T-S FNNs, standard Mamdani FNNs and T-S FNNs based on other algorithms (cooperative particle swarm optimization and particle swarm optimization) for CP variance handling. Therefore, it makes CP variance handling more effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Qin Wang

    2015-06-01

    Full Text Available Multiple sclerosis (MS is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS. Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12 is an oral formulation of the fumaric acid esters (FAE, containing the active metabolite dimethyl fumarate (DMF. Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF on mouse and rat neural stem/progenitor cells (NPCs and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2 treatment. In addition, utilizing the reactive oxygen species (ROS assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2 at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1. Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS.

  9. 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

  10. Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway.

    Directory of Open Access Journals (Sweden)

    Yue Li

    Full Text Available In the present study, we aim to elucidate the roles of caveolin-1(Cav-1, a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs. In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O₂ for 24 h and then switched to 21% O₂ for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O₂. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs.

  11. Neural Computations in Binaural Hearing

    Science.gov (United States)

    Wagner, Hermann

    Binaural hearing helps humans and animals to localize and unmask sounds. Here, binaural computations in the barn owl's auditory system are discussed. Barn owls use the interaural time difference (ITD) for azimuthal sound localization, and they use the interaural level difference (ELD) for elevational sound localization. ITD and ILD and their precursors are processed in separate neural pathways, the time pathway and the intensity pathway, respectively. Representation of ITD involves four main computational steps, while the representation of ILD is accomplished in three steps. In the discussion neural processing in the owl's auditory system is compared with neural computations present in mammals.

  12. Immunocytochemical Identification of Four Cell Types in the Pancreatic Islets of the Japanese Serow, Capricornis crispus : COMMUNICATION : Morphology

    OpenAIRE

    YASURO, ATOJI; YASUAKI, TAKADA; YOSHITAKA, SUZUKI; Makoto, Sugimura; Department of Veterinary Anatomy, Faculty of Agriculture, Gifu University; Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Hokkaido University

    1990-01-01

    The pancreatic islet of the Japanese serow was immunocytochemically examined. The islets were classified into large and small types, and both types of islets showed a similar composition of endocrine cells. The B cells were prominent and located at the periphery or throughout the islet . The A cells were less numerous and D and PP cells were sparse . The PP islets showing a majority of the PP cells were sometimes found. The large and small islets were detected irrespective of age of animals. ...

  13. The association and significance of H3K27me3 and a folate metabolic gene ACat2 in neural tube defects.

    Science.gov (United States)

    Zhai, Sifan; Zhao, Mingzuo; Zhou, Changcheng; Lu, Fenggang; Zhang, Huankai; Na, Li; Feng, Shanshan; Qiang, Xiaoxin; Du, Yong

    2016-11-03

    To study the association between the expression of H3K27me3 and ACat2 (a folate metabolic protein), in order to elucidate the protective mechanism of folic acid (FA) in neural tube defects (NTDs). Eighteen female SD rats were randomly divided into normal, NTD and FA group. NTD group was induced by all-trans retinoic acid (ATRA) at E10d. FA group was fed with FA supplementation since 2 weeks before pregnancy, followed by ATRA induction. At E15d, FA level in the embryonic neural tube was determined by ELISA. Neural stem cells (NSCs) were isolated. Cell proliferation was compared by CCK-8 assay. The differentiation potency was assessed by immunocytochemical staining. H3K27me3 expression was measured by immunofluorescence method and Western blot. ACat2 mRNA expression was detected by qRT-PCR. Cultured NSCs formed numerous Nestin-positive neurospheres. After 5 days, they differentiated into NSE-positive neurons and GFAP-positive astrocytes. When compared with controls, the FA level in NTD group was significantly lower, the ability of cell proliferation and differentiation was significantly reduced, H3K27me3 expression was increased, and ACat2 mRNA expression was decreased (P neural tube. The increased H3K27me3 expression might cause a disorder of folate metabolic pathway by silencing ACat2 expression, leading to reduced proliferation and differentiation of NSCs, and ultimately the occurrence of NTD. FA supplementation may reverse this process.

  14. Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Han Seol-Heui

    2010-11-01

    Full Text Available Abstract Background Prenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD. The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC and in vivo FASD models. Methods Neural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4 g/kg/day diluted with normal saline from E7 to E16 for in vivo FASD animal models. Expression level of proteins was investigated by western blot analysis and immunocytochemical assays. MTT was used for cell viability. Proliferative activity of NPCs was identified by BrdU incorporation, immunocytochemistry and FACS analysis. Results Reduced proliferation of NPCs by ethanol was demonstrated using BrdU incorporation, immunocytochemistry and FACS analysis. In addition, ethanol induced the imbalance between glutamatergic and GABAergic neuronal differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD with concomitant decrease in the expression of Mash1. Similar pattern of expression of those transcription factors was observed using an in vivo model of FASD as well as the increased expression of PSD-95 and decreased expression of GAD67. Conclusions These results suggest that ethanol induces hyper-differentiation of glutamatergic neuron through Pax6 pathway, which may underlie the hyper-excitability phenotype such as hyperactivity or seizure susceptibility in FASD patients.

  15. Interaction of antibodies with Entamoeba histolytica trophozoites from experimental amebic liver abscess: an immunocytochemical study.

    Science.gov (United States)

    Campos-Rodríguez, R; Jarillo-Luna, A; Ventura-Juárez, J; Shibayama, M; Pacheco-Yépez, J; Serrano-Luna, J; Tsutsumi, V

    2000-07-01

    Using immunocytochemical techniques, we studied the interaction of antibodies with Entamoeba histolytica trophozoites present during the development of amebic liver abscess. Hamsters were intrahepatically inoculated with HM1-IMSS axenic amebas and sacrificed at different days post-inoculation. IgG of rabbit anti-E. histolytica and IgG of rabbit anti-IgG of hamster were used, both labeled with peroxidase. With the rabbit anti-E. histolytica, all trophozoites present in hepatic lesions from 1-7 days post-inoculation were highly labeled. The IgG of rabbit anti-IgG of hamster intensively stained only those trophozoites present in lesions from 1-2 days post-inoculation. From day 3, the intensity and number of labeled trophozoites decreased progressively. The results suggest that the interaction between the amebas and the IgG of hamster is non-specific during the first 2 days. The absence of labeling in the chronic stages could be due to changes in the membrane antigens of the parasite or to alterations in the bloodstream around necrosis. Also, the anti-E. histolytica antibodies produced in the serum during the development of the hepatic disease are apparently incapable of reaching and interacting with the trophozoites present on the liver abscess. This can explain in part why antibodies do not have an important role in the defense of the host.

  16. Utility of an immunocytochemical assay using aqueous humor in the diagnosis of feline infectious peritonitis.

    Science.gov (United States)

    Felten, Sandra; Matiasek, Kaspar; Gruendl, Stefanie; Sangl, Laura; Hartmann, Katrin

    2017-05-10

    In cats suffering from feline infectious peritonitis (FIP) without effusion, antemortem diagnosis is challenging. Uveitis is common in these cats. It was the aim of this study to evaluate sensitivity and specificity of an immunocytochemical assay (ICC) in aqueous humor of cats suspected of having FIP. The study included 26 cats with immunohistochemically confirmed FIP and 12 control cats for which FIP was suspected due to similar clinical or laboratory changes, but which suffered from other diseases confirmed via histopathology. All aqueous humor samples were collected postmortem by paracentesis. ICC was carried out as avidin-biotin complex method. Sensitivity, specificity, and the overall accuracy including 95% confidence intervals (95% CI) were calculated. Immunocytochemistry was positive in 16 of 25 cats with FIP and 2 of 11 control cats (one cat with lymphoma, one with pulmonary adenocarcinoma). Aqueous humor samples of one cat with FIP and of one control cat were excluded from statistical analysis. Sensitivity was 64.0% (95% CI: 42.5-82.0); specificity 81.8% (95% CI: 48.2-97.7); and overall accuracy 69.4% (95% CI: 51.9-83.7). As false-positive results occurred and specificity is most important in the diagnosis of FIP, the diagnostic utility of ICC in aqueous humor is limited. Further studies are required to clarify the origin of false-positive ICC results. © 2017 American College of Veterinary Ophthalmologists.

  17. [Immunocytochemical analysis of the distribution and dynamics of lymphocyte antigens on freeze-fractured plasmatic membranes].

    Science.gov (United States)

    Di Lazzaro, C

    1989-01-01

    Label-fracture technique, which allows high resolution, coincident views of immunocytochemical markers on the cell surfaces and intramembrane particles (IMPs) over platinum/carbon replicas of the exoplasmic faces of the freeze-fractured plasma membranes, was used to analyze the surface distribution and dynamics of CD3, CD4, HLA class I and II lymphocyte surface antigens, all expressed on transmembrane proteins. In prefixed cells, the native distribution of the antigens was uniform over the cell surface. Coaggregation of IMPs induced by glycerol treatment at 37 degrees C before fixation revealed codistribution of the immunolabeling and the IMPs. Redistribution of the antigens, induced by treatment at 37 degrees C (for 20 min) with specific antibodies before fixation, resulted in capping of the immunolabeling in demarcated domains of the plasma membrane but failed to reveal correspondent domains of IMPs. This observation implies that migration of antigens into the patching/capping domains may be simultaneous with the exclusion of other membrane proteins from the same areas, as occurs during viral budding and receptor mediated endocytosis.

  18. Immunocytochemical Localization of Mandelonitrile Lyase in Mature Black Cherry (Prunus serotina Ehrh.) Seeds.

    Science.gov (United States)

    Wu, H C; Poulton, J E

    1991-08-01

    Mandelonitrile lyase (MDL, EC 4.1.2.10), which catalyzes the reversible dissociation of (R)-(+)-mandelonitrile to benzaldehyde and hydrogen cyanide, was purified to apparent homogeneity from mature black cherry (Prunus serotina Ehrh.) seeds by conventional protein purification techniques. This flavoprotein is monomeric with a subunit molecular mass of 57 kilodaltons. Glycoprotein character was shown by its binding to the affinity matrix concanavalin A-Sepharose 4B with subsequent elution by alpha-methyl-d-glucoside. Upon chemical deglycosylation by trifluoromethanesulfonic acid, the molecular mass was reduced to 50.9 kilodaltons. Two-dimensional gel analysis of deglycosylated MDL revealed the presence of several subunit isoforms of similar molecular mass but differing slightly in isoelectric point. Polyclonal antibodies were raised in New Zealand white rabbits against deglycosylated and untreated MDL. Antibody titers were determined by enzyme linked immunosorbent and dot immunobinding assays, while their specificities were assessed by Western immunoblot analysis. Antibodies raised against untreated lyase recognized several proteins in addition to MDL. In contrast, antisera raised against deglycosylated MDL were monospecific and were utilized for developmental and immunocytochemical localization studies. SDS-PAGE and immunoblotting analysis of seed proteins during fruit maturation showed that MDL first appeared in seeds shortly after cotyledons began development. In cotyledon cells of mature seeds, MDL was localized primarily in the cell wall with lesser amounts in the protein bodies, whereas in endosperm cells, this labeling pattern was reversed. N-terminal sequence data was gathered for future molecular approaches to the question of MDL microheterogeneity.

  19. Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor

    Directory of Open Access Journals (Sweden)

    Luis M.M. Flórez

    Full Text Available Abstract: Immunochemistry with anti-vimentin, anti-lysozyme, anti-alpha 1 antitrypsin, anti-CD3 and anti-CD79α antibodies has been used for characterization of primary cell culture in the transmissible venereal tumor (TVT. Samples for primary cell culture and immunohistochemistry assays were taken from eight dogs with cytological and clinical diagnosis of TVT. To validate the immunochemical results in the primary cell culture of TVT, a chromosome count was performed. For the statistical analysis, the Mann-Whitney test with p<0.05 was used. TVT tissues and culture cells showed intense anti-vimentin immunoreactivity, lightly to moderate immunoreactivity for anti-lysozyme, and mild for anti-alpha-antitrypsin. No marking was achieved for CD3 and CD79α. All culture cells showed chromosomes variable number of 56 to 68. This is the first report on the use of immunocytochemical characterization in cell culture of TVT. Significant statistic difference between immunochemistry in tissue and culture cell was not established, what suggests that the use of this technique may provide greater certainty for the confirmation of tumors in the primary culture. This fact is particularly important because in vitro culture of tumor tissues has been increasingly used to provide quick access to drug efficacy and presents relevant information to identify potential response to anticancer medicine; so it is possible to understand the behavior of the tumor.

  20. Fine-needle aspiration cytology of postirradiation sarcomas, including angiosarcoma, with immunocytochemical confirmation

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, J.F.; Lannin, D.L.; Larkin, E.W.; Feldman, P.; Frable, W.J. (East Carolina Univ. School of Medicine, Greenville, NC (USA))

    1989-01-01

    Postirradiation sarcomas are an unusual but well-recognized late effect of cancer therapy. In this article, a fine-needle aspiration (FNA) series of four cases is presented. There were three female patients and one male patient, with an age range of 28-55 yr (mean, 41). Two of the patients were irradiated for uterine cervical carcinoma while the other two received irradiation for malignant lymphoma. The time interval to the development of the postirradiation sarcoma ranged from 10 to greater than 20 yr. There were a postirradiation synovial sarcoma of the buttock region, malignant fibrous histiocytoma of the bone (femur), and rhabdomyosarcoma and angiosarcoma of the retroperitoneum. A spectrum of cytologic findings was encountered, reflecting the specific types of sarcomas. Immunocytochemical studies performed on the aspirated material from the angiosarcoma demonstrated the utility of immunoperoxidase stains for ULEX europaeus agglutinin-1 (UEA-1) and, to a lesser degree, factor VIII-related antigen antibody, confirming the vascular nature of this malignancy. The FNA findings from all four cases demonstrated cytologic features that allowed recognition of this unusual complication of irradiation treatment. This article confirms the utility of FNA cytology in following patients with previous malignancies and differentiating a postirradiation sarcoma from recurrent carcinoma.

  1. Dye coupling among immunocytochemically identified neurons in the supraoptic nucleus: increased incidence in lactating rats.

    Science.gov (United States)

    Hatton, G I; Yang, Q Z; Cobbett, P

    1987-06-01

    The hypothesis that electrotonic spread among oxytocinergic neurons contributes to synchronized bursting in the lactating rat leads to the prediction that coupling among oxytocinergic neurons would be stronger and more abundant in lactating than in non-lactating animals. We tested this prediction using, as an index of electrical coupling, transfer among neurons of the fluorescent dye Lucifer Yellow CH, which crosses gap junctions. Intracellular injections (total of 159) of the dye were made in supraoptic nucleus neurons in hypothalamic slices from virgin female and lactating rats. In virgins, 86 injections resulted in 76 single, 8 coupled pairs and 2 triplets of dye-filled neurons. In contrast, 73 injections in lactators yielded 51 single, 16 coupled pairs and 6 triplets, (greater than 100% increase) a difference significant at P less than 0.001. Immunocytochemical identification of the dye-filled cells revealed that there was an increase over virgins in coupling among both oxytocinergic and vasopressinergic neurons. These results are consistent with the hypothesis that electrical coupling is involved in synchronizing oxytocin cell bursting in lactators. They are also consistent with published data indicating that vasopressin neurons are metabolically activated (show increased glucose uptake) during suckling and may show correlated activity.

  2. Gut hormones in Salamandra salamandra. An immunocytochemical and electron microscopic investigation.

    Science.gov (United States)

    Buchan, A M; Polak, J M; Pearse, A G

    1980-01-01

    Histological, cytochemical and immunocytochemical methods were used in light and electron microscopical studies to demonstrate the presence of a neuroendocrine system in the gut of the urodele, Salamandra salamandra. Cytochemical stains capable of detecting peptide-producing endocrine cells demonstrate cells reacting with Masson's silver (argentaffin) method, Grimelius' argyrophil silver method, masked metachromasia method and the lead haematoxylin stain. Using antisera raised to a variety of mammalian gut peptides, cells containing bombesin-, gastrin-, somatostatin-, substance P- and glucagon-like immunoreactivity were indentified; vasoactive intestinal polypeptide- and substance P-like immunoreactivities were found in nerve fibres in the submucous and myenteric plexus. No immunoreactivity was detected from motilin, gastric inhibitory polypeptide, cholecystokinin or secretin. The ultrastructure of the immunoreactive cells and nerves was revealed by the semithin/thin method. All the cells indentified contained numerous electrondense secretory granules, which varied in their characteristic morphological structure from one cell type to another. The evidence collected in this study indicates that a complex neuroendocrine system regulating gut function is present in this amphibian and may have developed prior to the emergence of the phylum.

  3. Immunocytochemical and biochemical detection of alpha-L-fucosidase in Trypanosoma cruzi

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    Miletti L.C.

    2003-01-01

    Full Text Available The aim of the present study was to demonstrate the presence of alpha-L-fucosidase in Trypanosoma cruzi. Immunocytochemical and biochemical techniques were used to localize and characterize a membrane-associated, neutral-pH-optimum, alpha-L-fucosidase from the parasite. Light and electron microscopy localized the alpha-L-fucosidase specifically on the surface of the parasite and on membranes in the posterior region of the epimastigote stage. Although much less intense, labeling was also detected on the surface of trypomastigotes. At least 50% of the alpha-L-fucosidase activity was associated with epimastigote membrane solubilized with 1 M NaCl or 1% Triton X-100, suggesting that alpha-L-fucosidase is peripherally associated with membranes. The enzyme from epimastigotes had a neutral pH optimum (near 7 but displayed low specific activity when p-nitrophenyl-alpha-L-fucoside was employed as substrate (0.028 U/mg protein for epimastigotes and 0.015 U/mg protein for tissue culture-derived trypomastigotes. Polyacrylamide gel electrophoresis and Western blotting analysis both showed an expected 50-kDa polypeptide which was immunoreactive with anti-alpha-L-fucosidase antibodies.

  4. Immunocytochemical localization and subcellular site of lectin synthesis in developing wheat embryos

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    Raikhel, N.V.; Peumans, W.J.

    1986-04-01

    Appearance of wheat germ agglutinin (WGA) during wheat germ embryogenesis was studied using indirect immunocytochemical methods at the light and electron microscope levels. Developing embryos were labelled with (/sup 35/S) cysteine in pulse and pulse-chase experiments to study the synthesis and transport of the lectin to protein bodies (PB). The radical, and coleorhiza first accumulated WGA around 10 days post anthesis (DPA), while WGA was found in the epiblast and coleoptile 15 and 20 DPA respectively. At the subcellular level WGA can be seen first in a small developing PB which later fused with larger ones. WGA was distributed evenly throughout the PB. When tissue was pulse-labelled, fractionated on an isopycnic sucrose gradient and exposed to detergent, the incorporated radioactivity of released lectin coincided with the position of the endoplasmic reticulum (ER) marker enzyme NADH-cytochrome c reductase. Both radioactivity and enzyme activity shifted to a higher density in the presence of 2 mM Mg acetate, indicating that radioactive lectin was associated with the rough ER.

  5. Seeding neural progenitor cells on silicon-based neural probes.

    Science.gov (United States)

    Azemi, Erdrin; Gobbel, Glenn T; Cui, Xinyan Tracy

    2010-09-01

    Chronically implanted neural electrode arrays have the potential to be used as neural prostheses in patients with various neurological disorders. While these electrodes perform well in acute recordings, they often fail to function reliably in clinically relevant chronic settings because of glial encapsulation and the loss of neurons. Surface modification of these implants may provide a means of improving their biocompatibility and integration within host brain tissue. The authors proposed a method of improving the brain-implant interface by seeding the implant's surface with a layer of neural progenitor cells (NPCs) derived from adult murine subependyma. Neural progenitor cells may reduce the foreign body reaction by presenting a tissue-friendly surface and repair implant-induced injury and inflammation by releasing neurotrophic factors. In this study, the authors evaluated the growth and differentiation of NPCs on laminin-immobilized probe surfaces and explored the potential impact on transplant survival of these cells. Laminin protein was successfully immobilized on the silicon surface via covalent binding using silane chemistry. The growth, adhesion, and differentiation of NPCs expressing green fluorescent protein (GFP) on laminin-modified silicon surfaces were characterized in vitro by using immunocytochemical techniques. Shear forces were applied to NPC cultures in growth medium to evaluate their shearing properties. In addition, neural probes seeded with GFP-labeled NPCs cultured in growth medium for 14 days were implanted in murine cortex. The authors assessed the adhesion properties of these cells during implantation conditions. Moreover, the tissue response around NPC-seeded implants was observed after 1 and 7 days postimplantation. Significantly improved NPC attachment and growth was found on the laminin-immobilized surface compared with an unmodified control before and after shear force application. The NPCs grown on the laminin-immobilized surface

  6. Fate map of the chicken neural plate at stage 4.

    Science.gov (United States)

    Fernández-Garre, Pedro; Rodríguez-Gallardo, Lucia; Gallego-Díaz, Victoria; Alvarez, Ignacio S; Puelles, Luis

    2002-06-01

    A detailed fate map was obtained for the early chick neural plate (stages 3d/4). Numerous overlapping plug grafts were performed upon New-cultured chick embryos, using fixable carboxyfluorescein diacetate succinimidyl ester to label donor chick tissue. The specimens were harvested 24 hours after grafting and reached in most cases stages 9-11 (early neural tube). The label was detected immunocytochemically in wholemounts, and cross-sections were later obtained. The positions of the graft-derived cells were classified first into sets of purely neural, purely non-neural and mixed grafts. Comparisons between these sets established the neural plate boundary at stages 3d/4. Further analysis categorized graft contributions to anteroposterior and dorsoventral subdivisions of the early neural tube, including data on the floor plate and the eye field. The rostral boundary of the neural plate was contained within the earliest expression domain of the Ganf gene, and the overall shape of the neural plate was contrasted and discussed with regard to the expression patterns of the genes Plato, Sox2, Otx2 and Dlx5 (and others reported in the literature) at stages 3d/4.

  7. Immunocytochemical Localization of Mandelonitrile Lyase in Mature Black Cherry (Prunus serotina Ehrh.) Seeds 1

    Science.gov (United States)

    Wu, Hua-Cheng; Poulton, Jonathan E.

    1991-01-01

    Mandelonitrile lyase (MDL, EC 4.1.2.10), which catalyzes the reversible dissociation of (R)-(+)-mandelonitrile to benzaldehyde and hydrogen cyanide, was purified to apparent homogeneity from mature black cherry (Prunus serotina Ehrh.) seeds by conventional protein purification techniques. This flavoprotein is monomeric with a subunit molecular mass of 57 kilodaltons. Glycoprotein character was shown by its binding to the affinity matrix concanavalin A-Sepharose 4B with subsequent elution by α-methyl-d-glucoside. Upon chemical deglycosylation by trifluoromethanesulfonic acid, the molecular mass was reduced to 50.9 kilodaltons. Two-dimensional gel analysis of deglycosylated MDL revealed the presence of several subunit isoforms of similar molecular mass but differing slightly in isoelectric point. Polyclonal antibodies were raised in New Zealand white rabbits against deglycosylated and untreated MDL. Antibody titers were determined by enzyme linked immunosorbent and dot immunobinding assays, while their specificities were assessed by Western immunoblot analysis. Antibodies raised against untreated lyase recognized several proteins in addition to MDL. In contrast, antisera raised against deglycosylated MDL were monospecific and were utilized for developmental and immunocytochemical localization studies. SDS-PAGE and immunoblotting analysis of seed proteins during fruit maturation showed that MDL first appeared in seeds shortly after cotyledons began development. In cotyledon cells of mature seeds, MDL was localized primarily in the cell wall with lesser amounts in the protein bodies, whereas in endosperm cells, this labeling pattern was reversed. N-terminal sequence data was gathered for future molecular approaches to the question of MDL microheterogeneity. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:16668338

  8. Immunocytochemical studies of chicken somatotrophs and somatotroph granules before and after hatching.

    Science.gov (United States)

    Malamed, S; Gibney, J A; Cain, L D; Perez, F M; Scanes, C G

    1993-05-01

    Immunocytochemical methods were used to gain information about the embryonic development of chicken somatotrophs before and after hatching. To localize growth hormone, anterior pituitary sections were incubated with growth-hormone antibody, and then an indirect peroxidase method was used for light microscopy and an immunogold method for electron microscopy. The earliest evidence of embryonic somatotrophs was seen at 12 days. At this stage somatotrophs were sparse (0.2% of parenchymal cells) and their granules were pleomorphic with elongated ovoid and lozenge shapes predominating. Few of the immunogold-labeled somatotroph granules of the embryo were spherical until 15 days after fertilization. At 18 days, most of the granules were spherical (their shape in the adult chicken). During the six days between the 15-day-old embryo and the 1-day-old chick, the number of gold particles per granule section approximately doubled suggesting an increase in growth hormone content of the granules. This rise was the result of increases in the size of the granule sections and in the concentration of gold particles in the sections. During the embryonic period of 12-20 days, somatotrophs were not more than 3.6% of the anterior pituitary cell population. During the following two days, between the 20-day-old embryo and the 1-day-old chick, the percentage of somatotrophs in the pituitary parenchymal cell population rose rapidly from 3.6% to 20.7% and then increased slowly to 24.6% during the period of 1-5 days after hatching.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Expression of E-cadherin and involucrin in leukoplakia and oral cancer: an immunocytochemical and immunohistochemical study

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    Alessandra Dutra da SILVA

    2017-03-01

    Full Text Available Abstract To assess the immunocytochemical and immunohistochemical correlation of adhesion (E-cadherin and cell differentiation (involucrin molecules in oral leukoplakia and oral squamous cell carcinoma. Cytological samples and biopsies were obtained from male and female patients aged over 30 years with oral leukoplakia (n = 30 and oral squamous cell carcinoma (n = 22. Cell scrapings and the biopsy were performed at the site of the lesion and histological slides were prepared for the immunocytochemical analysis of exfoliated oral mucosal cells and for the immunohistochemical analysis of biopsy tissues using E-cadherin and involucrin. Spearman’s correlation and kappa coefficients were used to assess the correlation and level of agreement between the techniques. Immunostaining for E-cadherin and involucrin by both techniques was similar in the superficial layers of the histological sections compared with cell scrapings. However, there was no statistical correlation and agreement regarding the immunocytochemical and immunohistochemical expression of E-cadherin and involucrin in oral leukoplakia (R = 0.01, p = 0.958 (Kappa = 0.017, p = 0.92 or in oral squamous cell carcinoma (R = 0.26, p = 0.206 (Kappa = 0.36, p = 0.07. The immunoexpression of E-cadherin and involucrin in tissues is consistent with the expression patterns observed in exfoliated oral mucosal cells, despite the lack of a statistically significant correlation. There is an association of the histopathological characteristics of leukoplakia with the expression E-cadherin and of the microscopic aspects of oral squamous cell carcinoma with immunohistochemical expression of involucrin.

  10. Expression of E-cadherin and involucrin in leukoplakia and oral cancer: an immunocytochemical and immunohistochemical study.

    Science.gov (United States)

    Silva, Alessandra Dutra da; Maraschin, Bruna Jalfim; Laureano, Natalia Koerich; Daroit, Natália; Brochier, Fernanda; Bündrich, Leonardo; Visioli, Fernanda; Rados, Pantelis Varvaki

    2017-03-06

    To assess the immunocytochemical and immunohistochemical correlation of adhesion (E-cadherin) and cell differentiation (involucrin) molecules in oral leukoplakia and oral squamous cell carcinoma. Cytological samples and biopsies were obtained from male and female patients aged over 30 years with oral leukoplakia (n = 30) and oral squamous cell carcinoma (n = 22). Cell scrapings and the biopsy were performed at the site of the lesion and histological slides were prepared for the immunocytochemical analysis of exfoliated oral mucosal cells and for the immunohistochemical analysis of biopsy tissues using E-cadherin and involucrin. Spearman's correlation and kappa coefficients were used to assess the correlation and level of agreement between the techniques. Immunostaining for E-cadherin and involucrin by both techniques was similar in the superficial layers of the histological sections compared with cell scrapings. However, there was no statistical correlation and agreement regarding the immunocytochemical and immunohistochemical expression of E-cadherin and involucrin in oral leukoplakia (R = 0.01, p = 0.958) (Kappa = 0.017, p = 0.92) or in oral squamous cell carcinoma (R = 0.26, p = 0.206) (Kappa = 0.36, p = 0.07). The immunoexpression of E-cadherin and involucrin in tissues is consistent with the expression patterns observed in exfoliated oral mucosal cells, despite the lack of a statistically significant correlation. There is an association of the histopathological characteristics of leukoplakia with the expression E-cadherin and of the microscopic aspects of oral squamous cell carcinoma with immunohistochemical expression of involucrin.

  11. 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.

  12. Single-cell RT-PCR and immunocytochemical detection of mechanosensitive transient receptor potential channels in acutely isolated rat odontoblasts.

    Science.gov (United States)

    Kwon, Minsoo; Baek, Sang Hoon; Park, Chul-Kyu; Chung, Gehoon; Oh, Seog Bae

    2014-12-01

    Hydrostatic force applied to tooth pulp has long been suspected to be the direct cause of dental pain. However, the molecular and cellular identity of the transducer of the mechanical force in teeth is not clear. Growing number of literatures suggested that odontoblasts, secondary to its primary role as formation of tooth structure, might function as a cellular mechanical transducer in teeth. In order to determine whether odontoblasts could play a crucial role in transduction of hydrostatic force applied to dental pulp into electrical impulses, current study investigated the expression of stretch-activated transient receptor potential (TRP) channels in acutely isolated odontoblasts from adult rats by single cell reverse transcriptase polymerase chain reaction and immunocytochemical analysis. As the result, expression of TRPM7 (melastatin 7) was observed in majority (87%) of odontoblasts while mRNAs for TRPC1 (canonical 1), TRPC6 (canonical 6) and TRPV4 (vanilloid 4) were detected in small subpopulations of odontoblasts. TRPM3 (melastatin 3) was not detected in our experimental set-up. Immunocytochemical analysis further revealed TRPM7 expression at protein level. Expression of the mechanosensitive TRP channels provides additional evidence that supports the sensory roles of odontoblasts. Given that TRPM7 is a mechanosensitive ion channel with a kinase activity that plays a role in Mg(2+) homeostasis, it is possible that TRPM7 expressed in odontoblasts might play a central role in mineralization during dentin formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Purification, properties, and immunocytochemical localization of human liver peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase.

    Science.gov (United States)

    Reddy, M K; Usuda, N; Reddy, M N; Kuczmarski, E R; Rao, M S; Reddy, J K

    1987-01-01

    A molecular understanding of genetic disease in which peroxisomal functions are impaired depends on analysis of the structure of normal and mutant enzymes of peroxisomes. We report experiments describing the isolation, characterization, and immunocytochemical localization of enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme (PBE) of the peroxisomal fatty acid beta-oxidation system from normal human liver and compared it with that of rat liver enzyme. The human enzyme, purified approximately equal to 2300-fold by ion-exchange chromatography, is homogeneous as judged by NaDodSO4/PAGE. This PBE is localized exclusively in the matrix of peroxisomes in liver cells by the protein A/gold immunocytochemical method. The human PBE is similar to rat enzyme in size (Mr, approximately equal to 79,000), isoelectric point (pI, 9.8), pH optima, molecular structure as observed by rotary shadowing, and peptide pattern on NaDodSO4/PAGE after proteolytic digestion with Staphylococcus aureus V8 protease. The human and rat enzymes differed in their immunological properties by having partial identity with each other; this is reflected in their slightly dissimilar composition of the amino acids aspartic acid, threonine, glutamic acid, tyrosine, and glycine. COOH-terminal amino acid were similar for both the enzymes: -Gly-Ser-Leu-Ile-COOH. These results suggest that the human and rat liver PBE may be different in their amino acid sequences at their antigenic sites. Images PMID:3106963

  14. Combined use of immunocytochemical techniques and ligand-gold complexes for investigation of platelet membrane responses to surface activation.

    Science.gov (United States)

    Escolar, G; White, J G

    1994-07-01

    Exposure of blood platelets to foreign surfaces results in dramatic changes in physical appearance and conversion from a non-sticky to an adhesive state. Membrane glycoproteins and cytoskeletal assembly play a pivotal role in these interactions. Cytochemical techniques commonly applied for demonstration of macromolecules in tissues have been used for the localization of target glycoproteins on spread cells. The present review examines different experimental strategies and immunocytochemical techniques that can be combined to better understand the organization of platelet receptors during surface activation. Glycoprotein IIb-IIIa (GPIIb-IIIa) was localized by immunocytochemical techniques on fixed, surface-activated platelets. The distribution of functional fibrinogen receptors expressed on GPIIb-IIIa was revealed by incubation of fixed platelets with fibrinogen-gold conjugates (Fgn/Au). The movement of receptor complexes was investigated in additional experiments in which surface-activated platelets were interacted with Fgn/Au and then fixed at different periods. The overall impression of these observations suggests that fibrinogen receptors on surface-activated platelets do not redistribute spontaneously and that particulates (gold particles), rather than fibrinogen, may trigger the movement. These results are presented in detail and their significance discussed in the light of current theory. Applications and limitations of such techniques are also discussed.

  15. Smooth muscle cells can express cytokeratins of "simple" epithelium. Immunocytochemical and biochemical studies in vitro and in vivo.

    Science.gov (United States)

    Gown, A M; Boyd, H C; Chang, Y; Ferguson, M; Reichler, B; Tippens, D

    1988-08-01

    Cytokeratins are a set of 19 proteins that together constitute the class of intermediate filament protein expressed by epithelial cells and tumors. Using a panel of 9 different monoclonal anti-cytokeratin antibodies, the authors have performed immunocytochemistry on methanol-fixed, frozen sections and methacarn-fixed, paraffin-embedded tissue of human myometrial specimens. Anomalous cytokeratin expression (ACE) by smooth muscle cells was found in all specimens. Immunoblots of this tissue confirmed the presence of cytokeratin 19, and possibly 8. In addition, immunocytochemical studies demonstrated ACE in human fetal tissues within the intestinal muscularis and the heart, especially in the region of the aortic outflow tract, and in 8 of 19 cases of leiomyosarcoma from adults. Indirect immunofluorescence studies were also performed on cells explanted from myometrial tissue; the overwhelming majority of cells derived from these cultures were smooth muscle cells as verified by expression of muscle actins, and a subpopulation of these cells was found to be cytokeratin-positive. ACE was confirmed in vitro by double labeling experiments demonstrating simultaneous expression of muscle actins and cytokeratins within the same cell. The significance of this smooth muscle cell ACE is unknown, but it may be a phenotypic marker of smooth muscle in a proliferative state. ACE could be a source of confusion in the immunocytochemical analysis of poorly differentiated malignancies if a complete panel of antibodies is not employed.

  16. 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

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    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.

  17. Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.

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    Andreas Androutsellis-Theotokis

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  18. Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus).

    Science.gov (United States)

    Aoki, N; Yamaguchi, S; Kitajima, T; Takehara, A; Katagiri-Nakagawa, S; Matsui, R; Watanabe, D; Matsushima, T; Homma, K J

    2015-11-12

    Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Effects of rehabilitation training on apoptosis of nerve cells and the recovery of neural and motor functions in rats with ischemic stroke through the PI3K/Akt and Nrf2/ARE signaling pathways.

    Science.gov (United States)

    Jin, Xiao-Fei; Wang, Shan; Shen, Min; Wen, Xin; Han, Xin-Rui; Wu, Jun-Chang; Tang, Gao-Zhuo; Wu, Dong-Mei; Lu, Jun; Zheng, Yuan-Lin

    2017-09-01

    This study was designed in order to investigate the effects between rehabilitation training on the apoptosis of nerve cells and the recovery of neural and motor functions of rats with ischemic stroke by way of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and nuclear factor E2-related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathways. In total, 110 healthy adult male Sprague-Dawley (SD) rats were selected in order to take part in this study. Ninety SD rats were used in order to establish the middle cerebral artery occlusion (MCAO), among which 80 rats were randomly assigned as part of the natural recovery, natural recovery+Rp-PI3K (the rats injected with PI3K/Akt inhibitor LY294002), rehabilitation training, and rehabilitation training+Rp-PI3K groups. Meanwhile, 20 rats were selected as part of the sham operation group. The neural and motor functions of these rats were evaluated using a balance beam test and the Bederson score. The mRNA expressions of PI3K, Akt, Nrf2 and HO-1 were measured using an RT-qPCR. The protein expressions of PI3K, p-PI3K, Akt, p-Akt, Nrf2 and HO-1 were also detected by using western blotting and the immunohistochemistry process. The cell cycle and cell apoptosis were detected by using a flow cytometry and TUNEL assay. The sham operation group exhibited lower neural and motor function scores than other groups. At the 7, 14, and 21 d marks of this study, the neural and motor function scores were increased in the natural recovery, natural recovery+Rp-PI3K, and rehabilitation training+Rp-PI3K groups in comparison with the rehabilitation training group but found to be decreased in the natural recovery group in comparison with the natural recovery+Rp-PI3K group. In comparison with the sham operation group, expressions of PI3K, Nrf2 and HO-1, and proportions of p-PI3K/PI3K and p-Akt/Akt were all higher in the natural recovery, rehabilitation training, and rehabilitation training+Rp-PI3K groups. Same trends were

  20. Lithium Suppresses Astrogliogenesis by Neural Stem and Progenitor Cells by Inhibiting STAT3 Pathway Independently of Glycogen Synthase Kinase 3 Beta

    Science.gov (United States)

    Zhu, Zhenzhong; Kremer, Penny; Tadmori, Iman; Ren, Yi; Sun, Dongming; He, Xijing; Young, Wise

    2011-01-01

    Transplanted neural stem and progenitor cells (NSCs) produce mostly astrocytes in injured spinal cords. Lithium stimulates neurogenesis by inhibiting GSK3b (glycogen synthetase kinase 3-beta) and increasing WNT/beta catenin. Lithium suppresses astrogliogenesis but the mechanisms were unclear. We cultured NSCs from subventricular zone of neonatal rats and showed that lithium reduced NSC production of astrocytes as well as proliferation of glia restricted progenitor (GRP) cells. Lithium strongly inhibited STAT3 (signal transducer and activator of transcription 3) activation, a messenger system known to promote astrogliogenesis and cancer. Lithium abolished STAT3 activation and astrogliogenesis induced by a STAT3 agonist AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), suggesting that lithium suppresses astrogliogenesis by inhibiting STAT3. GSK3β inhibition either by a specific GSK3β inhibitor SB216763 or overexpression of GID5-6 (GSK3β Interaction Domain aa380 to 404) did not suppress astrogliogenesis and GRP proliferation. GSK3β inhibition also did not suppress STAT3 activation. Together, these results indicate that lithium inhibits astrogliogenesis through non-GSK3β-mediated inhibition of STAT. Lithium may increase efficacy of NSC transplants by increasing neurogenesis and reducing astrogliogenesis. Our results also may explain the strong safety record of lithium treatment of manic depression. Millions of people take high-dose (>1 gram/day) lithium carbonate for a lifetime. GSK3b inhibition increases WNT/beta catenin, associated with colon and other cancers. STAT3 inhibition may reduce risk for cancer. PMID:21931595

  1. The cell division control protein 42-Src family kinase-neural Wiskott-Aldrich syndrome protein pathway regulates human proplatelet formation.

    Science.gov (United States)

    Palazzo, A; Bluteau, O; Messaoudi, K; Marangoni, F; Chang, Y; Souquere, S; Pierron, G; Lapierre, V; Zheng, Y; Vainchenker, W; Raslova, H; Debili, N

    2016-12-01

    Essentials The role of the cytoskeleton during megakaryocyte differentiation was examined. Human megakaryocytes are derived from in vitro cultured CD34(+) cells. Cell division control protein 42 (CDC42) positively regulates proplatelet formation (PPF). Neural Wiskott-Aldrich syndrome protein, the main effector of CDC42 with Src positively regulates PPF. Background Cytoskeletal rearrangements are essential for platelet release. The RHO small GTPase family, as regulators of the actin cytoskeleton, play an important role in proplatelet formation (PPF). In the neuronal system, CDC42 is involved in axon formation, a process that combines elongation and branching as for PPF. Objective To analyze the role of CDC42 and its effectors of the Wiskott-Aldrich syndrome protein (WASP) family in PPF. Methods Human megakaryocytes (MKs) were obtained from CD34(+) cells. Inhibition of CDC42 in MKs was performed with the chemical inhibitor CASIN or with an active or a dominant-negative form of CDC42. The knock-down of N-WASP was obtained with a small hairpin RNA strategy Results Herein, we show that CDC42 activity increased during MK differentiation. The use of the chemical inhibitor CASIN or of an active or a dominant-negative form of CDC42 demonstrated that CDC42 positively regulated PPF in vitro. We determined that N-WASP, but not WASP, regulated PPF. We found that N-WASP knockdown led to a marked decrease in PPF, owing to a defect in the demarcation membrane system (DMS). This was associated with RHOA activation, and a concomitant augmentation in the phosphorylation of mysosin light chain 2. Phosphorylation of N-WASP, creating a primed form of N-WASP, increased during MK differentiation. Phosphorylation inhibition by two Src family kinase inhibitors decreased PPF. Conclusions We conclude that N-WASP positively regulates DMS development and PPF, and that the Src family kinases in association with CDC42 regulate PPF through N-WASP. © 2016 International Society on Thrombosis and

  2. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

    Directory of Open Access Journals (Sweden)

    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  3. A simple cost-effective modification improves the quality of immunocytochemical staining in cervical scrape samples characterized by presence of excess mucus

    OpenAIRE

    Pawar, Sagar; Mahantshetty, Umesh; Deodhar, Kedar; Teni, Tanuja

    2014-01-01

    Immunocytochemistry (ICC) is a very important tool in a diverse range of biomedical research as well as in diagnostic cytopathology. Smears prepared from cervical scrapes contain a large amount of overlying mucus that interferes with the standard immunocytochemical staining protocol. A modified ICC protocol is described, which involves pretreatment of these smears with 1 mg/ml solution of Ambroxol hydrochloride in methanol for 1 hour. Source of Ambroxol hydrochloride was a 30 mg Mucolite? tab...

  4. Brush cytology with immunocytochemical evaluation of VEGF expression versus biopsy in clinically precancerous laryngeal lesions: can we diagnose laryngeal cancer only with brush cytology?

    Science.gov (United States)

    Chatziavramidis, Angelos; Tsinaslanidou, Zinovia; Valeri, Rozalia; Konstantinidis, Iordanis; Constantinidis, Jannis

    2015-01-01

    Introduction. Laryngeal squamous cell carcinoma (LSCC) is the most common SCC of the head and neck. The high incidence of this malignancy and the low survival rate necessitate the development of novel diagnostic approaches. Aim of this study is to compare the diagnostic value of laryngeal brush cytology combined with VEGF immunocytochemistry versus histopathology of clinically precancerous lesions of the larynx. Material and Methods. Thirty patients with precancerous or suspected malignant laryngeal lesions underwent microlaryngoscopy, during which samples were taken for cytological, immunocytochemical, and histological analysis. Cytology and histology results were classified as follows: benign lesions, atypia/moderate dysplasia, and malignancy, whereas the expression of VEGF was evaluated as strong, moderate, weak, and zero expression, based on the percentage of cells stained. Results. The cytology results were in accordance with the histology results in 86.7% of the patients. The exfoliative cytology's sensitivity was estimated at 85% and its specificity at 90%. Its positive prognostic value was 94%, while its negative prognostic value was 75%. The additional immunocytochemical evaluation of VEGF expression increased all the noted parameters. Discussion. Exfoliative cytology of laryngeal lesions is a minimal-invasive, easily applicable procedure during microlaryngoscopy and reliable in terms of diagnostic value. Under certain conditions it could be held also in local anesthesia. Concurrent immunocytochemical analysis of VEGF expression further enhances its diagnostic value.

  5. Brush Cytology with Immunocytochemical Evaluation of VEGF Expression versus Biopsy in Clinically Precancerous Laryngeal Lesions: Can We Diagnose Laryngeal Cancer Only with Brush Cytology?

    Directory of Open Access Journals (Sweden)

    Angelos Chatziavramidis

    2015-01-01

    Full Text Available Introduction. Laryngeal squamous cell carcinoma (LSCC is the most common SCC of the head and neck. The high incidence of this malignancy and the low survival rate necessitate the development of novel diagnostic approaches. Aim of this study is to compare the diagnostic value of laryngeal brush cytology combined with VEGF immunocytochemistry versus histopathology of clinically precancerous lesions of the larynx. Material and Methods. Thirty patients with precancerous or suspected malignant laryngeal lesions underwent microlaryngoscopy, during which samples were taken for cytological, immunocytochemical, and histological analysis. Cytology and histology results were classified as follows: benign lesions, atypia/moderate dysplasia, and malignancy, whereas the expression of VEGF was evaluated as strong, moderate, weak, and zero expression, based on the percentage of cells stained. Results. The cytology results were in accordance with the histology results in 86.7% of the patients. The exfoliative cytology’s sensitivity was estimated at 85% and its specificity at 90%. Its positive prognostic value was 94%, while its negative prognostic value was 75%. The additional immunocytochemical evaluation of VEGF expression increased all the noted parameters. Discussion. Exfoliative cytology of laryngeal lesions is a minimal-invasive, easily applicable procedure during microlaryngoscopy and reliable in terms of diagnostic value. Under certain conditions it could be held also in local anesthesia. Concurrent immunocytochemical analysis of VEGF expression further enhances its diagnostic value.

  6. Neural crest contributions to the lamprey head

    Science.gov (United States)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

    The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.

  7. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  8. Immuno-cytochemical localization of indole-3-acetic acid during induction of somatic embryogenesis in cultured sunflower embryos.

    Science.gov (United States)

    Thomas, Clément; Bronner, Roberte; Molinier, Jean; Prinsen, Els; van Onckelen, Harry; Hahne, Günther

    2002-08-01

    Immature zygotic embryos of sunflower (Helianthus annuus L.) produce somatic embryos when cultured on medium supplemented with a cytokinin as the sole source of exogenous growth regulators. The timing of the induction phase and subsequent morphogenic events have been well characterized in previous work. We address here the question of the role of endogenous indole-3-acetic acid (IAA), since auxins are known to have a crucial role in the induction of somatic embryogenesis in many other culture and regeneration systems. The fact that in the sunflower system no exogenous auxin is required for the induction of somatic embryos makes this system very suitable for the study of the internal dynamics of IAA. We used an immuno-cytochemical approach to visualize IAA distribution within the explants before, during and after the induction phase. IAA accumulated transiently throughout cultured embryos during the induction phase. The detected signal was not uniform but certain tissues, such as the root cap and the root meristem, accumulated IAA in a more pronounced manner. IAA accumulation was not restricted to the reactive zone but the kinetics of endogenous variations strikingly mimic the pulse of IAA that is usually provoked by exogenous IAA application. The direct evidence presented here indicates that an endogenous auxin pulse is indeed among the first signals leading to the induction of somatic embryogenesis.

  9. Immunocytochemical detection of dentin matrix proteins in primary teeth from patients with dentinogenesis imperfecta associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    G. Orsini

    2014-10-01

    Full Text Available Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohistochemical analysis was used to assay Type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I associated with osteogenesis imperfecta (OI. In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05. Expressions of dentin matrix protein (DMP-1 and osteopontin (OPN were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immunolabeling for chondroitin sulfate (CS and biglycan (BGN was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultrastructural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins.

  10. Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology.

    Science.gov (United States)

    Oda, Tomohiro; Ogata, Sho; Kawaguchi, Saki; Minabe, Shinya; Dokyu, Misaki; Takahashi, Hiromi; Kumazawa, Fumihiko; Shimazaki, Hideyuki; Takano, Masashi; Hase, Kazuo; Ozeki, Yuichi; Kanoh, Soichiro; Nakanishi, Kuniaki

    2016-06-01

    Recently, claudin-4 (CL4) immunocytochemistry was reported to be useful for differential diagnosis in effusion cytology. We wondered whether CL4 might be useful for "single-shot" identification of metastatic carcinoma. The purpose of this study was to evaluate the usefulness of CL4 in effusion cytology. In total, 266 cases (169 metastatic carcinomas, eight malignant mesotheliomas, and 89 reactive mesothelial cells) were selected. Immunocytochemical examinations of cell-block sections were performed for CL4, Ber-EP4, and MOC-31. We used an arbitrary 4-tiered scale based on both staining intensity and positive-cell percentage among all target cells, and calculated a staining index score (sum of the above two scores). In a ROC-curve analysis, higher area-under-curve values were found for CL4 than for Ber-EP4 or MOC-31 (0.982, 0.942, and 0.926, respectively). Since CL4 exhibited similar or superior usefulness to Ber-EP4 and MOC-31, it could become the first choice for the above differential diagnosis in effusion cytology. Diagn. Cytopathol. 2016;44:499-504. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Immunocytochemical Detection of Dentin Matrix Proteins in Primary Teeth from Patients with Dentinogenesis Imperfecta Associated with Osteogenesis Imperfecta

    Science.gov (United States)

    Orsini, G.; Majorana, A.; Mazzoni, A.; Putignano, A.; Falconi, M.; Polimeni, A.; Breschi, L.

    2014-01-01

    Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohisto-chemical analysis was used to assay type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I) associated with osteogenesis imperfecta (OI). In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05). Expressions of dentin matrix protein-1 (DMP1) and osteopontin (OPN) were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immuno labeling for chondroitin sulfate (CS) and biglycan (BGN) was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultra-structural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins. PMID:25578972

  12. Reciprocal Neural Pathways and Associative Networks.

    Science.gov (United States)

    1982-12-15

    is that newly-born humans may have as much as 8 hours of REM sleep per day . There is also evidence to suggest that in the womb , especially in the...manner. Any purely psychological theory is hard pressed to explain the large amount of REM sleep in the womb , and any purely developmental theory must...useful for artificial intelligence machines of the future, especially those having extensive parallel processing, a learning mechanism and a certain amount

  13. 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...

  14. Sensing deep extreme environments: the receptor cell types, brain centers, and multi-layer neural packaging of hydrothermal vent endemic worms.

    Science.gov (United States)

    Shigeno, Shuichi; Ogura, Atsushi; Mori, Tsukasa; Toyohara, Haruhiko; Yoshida, Takao; Tsuchida, Shinji; Fujikura, Katsunori

    2014-01-01

    Deep-sea alvinellid worm species endemic to hydrothermal vents, such as Alvinella and Paralvinella, are considered to be among the most thermotolerant animals known with their adaptability to toxic heavy metals, and tolerance of highly reductive and oxidative stressful environments. Despite the number of recent studies focused on their overall transcriptomic, proteomic, and metabolic stabilities, little is known regarding their sensory receptor cells and electrically active neuro-processing centers, and how these can tolerate and function in such harsh conditions. We examined the extra- and intracellular organizations of the epidermal ciliated sensory cells and their higher centers in the central nervous system through immunocytochemical, ultrastructural, and neurotracing analyses. We observed that these cells were rich in mitochondria and possessed many electron-dense granules, and identified specialized glial cells and serial myelin-like repeats in the head sensory systems of Paralvinella hessleri. Additionally, we identified the major epidermal sensory pathways, in which a pair of distinct mushroom bodies-like or small interneuron clusters was observed. These sensory learning and memory systems are commonly found in insects and annelids, but the alvinellid inputs are unlikely derived from the sensory ciliary cells of the dorsal head regions. Our evidence provides insight into the cellular and system-wide adaptive structure used to sense, process, and combat the deep-sea hydrothermal vent environment. The alvinellid sensory cells exhibit characteristics of annelid ciliary types, and among the most unique features were the head sensory inputs and structure of the neural cell bodies of the brain, which were surrounded by multiple membranes. We speculated that such enhanced protection is required for the production of normal electrical signals, and to avoid the breakdown of the membrane surrounding metabolically fragile neurons from oxidative stress. Such pivotal

  15. 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.

  16. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  17. The Neural Crest in Cardiac Congenital Anomalies

    Science.gov (United States)

    Keyte, Anna; Hutson, Mary Redmond

    2012-01-01

    This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions. PMID:22595346

  18. Establishing a protocol for immunocytochemical staining and chromogenic in situ hybridization of Giemsa and Diff-Quick prestained cytological smears

    Directory of Open Access Journals (Sweden)

    Elsa Beraki

    2012-01-01

    Full Text Available Background: Protocols for immunocytochemical staining (ICC and in situ hybridization (ISH of air-dried Diff-Quick or May-Grünwald Giemsa (MGG-stained smears have been difficult to establish. An increasing need to be able to use prestained slides for ICC and ISH in specific cases led to this study, aiming at finding a robust protocol for both methods. Materials and Methods: The material consisted of MGG- and Diff-Quick-stained smears. After diagnosis, one to two diagnostic smears were stored in the department. Any additional smear(s containing diagnostic material were used for this study. The majority were fine needle aspirates (FNAC from the breast, comprising materials from fibroadenomas, fibrocystic disease, and carcinomas. A few were metastatic lesions (carcinomas and malignant melanomas. There were 64 prestained smears. Ten smears were Diff-Quick stained, and 54 were MGG stained. The antibodies used for testing ICC were Ki-67, ER, and PgR, CK MNF116 (pancytokeratin and E-cadherin. HER-2 Dual SISH was used to test ISH. Citrate, TRS, and TE buffers at pH6 and pH9 were tested, as well as, different heating times, microwave powers and antibody concentrations. The ICC was done on the Dako Autostainer (Dako®, Glostrup, Denmark, and HER-2 Dual SISH was done on the Ventana XT-machine (Ventana / Roche® , Strasbourg, France. Results: Optimal results were obtained with the TE buffer at pH 9, for both ICC and ISH. Antibody concentrations generally had to be higher than in the immunohistochemistry (IHC. The optimal microwave heat treatment included an initial high power boiling followed by low power boiling. No post fixation was necessary for ICC, whereas, 20 minutes post fixation in formalin (4% was necessary for ISH. Conclusions: Microwave heat treatment, with initial boiling at high power followed by boiling at low power and TE buffer at pH 9 were the key steps in the procedure. Antibody concentrations has to be adapted for each ICC marker. Post

  19. Immunocytochemical staining of endogenous nuclear proteins with the HIS-1 anti-poly-histidine monoclonal antibody: a potential source of error in His-tagged protein detection.

    Science.gov (United States)

    Chilumuri, Amrutha; Markiv, Anatoliy; Milton, Nathaniel G N

    2014-07-01

    Histidine-tagged proteins are widely used in biochemical studies and frequently detected with antibodies specific for the histidine tag. Immunocytochemistry is widely used in studies with overexpressed proteins to determine cellular localization and in the case of histidine-tagged proteins can be carried out with anti-polyhistidine antibodies. Recent studies have suggested that polyhistidine sequences are present within a small number of human proteins and may direct expression to the nucleus and nuclear speckles compartments of the cell. In this study immunocytochemical staining of human SH-SY5Y neuroblastoma cell lines with the HIS-1 anti-polyhistidine monoclonal antibody were determined. Results showed that the HIS-1 anti-polyhistidine monoclonal antibody stained endogenous nuclear proteins in SH-SY5Y cells. The stained proteins were contained within the nuclear membrane, but were not directly linked to DNA. In a histidine-tagged catalase overexpressing cell line the HIS-1 anti-polyhistidine monoclonal antibody showed nuclear staining, whilst staining with the CAT-505 anti-catalase monoclonal antibody showed primarily cytoplasmic staining. These results suggest that anti-polyhistidine antibody staining shows significant cross-reactivity with endogenous nuclear proteins in SH-SY5Y neuroblastoma cells and may not be suitable for localization studies of histidine-tagged proteins. Immunocytochemical studies with anti-polyhistidine antibodies and localization of histidine-tagged proteins must be confirmed with protein specific antibodies or other methodology. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Neural Tube Defects

    Science.gov (United States)

    ... vitamin, before and during pregnancy prevents most neural tube defects. Neural tube defects are usually diagnosed before the infant is ... or imaging tests. There is no cure for neural tube defects. The nerve damage and loss of function ...

  1. [Neural repair].

    Science.gov (United States)

    Kitada, Masaaki; Dezawa, Mari

    2008-05-01

    Recent progress of stem cell biology gives us the hope for neural repair. We have established methods to specifically induce functional Schwann cells and neurons from bone marrow stromal cells (MSCs). The effectiveness of these induced cells was evaluated by grafting them either into peripheral nerve injury, spinal cord injury, or Parkinson' s disease animal models. MSCs-derived Schwann cells supported axonal regeneration and re-constructed myelin to facilitate the functional recovery in peripheral and spinal cord injury. MSCs-derived dopaminergic neurons integrated into host striatum and contributed to behavioral repair. In this review, we introduce the differentiation potential of MSCs and finally discuss about their benefits and drawbacks of these induction systems for cell-based therapy in neuro-traumatic and neuro-degenerative diseases.

  2. [IMMUNOCYTOCHEMICAL ANALYSIS OF THE DISTURBANCES IN THE STRUCTURE OF SYNAPTONEMAL COMPLEXES IN SPERMATOCYTE NUCLEI IN MICE UNDER EXPOSURE TO ROCKET FUEL COMPONENT].

    Science.gov (United States)

    Lovinskaya, A V; Kolumbayeva, S Zh; Abilev, S K; Kolomiets, O L

    2016-01-01

    There was performed an assessment of genotoxic effects of rocket fuel component--unsymmetrical dimethylhydrazine (UDMH, heptyl)--on forming germ cells of male mice. Immunocytochemically there was studied the structure of meiotic nuclei at different times after the intraperitoneal administration of UDMH to male mice. There were revealed following types of disturbances of the structure of synaptonemal complexes (SCs) of meiotic chromosomes: single and multiple fragments of SCs associations of autosomes with a sex bivalent, atypical structure of the SCs with a frequency higher than the reference level. In addition, there were found the premature desinapsis of sex bivalents, the disorder offormation of the genital corpuscle and ring SCs. Established disorders in SCs of spermatocytes, analyzed at 38th day after the 10-days intoxication of animal by the component of rocket fuel, attest to the risk of permanent persistence of chromosomal abnormalities occurring in the pool of stem cells.

  3. Metastatic colorectal adenocarcinoma in cervicovaginal cytology specimens confirmed by immunocytochemical stains on liquid base specimens: Two study cases with review of the literature

    Directory of Open Access Journals (Sweden)

    Muhammad Zulfiqar

    2013-01-01

    Full Text Available Only a few cases of adenocarcinoma (ACA metastatic to the female lower genital tract diagnosed on cervicovaginal Pap smear have been reported during the past several decades. Both conventional and liquid based cytology (LBC have limited sensitivity and specificity in diagnosing metastatic disease and immunocytochemical (ICC staining may be needed for confirming the diagnosis. We present two cases of metastatic colorectal ACA diagnosed on cervicovaginal ThinPrep (TP Pap smears, with one confirmed by ICC staining method. Recognition of extra-uterine malignancy in the cervicovaginal cytology specimen is critical for the disease diagnosis, prognosis, and the treatment. ICC staining performed on the residual LBC specimen is an important methodology to confirm the diagnosis.

  4. A simple cost-effective modification improves the quality of immunocytochemical staining in cervical scrape samples characterized by presence of excess mucus

    Science.gov (United States)

    Pawar, Sagar; Mahantshetty, Umesh; Deodhar, Kedar; Teni, Tanuja

    2014-01-01

    Immunocytochemistry (ICC) is a very important tool in a diverse range of biomedical research as well as in diagnostic cytopathology. Smears prepared from cervical scrapes contain a large amount of overlying mucus that interferes with the standard immunocytochemical staining protocol. A modified ICC protocol is described, which involves pretreatment of these smears with 1 mg/ml solution of Ambroxol hydrochloride in methanol for 1 hour. Source of Ambroxol hydrochloride was a 30 mg Mucolite™ tablet, at a cost of 1.70 rupees (∼3·5 US cents) per tablet. This mucolytic solution effectively clears the mucus, facilitating the accessibility of the antibody to the antigenic determinants. This pretreatment resulted in the increased percentage of positively stained cells as well as staining intensity, leading to improved overall ICC staining and score. This is a novel modification that can be cost-effectively applied in ICC staining protocols for cytology samples characterized by the presence of excess mucus. PMID:25620823

  5. A comparative immunocytochemical study using an antiserum against a synthetic analogue of the corpora cardiaca peptide Pea-CAH-I (MI, neurohormone D) of Periplaneta americana.

    Science.gov (United States)

    Eckert, M; Gabriel, J; Birkenbeil, H; Greiner, G; Rapus, J; Gäde, G

    1996-06-01

    An antiserum against the octapeptide Pea-CAH-I, a member of the adipokinetic hormone/red pigment-concentrating hormone family, has been produced for immunocytochemical staining in insects and various other invertebrate species. The anti-Pea-CAH-I serum stains the glandular corpora cardiaca cells of those insect species that synthesize identical or structurally similar peptides. In the corpora cardiaca of species producing peptides with a different C-terminus, these cells remain unstained. Pea-CAH-I-like immunoreactivity has also been found in neurons of the central nervous system of all invertebrate orders studied. The antiserum recognizes the C-terminal sequence Pro-Asn-Trp-NH2 of the Pea-CAH-I molecule as established by enzyme immunoassay. The widespread Pea-CAH-I-like immunoreactivity in all nervous systems of the studied animals probably does not reflect the presence of Pea-CAH-I but the occurrence of peptides carrying similar epitopes.

  6. Evaluation of double immunocytochemical staining for CK20 and P53 as a potential adjunct to cytology for urothelial cancer diagnosis.

    Science.gov (United States)

    Lenos, M; Katafigiotis, I; Vrettou, K; Papaioannou, D; Malta, F; Trigka, E-A; Sousouris, S; Constantinides, C; Mikou, P

    2017-04-01

    To evaluate double immunocytochemical staining with p53 and CK20, as a tool for improving the accuracy of urinary cytology. The aim of the present study was to clarify the diagnostic significance of the expression of these markers and to investigate the possibility of using this information for better monitoring of bladder cancer patients during follow-up. One hundred and twenty-five urine cytology cases were retrieved with corresponding histology from our files. One ThinPrep® smear was available for each of them and dual immunocytological staining for p53 and CK20 was performed. Eleven cases were excluded from the study because of hypocellularity. The material comprised 58 malignant, 36 atypical and 20 negative for malignancy cases. Immunocytochemistry was evaluated by two cytopathologists, blinded to the histological diagnosis or follow-up data. A cut-off threshold of five stained atypical cells, according to the literature, was used for evaluation. Fifty-two out of 58 malignant cases were positive for at least one of the markers (89.6%). In the atypical and negative groups, 18 (50%) and 5 (25%) cases were positive, respectively. Accuracy parameters evaluation for cytology versus the combination of cytology with immunocytological staining were: sensitivity 73.4% versus 91.1%, specificity 100% versus 74.3%, positive predictive value (PPV) 100% versus 88.9% and negative predictive value (NPV) 62.5% versus 78.8%. Double immunocytochemical staining for p53 and CK20 is easy to perform and evaluate and can improve cytology sensitivity. It is helpful in establishing a diagnosis of malignancy and may be used as a triage tool to select patients that require cystoscopy during clinical follow-up. © 2016 John Wiley & Sons Ltd.

  7. Immunocytochemical studies on the nuclear ubiquitous casein and cyclin-dependent kinases substrate following 5-aminolevulinicacid-mediated photodynamic therapy on MCF-7 cells.

    Science.gov (United States)

    Hotowy, Katarzyna; Woźniak, Marta; Duś, Kamila; Czapińska, Elżbieta; Osiecka, Beata; Krzystek-Korpacka, Małgorzata; Bronowicz, Andrzej; Wiśniewski, Jacek; Gamian, Andrzej; Terlecki, Grzegorz; Ziółkowski, Piotr

    2013-12-01

    Recent data indicates that nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) may play role in tumor growth. In present study authors examined whether photodynamic therapy with 5-aminolevulinic acid (5-ALA) induces NUCKS expression in breast cancer cell line, MCF-7. In the experiment concentration of 5-ALA was 6.5mM. Excitation wavelength was 630 ± 20 nm, total light dose of light 5 or 10 J/cm(2) and irradiance 60 mW/cm(2) was used. Cells were collected at established time points and Western blot and immunocytochemical studies were performed using antibody against NUCKS. Studies proved strong cytotoxic effects in cells following PDT with 6.5mM of precursor and 10 J/cm(2). Western blot analysis revealed the strongest expression of NUCKS at 7h after PDT. At next time points, 18 and 24h, expression of NUCKS decreased and became similar to that of control group. Further immunocytochemical studies showed very strong expression of NUCKS following PDT with 5-ALA and light irradiation of 5 J/cm(2). Early, at 0 h, that expression was predominantly seen in nuclei, while at 7h expression of NUCKS was observed in disseminated manner within entire cells in both nuclei and cytoplasm, with prevalence of cytoplasmic staining. Authors suggest that NUCKS is involved in cellular responses following PDT, and since parallel induction of NUCKS and proapoptotic marker Bax and inhibition of anti-apoptotic Bcl-2 was observed, this protein might also be involved in induction of apoptosis following PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Estrogenic and anti-estrogenic regulation of estrogen receptor in MCF-7 breast-cancer cells: comparison of immunocytochemical data with biochemical measurements.

    Science.gov (United States)

    Seo, H S; Larsimont, D; Querton, G; El Khissiin, A; Laios, I; Legros, N; Leclercq, G

    1998-12-09

    Data from immunocytochemical assessment of estrogen receptor (ER) regulation in MCF-7 cells under estrogenic and anti-estrogenic stimulation were compared with those obtained by enzyme immunoassay (Abbott ER-EIA). Similar trends were observed, although ER level variations were less marked when assessed immunocytochemically. We confirmed reports of ER disappearance in the presence of estrogens (Es; E2 and DES) and pure anti-estrogens (AEs; RU 58,668 and ICI 164,384) as well as its increase with partial AEs (4-OH-TAM and RU 39,119). E2-induced ER down-regulation was partly blocked by actinomycin D (AMD), okadaic acid (OK) and cycloheximide (CHX) when assessed by these 2 methods. Down-regulation by pure AEs was not impeded by CHX, indicating that they operate differently from Es (i.e., transformation of ER to a form sensitive to constitutive degradation activity). In situ pre-labeling of the cells with [3H]TAZ indicated that all investigated ligands eliminate pre-existing ER through binding to newly synthetized receptors, since [3H]TAZ co-valently associates with ER; E2 and RU 58,668 were more effective than 4-OH-TAM in this regard. CHX blocked ER disappearance even in the presence of pure AEs, which is in contrast to the data established with cells not pre-exposed to [3H]TAZ. Nuclear location of [3H]TAZ-ER complexes may explain this discrepancy, since pure AE-ER complexes were reported to be incapable of nuclear translocation.

  9. Introduction to neural networks

    CERN Document Server

    James, Frederick E

    1994-02-02

    1. Introduction and overview of Artificial Neural Networks. 2,3. The Feed-forward Network as an inverse Problem, and results on the computational complexity of network training. 4.Physics applications of neural networks.

  10. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  11. Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction

    Directory of Open Access Journals (Sweden)

    Kinnamon Sue C

    2001-04-01

    Full Text Available Abstract Background Taste receptor cells are responsible for transducing chemical stimuli into electrical signals that lead to the sense of taste. An important second messenger in taste transduction is IP3, which is involved in both bitter and sweet transduction pathways. Several components of the bitter transduction pathway have been identified, including the T2R/TRB taste receptors, phospholipase C β2, and the G protein subunits α-gustducin, β3, and γ13. However, the identity of the IP3 receptor subtype in this pathway is not known. In the present study we used immunocytochemistry on rodent taste tissue to identify the IP3 receptors expressed in taste cells and to examine taste bud expression patterns for IP3R3. Results Antibodies against Type I, II, and III IP3 receptors were tested on sections of rat and mouse circumvallate papillae. Robust cytoplasmic labeling for the Type III IP3 receptor (IP3R3 was found in a large subset of taste cells in both species. In contrast, little or no immunoreactivity was seen with antibodies against the Type I or Type II IP3 receptors. To investigate the potential role of IP3R3 in bitter taste transduction, we used double-label immunocytochemistry to determine whether IP3R3 is expressed in the same subset of cells expressing other bitter signaling components. IP3R3 immunoreactive taste cells were also immunoreactive for PLCβ2 and γ13. Alpha-gustducin immunoreactivity was present in a subset of IP3R3, PLCβ2, and γ13 positive cells. Conclusions IP3R3 is the dominant form of the IP3 receptor expressed in taste cells and our data suggest it plays an important role in bitter taste transduction.

  12. Neural plasticity and its initiating conditions in tinnitus.

    Science.gov (United States)

    Roberts, L E

    2017-12-12

    Deafferentation caused by cochlear pathology (which can be hidden from the audiogram) activates forms of neural plasticity in auditory pathways, generating tinnitus and its associated conditions including hyperacusis. This article discusses tinnitus mechanisms and suggests how these mechanisms may relate to those involved in normal auditory information processing. Research findings from animal models of tinnitus and from electromagnetic imaging of tinnitus patients are reviewed which pertain to the role of deafferentation and neural plasticity in tinnitus and hyperacusis. Auditory neurons compensate for deafferentation by increasing their input/output functions (gain) at multiple levels of the auditory system. Forms of homeostatic plasticity are believed to be responsible for this neural change, which increases the spontaneous and driven activity of neurons in central auditory structures in animals expressing behavioral evidence of tinnitus. Another tinnitus correlate, increased neural synchrony among the affected neurons, is forged by spike-timing-dependent neural plasticity in auditory pathways. Slow oscillations generated by bursting thalamic neurons verified in tinnitus animals appear to modulate neural plasticity in the cortex, integrating tinnitus neural activity with information in brain regions supporting memory, emotion, and consciousness which exhibit increased metabolic activity in tinnitus patients. The latter process may be induced by transient auditory events in normal processing but it persists in tinnitus, driven by phantom signals from the auditory pathway. Several tinnitus therapies attempt to suppress tinnitus through plasticity, but repeated sessions will likely be needed to prevent tinnitus activity from returning owing to deafferentation as its initiating condition.

  13. Revolutionary Pathways

    DEFF Research Database (Denmark)

    Colgan, Jeff; Lucas, Edward

    2017-01-01

    How much and in what ways do individual leaders matter for international politics? This article sheds new light on these questions by considering the consequences of domestic revolutions in international relations. We argue that revolutions have international effects due to two separate pathways......, one associated with the event and one associated with the new leader's administration. In the first pathway, a revolutionary event disrupts established relationships and perceptions, creating uncertainty both within the state and abroad. In the second pathway, revolutions put individuals into office...... who are more willing to challenge the status quo and who have publicly committed to a sustained shift in policies during their administration. These two distinct pathways suggest that the important question about revolutions is not whether leaders or events matter most but rather the conditions under...

  14. [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

  15. Stroke pathways.

    Science.gov (United States)

    Venketasubramanian, N

    2001-07-01

    Stroke pathways are task-orientated structured multidisciplinary care plans which detail essential steps and interventions during the period of care of a "typical" stroke patient. Pathway development and implementation are best achieved by an appointed champion leading a multidisciplinary team of health care workers and administrators, who will also be the end users of the pathway. Pathway development involves reviews of existing clinical practice guidelines and pathways, followed by documentation, interdigitation and prioritization of care requirements at different time points in the various spheres, taking into consideration local philosophies and practices. These spheres could include investigations, pharmacologic treatment, rehabilitative therapy, nursing measures, and patient education. This would result in evidence-based holistic quality care, wide support base, efficient service provision, reduced costs and length of stay, less practice variation, improved communication among disciplines, enhanced patient-staff relationship, ease of audit and research opportunities. Components of the pathway could include a patient summary sheet, multidisciplinary record of the various activities structured on a day-to-day basis, sign-off columns for staff responsible for performing those activity, variance sheet, and separate protocols for specific issues. Implementation requires training of users, pilot runs, feedback, regular revisions, monitoring of compliance, and analysis of variances. Widespread implementation of pathways may be hindered by lack of support, and concerns about increased time requirements and costs, stifling of innovation, restriction of application of clinical judgement, lack of applicability to all patients, misuse and legal issues. However, a well-designed pathway will ensure quality care in a cost-efficient manner, benefiting the patient, carer and the health care service.

  16. Immunocytochemical localization of choline acetyltransferase and muscarinic ACh receptors in the antenna during development of the sphinx moth Manduca sexta.

    Science.gov (United States)

    Clark, Julie; Meisner, Shannon; Torkkeli, Päivi H

    2005-04-01

    Immunocytochemistry with monoclonal antibodies was used to investigate the locations of muscarinic acetylcholine receptors (mAChR) and choline acetyltransferase (ChAT) in sections of the developing antennae of the moth Manduca sexta. The results were correlated with a previous morphological investigation in the developing antennae which allowed us to locate different cell types at various stages of development. Our findings indicated that the muscarinic cholinergic system was not restricted to the sensory neurons but was also present in glial and epidermal cells. By day 4-5 of adult development, immunoreactivity against both antibodies was present in the axons of the antennal nerve, and more intense labeling was present in sections from older pupae. At days 4-9, the cell bodies of the sensory neurons in the basal part of the epidermis were also intensely immunolabeled by the anti-mAChR antibody. In mature flagella, large numbers of cells, some with processes into hairs, were strongly labeled by both antibodies. Antennal glial cells were intensely immunolabeled with both antibodies by days 4-5, but in later stages, it was not possible to discriminate between glial and neural staining. At days 4-9, we observed a distinctly labeled layer of epidermal cells close to the developing cuticle. The expression of both ChAT and mAChRs by neurons in moth antennae may allow the regulation of excitability by endogenous ACh. Cholinergic communication between neurons and glia may be part of the system that guides axon elongation during development. The cholinergic system in the apical part of the developing epidermis could be involved in cuticle formation.

  17. Infection dynamics of western equine encephalomyelitis virus (Togaviridae: Alphavirus) in four strains of Culex tarsalis (Diptera: Culicidae): an immunocytochemical study.

    Science.gov (United States)

    Oviedo, Marco V Neira; Romoser, William S; James, Calvin Bl; Mahmood, Farida; Reisen, William K

    2011-04-18

    BACKGROUND: Vector competence describes the efficiency with which vector arthropods become infected with and transmit pathogens and depends on interactions between pathogen and arthropod genetics as well as environmental factors. For arbovirus transmission, the female mosquito ingests viremic blood, the virus infects and replicates in midgut cells, escapes from the midgut, and disseminates to other tissues, including the salivary glands. Virus-laden saliva is then injected into a new host. For transmission to occur, the virus must overcome several "barriers", including barriers to midgut infection and/or escape and salivary infection and/or escape. By examining the spatial/temporal infection dynamics of Culex tarsalis strains infected with western equine encephalomyelitis virus (WEEV), we identified tissue tropisms and potential tissue barriers, and evaluated the effects of viral dose and time postingestion. METHODS: Using immunostained paraffin sections, WEEV antigens were tracked in four Cx. tarsalis strains: two recently colonized California field strains - Coachella Valley, Riverside County (COAV) and Kern National Wildlife Refuge (KNWR); and two laboratory strains selected for WEEV susceptibility (high viremia producer, HVP), and WEEV resistance (WR). RESULTS AND CONCLUSIONS: Tissues susceptible to WEEV infection included midgut epithelium, neural ganglia, trachea, chorionated eggs, and salivary glands. Neuroendocrine cells in the retrocerebral complex were occasionally infected, indicating the potential for behavioral effects. The HVP and COAV strains vigorously supported viral growth, whereas the WR and KNWR strains were less competent. Consistent with earlier studies, WEEV resistance appeared to be related to a dose-dependent midgut infection barrier, and a midgut escape barrier. The midgut escape barrier was not dependent upon the ingested viral dose. Consistent with midgut infection modulation, disseminated infections were less common in the WR and KNWR

  18. Immunocytochemical localization of secretory phospholipase A(2)-like protein in the pituitary gland and surrounding tissue of the bullfrog, Rana catesbeiana.

    Science.gov (United States)

    Yaoi, Y; Kikuyama, S; Hayashi, H; Hanaoka, Y; Sakai, M; Tanaka, S

    2001-05-01

    Previously, we obtained a protein that has considerable amino acid sequence homology with secretory phospholipase A(2) (PLA(2)) from a bullfrog pituitary fraction obtained during the purification of thyrotropin (TSH). Subsequently, partial amino acid sequence (N-terminal 45 amino acid residues) analysis revealed this protein to be identical to the N-terminal amino acid sequence of otoconin-22, the major protein of aragonitic otoconia in the Xenopus saccule. In this study we developed an antibody against the N-terminal peptide of the bullfrog protein and applied it for immunocytochemical study of the pituitary and its surrounding tissue. Western blotting analysis showed that this antibody recognizes a 20.4-kD protein that has a molecular mass close to that of otoconin-22. Immunohistochemical reaction with the antibody was not found in any anterior pituitary cells but was intense in the monolayer epithelial cells of the endolymphatic sac surrounding the pituitary gland, which is a major storage site of calcium carbonate in amphibians. An electron microscopic study revealed that the cuboidal cells in the endolymphatic sac contained large, polymorphic secretory granules in their apical cytoplasm. Immunogold particles indicating the presence of a PLA(2)-like protein were observed predominately in these secretory granules. These findings support the view that this PLA(2)-like protein obtained during purification of TSH was derived from the endolymphatic sac adhering to the pituitary and that this protein is a bullfrog otoconin. (J Histochem Cytochem 49:631-637, 2001)

  19. Application of in situ hybridization, cytochemical and immunocytochemical techniques for the investigation of peroxisomes. A review including novel data. Robert Feulgen Prize Lecture 1997.

    Science.gov (United States)

    Baumgart, E

    1997-09-01

    In situ hybridization, cytochemical and immunocytochemical techniques have contributed significantly to the understanding of the biology of peroxisomes, since they permit in situ demonstration of the sites of synthesis and distribution of peroxisomal proteins without the necessity of homogenization and subcellular fractionation of tissues or cultured cells. This article reviews the results of research on mammalian peroxisomal metabolism, biogenesis and proliferation in which morphological techniques have played a significant role in the elucidation of the biological problem. Some new data on peroxisomal heterogeneity and morphogenesis are included. The morphological methods applied have made it possible to characterize the differences in distribution of mRNAs encoding peroxisomal proteins in different tissues, as well as to monitor the marked heterogeneity in the protein composition and in the activity of specific enzymes in the peroxisomal population of single cells, or in tissues with complex organization (e.g. liver and kidney). In addition, the dynamic alterations and high plasticity of the peroxisomal compartment--partly dependent on contact of the peroxisomes to the microtubular network-are presented.

  20. Function and immunocytochemical localization of two novel odorant-binding proteins in olfactory sensilla of the scarab beetle Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae).

    Science.gov (United States)

    Deng, Sisi; Yin, Jiao; Zhong, Tao; Cao, Yazhong; Li, Kebin

    2012-02-01

    Odorant-binding proteins (OBPs) are found in both insects and vertebrates, and it is believed that they are involved in chemical communication. In this study, we identify and express 2 OBPs from the scarab beetle, Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae). HoblOBP1 shows more similarities with other scarab beetle OBPs, whereas HoblOBP2 is more diverse. N-phenyl-1-naphthylamine (1-NPN) is used as a fluorescent probe in ligand-binding experiment, and results indicate that both HoblOBPs prefer plant volatiles to putative H. oblita sex pheromones. HoblOBP1 shows binding affinity to a wider range of test compounds, but HoblOBP2 displays more specific binding affinity. Cinnamaldehyde and 2,4-di-tert-butylphenol bind to HoblOBP1 can elicit strong electrophysiological responses of the antennae from female H. oblita adults, respectively. Methyl salicylate also shows good affinity to HoblOBP2 and it can elicit moderate electrophysiological responses. Although, β-ionone is one of the ligands of the strongest binding, it elicits a weak electrophysiological response. In the immunocytochemical analysis, we observe that HoblOBP1 and HoblOBP2 are coexpressed in sensilla basiconica and placodea in both sexes.

  1. Metastasis of colon cancer to the thyroid gland: a case diagnosed on fine-needle aspirate by a combined cytological, immunocytochemical, and molecular approach.

    Science.gov (United States)

    Cozzolino, Immacolata; Malapelle, Umberto; Carlomagno, Chiara; Palombini, Lucio; Troncone, Giancarlo

    2010-12-01

    Fine-needle aspiration (FNA) with cytological evaluation reliably diagnoses primary and secondary thyroid neoplasms. However, identifying the primary origin of a metastatic process involving the thyroid gland is challenging. In particular, metastasis of colon cancer to the thyroid gland is very rare. In this case report, a right lobe solid thyroid nodule in a 66-year-old male was aspirated. FNA cytology showed necrosis and atypical tall columnar cells; since, the patient at age 60 had undergone surgery for a sigmoid-rectal cancer metastasizing to the liver and subsequently to the lung, a suspicion of metastasis from colon cancer was raised. This was corroborated by cell-block immunocytochemistry showing a cytokeratin (CK) 7 negative/CK20-positive staining pattern; thyreoglobulin and TTF-1 were both negative. Since KRAS codon 12/13 mutations frequently occur in colon cancer, whereas they are extremely uncommon in primary thyroid tumors, DNA was extracted from the aspirated cells, and KRAS mutational analysis was carried out. The codon 12 G12D mutation was found; the same mutation was evident in the primary cancer of the colon and in its liver and lung metastasis. Thus, a combined cytological, immunocytochemical and molecular approach unquestionably correlated metastatic adenocarcinoma cells aspirated from the thyroid to a colo-rectal origin. © 2010 Wiley-Liss, Inc.

  2. Immunocytochemical Characterization of Alzheimer Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

    Directory of Open Access Journals (Sweden)

    Iván Carrera

    2013-01-01

    Full Text Available APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD, which overexpress mutated forms of the gene for human amyloid precursor protein (APP and presenilin 1 (PS1, have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol. Our findings showed that administration of amyloid-β1−42 (Aβ and sphingosine-1-phosphate emulsified in liposome complex (EB101 to APP/PS1 mice before onset of Aβ deposition (7 weeks of age and/or at an older age (35 weeks of age is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

  3. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  4. Genetics and development of neural tube defects

    Science.gov (United States)

    Copp, Andrew J.; Greene, Nicholas D. E.

    2014-01-01

    Congenital defects of neural tube closure (neural tube defects; NTDs) are among the commonest and most severe disorders of the fetus and newborn. Disturbance of any of the sequential events of embryonic neurulation produce NTDs, with the phenotype (e.g. anencephaly, spina bifida) varying depending on the region of neural tube that remains open. While mutation of more than 200 genes is known to cause NTDs in mice, the pattern of occurrence in humans suggests a multifactorial polygenic or oligogenic aetiology. This emphasises the importance of gene-gene and gene-environment interactions in the origin of these defects. A number of cell biological functions are essential for neural tube closure, with defects of the cytoskeleton, cell cycle and molecular regulation of cell viability prominent among the mouse NTD mutants. Many transcriptional regulators and proteins that affect chromatin structure are also required for neural tube closure, although the downstream molecular pathways regulated by these proteins is unknown. Some key signalling pathways for NTDs have been identified: over-activation of sonic hedgehog signalling and loss of function in the planar cell polarity (non-canonical Wnt) pathway are potent causes of NTD, with requirements also for retinoid and inositol signalling. Folic acid supplementation is an effective method for primary prevention of a proportion of NTDs, in both humans and mice, although the embryonic mechanism of folate action remains unclear. Folic acid-resistant cases can be prevented by inositol supplementation in mice, raising the possibility that this could lead to an additional preventive strategy for human NTDs in future. PMID:19918803

  5. Infection dynamics of western equine encephalomyelitis virus (Togaviridae: Alphavirus in four strains of Culex tarsalis (Diptera: Culicidae: an immunocytochemical study

    Directory of Open Access Journals (Sweden)

    Neira Oviedo MV

    2011-04-01

    Full Text Available Marco V Neira Oviedo1,2, William S Romoser1, Calvin BL James1, Farida Mahmood3, William K Reisen31Tropical Disease Institute, Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, OH, USA; 2Oxitec Inc, Oxford, England; 3Center for Vectorborne Diseases, School of Veterinary Medicine, University of California, Davis, CA, USABackground: Vector competence describes the efficiency with which vector arthropods become infected with and transmit pathogens and depends on interactions between pathogen and arthropod genetics as well as environmental factors. For arbovirus transmission, the female mosquito ingests viremic blood, the virus infects and replicates in midgut cells, escapes from the midgut, and disseminates to other tissues, including the salivary glands. Virus-laden saliva is then injected into a new host. For transmission to occur, the virus must overcome several "barriers", including barriers to midgut infection and/or escape and salivary infection and/or escape. By examining the spatial/temporal infection dynamics of Culex tarsalis strains infected with western equine encephalomyelitis virus (WEEV, we identified tissue tropisms and potential tissue barriers, and evaluated the effects of viral dose and time postingestion.Methods: Using immuno-stained paraffin sections, WEEV antigens were tracked in four Cx. tarsalis strains: two recently colonized California field strains – Coachella Valley, Riverside County (COAV and Kern National Wildlife Refuge (KNWR; and two laboratory strains selected for WEEV susceptibility (high viremia producer, HVP, and WEEV resistance (WR.Results and conclusions: Tissues susceptible to WEEV infection included midgut epithelium, neural ganglia, trachea, chorionated eggs, and salivary glands. Neuroendocrine cells in the retrocerebral complex were occasionally infected, indicating the potential for behavioral effects. The HVP and COAV strains vigorously supported viral growth

  6. Epigallocatechin-3-gallate and related phenol compounds redirect the amyloidogenic aggregation pathway of ataxin-3 towards non-toxic aggregates and prevent toxicity in neural cells and Caenorhabditis elegans animal model.

    Science.gov (United States)

    Visentin, Cristina; Pellistri, Francesca; Natalello, Antonino; Vertemara, Jacopo; Bonanomi, Marcella; Gatta, Elena; Penco, Amanda; Relini, Annalisa; De Gioia, Luca; Airoldi, Cristina; Regonesi, Maria E; Tortora, Paolo

    2017-09-01

    The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resistant aggregates. Here, we have characterized other related phenol compounds, although smaller in size, i.e. (-)-epigallocatechin gallate (EGC), and gallic acid (GA). We analysed the aggregation pattern of ATX3-Q55 and of the N-terminal globular Josephin domain (JD) by assessing the time course of the soluble protein, as well its structural features by FTIR and AFM, in the presence and the absence of the mentioned compounds. All of them redirected the aggregation pattern towards soluble, SDS-resistant aggregates. They also prevented the appearance of ordered side-chain hydrogen bonding in ATX3-Q55, which is the hallmark of polyQ-related amyloids. Molecular docking analyses on the JD highlighted three interacting regions, including the central, aggregation-prone one. All three compounds bound to each of them, although with different patterns. This might account for their capability to prevent amyloidogenesis. Saturation transfer difference NMR experiments also confirmed EGCG and EGC binding to monomeric JD. ATX3-Q55 pre-incubation with any of the three compounds prevented its calcium-influx-mediated cytotoxicity towards neural cells. Finally, all the phenols significantly reduced toxicity in a transgenic Caenorhabditis elegans strain expressing an expanded ATX3. Overall, our results show that the three polyphenols act in a substantially similar manner. GA, however, might be more suitable for antiamyloid treatments due to its simpler structure and higher chemical stability. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    In contemporary consciousness studies the phenomenon of neural plasticity has received little attention despite the fact that neural plasticity is of still increased interest in neuroscience. We will, however, argue that neural plasticity could be of great importance to consciousness studies....... If consciousness is related to neural processes it seems, at least prima facie, that the ability of the neural structures to change should be reflected in a theory of this relationship "Neural plasticity" refers to the fact that the brain can change due to its own activity. The brain is not static but rather...... a dynamic entity, which physical structure changes according to its use and environment. This change may take the form of growth of new neurons, the creation of new networks and structures, and change within network structures, that is, changes in synaptic strengths. Plasticity raises questions about...

  8. Statistical Physics, Neural Networks, Brain Studies

    OpenAIRE

    TOULOUSE, Gérard

    2014-01-01

    An overview of some aspects of a vast domain, located at the crossroads of physics, biology and computer science is presented: 1) During the last fifteen years, physicists advancing along various pathways have come into contact with biology (computational neurosciences) and engineering (formal neural nets). 2) This move may actually be viewed as one component in a larger picture. A prominent trend of recent years, observable over many countries, has been the establishment of interdis...

  9. Shared molecular networks in orofacial and neural tube development.

    Science.gov (United States)

    Kousa, Youssef A; Mansour, Tamer A; Seada, Haitham; Matoo, Samaneh; Schutte, Brian C

    2017-01-30

    Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality. We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA-Seq data to identify which of these genes are expressed in both tissues during development. We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes. These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169-179, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection...... of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  11. Fuzzy and neural control

    Science.gov (United States)

    Berenji, Hamid R.

    1992-01-01

    Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

  12. Neural tube closure: cellular, molecular and biomechanical mechanisms.

    Science.gov (United States)

    Nikolopoulou, Evanthia; Galea, Gabriel L; Rolo, Ana; Greene, Nicholas D E; Copp, Andrew J

    2017-02-15

    Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations - 'neural tube defects' - that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. Here, we review these cellular, molecular and biomechanical mechanisms involved in neural tube closure, based on studies of various vertebrate species, focusing on the most recent advances in the field. © 2017. Published by The Company of Biologists Ltd.

  13. What Is Neural Plasticity?

    Science.gov (United States)

    von Bernhardi, Rommy; Bernhardi, Laura Eugenín-von; Eugenín, Jaime

    2017-01-01

    "Neural plasticity" refers to the capacity of the nervous system to modify itself, functionally and structurally, in response to experience and injury. As the various chapters in this volume show, plasticity is a key component of neural development and normal functioning of the nervous system, as well as a response to the changing environment, aging, or pathological insult. This chapter discusses how plasticity is necessary not only for neural networks to acquire new functional properties, but also for them to remain robust and stable. The article also reviews the seminal proposals developed over the years that have driven experiments and strongly influenced concepts of neural plasticity.

  14. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  15. A neural flow estimator

    DEFF Research Database (Denmark)

    Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik

    1995-01-01

    is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V......This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...

  16. Signaling Pathways in Melanogenesis

    Directory of Open Access Journals (Sweden)

    Stacey A. N. D’Mello

    2016-07-01

    Full Text Available Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis.

  17. Neural Networks: Implementations and Applications

    NARCIS (Netherlands)

    Vonk, E.; Veelenturf, L.P.J.; Jain, L.C.

    1996-01-01

    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  18. An immunocytochemical investigation of glial morphology in the Pacific hagfish: radial and astrocyte-like glia have the same phylogenetic age.

    Science.gov (United States)

    Wicht, H; Derouiche, A; Korf, H W

    1994-09-01

    This study attempts to reconstruct the early phylogenetic history of macroglial cells among craniates. Since glia does not fossilize, such a reconstruction must be based on a cladistic comparison of glial characters in the Recent craniate taxa (hagfishes, lampreys, and gnathostomes); however, there are only few data on glial morphology and none on glial immunocytochemistry in hagfishes. Therefore, we investigated the presence and localization of various macroglia-specific epitopes in the brain and spinal cord of the Pacific hagfish, Eptatretus stouti (Myxinoidea) by means of immunocytochemistry. Antibodies directed against S100-protein and vimentin showed no cross reactivity. Antibodies directed against glial fibrillary acidic protein and glutamine synthetase labelled various glial structures. Glial fibrillary acidic protein-like immunoreactivity was observed in ependymal cells with radially oriented processes in some regions. However, throughout the entire CNS, labelling of non-ependymal cells and their processes prevailed. The processes of these cells made occasional vascular contacts and they also made contacts with neuronal perikarya. Glutamine synthetase-like immunoreactivity was also found in some processes with radial orientation and in ependymal cells; but the antibody stained mainly non-ependymal cells which gave rise to a felt-like meshwork of interdigitating fine and very fine processes penetrating the neuropil of the entire brain. Additionally, there was labelling in the walls of blood vessels and in processes enwrapping individual neurons. The occurrence of glial fibrillary acidic protein- and glutamine synthetase-like immunoreactivity in non-ependymal glial elements in the brain of hagfishes and the relative scarcity of labelling in radial glial elements necessitates a re-interpretation of the evolutionary history of glial cells. Non-ependymal macroglia with immunocytochemical and morphological characters resembling typical (mammalian) astrocytes

  19. Immunocytochemical Characterization of Alzheimer’s Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

    Directory of Open Access Journals (Sweden)

    Ivan Carrera

    2014-03-01

    Full Text Available Introduction: APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD, which overexpress mutated forms of the gene for the human amyloid precursor protein (APP and presenilin 1 (PS1, have provided robust neuropathological hallmarks of an AD-like pattern at early ages. This study aimed to characterize immunocytochemical patterns of the AD mouse brain, which is treated with the EB101 vaccine, as a model for human AD. Material and methods: In this novel vaccine, a new approach has been taken to circumvent past failures with Aβ vaccines by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol. Results: Our findings showed that the administration of amyloid-β1−42 (Aβ and sphingosine-1-phosphate emulsified in liposome complex (EB101 to APP/PS1 mice before the onset of Aβ brain deposition (at 7 weeks of age and/or at an older age (35 weeks of age can be effective in both halting the progression and clearing the AD-like neuropathological hallmarks. In addition, passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus in the brain of treated mice was notably reduced. Conclusion: These results provide strong evidence that immunization with the EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

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

    Directory of Open Access Journals (Sweden)

    Joji eTsunada

    2014-06-01

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

  1. Critical Branching Neural Networks

    Science.gov (United States)

    Kello, Christopher T.

    2013-01-01

    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

  2. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette

    1994-01-01

    Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse.......Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse....

  3. Role of ciliary neurotrophic factor in the proliferation and differentiation of neural stem cells.

    Science.gov (United States)

    Ding, Jun; He, Zhili; Ruan, Juan; Ma, Zilong; Liu, Ying; Gong, Chengxin; Iqbal, Khalid; Sun, Shenggang; Chen, Honghui

    2013-01-01

    Ciliary neurotrophic factor (CNTF) is a pleiotropic cytokine that has been fully studied for its structure, receptor, and signaling pathways and its multiplex effects on neural system, skeletal muscle, and weight control. Recent research demonstrates that CNTF also plays an important role in neurogenesis and the differentiation of neural stem cells. In this article, we summarize the general characteristics of CNTF and its function on neural stem cells, which could be a valuable therapeutic strategy in treating neurological disorders.

  4. The neural subjective frame: from bodily signals to perceptual consciousness

    Science.gov (United States)

    Park, Hyeong-Dong; Tallon-Baudry, Catherine

    2014-01-01

    The report ‘I saw the stimulus’ operationally defines visual consciousness, but where does the ‘I’ come from? To account for the subjective dimension of perceptual experience, we introduce the concept of the neural subjective frame. The neural subjective frame would be based on the constantly updated neural maps of the internal state of the body and constitute a neural referential from which first person experience can be created. We propose to root the neural subjective frame in the neural representation of visceral information which is transmitted through multiple anatomical pathways to a number of target sites, including posterior insula, ventral anterior cingulate cortex, amygdala and somatosensory cortex. We review existing experimental evidence showing that the processing of external stimuli can interact with visceral function. The neural subjective frame is a low-level building block of subjective experience which is not explicitly experienced by itself which is necessary but not sufficient for perceptual experience. It could also underlie other types of subjective experiences such as self-consciousness and emotional feelings. Because the neural subjective frame is tightly linked to homeostatic regulations involved in vigilance, it could also make a link between state and content consciousness. PMID:24639580

  5. Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

    Directory of Open Access Journals (Sweden)

    Paige Snider

    2007-01-01

    Full Text Available Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators. Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest

  6. Expression of nestin by neural cells in the adult rat and human brain.

    Science.gov (United States)

    Hendrickson, Michael L; Rao, Abigail J; Demerdash, Omar N A; Kalil, Ronald E

    2011-04-07

    Neurons and glial cells in the developing brain arise from neural progenitor cells (NPCs). Nestin, an intermediate filament protein, is thought to be expressed exclusively by NPCs in the normal brain, and is replaced by the expression of proteins specific for neurons or glia in differentiated cells. Nestin expressing NPCs are found in the adult brain in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus. While significant attention has been paid to studying NPCs in the SVZ and SGZ in the adult brain, relatively little attention has been paid to determining whether nestin-expressing neural cells (NECs) exist outside of the SVZ and SGZ. We therefore stained sections immunocytochemically from the adult rat and human brain for NECs, observed four distinct classes of these cells, and present here the first comprehensive report on these cells. Class I cells are among the smallest neural cells in the brain and are widely distributed. Class II cells are located in the walls of the aqueduct and third ventricle. Class IV cells are found throughout the forebrain and typically reside immediately adjacent to a neuron. Class III cells are observed only in the basal forebrain and closely related areas such as the hippocampus and corpus striatum. Class III cells resemble neurons structurally and co-express markers associated exclusively with neurons. Cell proliferation experiments demonstrate that Class III cells are not recently born. Instead, these cells appear to be mature neurons in the adult brain that express nestin. Neurons that express nestin are not supposed to exist in the brain at any stage of development. That these unique neurons are found only in brain regions involved in higher order cognitive function suggests that they may be remodeling their cytoskeleton in supporting the neural plasticity required for these functions.

  7. Immunocytochemical determination of the estrogen-regulated proteins Mr 24,000, Mr 52,000 and DF3 breast cancer associated antigen: clinical value in advanced breast cancer and correlation with estrogen receptor.

    Science.gov (United States)

    Damstrup, L; Andersen, J; Kufe, D W; Hayes, D F; Poulsen, H S

    1992-01-01

    The Mr 24,000 and Mr 52,000 estrogen-regulated cytosol proteins, and the breast cancer-associated antigen DF3 have been studied in an immunocytochemical assay. Primary tumor specimens from 119 patients with advanced breast cancer who received endocrine therapy have been studied. Monoclonal antibodies were used for the detection of the proteins in formalin-fixed paraffin-embedded blocks. No correlation between Mr 52,000-positive specimens and the presence of estrogen receptor (ER) could be established (p = 0.87, chi-square test) whereas a statistically significant association between Mr 24,000 (p = 0.0002), DF3 antigen (p = 0.044) and ER was demonstrated. No intercorrelation was found between Mr 24,000 and Mr 52,000 or DF3 (p = 0.63, 0.98 and 0.12 respectively). Clinical response was evaluated for immunocytochemical findings, Mr 24,000 (p = 0.37), Mr 52,000 (p = 0.61) and DF3 (p = 0.68) showed no association whereas ER was statistically correlated (p = 0.00005). Neither overall survival nor disease-free survival correlated to Mr 24,000 (p = 0.18 and 0.75 respectively, logrank test), Mr 52,000 (p = 0.095 and 0.38), or DF3 (p = 0.22 and 0.13) staining, whereas ER-positive tumors did (p = 0.00005). Discrimination between ER-positive responders and ER-positive non-responders was not possible using either Mr 52,000, Mr 24,000 or DF3 staining. Based on our findings we conclude that immunocytochemical staining for Mr 52,000, Mr 24,000 or DF3 cannot be used as a marker to predict response to endocrine therapy in patients with advanced or recurrent breast cancer.

  8. Neural correlates of motor learning, transfer of learning, and learning to learn.

    Science.gov (United States)

    Seidler, Rachael D

    2010-01-01

    Recent studies on the neural bases of sensorimotor adaptation demonstrate that the cerebellar and striatal thalamocortical pathways contribute to early learning. Transfer of learning involves a reduction in the contribution of early learning networks and increased reliance on the cerebellum. The neural correlates of learning to learn remain to be determined but likely involve enhanced functioning of the general aspects of early learning.

  9. G-protein-coupled receptor signaling and neural tube closure defects.

    Science.gov (United States)

    Shimada, Issei S; Mukhopadhyay, Saikat

    2017-01-30

    Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets. Recent studies implicate several GPCRs and downstream signaling pathways in neural tube development and closure. In this review, we will discuss our current understanding of GPCR signaling pathways in pathogenesis of NTDs. Notable examples include the orphan primary cilia-localized GPCR, Gpr161 that regulates the basal suppression machinery of sonic hedgehog pathway by means of activation of cAMP-protein kinase A signaling in the neural tube, and protease-activated receptors that are activated by a local network of membrane-tethered proteases during neural tube closure involving the surface ectoderm. Understanding the role of these GPCR-regulated pathways in neural tube development and closure is essential toward identification of underlying genetic causes to prevent NTDs. Birth Defects Research 109:129-139, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Dynamics of neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-01

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  11. Designing pathways

    DEFF Research Database (Denmark)

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  12. ANT Advanced Neural Tool

    Energy Technology Data Exchange (ETDEWEB)

    Labrador, I.; Carrasco, R.; Martinez, L.

    1996-07-01

    This paper describes a practical introduction to the use of Artificial Neural Networks. Artificial Neural Nets are often used as an alternative to the traditional symbolic manipulation and first order logic used in Artificial Intelligence, due the high degree of difficulty to solve problems that can not be handled by programmers using algorithmic strategies. As a particular case of Neural Net a Multilayer Perception developed by programming in C language on OS9 real time operating system is presented. A detailed description about the program structure and practical use are included. Finally, several application examples that have been treated with the tool are presented, and some suggestions about hardware implementations. (Author) 15 refs.

  13. Pathway collages: personalized multi-pathway diagrams.

    Science.gov (United States)

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  14. 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

  15. Hidden neural networks

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose; Riis, Søren Kamaric

    1999-01-01

    A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability...... parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum...... likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear...

  16. [Neural codes for perception].

    Science.gov (United States)

    Romo, R; Salinas, E; Hernández, A; Zainos, A; Lemus, L; de Lafuente, V; Luna, R

    This article describes experiments designed to show the neural codes associated with the perception and processing of tactile information. The results of these experiments have shown the neural activity correlated with tactile perception. The neurones of the primary somatosensory cortex (S1) represent the physical attributes of tactile perception. We found that these representations correlated with tactile perception. By means of intracortical microstimulation we demonstrated the causal relationship between S1 activity and tactile perception. In the motor areas of the frontal lobe is to be found the connection between sensorial and motor representation whilst decisions are being taken. S1 generates neural representations of the somatosensory stimuli which seen to be sufficient for tactile perception. These neural representations are subsequently processed by central areas to S1 and seem useful in perception, memory and decision making.

  17. Neural Oscillators Programming Simplified

    Directory of Open Access Journals (Sweden)

    Patrick McDowell

    2012-01-01

    Full Text Available The neurological mechanism used for generating rhythmic patterns for functions such as swallowing, walking, and chewing has been modeled computationally by the neural oscillator. It has been widely studied by biologists to model various aspects of organisms and by computer scientists and robotics engineers as a method for controlling and coordinating the gaits of walking robots. Although there has been significant study in this area, it is difficult to find basic guidelines for programming neural oscillators. In this paper, the authors approach neural oscillators from a programmer’s point of view, providing background and examples for developing neural oscillators to generate rhythmic patterns that can be used in biological modeling and robotics applications.

  18. Neural cryptography with feedback.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  19. Neural cryptography with feedback

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  20. Neural network applications

    Science.gov (United States)

    Padgett, Mary L.; Desai, Utpal; Roppel, T.A.; White, Charles R.

    1993-01-01

    A design procedure is suggested for neural networks which accommodates the inclusion of such knowledge-based systems techniques as fuzzy logic and pairwise comparisons. The use of these procedures in the design of applications combines qualitative and quantitative factors with empirical data to yield a model with justifiable design and parameter selection procedures. The procedure is especially relevant to areas of back-propagation neural network design which are highly responsive to the use of precisely recorded expert knowledge.

  1. Building Neural Net Software

    OpenAIRE

    Neto, João Pedro; Costa, José Félix

    1999-01-01

    In a recent paper [Neto et al. 97] we showed that programming languages can be translated on recurrent (analog, rational weighted) neural nets. The goal was not efficiency but simplicity. Indeed we used a number-theoretic approach to machine programming, where (integer) numbers were coded in a unary fashion, introducing a exponential slow down in the computations, with respect to a two-symbol tape Turing machine. Implementation of programming languages in neural nets turns to be not only theo...

  2. NEMEFO: NEural MEteorological FOrecast

    Energy Technology Data Exchange (ETDEWEB)

    Pasero, E.; Moniaci, W.; Meindl, T.; Montuori, A. [Polytechnic of Turin (Italy). Dept. of Electronics

    2004-07-01

    Artificial Neural Systems are a well-known technique used to classify and recognize objects. Introducing the time dimension they can be used to forecast numerical series. NEMEFO is a ''nowcasting'' tool, which uses both statistical and neural systems to forecast meteorological data in a restricted area close to a meteorological weather station in a short time range (3 hours). Ice, fog, rain are typical events which can be anticipated by NEMEFO. (orig.)

  3. DHODH modulates transcriptional elongation in the neural crest and melanoma.

    Science.gov (United States)

    White, Richard Mark; Cech, Jennifer; Ratanasirintrawoot, Sutheera; Lin, Charles Y; Rahl, Peter B; Burke, Christopher J; Langdon, Erin; Tomlinson, Matthew L; Mosher, Jack; Kaufman, Charles; Chen, Frank; Long, Hannah K; Kramer, Martin; Datta, Sumon; Neuberg, Donna; Granter, Scott; Young, Richard A; Morrison, Sean; Wheeler, Grant N; Zon, Leonard I

    2011-03-24

    Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.

  4. The relationship between Sonic hedgehog signalling, cilia and neural tube defects

    Science.gov (United States)

    Murdoch, Jennifer N.; Copp, Andrew J.

    2013-01-01

    The Hedgehog signalling pathway is essential for many aspects of normal embryonic development, including formation and patterning of the neural tube. Absence of Shh ligand is associated with the midline defect holoprosencephaly, while increased Shh signalling is associated with exencephaly and spina bifida. To complicate this apparently simple relationship, mutation of proteins required for function of cilia often leads to impaired Shh signalling and to disruption of neural tube closure. In this manuscript, we review the literature on Shh pathway mutants and discuss the relationship between Shh signalling, cilia and neural tube defects. PMID:20544799

  5. Neural reuse: a fundamental organizational principle of the brain.

    Science.gov (United States)

    Anderson, Michael L

    2010-08-01

    An emerging class of theories concerning the functional structure of the brain takes the reuse of neural circuitry for various cognitive purposes to be a central organizational principle. According to these theories, it is quite common for neural circuits established for one purpose to be exapted (exploited, recycled, redeployed) during evolution or normal development, and be put to different uses, often without losing their original functions. Neural reuse theories thus differ from the usual understanding of the role of neural plasticity (which is, after all, a kind of reuse) in brain organization along the following lines: According to neural reuse, circuits can continue to acquire new uses after an initial or original function is established; the acquisition of new uses need not involve unusual circumstances such as injury or loss of established function; and the acquisition of a new use need not involve (much) local change to circuit structure (e.g., it might involve only the establishment of functional connections to new neural partners). Thus, neural reuse theories offer a distinct perspective on several topics of general interest, such as: the evolution and development of the brain, including (for instance) the evolutionary-developmental pathway supporting primate tool use and human language; the degree of modularity in brain organization; the degree of localization of cognitive function; and the cortical parcellation problem and the prospects (and proper methods to employ) for function to structure mapping. The idea also has some practical implications in the areas of rehabilitative medicine and machine interface design.

  6. Neural network optimization, components, and design selection

    Science.gov (United States)

    Weller, Scott W.

    1990-07-01

    Neural Networks are part of a revived technology which has received a lot of hype in recent years. As is apt to happen in any hyped technology, jargon and predictions make its assimilation and application difficult. Nevertheless, Neural Networks have found use in a number of areas, working on non-trivial and noncontrived problems. For example, one net has been trained to "read", translating English text into phoneme sequences. Other applications of Neural Networks include data base manipulation and the solving of muting and classification types of optimization problems. Neural Networks are constructed from neurons, which in electronics or software attempt to model but are not constrained by the real thing, i.e., neurons in our gray matter. Neurons are simple processing units connected to many other neurons over pathways which modify the incoming signals. A single synthetic neuron typically sums its weighted inputs, runs this sum through a non-linear function, and produces an output. In the brain, neurons are connected in a complex topology: in hardware/software the topology is typically much simpler, with neurons lying side by side, forming layers of neurons which connect to the layer of neurons which receive their outputs. This simplistic model is much easier to construct than the real thing, and yet can solve real problems. The information in a network, or its "memory", is completely contained in the weights on the connections from one neuron to another. Establishing these weights is called "training" the network. Some networks are trained by design -- once constructed no further learning takes place. Other types of networks require iterative training once wired up, but are not trainable once taught Still other types of networks can continue to learn after initial construction. The main benefit to using Neural Networks is their ability to work with conflicting or incomplete ("fuzzy") data sets. This ability and its usefulness will become evident in the following

  7. Conducting Polymers for Neural Prosthetic and Neural Interface Applications

    Science.gov (United States)

    2015-01-01

    Neural interfacing devices are an artificial mechanism for restoring or supplementing the function of the nervous system lost as a result of injury or disease. Conducting polymers (CPs) are gaining significant attention due to their capacity to meet the performance criteria of a number of neuronal therapies including recording and stimulating neural activity, the regeneration of neural tissue and the delivery of bioactive molecules for mediating device-tissue interactions. CPs form a flexible platform technology that enables the development of tailored materials for a range of neuronal diagnostic and treatment therapies. In this review the application of CPs for neural prostheses and other neural interfacing devices are discussed, with a specific focus on neural recording, neural stimulation, neural regeneration, and therapeutic drug delivery. PMID:26414302

  8. A Translational Approach to Vocalization Deficits and Neural Recovery after Behavioral Treatment in Parkinson Disease

    Science.gov (United States)

    Ciucci, Michelle R.; Vinney, Lisa; Wahoske, Emerald J.; Connor, Nadine P.

    2010-01-01

    Parkinson disease is characterized by a complex neuropathological profile that primarily affects dopaminergic neural pathways in the basal ganglia, including pathways that modulate cranial sensorimotor functions such as swallowing, voice and speech. Prior work from our lab has shown that the rat model of unilateral 6-hydroxydopamine infusion to…

  9. Hyperbolic Hopfield neural networks.

    Science.gov (United States)

    Kobayashi, M

    2013-02-01

    In recent years, several neural networks using Clifford algebra have been studied. Clifford algebra is also called geometric algebra. Complex-valued Hopfield neural networks (CHNNs) are the most popular neural networks using Clifford algebra. The aim of this brief is to construct hyperbolic HNNs (HHNNs) as an analog of CHNNs. Hyperbolic algebra is a Clifford algebra based on Lorentzian geometry. In this brief, a hyperbolic neuron is defined in a manner analogous to a phasor neuron, which is a typical complex-valued neuron model. HHNNs share common concepts with CHNNs, such as the angle and energy. However, HHNNs and CHNNs are different in several aspects. The states of hyperbolic neurons do not form a circle, and, therefore, the start and end states are not identical. In the quantized version, unlike complex-valued neurons, hyperbolic neurons have an infinite number of states.

  10. Neural Semantic Encoders.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Yu, Hong

    2017-04-01

    We present a memory augmented neural network for natural language understanding: Neural Semantic Encoders. NSE is equipped with a novel memory update rule and has a variable sized encoding memory that evolves over time and maintains the understanding of input sequences through read, compose and write operations. NSE can also access multiple and shared memories. In this paper, we demonstrated the effectiveness and the flexibility of NSE on five different natural language tasks: natural language inference, question answering, sentence classification, document sentiment analysis and machine translation where NSE achieved state-of-the-art performance when evaluated on publically available benchmarks. For example, our shared-memory model showed an encouraging result on neural machine translation, improving an attention-based baseline by approximately 1.0 BLEU.

  11. The neural crest and neural crest cells: discovery and significance ...

    Indian Academy of Sciences (India)

    In this paper I provide a brief overview of the major phases of investigation into the neural crest and the major players involved, discuss how the origin of the neural crest relates to the origin of the nervous system in vertebrate embryos, discuss the impact on the germ-layer theory of the discovery of the neural crest and of ...

  12. Mechanotransduction of Neural Cells Through Cell–Substrate Interactions

    Science.gov (United States)

    Stukel, Jessica M.

    2016-01-01

    Neurons and neural stem cells are sensitive to their mechanical and topographical environment, and cell–substrate binding contributes to this sensitivity to activate signaling pathways for basic cell functions. Many transmembrane proteins transmit signals into and out of the cell, including integrins, growth factor receptors, G-protein-coupled receptors, cadherins, cell adhesion molecules, and ion channels. Specifically, integrins are one of the main transmembrane proteins that transmit force across the cell membrane between a cell and its extracellular matrix, making them critical in the study of cell–material interactions. This review focuses on mechanotransduction, defined as the conversion of force a cell generates through cell–substrate bonds to a chemical signal, of neural cells. The chemical signals relay information via pathways through the cellular cytoplasm to the nucleus, where signaling events can affect gene expression. Pathways and the cellular response initiated by substrate binding are explored to better understand their effect on neural cells mechanotransduction. As the results of mechanotransduction affect cell adhesion, cell shape, and differentiation, knowledge regarding neural mechanotransduction is critical for most regenerative strategies in tissue engineering, where novel environments are developed to improve conduit design for central and peripheral nervous system repair in vivo. PMID:26669274

  13. Mechanotransduction of Neural Cells Through Cell-Substrate Interactions.

    Science.gov (United States)

    Stukel, Jessica M; Willits, Rebecca Kuntz

    2016-06-01

    Neurons and neural stem cells are sensitive to their mechanical and topographical environment, and cell-substrate binding contributes to this sensitivity to activate signaling pathways for basic cell functions. Many transmembrane proteins transmit signals into and out of the cell, including integrins, growth factor receptors, G-protein-coupled receptors, cadherins, cell adhesion molecules, and ion channels. Specifically, integrins are one of the main transmembrane proteins that transmit force across the cell membrane between a cell and its extracellular matrix, making them critical in the study of cell-material interactions. This review focuses on mechanotransduction, defined as the conversion of force a cell generates through cell-substrate bonds to a chemical signal, of neural cells. The chemical signals relay information via pathways through the cellular cytoplasm to the nucleus, where signaling events can affect gene expression. Pathways and the cellular response initiated by substrate binding are explored to better understand their effect on neural cells mechanotransduction. As the results of mechanotransduction affect cell adhesion, cell shape, and differentiation, knowledge regarding neural mechanotransduction is critical for most regenerative strategies in tissue engineering, where novel environments are developed to improve conduit design for central and peripheral nervous system repair in vivo.

  14. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

    The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks.......The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks....

  15. Deconvolution using a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, S.K.

    1990-11-15

    Viewing one dimensional deconvolution as a matrix inversion problem, we compare a neural network backpropagation matrix inverse with LMS, and pseudo-inverse. This is a largely an exercise in understanding how our neural network code works. 1 ref.

  16. [Neural mechanism of blindsight].

    Science.gov (United States)

    Yoshida, Masatoshi

    2013-06-01

    "Blindsight" is a phenomenon whereby hemianopic patients with damage in the primary visual cortex (V1) are able to process visual information in their blind visual field. Two pathways that bypass the V1 may be responsible for this residual vision. The first pathway is the retinotectal pathway in which the superior colliculus in the midbrain receives direct retinal signals and sends them to the extrastriate cortex via the pulvinar. The second pathway is the geniculo-extrastriate pathway in which direct retinal input to the lateral geniculate nucleus is sent straight to the extrastriate cortex. Herein, I summarize evidence supporting the involvement of either pathway. The evidence was obtained from anatomical, neurophysiological, imaging, and behavioral studies carried out on macaque monkeys and humans. I emphasize three points: 1) crosstalk exists between the retinotectal pathway and the geniculo-extrastriate pathway, that is, the projection from the superficial layer of the superior colliculus to the koniocellular layer of the lateral geniculate nucleus; 2) three visual channels (the luminance in the magnocellular pathway, the red-green opponency in the parvocellular pathway, and the blue-yellow opponency in the koniocellular pathway) are not independent, as previously assumed; and 3) a global reorganization in the brain circuit occurs following the lesions of the V1 and subsequent recovery. Finally, I introduce a recent study that employed a saliency computational model to quantitatively evaluate the residual visual channels in blindsight monkeys during free-viewing behavior. Their findings suggest that plastic changes occur in the color-processing pathways.

  17. The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

    Science.gov (United States)

    Jiráková, Klára; Šeneklová, Monika; Jirák, Daniel; Turnovcová, Karolína; Vosmanská, Magda; Babič, Michal; Horák, Daniel; Veverka, Pavel; Jendelová, Pavla

    2016-01-01

    Introduction Magnetic resonance (MR) imaging is suitable for noninvasive long-term tracking. We labeled human induced pluripotent stem cell-derived neural precursors (iPSC-NPs) with two types of iron-based nanoparticles, silica-coated cobalt zinc ferrite nanoparticles (CZF) and poly-l-lysine-coated iron oxide superparamagnetic nanoparticles (PLL-coated γ-Fe2O3) and studied their effect on proliferation and neuronal differentiation. Materials and methods We investigated the effect of these two contrast agents on neural precursor cell proliferation and differentiation capability. We further defined the intracellular localization and labeling efficiency and analyzed labeled cells by MR. Results Cell proliferation was not affected by PLL-coated γ-Fe2O3 but was slowed down in cells labeled with CZF. Labeling efficiency, iron content and relaxation rates measured by MR were lower in cells labeled with CZF when compared to PLL-coated γ-Fe2O3. Cytoplasmic localization of both types of nanoparticles was confirmed by transmission electron microscopy. Flow cytometry and immunocytochemical analysis of specific markers expressed during neuronal differentiation did not show any significant differences between unlabeled cells or cells labeled with both magnetic nanoparticles. Conclusion Our results show that cells labeled with PLL-coated γ-Fe2O3 are suitable for MR detection, did not affect the differentiation potential of iPSC-NPs and are suitable for in vivo cell therapies in experimental models of central nervous system disorders. PMID:27920532

  18. Human neural stem cell-derived cultures in three-dimensional substrates form spontaneously functional neuronal networks.

    Science.gov (United States)

    Smith, Imogen; Silveirinha, Vasco; Stein, Jason L; de la Torre-Ubieta, Luis; Farrimond, Jonathan A; Williamson, Elizabeth M; Whalley, Benjamin J

    2017-04-01

    Differentiated human neural stem cells were cultured in an inert three-dimensional (3D) scaffold and, unlike two-dimensional (2D) but otherwise comparable monolayer cultures, formed spontaneously active, functional neuronal networks that responded reproducibly and predictably to conventional pharmacological treatments to reveal functional, glutamatergic synapses. Immunocytochemical and electron microscopy analysis revealed a neuronal and glial population, where markers of neuronal maturity were observed in the former. Oligonucleotide microarray analysis revealed substantial differences in gene expression conferred by culturing in a 3D vs a 2D environment. Notable and numerous differences were seen in genes coding for neuronal function, the extracellular matrix and cytoskeleton. In addition to producing functional networks, differentiated human neural stem cells grown in inert scaffolds offer several significant advantages over conventional 2D monolayers. These advantages include cost savings and improved physiological relevance, which make them better suited for use in the pharmacological and toxicological assays required for development of stem cell-based treatments and the reduction of animal use in medical research. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Neural Network Ensembles

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Salamon, Peter

    1990-01-01

    We propose several means for improving the performance an training of neural networks for classification. We use crossvalidation as a tool for optimizing network parameters and architecture. We show further that the remaining generalization error can be reduced by invoking ensembles of similar...... networks....

  20. Neural systems for control

    National Research Council Canada - National Science Library

    Omidvar, Omid; Elliott, David L

    1997-01-01

    ... is reprinted with permission from A. Barto, "Reinforcement Learning," Handbook of Brain Theory and Neural Networks, M.A. Arbib, ed.. The MIT Press, Cambridge, MA, pp. 804-809, 1995. Chapter 4, Figures 4-5 and 7-9 and Tables 2-5, are reprinted with permission, from S. Cho, "Map Formation in Proprioceptive Cortex," International Jour...

  1. Neural Tube Defects

    Science.gov (United States)

    ... pregnancies each year in the United States. A baby’s neural tube normally develops into the brain and spinal cord. ... fluid in the brain. This is called hydrocephalus. Babies with this condition are treated with surgery to insert a tube (called a shunt) into the brain. The shunt ...

  2. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    Science.gov (United States)

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  3. Neural Tube Defects, Folic Acid and Methylation

    Science.gov (United States)

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  4. Neural Tube Defects, Folic Acid and Methylation

    Directory of Open Access Journals (Sweden)

    Henk J. Blom

    2013-09-01

    Full Text Available Neural tube defects (NTDs are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

  5. A new role for interferon gamma in neural stem/precursor cell dysregulation

    Directory of Open Access Journals (Sweden)

    Hartung Hans-Peter

    2011-03-01

    Full Text Available Abstract Background The identification of factors that compromise neurogenesis is aimed at improving stem cell-based approaches in the field of regenerative medicine. Interferon gamma (IFNγ is a main pro-inflammatory cytokine and up-regulated during several neurological diseases. IFNγ is generally thought to beneficially enhance neurogenesis from fetal or adult neural stem/precursor cells (NSPCs. Results We now provide direct evidence to the contrary that IFNγ induces a dysfunctional stage in a substantial portion of NSPC-derived progeny in vitro characterized by simultaneous expression of glial fibrillary acid protein (GFAP and neuronal markers, an abnormal gene expression and a functional phenotype neither typical for neurons nor for mature astrocytes. Dysfunctional development of NSPCs under the influence of IFNγ was finally demonstrated by applying the microelectrode array technology. IFNγ exposure of NSPCs during an initial 7-day proliferation period prevented the subsequent adequate differentiation and formation of functional neuronal networks. Conclusions Our results show that immunocytochemical analyses of NSPC-derived progeny are not necessarily indicating the correct cellular phenotype specifically under inflammatory conditions and that simultaneous expression of neuronal and glial markers rather point to cellular dysregulation. We hypothesize that inhibiting the impact of IFNγ on NSPCs during neurological diseases might contribute to effective neurogenesis and regeneration.

  6. Neural correlates of eating disorders: translational potential

    Directory of Open Access Journals (Sweden)

    McAdams CJ

    2015-09-01

    Full Text Available Carrie J McAdams,1,2 Whitney Smith1 1University of Texas at Southwestern Medical Center, 2Department of Psychiatry, Texas Health Presbyterian Hospital of Dallas, Dallas, TX, USA Abstract: Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychological, biological, and social factors. Treatment of eating disorders is challenging as there are few evidence-based treatments and limited understanding of the mechanisms that result in sustained recovery. In the last 20 years, we have begun to identify neural pathways that are altered in eating disorders. Consideration of how these pathways may contribute to an eating disorder can provide an understanding of expected responses to treatments. Eating disorder behaviors include restrictive eating, compulsive overeating, and purging behaviors after eating. Eating disorders are associated with changes in many neural systems. In this targeted review, we focus on three cognitive processes associated with neurocircuitry differences in subjects with eating disorders such as reward, decision-making, and social behavior. We briefly examine how each of these systems function in healthy people, using Neurosynth meta-analysis to identify key regions commonly implicated in these circuits. We review the evidence for disruptions of these regions and systems in eating disorders. Finally, we describe psychiatric and psychological treatments that are likely to function by impacting these regions. Keywords: anorexia nervosa, bulimia nervosa, social cognition, reward processing, decision-making

  7. Bioprinting for Neural Tissue Engineering.

    Science.gov (United States)

    Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

    2018-01-01

    Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Multiple Pathways Linking Racism to Health Outcomes

    Science.gov (United States)

    Harrell, Camara Jules P.; Burford, Tanisha I.; Cage, Brandi N.; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

    2012-01-01

    This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism’s impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society. PMID:22518195

  9. A dual-immunocytochemical method to localize c-fos protein in specific neurons based on their content of neuropeptides and connectivity

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Larsen, P J; Sørensen, G G

    1994-01-01

    Enhanced expression of the immediate early gene c-fos has been used as a marker of cellular activation in many different neuronal pathways. We wished to determine the neurochemical content and the connectivity of neurons, in which expression of c-fos is induced. For this purpose, a dual...

  10. Neural network technologies

    Science.gov (United States)

    Villarreal, James A.

    1991-01-01

    A whole new arena of computer technologies is now beginning to form. Still in its infancy, neural network technology is a biologically inspired methodology which draws on nature's own cognitive processes. The Software Technology Branch has provided a software tool, Neural Execution and Training System (NETS), to industry, government, and academia to facilitate and expedite the use of this technology. NETS is written in the C programming language and can be executed on a variety of machines. Once a network has been debugged, NETS can produce a C source code which implements the network. This code can then be incorporated into other software systems. Described here are various software projects currently under development with NETS and the anticipated future enhancements to NETS and the technology.

  11. Analysis of neural data

    CERN Document Server

    Kass, Robert E; Brown, Emery N

    2014-01-01

    Continual improvements in data collection and processing have had a huge impact on brain research, producing data sets that are often large and complicated. By emphasizing a few fundamental principles, and a handful of ubiquitous techniques, Analysis of Neural Data provides a unified treatment of analytical methods that have become essential for contemporary researchers. Throughout the book ideas are illustrated with more than 100 examples drawn from the literature, ranging from electrophysiology, to neuroimaging, to behavior. By demonstrating the commonality among various statistical approaches the authors provide the crucial tools for gaining knowledge from diverse types of data. Aimed at experimentalists with only high-school level mathematics, as well as computationally-oriented neuroscientists who have limited familiarity with statistics, Analysis of Neural Data serves as both a self-contained introduction and a reference work.

  12. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  13. Neural networks for triggering

    Energy Technology Data Exchange (ETDEWEB)

    Denby, B. (Fermi National Accelerator Lab., Batavia, IL (USA)); Campbell, M. (Michigan Univ., Ann Arbor, MI (USA)); Bedeschi, F. (Istituto Nazionale di Fisica Nucleare, Pisa (Italy)); Chriss, N.; Bowers, C. (Chicago Univ., IL (USA)); Nesti, F. (Scuola Normale Superiore, Pisa (Italy))

    1990-01-01

    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab.

  14. 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. .

  15. Neurally-mediated sincope.

    Science.gov (United States)

    Can, I; Cytron, J; Jhanjee, R; Nguyen, J; Benditt, D G

    2009-08-01

    Syncope is a syndrome characterized by a relatively sudden, temporary and self-terminating loss of consciousness; the causes may vary, but they have in common a temporary inadequacy of cerebral nutrient flow, usually due to a fall in systemic arterial pressure. However, while syncope is a common problem, it is only one explanation for episodic transient loss of consciousness (TLOC). Consequently, diagnostic evaluation should start with a broad consideration of real or seemingly real TLOC. Among those patients in whom TLOC is deemed to be due to ''true syncope'', the focus may then reasonably turn to assessing the various possible causes; in this regard, the neurally-mediated syncope syndromes are among the most frequently encountered. There are three common variations: vasovagal syncope (often termed the ''common'' faint), carotid sinus syndrome, and the so-called ''situational faints''. Defining whether the cause is due to a neurally-mediated reflex relies heavily on careful history taking and selected testing (e.g., tilt-test, carotid massage). These steps are important. Despite the fact that neurally-mediated faints are usually relatively benign from a mortality perspective, they are nevertheless only infrequently an isolated event; neurally-mediated syncope tends to recur, and physical injury resulting from falls or accidents, diminished quality-of-life, and possible restriction from employment or avocation are real concerns. Consequently, defining the specific form and developing an effective treatment strategy are crucial. In every case the goal should be to determine the cause of syncope with sufficient confidence to provide patients and family members with a reliable assessment of prognosis, recurrence risk, and treatment options.

  16. The Neural Noisy Channel

    OpenAIRE

    Yu, Lei; Blunsom, Phil; Dyer, Chris; Grefenstette, Edward; Kocisky, Tomas

    2016-01-01

    We formulate sequence to sequence transduction as a noisy channel decoding problem and use recurrent neural networks to parameterise the source and channel models. Unlike direct models which can suffer from explaining-away effects during training, noisy channel models must produce outputs that explain their inputs, and their component models can be trained with not only paired training samples but also unpaired samples from the marginal output distribution. Using a latent variable to control ...

  17. A neural network model of attention-modulated neurodynamics.

    Science.gov (United States)

    Gu, Yuqiao; Liljenström, Hans

    2007-12-01

    Visual attention appears to modulate cortical neurodynamics and synchronization through various cholinergic mechanisms. In order to study these mechanisms, we have developed a neural network model of visual cortex area V4, based on psychophysical, anatomical and physiological data. With this model, we want to link selective visual information processing to neural circuits within V4, bottom-up sensory input pathways, top-down attention input pathways, and to cholinergic modulation from the prefrontal lobe. We investigate cellular and network mechanisms underlying some recent analytical results from visual attention experimental data. Our model can reproduce the experimental findings that attention to a stimulus causes increased gamma-frequency synchronization in the superficial layers. Computer simulations and STA power analysis also demonstrate different effects of the different cholinergic attention modulation action mechanisms.

  18. Neural Based Orthogonal Data Fitting The EXIN Neural Networks

    CERN Document Server

    Cirrincione, Giansalvo

    2008-01-01

    Written by three leaders in the field of neural based algorithms, Neural Based Orthogonal Data Fitting proposes several neural networks, all endowed with a complete theory which not only explains their behavior, but also compares them with the existing neural and traditional algorithms. The algorithms are studied from different points of view, including: as a differential geometry problem, as a dynamic problem, as a stochastic problem, and as a numerical problem. All algorithms have also been analyzed on real time problems (large dimensional data matrices) and have shown accurate solutions. Wh

  19. The Incremental Induction of Neuroprotective Properties by Multiple Therapeutic Strategies for Primary and Secondary Neural Injury

    Directory of Open Access Journals (Sweden)

    Seunghoon Lee

    2015-08-01

    Full Text Available Neural diseases including injury by endogenous factors, traumatic brain injury, and degenerative neural injury are eventually due to reactive oxygen species (ROS. Thus ROS generation in neural tissues is a hallmark feature of numerous forms of neural diseases. Neural degeneration and the neural damage process is complex, involving a vast array of tissue structure, transcriptional/translational, electrochemical, metabolic, and functional events within the intact neighbors surrounding injured neural tissues. During aging, multiple changes involving physical, chemical, and biochemical processes occur from the molecular to the morphological levels in neural tissues. Among many recommended therapeutic candidates, melatonin also plays a role in protecting the nervous system from anti-inflammation and efficiently safeguards neuronal cells via antioxidants and other endogenous/exogenous beneficial factors. Therefore, given the wide range of mechanisms responsible for neuronal damage, multi-action drugs or therapies for the treatment of neural injury that make use of two or more agents and target several pathways may have greater efficacy in promoting functional recovery than a single therapy alone.

  20. 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.

  1. A model for the neural control of pineal periodicity

    Science.gov (United States)

    de Oliveira Cruz, Frederico Alan; Soares, Marilia Amavel Gomes; Cortez, Celia Martins

    2016-12-01

    The aim of this work was verify if a computational model associating the synchronization dynamics of coupling oscillators to a set of synaptic transmission equations would be able to simulate the control of pineal by a complex neural pathway that connects the retina to this gland. Results from the simulations showed that the frequency and temporal firing patterns were in the range of values found in literature.

  2. Neural Correlates of Stimulus Reportability

    OpenAIRE

    Hulme, Oliver J.; Friston, Karl F.; Zeki, Semir

    2009-01-01

    Most experiments on the “neural correlates of consciousness” employ stimulus reportability as an operational definition of what is consciously perceived. The interpretation of such experiments therefore depends critically on understanding the neural basis of stimulus reportability. Using a high volume of fMRI data, we investigated the neural correlates of stimulus reportability using a partial report object detection paradigm. Subjects were presented with a random array of circularly arranged...

  3. Symbolic processing in neural networks

    OpenAIRE

    Neto, João Pedro; Hava T Siegelmann; Costa,J.Félix

    2003-01-01

    In this paper we show that programming languages can be translated into recurrent (analog, rational weighted) neural nets. Implementation of programming languages in neural nets turns to be not only theoretical exciting, but has also some practical implications in the recent efforts to merge symbolic and sub symbolic computation. To be of some use, it should be carried in a context of bounded resources. Herein, we show how to use resource bounds to speed up computations over neural nets, thro...

  4. [Artificial neural networks in Neurosciences].

    Science.gov (United States)

    Porras Chavarino, Carmen; Salinas Martínez de Lecea, José María

    2011-11-01

    This article shows that artificial neural networks are used for confirming the relationships between physiological and cognitive changes. Specifically, we explore the influence of a decrease of neurotransmitters on the behaviour of old people in recognition tasks. This artificial neural network recognizes learned patterns. When we change the threshold of activation in some units, the artificial neural network simulates the experimental results of old people in recognition tasks. However, the main contributions of this paper are the design of an artificial neural network and its operation inspired by the nervous system and the way the inputs are coded and the process of orthogonalization of patterns.

  5. Neural Correlates of Face Detection

    National Research Council Canada - National Science Library

    Xu, Xiaokun; Biederman, Irving

    2014-01-01

    Although face detection likely played an essential adaptive role in our evolutionary past and in contemporary social interactions, there have been few rigorous studies investigating its neural correlates...

  6. How learning to abstract shapes neural sound representations

    Directory of Open Access Journals (Sweden)

    Anke eLey

    2014-06-01

    Full Text Available The transformation of acoustic signals into abstract perceptual representations is the essence of the efficient and goal-directed neural processing of sounds in complex natural environments. While the human and animal auditory system is perfectly equipped to process the spectrotemporal sound features, adequate sound identification and categorization require neural sound representations that are invariant to irrelevant stimulus parameters. Crucially, what is relevant and irrelevant is not necessarily intrinsic to the physical stimulus structure but needs to be learned over time, often through integration of information from other senses. This review discusses the main principles underlying categorical sound perception with a special focus on the role of learning and neural plasticity. We examine the role of different neural structures along the auditory processing pathway in the formation of abstract sound representations with respect to hierarchical as well as dynamic and distributed processing models. Whereas most fMRI studies on categorical sound processing employed speech sounds, the emphasis of the current review lies on the contribution of empirical studies using natural or artificial sounds that enable separating acoustic and perceptual processing levels and avoid interference with existing category representations. Finally, we discuss the opportunities of modern analyses techniques (such as multivariate pattern analysis in studying categorical sound representations. With their increased sensitivity to distributed activation changes - even in absence of changes in overall signal level - these analyses techniques provide a promising tool to reveal the neural underpinnings of perceptually invariant sound representations.

  7. Artificial neural networks modeling gene-environment interaction

    Directory of Open Access Journals (Sweden)

    Günther Frauke

    2012-05-01

    Full Text Available Abstract Background Gene-environment interactions play an important role in the etiological pathway of complex diseases. An appropriate statistical method for handling a wide variety of complex situations involving interactions between variables is still lacking, especially when continuous variables are involved. The aim of this paper is to explore the ability of neural networks to model different structures of gene-environment interactions. A simulation study is set up to compare neural networks with standard logistic regression models. Eight different structures of gene-environment interactions are investigated. These structures are characterized by penetrance functions that are based on sigmoid functions or on combinations of linear and non-linear effects of a continuous environmental factor and a genetic factor with main effect or with a masking effect only. Results In our simulation study, neural networks are more successful in modeling gene-environment interactions than logistic regression models. This outperfomance is especially pronounced when modeling sigmoid penetrance functions, when distinguishing between linear and nonlinear components, and when modeling masking effects of the genetic factor. Conclusion Our study shows that neural networks are a promising approach for analyzing gene-environment interactions. Especially, if no prior knowledge of the correct nature of the relationship between co-variables and response variable is present, neural networks provide a valuable alternative to regression methods that are limited to the analysis of linearly separable data.

  8. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Piya Prajumwongs

    2016-01-01

    Full Text Available Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

  9. Neural systems for tactual memories.

    Science.gov (United States)

    Bonda, E; Petrides, M; Evans, A

    1996-04-01

    1. The aim of this study was to investigate the neural systems involved in the memory processing of experiences through touch. 2. Regional cerebral blood flow was measured with positron emission tomography by means of the water bolus H2(15)O methodology in human subjects as they performed tasks involving different levels of tactual memory. In one of the experimental tasks, the subjects had to palpate nonsense shapes to match each one to a previously learned set, thus requiring constant reference to long-term memory. The other experimental task involved judgements of the recent recurrence of shapes during the scanning period. A set of three control tasks was used to control for the type of exploratory movements and sensory processing inherent in the two experimental tasks. 3. Comparisons of the distribution of activity between the experimental and the control tasks were carried out by means of the subtraction method. In relation to the control conditions, the two experimental tasks requiring memory resulted in significant changes within the posteroventral insula and the central opercular region. In addition, the task requiring recall from long-term memory yielded changes in the perirhinal cortex. 4. The above findings demonstrated that a ventrally directed parietoinsular pathway, leading to the posteroventral insula and the perirhinal cortex, constitutes a system by which long-lasting representations of tactual experiences are formed. It is proposed that the posteroventral insula is involved in tactual feature analysis, by analogy with the similar role of the inferotemporal cortex in vision, whereas the perirhinal cortex is further involved in the integration of these features into long-lasting representations of somatosensory experiences.

  10. Optics in neural computation

    Science.gov (United States)

    Levene, Michael John

    In all attempts to emulate the considerable powers of the brain, one is struck by both its immense size, parallelism, and complexity. While the fields of neural networks, artificial intelligence, and neuromorphic engineering have all attempted oversimplifications on the considerable complexity, all three can benefit from the inherent scalability and parallelism of optics. This thesis looks at specific aspects of three modes in which optics, and particularly volume holography, can play a part in neural computation. First, holography serves as the basis of highly-parallel correlators, which are the foundation of optical neural networks. The huge input capability of optical neural networks make them most useful for image processing and image recognition and tracking. These tasks benefit from the shift invariance of optical correlators. In this thesis, I analyze the capacity of correlators, and then present several techniques for controlling the amount of shift invariance. Of particular interest is the Fresnel correlator, in which the hologram is displaced from the Fourier plane. In this case, the amount of shift invariance is limited not just by the thickness of the hologram, but by the distance of the hologram from the Fourier plane. Second, volume holography can provide the huge storage capacity and high speed, parallel read-out necessary to support large artificial intelligence systems. However, previous methods for storing data in volume holograms have relied on awkward beam-steering or on as-yet non- existent cheap, wide-bandwidth, tunable laser sources. This thesis presents a new technique, shift multiplexing, which is capable of very high densities, but which has the advantage of a very simple implementation. In shift multiplexing, the reference wave consists of a focused spot a few millimeters in front of the hologram. Multiplexing is achieved by simply translating the hologram a few tens of microns or less. This thesis describes the theory for how shift

  11. Rapid neural circuit switching mediated by synaptic plasticity during neural morphallactic regeneration.

    Science.gov (United States)

    Lybrand, Zane R; Zoran, Mark J

    2012-09-01

    The aquatic oligochaete, Lumbriculus variegatus (Lumbriculidae), undergoes a rapid regenerative transformation of its neural circuits following body fragmentation. This type of nervous system plasticity, called neural morphallaxis, involves the remodeling of the giant fiber pathways that mediate rapid head and tail withdrawal behaviors. Extra- and intracellular electrophysiological recordings demonstrated that changes in cellular properties and synaptic connections underlie neurobehavioral plasticity during morphallaxis. Sensory-to-giant interneuron connections, undetectable prior to body injury, emerged within hours of segment amputation. The appearance of functional synaptic transmission was followed by interneuron activation, coupling of giant fiber spiking to motor outputs and overt segmental shortening. The onset of morphallactic plasticity varied along the body axis and emerged more rapidly in segments closer to regions of sensory field overlap between the two giant fiber pathways. The medial and lateral giant fibers were simultaneously activated during a transient phase of network remodeling. Thus, synaptic plasticity at sensory-to-giant interneuron connections mediates escape circuit morphallaxis in this regenerating annelid worm. Copyright © 2011 Wiley Periodicals, Inc.

  12. The neural substrate of the vestibulocollic reflex. What needs to be learned.

    Science.gov (United States)

    Wilson, V J; Schor, R H

    1999-12-01

    The purpose of this review is to assess the role of short-latency pathways in the vestibulocollic reflex (VCR). First the current knowledge about the disynaptic and trisynaptic pathways linking semicircular canal and otolith afferents with cat neck motoneurons is summarized. We then discuss whether these pathways are sufficient or necessary to produce the responses observed in neck muscles by natural vestibular stimulation and conclude that they are neither. Finally, alternate pathways are considered, most likely involving reticulospinal fibers, which are an important part of the neural substrate of the VCR.

  13. Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway

    Directory of Open Access Journals (Sweden)

    Joel R. Frandsen

    2018-04-01

    Full Text Available The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases – including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder – are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural cells. Novel flavonoids could be designed, synthesized and tested to protect against neurodegenerative diseases through regulating the glyoxalase pathway. Keywords: Glyoxalase pathway, Neuron, Flavonoid, Antioxidant, Neurodegenerative disease, Neuroprotection, Detoxification, Neurons viable

  14. Analysis of neural networks

    CERN Document Server

    Heiden, Uwe

    1980-01-01

    The purpose of this work is a unified and general treatment of activity in neural networks from a mathematical pOint of view. Possible applications of the theory presented are indica­ ted throughout the text. However, they are not explored in de­ tail for two reasons : first, the universal character of n- ral activity in nearly all animals requires some type of a general approach~ secondly, the mathematical perspicuity would suffer if too many experimental details and empirical peculiarities were interspersed among the mathematical investigation. A guide to many applications is supplied by the references concerning a variety of specific issues. Of course the theory does not aim at covering all individual problems. Moreover there are other approaches to neural network theory (see e.g. Poggio-Torre, 1978) based on the different lev­ els at which the nervous system may be viewed. The theory is a deterministic one reflecting the average be­ havior of neurons or neuron pools. In this respect the essay is writt...

  15. Artificial Neural Networks·

    Indian Academy of Sciences (India)

    differences between biological neural networks (BNNs) of the brain and ANN s. A thorough understanding of ... neurons. Artificial neural models are loosely based on biology since a complete understanding of the .... A learning scheme for updating a neuron's connections (weights) was proposed by Donald Hebb in 1949.

  16. Neural Networks for Optimal Control

    DEFF Research Database (Denmark)

    Sørensen, O.

    1995-01-01

    Two neural networks are trained to act as an observer and a controller, respectively, to control a non-linear, multi-variable process.......Two neural networks are trained to act as an observer and a controller, respectively, to control a non-linear, multi-variable process....

  17. The Neural Support Vector Machine

    NARCIS (Netherlands)

    Wiering, Marco; van der Ree, Michiel; Embrechts, Mark; Stollenga, Marijn; Meijster, Arnold; Nolte, A; Schomaker, Lambertus

    2013-01-01

    This paper describes a new machine learning algorithm for regression and dimensionality reduction tasks. The Neural Support Vector Machine (NSVM) is a hybrid learning algorithm consisting of neural networks and support vector machines (SVMs). The output of the NSVM is given by SVMs that take a

  18. Neural fields theory and applications

    CERN Document Server

    Graben, Peter; Potthast, Roland; Wright, James

    2014-01-01

    With this book, the editors present the first comprehensive collection in neural field studies, authored by leading scientists in the field - among them are two of the founding-fathers of neural field theory. Up to now, research results in the field have been disseminated across a number of distinct journals from mathematics, computational neuroscience, biophysics, cognitive science and others. Starting with a tutorial for novices in neural field studies, the book comprises chapters on emergent patterns, their phase transitions and evolution, on stochastic approaches, cortical development, cognition, robotics and computation, large-scale numerical simulations, the coupling of neural fields to the electroencephalogram and phase transitions in anesthesia. The intended readership are students and scientists in applied mathematics, theoretical physics, theoretical biology, and computational neuroscience. Neural field theory and its applications have a long-standing tradition in the mathematical and computational ...

  19. The Neural Correlates of Race

    Science.gov (United States)

    Ito, Tiffany A.; Bartholow, Bruce D.

    2009-01-01

    Behavioral analyses are a natural choice for understanding the wide-ranging behavioral consequences of racial stereotyping and prejudice. However, neuroimaging and electrophysiological research has recently considered the neural mechanisms that underlie racial categorization and the activation and application of racial stereotypes and prejudice, revealing exciting new insights. Work reviewed here points to the importance of neural structures previously associated with face processing, semantic knowledge activation, evaluation, and self-regulatory behavioral control, allowing for the specification of a neural model of race processing. We show how research on the neural correlates of race can serve to link otherwise disparate lines of evidence on the neural underpinnings of a broad array of social-cognitive phenomena, and consider implications for effecting change in race relations. PMID:19896410

  20. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... examined, and it appears that considering 'normal' neural network models with, say, 500 samples, the problem of over-fitting is neglible, and therefore it is not taken into consideration afterwards. Numerous model types, often met in control applications, are implemented as neural network models...... Kalmann filter) representing state space description. The potentials of neural networks for control of non-linear processes are also examined, focusing on three different groups of control concepts, all considered as generalizations of known linear control concepts to handle also non-linear processes...

  1. Natural neural projection dynamics underlying social behavior.

    Science.gov (United States)

    Gunaydin, Lisa A; Grosenick, Logan; Finkelstein, Joel C; Kauvar, Isaac V; Fenno, Lief E; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J; Airan, Raag D; Zalocusky, Kelly A; Tye, Kay M; Anikeeva, Polina; Malenka, Robert C; Deisseroth, Karl

    2014-06-19

    Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Dynamic Encoding of Acoustic Features in Neural Responses to Continuous Speech.

    Science.gov (United States)

    Khalighinejad, Bahar; Cruzatto da Silva, Guilherme; Mesgarani, Nima

    2017-02-22

    Humans are unique in their ability to communicate using spoken language. However, it remains unclear how the speech signal is transformed and represented in the brain at different stages of the auditory pathway. In this study, we characterized electroencephalography responses to continuous speech by obtaining the time-locked responses to phoneme instances (phoneme-related potential). We showed that responses to different phoneme categories are organized by phonetic features. We found that each instance of a phoneme in continuous speech produces multiple distinguishable neural responses occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Comparing the patterns of phoneme similarity in the neural responses and the acoustic signals confirms a repetitive appearance of acoustic distinctions of phonemes in the neural data. Analysis of the phonetic and speaker information in neural activations revealed that different time intervals jointly encode the acoustic similarity of both phonetic and speaker categories. These findings provide evidence for a dynamic neural transformation of low-level speech features as they propagate along the auditory pathway, and form an empirical framework to study the representational changes in learning, attention, and speech disorders.SIGNIFICANCE STATEMENT We characterized the properties of evoked neural responses to phoneme instances in continuous speech. We show that each instance of a phoneme in continuous speech produces several observable neural responses at different times occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Each temporal event explicitly encodes the acoustic similarity of phonemes, and linguistic and nonlinguistic information are best represented at different time intervals. Finally, we show a joint encoding of phonetic and speaker information, where the neural representation of speakers is dependent on phoneme category. These findings provide compelling new evidence for

  3. The NPY system and its neural and neuroendocrine regulation of bone.

    Science.gov (United States)

    Khor, Ee Cheng; Baldock, Paul

    2012-06-01

    The past decade has seen a significant expansion of our understanding of the interaction between the neural system and bone. While innervation of bone was long appreciated, the discovery of central relays from the hypothalamus to the cells of bone has seen the identification of a number of efferent neural pathways to bone. The neuropeptide Y (NPY) system has proven to represent a major central pathway, regulating the activity of osteoblasts and osteoclasts, through signaling of central and peripheral ligands, through specific receptors within the hypothalamus and the osteoblast. Moreover, this pathway is now recognized as acting to coordinate both skeletal and energy homeostasis. This review examines the mechanism and actions of the NPY pathway to regulate bone mass and bone cell activity.

  4. Differential Expression of Matrix Metalloproteinase-2 Expression in Disseminated Tumor Cells and Micrometastasis in Bone Marrow of Patients with Nonmetastatic and Metastatic Prostate Cancer: Theoretical Considerations and Clinical Implications—An Immunocytochemical Study

    Directory of Open Access Journals (Sweden)

    Nigel P. Murray

    2012-01-01

    Full Text Available Matrix metalloproteinase-2 (MMP-2 is important in the dissemination and invasion of tumor cells and activates angiogenesis. We present an immunocytochemical study of MMP-2 expression in circulating prostate cells (CPCs, disseminated tumor cells (DTCs, and micrometastasis (mM in bone marrow of men with prostate cancer. Methods and Patients. Tumor cells were identified with anti-PSA immunocytochemistry. Positive samples underwent processing with anti-MMP-2, its expression was compared with Gleason score, concordance of expression, and metastatic and nonmetastatic disease. Results. 215 men participated, CPCs were detected in 62.7%, DTCs in 62.2%, and mM in 71.4% in nonmetastatic cancer; in metastatic cancer all had CPCs, DTCs, and mM detected. All CPCs and DTCs expressed MMP-2; in mM MMP-2 expression was positively associated with increasing Gleason score. MMP-2 expression in CPCs and DTCs showed concordance. In low grade tumors, mM and surrounding stromal cells were MMP-2 negative, with variable expression in high grade tumors; in metastatic disease, both mM and stromal cells were MMP-2 positive. Conclusions. CPCs and DTCs are different from mM, with inhibition of MMP-2 expression in mM of low grade tumors. With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors.

  5. Differential Expression of Matrix Metalloproteinase-2 Expression in Disseminated Tumor Cells and Micrometastasis in Bone Marrow of Patients with Nonmetastatic and Metastatic Prostate Cancer: Theoretical Considerations and Clinical Implications—An Immunocytochemical Study

    Science.gov (United States)

    Murray, Nigel P.; Reyes, Eduardo; Tapia, Pablo; Badínez, Leonardo; Orellana, Nelson

    2012-01-01

    Matrix metalloproteinase-2 (MMP-2) is important in the dissemination and invasion of tumor cells and activates angiogenesis. We present an immunocytochemical study of MMP-2 expression in circulating prostate cells (CPCs), disseminated tumor cells (DTCs), and micrometastasis (mM) in bone marrow of men with prostate cancer. Methods and Patients. Tumor cells were identified with anti-PSA immunocytochemistry. Positive samples underwent processing with anti-MMP-2, its expression was compared with Gleason score, concordance of expression, and metastatic and nonmetastatic disease. Results. 215 men participated, CPCs were detected in 62.7%, DTCs in 62.2%, and mM in 71.4% in nonmetastatic cancer; in metastatic cancer all had CPCs, DTCs, and mM detected. All CPCs and DTCs expressed MMP-2; in mM MMP-2 expression was positively associated with increasing Gleason score. MMP-2 expression in CPCs and DTCs showed concordance. In low grade tumors, mM and surrounding stromal cells were MMP-2 negative, with variable expression in high grade tumors; in metastatic disease, both mM and stromal cells were MMP-2 positive. Conclusions. CPCs and DTCs are different from mM, with inhibition of MMP-2 expression in mM of low grade tumors. With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors. PMID:23227342

  6. An Optoelectronic Neural Network

    Science.gov (United States)

    Neil, Mark A. A.; White, Ian H.; Carroll, John E.

    1990-02-01

    We describe and present results of an optoelectronic neural network processing system. The system uses an algorithm based on the Hebbian learning rule to memorise a set of associated vector pairs. Recall occurs by the processing of the input vector with these stored associations in an incoherent optical vector multiplier using optical polarisation rotating liquid crystal spatial light modulators to store the vectors and an optical polarisation shadow casting technique to perform multiplications. Results are detected on a photodiode array and thresholded electronically by a controlling microcomputer. The processor is shown to work in autoassociative and heteroassociative modes with up to 10 stored memory vectors of length 64 (equivalent to 64 neurons) and a cycle time of 50ms. We discuss the limiting factors at work in this system, how they affect its scalability and the general applicability of its principles to other systems.

  7. Neural Darwinism and consciousness.

    Science.gov (United States)

    Seth, Anil K; Baars, Bernard J

    2005-03-01

    Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the 'dynamic core'). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well.

  8. Cortical neural prosthetics.

    Science.gov (United States)

    Schwartz, Andrew B

    2004-01-01

    Control of prostheses using cortical signals is based on three elements: chronic microelectrode arrays, extraction algorithms, and prosthetic effectors. Arrays of microelectrodes are permanently implanted in cerebral cortex. These arrays must record populations of single- and multiunit activity indefinitely. Information containing position and velocity correlates of animate movement needs to be extracted continuously in real time from the recorded activity. Prosthetic arms, the current effectors used in this work, need to have the agility and configuration of natural arms. Demonstrations using closed-loop control show that subjects change their neural activity to improve performance with these devices. Adaptive-learning algorithms that capitalize on these improvements show that this technology has the capability of restoring much of the arm movement lost with immobilizing deficits.

  9. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

  10. Gallium nitride induces neuronal differentiation markers in neural stem/precursor cells derived from rat cerebral cortex.

    Science.gov (United States)

    Chen, Chi-Ruei; Li, Yi-Chen; Young, Tai-Horng

    2009-09-01

    In the present study, gallium nitride (GaN) was used as a substrate to culture neural stem/precursor cells (NSPCs), isolated from embryonic rat cerebral cortex, to examine the effect of GaN on the behavior of NSPCs in the presence of basic fibroblast growth factor (bFGF) in serum-free medium. Morphological studies showed that neurospheres maintained their initial shape and formed many long and thick processes with the fasciculate feature on GaN. Immunocytochemical characterization showed that GaN could induce the differentiation of NSPCs into neurons and astrocytes. Compared to poly-d-lysine (PDL), the most common substrate used for culturing neurons, there was considerable expression of synapsin I for differentiated neurons on GaN, suggesting GaN could induce the differentiation of NSPCs towards the mature differentiated neurons. Western blot analysis showed that the suppression of glycogen synthase kinase-3beta (GSK-3beta) activity was one of the effects of GaN-promoted NSPC differentiation into neurons. Finally, compared to PDL, GaN could significantly improve cell survival to reduce cell death after long-term culture. These results suggest that GaN potentially has a combination of electric characteristics suitable for developing neuron and/or NSPC chip systems.

  11. Convergent evolution of neural systems in ctenophores.

    Science.gov (United States)

    Moroz, Leonid L

    2015-02-15

    Neurons are defined as polarized secretory cells specializing in directional propagation of electrical signals leading to the release of extracellular messengers - features that enable them to transmit information, primarily chemical in nature, beyond their immediate neighbors without affecting all intervening cells en route. Multiple origins of neurons and synapses from different classes of ancestral secretory cells might have occurred more than once during ~600 million years of animal evolution with independent events of nervous system centralization from a common bilaterian/cnidarian ancestor without the bona fide central nervous system. Ctenophores, or comb jellies, represent an example of extensive parallel evolution in neural systems. First, recent genome analyses place ctenophores as a sister group to other animals. Second, ctenophores have a smaller complement of pan-animal genes controlling canonical neurogenic, synaptic, muscle and immune systems, and developmental pathways than most other metazoans. However, comb jellies are carnivorous marine animals with a complex neuromuscular organization and sophisticated patterns of behavior. To sustain these functions, they have evolved a number of unique molecular innovations supporting the hypothesis of massive homoplasies in the organization of integrative and locomotory systems. Third, many bilaterian/cnidarian neuron-specific genes and 'classical' neurotransmitter pathways are either absent or, if present, not expressed in ctenophore neurons (e.g. the bilaterian/cnidarian neurotransmitter, γ-amino butyric acid or GABA, is localized in muscles and presumed bilaterian neuron-specific RNA-binding protein Elav is found in non-neuronal cells). Finally, metabolomic and pharmacological data failed to detect either the presence or any physiological action of serotonin, dopamine, noradrenaline, adrenaline, octopamine, acetylcholine or histamine - consistent with the hypothesis that ctenophore neural systems evolved

  12. Cooperating attackers in neural cryptography.

    Science.gov (United States)

    Shacham, Lanir N; Klein, Einat; Mislovaty, Rachel; Kanter, Ido; Kinzel, Wolfgang

    2004-06-01

    A successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The success of the advanced attacker presented here, called the "majority-flipping attacker," does not decay with the parameters of the model. This attacker's outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations.

  13. Cooperating attackers in neural cryptography

    Science.gov (United States)

    Shacham, Lanir N.; Klein, Einat; Mislovaty, Rachel; Kanter, Ido; Kinzel, Wolfgang

    2004-06-01

    A successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The success of the advanced attacker presented here, called the “majority-flipping attacker,” does not decay with the parameters of the model. This attacker’s outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations.

  14. Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT1 receptor with neuronal and glial markers

    Directory of Open Access Journals (Sweden)

    McMillan Catherine R

    2004-10-01

    Full Text Available Abstract Background In order to optimize the potential benefits of neural stem cell (NSC transplantation for the treatment of neurodegenerative disorders, it is necessary to understand their biological characteristics. Although neurotrophin transduction strategies are promising, alternative approaches such as the modulation of intrinsic neurotrophin expression by NSCs, could also be beneficial. Therefore, utilizing the C17.2 neural stem cell line, we have examined the expression of selected neurotrophic factors under different in vitro conditions. In view of recent evidence suggesting a role for the pineal hormone melatonin in vertebrate development, it was also of interest to determine whether its G protein-coupled MT1 and MT2 receptors are expressed in NSCs. Results RT-PCR analysis revealed robust expression of glial cell-line derived neurotrophic factor (GDNF, brain-derived neurotrophic factor (BDNF and nerve growth factor (NGF in undifferentiated cells maintained for two days in culture. After one week, differentiating cells continued to exhibit high expression of BDNF and NGF, but GDNF expression was lower or absent, depending on the culture conditions utilized. Melatonin MT1 receptor mRNA was detected in NSCs maintained for two days in culture, but the MT2 receptor was not seen. An immature MT1 receptor of about 30 kDa was detected by western blotting in NSCs cultured for two days, whereas a mature receptor of about 40 – 45 kDa was present in cells maintained for longer periods. Immunocytochemical studies demonstrated that the MT1 receptor is expressed in both neural (β-tubulin III positive and glial (GFAP positive progenitor cells. An examination of the effects of melatonin on neurotrophin expression revealed that low physiological concentrations of this hormone caused a significant induction of GDNF mRNA expression in NSCs following treatment for 24 hours. Conclusions The phenotypic characteristics of C17.2 cells suggest that they are

  15. Neural Manifolds for the Control of Movement.

    Science.gov (United States)

    Gallego, Juan A; Perich, Matthew G; Miller, Lee E; Solla, Sara A

    2017-06-07

    The analysis of neural dynamics in several brain cortices has consistently uncovered low-dimensional manifolds that capture a significant fraction of neural variability. These neural manifolds are spanned by specific patterns of correlated neural activity, the "neural modes." We discuss a model for neural control of movement in which the time-dependent activation of these neural modes is the generator of motor behavior. This manifold-based view of motor cortex may lead to a better understanding of how the brain controls movement. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 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.

  17. Neural progestin receptors and female sexual behavior

    Science.gov (United States)

    Mani, Shaila K.; Blaustein, Jeffrey D.

    2012-01-01

    The steroid hormone, progesterone, modulates neuroendocrine functions in the central nervous system resulting in integration of reproduction and reproductive behaviors in female mammals. Although it is widely recognized that progesterone’s effects on female sex behavior are mediated by the classical neural progestin receptors (PRs) functioning as “ligand-dependent” transcription factors to regulate genes and genomic networks, additional mechanisms of PR activation also contribute to the behavioral response. Cellular and molecular evidence indicates that PRs can be activated in a ligand-independent manner by neurotransmitters, growth factors, cyclic nucleotides, progestin metabolites and mating stimuli. The rapid responses of progesterone may be mediated by a variety of PR types, including membrane-associated PRs or extra-nuclear PRs. Furthermore, these rapid, non-classical progesterone actions involving cytoplasmic kinase signaling and/or extra-nuclear PRs also converge with classical PR-mediated, transcription dependent pathway to regulate reproductive behaviors. In this review, we summarize some of the history of the study of the role of PRs in reproductive behaviors, and update the status of PR-mediated mechanisms involved in the facilitation of female sex behavior. We present an integrative model of PR activation via crosstalk and convergence of multiple signaling pathways. PMID:22538437

  18. Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex

    Science.gov (United States)

    Remedios, Ryan; Kennedy, Ann; Zelikowsky, Moriel; Grewe, Benjamin F.; Schnitzer, Mark J.; Anderson, David J.

    2017-10-01

    All animals possess a repertoire of innate (or instinctive) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown. Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents. We used microendoscopy to image Esr1+ neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.

  19. Future Climate of Colombo Downscaled with SDSM-Neural Network

    Directory of Open Access Journals (Sweden)

    Singay Dorji

    2017-03-01

    Full Text Available The Global Climate Model (GCM run at a coarse spatial resolution cannot be directly used for climate impact studies. Downscaling is required to extract the sub-grid and local scale information. This paper investigates if the artificial neural network (ANN is better than the widely-used regression-based statistical downscaling model (SDSM for downscaling climate for a site in Colombo, Sri Lanka. Based on seasonal and annual model biases and the root mean squared error (RMSE, the ANN performed better than the SDSM for precipitation. This paper proposes a novel methodology for improving climate predictions by combining SDSM with neural networks. This method will allow a user to apply SDSM with a neural network model for higher skills in downscaling. The study uses the Canadian Earth System Model (CanESM2 of the IPCC Fifth Assessment Report, reanalysis from the National Center for Environmental Prediction (NCEP, and the Asian Precipitation Highly Resolved Observational Data Integration towards Evaluation of Water Resources (APHRODITE project data as the observation. SDSM and the focused time-delayed neural network (TDNN models are used for the downscaling. The projected annual increase for Representative Concentration Pathway (RCP is 8.5; the average temperature is 2.83 °C (SDSM and 3.03 °C (TDNN, and rainfall is 33% (SDSM and 63% (TDNN for 2080’s.

  20. Epidemiology of neural tube defects

    National Research Council Canada - National Science Library

    Seidahmed, Mohammed Z; Abdelbasit, Omar B; Shaheed, Meeralebbae M; Alhussein, Khalid A; Miqdad, Abeer M; Khalil, Mohamed I; Al-Enazy, Naif M; Salih, Mustafa A

    2014-01-01

    To find the prevalence of neural tube defects (NTDs), and compare the findings with local and international data, and highlight the important role of folic acid supplementation and flour fortification with folic acid in preventing NTDs...

  1. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... study of the networks themselves. With this end in view the following restrictions have been made: - Amongst numerous neural network structures, only the Multi Layer Perceptron (a feed-forward network) is applied. - Amongst numerous training algorithms, only four algorithms are examined, all...... in a recursive form (sample updating). The simplest is the Back Probagation Error Algorithm, and the most complex is the recursive Prediction Error Method using a Gauss-Newton search direction. - Over-fitting is often considered to be a serious problem when training neural networks. This problem is specifically...

  2. Memristor-based neural networks

    Science.gov (United States)

    Thomas, Andy

    2013-03-01

    The synapse is a crucial element in biological neural networks, but a simple electronic equivalent has been absent. This complicates the development of hardware that imitates biological architectures in the nervous system. Now, the recent progress in the experimental realization of memristive devices has renewed interest in artificial neural networks. The resistance of a memristive system depends on its past states and exactly this functionality can be used to mimic the synaptic connections in a (human) brain. After a short introduction to memristors, we present and explain the relevant mechanisms in a biological neural network, such as long-term potentiation and spike time-dependent plasticity, and determine the minimal requirements for an artificial neural network. We review the implementations of these processes using basic electric circuits and more complex mechanisms that either imitate biological systems or could act as a model system for them.

  3. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    simulated process and compared. The closing chapter describes some practical experiments, where the different control concepts and training methods are tested on the same practical process operating in very noisy environments. All tests confirm that neural networks also have the potential to be trained......The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... study of the networks themselves. With this end in view the following restrictions have been made: - Amongst numerous neural network structures, only the Multi Layer Perceptron (a feed-forward network) is applied. - Amongst numerous training algorithms, only four algorithms are examined, all...

  4. 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.

  5. Complex-Valued Neural Networks

    CERN Document Server

    Hirose, Akira

    2012-01-01

    This book is the second enlarged and revised edition of the first successful monograph on complex-valued neural networks (CVNNs) published in 2006, which lends itself to graduate and undergraduate courses in electrical engineering, informatics, control engineering, mechanics, robotics, bioengineering, and other relevant fields. In the second edition the recent trends in CVNNs research are included, resulting in e.g. almost a doubled number of references. The parametron invented in 1954 is also referred to with discussion on analogy and disparity. Also various additional arguments on the advantages of the complex-valued neural networks enhancing the difference to real-valued neural networks are given in various sections. The book is useful for those beginning their studies, for instance, in adaptive signal processing for highly functional sensing and imaging, control in unknown and changing environment, robotics inspired by human neural systems, and brain-like information processing, as well as interdisciplina...

  6. CHARGEd with neural crest defects.

    Science.gov (United States)

    Pauli, Silke; Bajpai, Ruchi; Borchers, Annette

    2017-10-30

    Neural crest cells are highly migratory pluripotent cells that give rise to diverse derivatives including cartilage, bone, smooth muscle, pigment, and endocrine cells as well as neurons and glia. Abnormalities in neural crest-derived tissues contribute to the etiology of CHARGE syndrome, a complex malformation disorder that encompasses clinical symptoms like coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. Mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene are causative of CHARGE syndrome and loss-of-function data in different model systems have firmly established a role of CHD7 in neural crest development. Here, we will summarize our current understanding of the function of CHD7 in neural crest development and discuss possible links of CHARGE syndrome to other developmental disorders. © 2017 Wiley Periodicals, Inc.

  7. Neural components of altruistic punishment.

    Science.gov (United States)

    Du, Emily; Chang, Steve W C

    2015-01-01

    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.

  8. Pansharpening by Convolutional Neural Networks

    National Research Council Canada - National Science Library

    Masi, Giuseppe; Cozzolino, Davide; Verdoliva, Luisa; Scarpa, Giuseppe

    2016-01-01

    A new pansharpening method is proposed, based on convolutional neural networks. We adapt a simple and effective three-layer architecture recently proposed for super-resolution to the pansharpening problem...

  9. Pathways to Metallic Hydrogen

    OpenAIRE

    Silvera, Isaac F.; Deemyad, Shanti

    2008-01-01

    The traditional pathway that researchers have used in the goal of producing atomic metallic hydrogen is to compress samples with megabar pressures at low temperature. A number of phases have been observed in solid hydrogen and its isotopes, but all are in the insulating phase. The results of experiment and theory for this pathway are reviewed. In recent years a new pathway has become the focus of this challenge of producing metallic hydrogen, namely a path along the melting line. It has bee...

  10. Neural systems for social cognition in Klinefelter syndrome (47.XXY) : evidence from fMRI

    NARCIS (Netherlands)

    van Rijn, S.; Swaab, H; Baas, D; de Haan, E; Kahn, R.S.; Aleman, A.

    Klinefelter syndrome (KS) is a chromosomal condition (47, XXY) that may help us to unravel gene-brain behavior pathways to psychopathology. The phenotype includes social cognitive impairments and increased risk for autism traits. We used functional MRI to study neural mechanisms underlying social

  11. What are artificial neural networks?

    DEFF Research Database (Denmark)

    Krogh, Anders

    2008-01-01

    Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb......Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb...

  12. Indices for Testing Neural Codes

    OpenAIRE

    Jonathan D. Victor; Nirenberg, Sheila

    2008-01-01

    One of the most critical challenges in systems neuroscience is determining the neural code. A principled framework for addressing this can be found in information theory. With this approach, one can determine whether a proposed code can account for the stimulus-response relationship. Specifically, one can compare the transmitted information between the stimulus and the hypothesized neural code with the transmitted information between the stimulus and the behavioral response. If the former is ...

  13. Biologically Inspired Modular Neural Networks

    OpenAIRE

    Azam, Farooq

    2000-01-01

    This dissertation explores the modular learning in artificial neural networks that mainly driven by the inspiration from the neurobiological basis of the human learning. The presented modularization approaches to the neural network design and learning are inspired by the engineering, complexity, psychological and neurobiological aspects. The main theme of this dissertation is to explore the organization and functioning of the brain to discover new structural and learning ...

  14. Anterior Hox Genes Interact with Components of the Neural Crest Specification Network to Induce Neural Crest Fates

    Science.gov (United States)

    Gouti, Mina; Briscoe, James; Gavalas, Anthony

    2011-01-01

    Hox genes play a central role in neural crest (NC) patterning particularly in the cranial region of the body. Despite evidence that simultaneous loss of Hoxa1 and Hoxb1 function resulted in NC specification defects, the role of Hox genes in NC specification has remained unclear due to extended genetic redundancy among Hox genes. To circumvent this problem, we expressed anterior Hox genes in the trunk neural tube of the developing chick embryo. This demonstrated that anterior Hox genes play a central role in NC cell specification by rapidly inducing the key transcription factors Snail2 and Msx1/2 and a neural progenitor to NC cell fate switch characterized by cell adhesion changes and an epithelial-to-mesenchymal transition (EMT). Cells delaminated from dorsal and medial neural tube levels and generated ectopic neurons, glia progenitors, and melanocytes. The mobilization of the NC genetic cascade was dependent upon bone morphogenetic protein signaling and optimal levels of Notch signaling. Therefore, anterior Hox patterning genes participate in NC specification and EMT by interacting with NC-inducing signaling pathways and regulating the expression of key genes involved in these processes. Stem Cells 2011;29:858–870 PMID:21433221

  15. Neural-like growing networks

    Science.gov (United States)

    Yashchenko, Vitaliy A.

    2000-03-01

    On the basis of the analysis of scientific ideas reflecting the law in the structure and functioning the biological structures of a brain, and analysis and synthesis of knowledge, developed by various directions in Computer Science, also there were developed the bases of the theory of a new class neural-like growing networks, not having the analogue in world practice. In a base of neural-like growing networks the synthesis of knowledge developed by classical theories - semantic and neural of networks is. The first of them enable to form sense, as objects and connections between them in accordance with construction of the network. With thus each sense gets a separate a component of a network as top, connected to other tops. In common it quite corresponds to structure reflected in a brain, where each obvious concept is presented by certain structure and has designating symbol. Secondly, this network gets increased semantic clearness at the expense owing to formation not only connections between neural by elements, but also themselves of elements as such, i.e. here has a place not simply construction of a network by accommodation sense structures in environment neural of elements, and purely creation of most this environment, as of an equivalent of environment of memory. Thus neural-like growing networks are represented by the convenient apparatus for modeling of mechanisms of teleological thinking, as a fulfillment of certain psychophysiological of functions.

  16. Flexibility of neural stem cells

    Directory of Open Access Journals (Sweden)

    Eumorphia eRemboutsika

    2011-04-01

    Full Text Available Embryonic cortical neural stem cells are self-renewing progenitors that can differentiate into neurons and glia. We generated neurospheres from the developing cerebral cortex using a mouse genetic model that allows for lineage selection and found that the self-renewing neural stem cells are restricted to Sox2 expressing cells. Under normal conditions, embryonic cortical neurospheres are heterogeneous with regard to Sox2 expression and contain astrocytes, neural stem cells and neural progenitor cells sufficiently plastic to give rise to neural crest cells when transplanted into the hindbrain of E1.5 chick and E8 mouse embryos. However, when neurospheres are maintained under lineage selection, such that all cells express Sox2, neural stem cells maintain their Pax6+ cortical radial glia identity and exhibit a more restricted fate in vitro and after transplantation. These data demonstrate that Sox2 preserves the cortical identity and regulates the plasticity of self-renewing Pax6+ radial glia cells.

  17. Perlecan is required for FGF-2 signaling in the neural stem cell niche

    Directory of Open Access Journals (Sweden)

    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  18. Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (PhosphoProteomic Profiling

    Directory of Open Access Journals (Sweden)

    Ilyas Singec

    2016-09-01

    Full Text Available Controlled differentiation of human embryonic stem cells (hESCs can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs. This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families, phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt.

  19. Alterations of the visual pathways in congenital blindness

    DEFF Research Database (Denmark)

    Ptito, Maurice; Schneider, Fabien C G; Paulson, Olaf B

    2008-01-01

    We used whole brain MRI voxel-based morphometry (VBM) to study the anatomical organization of the visual system in congenitally blind (CB) adults. Eleven CB without a history of visual perception were compared with 21 age- and sex-matched normal-sighted controls (NS). CB showed significant atroph...... somatosensory or auditory inputs, suggesting a reorganization of the neural pathways that transmit sensory information to the visual cortex....

  20. Spiking modular neural networks: A neural network modeling approach for hydrological processes

    National Research Council Canada - National Science Library

    Kamban Parasuraman; Amin Elshorbagy; Sean K. Carey

    2006-01-01

    .... In this study, a novel neural network model called the spiking modular neural networks (SMNNs) is proposed. An SMNN consists of an input layer, a spiking layer, and an associator neural network layer...

  1. Hox genes: choreographers in neural development, architects of circuit organization.

    Science.gov (United States)

    Philippidou, Polyxeni; Dasen, Jeremy S

    2013-10-02

    The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This Review highlights the functions and mechanisms of Hox gene networks and their multifaceted roles during neuronal specification and connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. 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.

  3. Cracking the neural code, treating paralysis and the future of bioelectronic medicine.

    Science.gov (United States)

    Bouton, C

    2017-07-01

    The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our overall health. Scientists and engineers have been working for decades to tap into this network and 'crack the neural code' by decoding neural signals and learning how to 'speak' the language of the nervous system. Progress has been made in developing neural decoding methods to decipher brain activity and bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and for diagnosing brain-related diseases such as Parkinson's and Alzheimer's disease. In a recent first-in-human study involving paralysis, a paralysed male study participant regained movement in his hand, years after his injury, through the use of a bioelectronic neural bypass. This work combined neural decoding and neurostimulation methods to translate and re-route signals around damaged neural pathways within the central nervous system. By extending these methods to decipher neural messages in the peripheral nervous system, status information from our bodily functions and specific organs could be gained. This, one day, could allow real-time diagnostics to be performed to give us a deeper insight into a patient's condition, or potentially even predict disease or allow early diagnosis. The future of bioelectronic medicine is extremely bright and is wide open as new diagnostic and treatment options are developed for patients around the world. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  4. Small molecule GSK-3 inhibitors increase neurogenesis of human neural progenitor cells.

    Science.gov (United States)

    Lange, Christian; Mix, Eilhard; Frahm, Jana; Glass, Anne; Müller, Jana; Schmitt, Oliver; Schmöle, Anne-Caroline; Klemm, Kristin; Ortinau, Stefanie; Hübner, Rayk; Frech, Moritz J; Wree, Andreas; Rolfs, Arndt

    2011-01-13

    Human neural progenitor cells provide a source for cell replacement therapy to treat neurodegenerative diseases. Therefore, there is great interest in mechanisms and tools to direct the fate of multipotent progenitor cells during their differentiation to increase the yield of a desired cell type. We tested small molecule inhibitors of glycogen synthase kinase-3 (GSK-3) for their functionality and their influence on neurogenesis using the human neural progenitor cell line ReNcell VM. Here we report the enhancement of neurogenesis of human neural progenitor cells by treatment with GSK-3 inhibitors. We tested different small molecule inhibitors of GSK-3 i.e. LiCl, sodium-valproate, kenpaullone, indirubin-3-monoxime and SB-216763 for their ability to inhibit GSK-3 in human neural progenitor cells. The highest in situ GSK-3 inhibitory effect of the drugs was found for kenpaullone and SB-216763. Accordingly, kenpaullone and SB-216763 were the only drugs tested in this study to stimulate the Wnt/β-catenin pathway that is antagonized by GSK-3. Analysis of human neural progenitor differentiation revealed an augmentation of neurogenesis by SB-216763 and kenpaullone, without changing cell cycle exit or cell survival. Small molecule inhibitors of GSK-3 enhance neurogenesis of human neural progenitor cells and may be used to direct the differentiation of neural stem and progenitor cells in therapeutic applications. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Evaluation of neural gene expression in serum treated embryonic stem cells in Alzheimer′s patients

    Directory of Open Access Journals (Sweden)

    Leila Dehghani

    2013-01-01

    Full Text Available Background: Previous studies confirmed that neural gene expression in embryonic stem cells (ESC could influence by chemical compounds through stimulating apoptotic pathway. We aimed to use ESCs-derived neural cells by embryoid body formation as an in vitro model for determination of neural gene expression changes in groups that treated by sera from Alzheimer′s patients and compare with healthy individuals. Materials and Methods: ESC line which was derived from the C57BL/6 mouse strain was used throughout this study. ESC-derived neural cells were treated with serum from Alzheimer′s patient and healthy individual. Neural gene expression was assessed in both groups by quantitative real-time polymerase chain reaction analysis. The data was analyzed by SPSS Software (version 18. Results: Morphologically, the reducing in neurite out-growth was observed in neural cells in group, which treated by serum from Alzheimer′s patient, while neurite growth was natural in appearance in control group. Microtubule-associated protein 2 and glial fibrillary acidic protein expression significantly reduced in the Alzheimer′s patient group compared with the control group. Nestin expression did not significantly differ among the groups. Conclusion: Neural gene expression could be reduced in serum treated ESC in Alzheimer′s patients.

  6. Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

    Directory of Open Access Journals (Sweden)

    Callihan Phillip

    2008-12-01

    Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

  7. Virus-like particle production with yeast: ultrastructural and immunocytochemical insights into Pichia pastoris producing high levels of the Hepatitis B surface antigen

    Directory of Open Access Journals (Sweden)

    Adnan Ahmad

    2011-06-01

    Full Text Available Abstract Background A protective immune response against Hepatitis B infection can be obtained through the administration of a single viral polypeptide, the Hepatitis B surface antigen (HBsAg. Thus, the Hepatitis B vaccine is generated through the utilization of recombinant DNA technology, preferentially by using yeast-based expression systems. However, the polypeptide needs to assemble into spherical particles, so-called virus-like particles (VLPs, to elicit the required protective immune response. So far, no clear evidence has been presented showing whether HBsAg assembles in vivo inside the yeast cell into VLPs or later in vitro during down-stream processing and purification. Results High level production of HBsAg was carried out with recombinant Pichia pastoris using the methanol inducible AOX1 expression system. The recombinant vaccine was isolated in form of VLPs after several down-stream steps from detergent-treated cell lysates. Search for the intracellular localization of the antigen using electron microscopic studies in combination with immunogold labeling revealed the presence of HBsAg in an extended endoplasmic reticulum where it was found to assemble into defined multi-layered, lamellar structures. The distance between two layers was determined as ~6 nm indicating that these lamellas represent monolayers of well-ordered HBsAg subunits. We did not find any evidence for the presence of VLPs within the endoplasmic reticulum or other parts of the yeast cell. Conclusions It is concluded that high level production and intrinsic slow HBsAg VLP assembly kinetics are leading to retention and accumulation of the antigen in the endoplasmic reticulum where it assembles at least partly into defined lamellar structures. Further transport of HBsAg to the Golgi apparatus is impaired thus leading to secretory pathway disfunction and the formation of an extended endoplasmic reticulum which bulges into irregular cloud-shaped formations. As VLPs were

  8. Career Pathways in Indiana

    Science.gov (United States)

    McCaskey, Steve; Johnson, Tricia

    2010-01-01

    The revisions to the Carl D. Perkins Career and Technical Education Act of 2006 require that career and technical education (CTE) programs provide students with a clear pathway from secondary to postsecondary education, and into high-wage, high-skill and high-demand careers. States nationwide are developing programs, called career pathways, to…

  9. Ontogeny, immunocytochemical localization, and biochemical properties of the pregnancy-associated uterine elastase/cathepsin-G protease inhibitor, antileukoproteinase (ALP): monospecific antibodies to a synthetic peptide recognize native ALP.

    Science.gov (United States)

    Simmen, R C; Michel, F J; Fliss, A E; Smith, L C; Fliss, M F

    1992-04-01

    Expression of the mRNA encoding the elastase/cathepsin-G protease inhibitor, antileukoproteinase (ALP), is highest in pig uterus during mid- and late pregnancy, suggesting a stage of pregnancy-dependent role for ALP in feto-maternal interactions. To elucidate a function for ALP in these events, immunogenic probes were developed to localize sites of ALP expression in the environment of the developing fetus. Monospecific antibodies raised against a 16-mer synthetic peptide corresponding to residues 21-36 (ALP 16P) of the deduced amino acid sequence of pig uterine ALP were generated by active immunization of sheep. ALP 16P conjugated to keyhole limpet hemocyanin elicited high titer antibodies that were specific to ALP. The antipeptide antibodies were used to characterize pig uterine ALP from allantoic fluids. Uterine ALP has an approximate mol wt of 14,000 and a pI of 8.2 and exhibits elastase inhibitor activity. Amino-terminal amino acid sequencing of uterine ALP indicated the sequence AENALKGGACPPRKIVQC, which has 44% identity with the corresponding region in human bronchial ALP. RIA for ALP, developed using ALP 16P as standard and iodinated tracer, demonstrated the presence of immunoreactive ALP in early, mid-, and late pregnant endometrium and myometrium, placenta, allantoic fluids, fetal cord blood, and fetal liver. ALP was undetectable in the maternal circulation. The ALP levels in endometrium, allantoic fluids, and fetal cord blood changed with the stage of pregnancy; however, ALP content in placenta, myometrium, and fetal liver, although different among tissues, remained invariant during gestation. By immunocytochemical analyses, ALP was localized in the glandular epithelium of the uterus, in placenta, and in fetal liver, consistent with the presence of immunoreactive ALP as measured by RIA. The localization of uterine ALP in placenta and its corresponding transport to fetal circulation provide strong evidence to support a physiological function for the

  10. Fractional Hopfield Neural Networks: Fractional Dynamic Associative Recurrent Neural Networks.

    Science.gov (United States)

    Pu, Yi-Fei; Yi, Zhang; Zhou, Ji-Liu

    2017-10-01

    This paper mainly discusses a novel conceptual framework: fractional Hopfield neural networks (FHNN). As is commonly known, fractional calculus has been incorporated into artificial neural networks, mainly because of its long-term memory and nonlocality. Some researchers have made interesting attempts at fractional neural networks and gained competitive advantages over integer-order neural networks. Therefore, it is naturally makes one ponder how to generalize the first-order Hopfield neural networks to the fractional-order ones, and how to implement FHNN by means of fractional calculus. We propose to introduce a novel mathematical method: fractional calculus to implement FHNN. First, we implement fractor in the form of an analog circuit. Second, we implement FHNN by utilizing fractor and the fractional steepest descent approach, construct its Lyapunov function, and further analyze its attractors. Third, we perform experiments to analyze the stability and convergence of FHNN, and further discuss its applications to the defense against chip cloning attacks for anticounterfeiting. The main contribution of our work is to propose FHNN in the form of an analog circuit by utilizing a fractor and the fractional steepest descent approach, construct its Lyapunov function, prove its Lyapunov stability, analyze its attractors, and apply FHNN to the defense against chip cloning attacks for anticounterfeiting. A significant advantage of FHNN is that its attractors essentially relate to the neuron's fractional order. FHNN possesses the fractional-order-stability and fractional-order-sensitivity characteristics.

  11. Neural Differentiation of Human Adipose Tissue-Derived Stem Cells Involves Activation of the Wnt5a/JNK Signalling

    Directory of Open Access Journals (Sweden)

    Sujeong Jang

    2015-01-01

    Full Text Available Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of ß-catenin and GSK3ß. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased. Thus, this study shows for the first time how a single Wnt5a ligand can activate the neural differentiation pathway through the activation of Wnt5a/JNK pathway by binding Fzd3 and Fzd5 and directing Axin/GSK-3ß in hADSCs.

  12. Myelin plasticity, neural activity, and traumatic neural injury.

    Science.gov (United States)

    Kondiles, Bethany R; Horner, Philip J

    2018-02-01

    The possibility that adult organisms exhibit myelin plasticity has recently become a topic of great interest. Many researchers are exploring the role of myelin growth and adaptation in daily functions such as memory and motor learning. Here we consider evidence for three different potential categories of myelin plasticity: the myelination of previously bare axons, remodeling of existing sheaths, and the removal of a sheath with replacement by a new internode. We also review evidence that points to the importance of neural activity as a mechanism by which oligodendrocyte precursor cells (OPCs) are cued to differentiate into myelinating oligodendrocytes, which may potentially be an important component of myelin plasticity. Finally, we discuss demyelination in the context of traumatic neural injury and present an argument for altering neural activity as a potential therapeutic target for remyelination following injury. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 108-122, 2018. © 2017 Wiley Periodicals, Inc.

  13. Multigradient for Neural Networks for Equalizers

    Directory of Open Access Journals (Sweden)

    Chulhee Lee

    2003-06-01

    Full Text Available Recently, a new training algorithm, multigradient, has been published for neural networks and it is reported that the multigradient outperforms the backpropagation when neural networks are used as a classifier. When neural networks are used as an equalizer in communications, they can be viewed as a classifier. In this paper, we apply the multigradient algorithm to train the neural networks that are used as equalizers. Experiments show that the neural networks trained using the multigradient noticeably outperforms the neural networks trained by the backpropagation.

  14. Understanding perception through neural "codes".

    Science.gov (United States)

    Freeman, Walter J

    2011-07-01

    A major challenge for cognitive scientists is to deduce and explain the neural mechanisms of the rapid transposition between stimulus energy and recalled memory-between the specific (sensation) and the generic (perception)-in both material and mental aspects. Researchers are attempting three explanations in terms of neural codes. The microscopic code: cellular neurobiologists correlate stimulus properties with the rates and frequencies of trains of action potentials induced by stimuli and carried by topologically organized axons. The mesoscopic code: cognitive scientists formulate symbolic codes in trains of action potentials from feature-detector neurons of phonemes, lines, odorants, vibrations, faces, etc., that object-detector neurons bind into representations of stimuli. The macroscopic code: neurodynamicists extract neural correlates of stimuli and associated behaviors in spatial patterns of oscillatory fields of dendritic activity, which self-organize and evolve on trajectories through high-dimensional brain state space. This multivariate code is expressed in landscapes of chaotic attractors. Unlike other scientific codes, such as DNA and the periodic table, these neural codes have no alphabet or syntax. They are epistemological metaphors that experimentalists need to measure neural activity and engineers need to model brain functions. My aim is to describe the main properties of the macroscopic code and the grand challenge it poses: how do very large patterns of textured synchronized oscillations form in cortex so quickly? © 2010 IEEE

  15. Neural correlates of stimulus reportability.

    Science.gov (United States)

    Hulme, Oliver J; Friston, Karl F; Zeki, Semir

    2009-08-01

    Most experiments on the "neural correlates of consciousness" employ stimulus reportability as an operational definition of what is consciously perceived. The interpretation of such experiments therefore depends critically on understanding the neural basis of stimulus reportability. Using a high volume of fMRI data, we investigated the neural correlates of stimulus reportability using a partial report object detection paradigm. Subjects were presented with a random array of circularly arranged disc-stimuli and were cued, after variable delays (following stimulus offset), to report the presence or absence of a disc at the cued location, using variable motor actions. By uncoupling stimulus processing, decision, and motor response, we were able to use signal detection theory to deconstruct the neural basis of stimulus reportability. We show that retinotopically specific responses in the early visual cortex correlate with stimulus processing but not decision or report; a network of parietal/temporal regions correlates with decisions but not stimulus presence, whereas classical motor regions correlate with report. These findings provide a basic framework for understanding the neural basis of stimulus reportability without the theoretical burden of presupposing a relationship between reportability and consciousness.

  16. Neural Approaches to Machine Consciousness

    Science.gov (United States)

    Aleksander, Igor; Eng., F. R.

    2008-10-01

    `Machine Consciousness', which some years ago might have been suppressed as an inappropriate pursuit, has come out of the closet and is now a legitimate area of research concern. This paper briefly surveys the last few years of worldwide research in this area which divides into rule-based and neural approaches and then reviews the work of the author's laboratory during the last ten years. The paper develops a fresh perspective on this work: it is argued that neural approaches, in this case, digital neural systems, can address phenomenological consciousness. Important clarifications of phenomenology and virtuality which enter this modelling are explained in the early parts of the paper. In neural models, phenomenology is a form of depictive inner representation that has five specific axiomatic features: a sense of self-presence in an external world; a sense of imagination of past experience and fiction; a sense of attention; a capacity for planning; a sense of emotion-based volition that influences planning. It is shown that these five features have separate but integrated support in dynamic neural systems.

  17. Neural recording and modulation technologies

    Science.gov (United States)

    Chen, Ritchie; Canales, Andres; Anikeeva, Polina

    2017-01-01

    In the mammalian nervous system, billions of neurons connected by quadrillions of synapses exchange electrical, chemical and mechanical signals. Disruptions to this network manifest as neurological or psychiatric conditions. Despite decades of neuroscience research, our ability to treat or even to understand these conditions is limited by the capability of tools to probe the signalling complexity of the nervous system. Although orders of magnitude smaller and computationally faster than neurons, conventional substrate-bound electronics do not recapitulate the chemical and mechanical properties of neural tissue. This mismatch results in a foreign-body response and the encapsulation of devices by glial scars, suggesting that the design of an interface between the nervous system and a synthetic sensor requires additional materials innovation. Advances in genetic tools for manipulating neural activity have fuelled the demand for devices that are capable of simultaneously recording and controlling individual neurons at unprecedented scales. Recently, flexible organic electronics and bio- and nanomaterials have been developed for multifunctional and minimally invasive probes for long-term interaction with the nervous system. In this Review, we discuss the design lessons from the quarter-century-old field of neural engineering, highlight recent materials-driven progress in neural probes and look at emergent directions inspired by the principles of neural transduction.

  18. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure

    Directory of Open Access Journals (Sweden)

    Erica M. McGreevy

    2015-01-01

    Full Text Available Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock, to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP pathway, to direct the polarized cellular behaviors that drive convergent extension (CE movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

  19. EDITORIAL: Commercial opportunities for neural engineers

    Science.gov (United States)

    Cavuoto, James

    2008-03-01

    of the device in 2000. Anthony Ignagni, who worked with Mortimer and Onders as project director and chief biomedical engineer, became a co-founder of Synapse and is currently president and CEO. Afferent Corp., Providence, RI, a manufacturer of sensory stimulation systems based on research at Boston University, Afferent's technology is based on work by James Collins, professor of biomedical engineering at Boston University, who showed that low-level stochastic, or random, vibrations improved sense of touch. Collins went on to demonstrate that generating a subthreshold noise in the sensory pathways with a random electrical stimulation improves detectability of weak mechanical stimuli. In 1999 entrepreneur Jason Harry licensed the stochastic resonance technology from Boston University and received help from the Community Technology Fund-the university's technology transfer incubator. NeuroNexus Technologies, Inc., Ann Arbor, MI, a manufacturer of implanted neural probes, based on a program at the University of Michigan. NeuroNexus was spun out of UM's Center for Neural Communications Technology. Daryl Kipke, head of the Neural Engineering Laboratory at the university, started up NeuroNexus with several colleagues and currently serves as president and CEO. Commercialization issues were discussed recently at a preconference workshop at the 2007 meeting of the International Neuromodulation Society in Acapulco, Mexico. In the session, which was chaired by Chris Coburn of the Cleveland Clinic, neurotech entrepreneurs John Bowers from Northstar Neuroscience and Ben Pless, formerly of NeuroPace, shared their experiences bringing neuromodulation therapies to market. Coburn related his observations from the Cleveland Clinic, which has spun off 22 companies over the last five years. He cited several factors that would influence a neurotech startup's market potential, such as identifying the regulatory pathway, any predicate devices that exist, and the revenue potential for

  20. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in inflamma

  1. 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.

  2. Neural networks and statistical learning

    CERN Document Server

    Du, Ke-Lin

    2014-01-01

    Providing a broad but in-depth introduction to neural network and machine learning in a statistical framework, this book provides a single, comprehensive resource for study and further research. All the major popular neural network models and statistical learning approaches are covered with examples and exercises in every chapter to develop a practical working understanding of the content. Each of the twenty-five chapters includes state-of-the-art descriptions and important research results on the respective topics. The broad coverage includes the multilayer perceptron, the Hopfield network, associative memory models, clustering models and algorithms, the radial basis function network, recurrent neural networks, principal component analysis, nonnegative matrix factorization, independent component analysis, discriminant analysis, support vector machines, kernel methods, reinforcement learning, probabilistic and Bayesian networks, data fusion and ensemble learning, fuzzy sets and logic, neurofuzzy models, hardw...

  3. Multiprocessor Neural Network in Healthcare.

    Science.gov (United States)

    Godó, Zoltán Attila; Kiss, Gábor; Kocsis, Dénes

    2015-01-01

    A possible way of creating a multiprocessor artificial neural network is by the use of microcontrollers. The RISC processors' high performance and the large number of I/O ports mean they are greatly suitable for creating such a system. During our research, we wanted to see if it is possible to efficiently create interaction between the artifical neural network and the natural nervous system. To achieve as much analogy to the living nervous system as possible, we created a frequency-modulated analog connection between the units. Our system is connected to the living nervous system through 128 microelectrodes. Two-way communication is provided through A/D transformation, which is even capable of testing psychopharmacons. The microcontroller-based analog artificial neural network can play a great role in medical singal processing, such as ECG, EEG etc.

  4. Principles of neural information processing

    CERN Document Server

    Seelen, Werner v

    2016-01-01

    In this fundamental book the authors devise a framework that describes the working of the brain as a whole. It presents a comprehensive introduction to the principles of Neural Information Processing as well as recent and authoritative research. The books´ guiding principles are the main purpose of neural activity, namely, to organize behavior to ensure survival, as well as the understanding of the evolutionary genesis of the brain. Among the developed principles and strategies belong self-organization of neural systems, flexibility, the active interpretation of the world by means of construction and prediction as well as their embedding into the world, all of which form the framework of the presented description. Since, in brains, their partial self-organization, the lifelong adaptation and their use of various methods of processing incoming information are all interconnected, the authors have chosen not only neurobiology and evolution theory as a basis for the elaboration of such a framework, but also syst...

  5. Performance sustaining intracortical neural prostheses

    Science.gov (United States)

    Nuyujukian, Paul; Kao, Jonathan C.; Fan, Joline M.; Stavisky, Sergey D.; Ryu, Stephen I.; Shenoy, Krishna V.

    2014-12-01

    Objective. Neural prostheses, or brain-machine interfaces, aim to restore efficient communication and movement ability to those suffering from paralysis. A major challenge these systems face is robust performance, particularly with aging signal sources. The aim in this study was to develop a neural prosthesis that could sustain high performance in spite of signal instability while still minimizing retraining time. Approach. We trained two rhesus macaques implanted with intracortical microelectrode arrays 1-4 years prior to this study to acquire targets with a neurally-controlled cursor. We measured their performance via achieved bitrate (bits per second, bps). This task was repeated over contiguous days to evaluate the sustained performance across time. Main results. We found that in the monkey with a younger (i.e., two year old) implant and better signal quality, a fixed decoder could sustain performance for a month at a rate of 4 bps, the highest achieved communication rate reported to date. This fixed decoder was evaluated across 22 months and experienced a performance decline at a rate of 0.24 bps yr-1. In the monkey with the older (i.e., 3.5 year old) implant and poorer signal quality, a fixed decoder could not sustain performance for more than a few days. Nevertheless, performance in this monkey was maintained for two weeks without requiring additional online retraining time by utilizing prior days’ experimental data. Upon analysis of the changes in channel tuning, we found that this stability appeared partially attributable to the cancelling-out of neural tuning fluctuations when projected to two-dimensional cursor movements. Significance. The findings in this study (1) document the highest-performing communication neural prosthesis in monkeys, (2) confirm and extend prior reports of the stability of fixed decoders, and (3) demonstrate a protocol for system stability under conditions where fixed decoders would otherwise fail. These improvements to decoder

  6. Genetic manipulation of specific neural circuits by use of a viral vector system.

    Science.gov (United States)

    Kobayashi, Kenta; Kato, Shigeki; Kobayashi, Kazuto

    2017-01-05

    To understand the mechanisms underlying higher brain functions, we need to analyze the roles of specific neuronal pathways or cell types forming the complex neural networks. In the neuroscience field, the transgenic approach has provided a useful gene engineering tool for experimental studies of neural functions. The conventional transgenic technique requires the appropriate promoter regions that drive a neuronal type-specific gene expression, but the promoter sequences specifically functioning in each neuronal type are limited. Previously, we developed novel types of lentiviral vectors showing high efficiency of retrograde gene transfer in the central nervous system, termed highly efficient retrograde gene transfer (HiRet) vector and neuron-specific retrograde gene transfer (NeuRet) vector. The HiRet and NeuRet vectors enable genetical manipulation of specific neural pathways in diverse model animals in combination with conditional cell targeting, synaptic transmission silencing, and gene expression systems. These newly developed vectors provide powerful experimental strategies to investigate, more precisely, the machineries exerting various neural functions. In this review, we give an outline of the HiRet and NeuRet vectors and describe recent representative applications of these viral vectors for studies on neural circuits.

  7. 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.

  8. [Neural mechanisms of mastication].

    Science.gov (United States)

    Inoue, Tomio

    2015-02-01

    Abstract Comminution of food by mastication contributes to an increase in the efficiency of energy intake from food, which supports the high metabolic rate of mammals. The central pattern-generating circuit for mastication produces motor commands for mastication by using sensory information from periodontal mechanoreceptors and muscle spindles in the jaw-closing muscles. The motor commands that are glutamatergic, glycinergic, and GABAergic are transmitted to motoneurons for the jaw, tongue, etc., through premotor neurons that are located in the supratrigeminal region, reticular formation dorsal to the facial nucleus, etc. Our previous studies of N-methyl-D-aspartate-induced fictive suckling using isolated brainstem-spinal cord preparations obtained from neonatal mice revealed that the neuronal network that contributes to the synchronized activity of the jaw and tongue muscles is located in both the right and left sides. The network of either side sends its command to the trigeminal motoneurons mainly via the commissural pathway, while the command is sent to the hypoglossal motoneurons on the same side.

  9. [Neural basis of pain].

    Science.gov (United States)

    Calvino, Bernard

    2006-03-01

    Main elements concerning the physiology of pain are described, as well as the structures of the nervous system at the origin of the central control of pain: peripheral fibres (small diameter myelinated A delta and unmyelinated C fibres); spinal ascending pathways; cerebral structures relaying nociceptive information (medial and ventro-postero-lateral thalamic relays); SI and SII cortical areas; spinal segmentary and supraspinal excitatory and inhibitory controls; diffuse noxious inhibitory controls (DNIC). Chronic pain is a result of two processes: peripheral and central sensitization, in relation with inflammation and nerve injury at peripheral level and with neuroplasticity at central level. Neurotrophins, mainly NGF and BDNF and their receptors (LNTR, TrkA and TrkB) are involved in these processes. Pain is a result of an unpleasant emotional experience: its various components, mainly the emotional one, may be increased or decreased considering the different characteristics of the stimulus and of the affective state of the patient, as well as the context in which this stimulus is applied. The role of physiological systems, unconnected with those classically involved in the physiology of nociception and pain, such as the motor cortex in phantom limb pain, are described in conclusion, to focus on the extreme complexity of the control systems of pain in humans.

  10. Neural Decoder for Topological Codes

    Science.gov (United States)

    Torlai, Giacomo; Melko, Roger G.

    2017-07-01

    We present an algorithm for error correction in topological codes that exploits modern machine learning techniques. Our decoder is constructed from a stochastic neural network called a Boltzmann machine, of the type extensively used in deep learning. We provide a general prescription for the training of the network and a decoding strategy that is applicable to a wide variety of stabilizer codes with very little specialization. We demonstrate the neural decoder numerically on the well-known two-dimensional toric code with phase-flip errors.

  11. Computer simulations of neural mechanisms explaining upper and lower limb excitatory neural coupling

    Directory of Open Access Journals (Sweden)

    Ferris Daniel P

    2010-12-01

    Full Text Available Abstract Background When humans perform rhythmic upper and lower limb locomotor-like movements, there is an excitatory effect of upper limb exertion on lower limb muscle recruitment. To investigate potential neural mechanisms for this behavioral observation, we developed computer simulations modeling interlimb neural pathways among central pattern generators. We hypothesized that enhancement of muscle recruitment from interlimb spinal mechanisms was not sufficient to explain muscle enhancement levels observed in experimental data. Methods We used Matsuoka oscillators for the central pattern generators (CPG and determined parameters that enhanced amplitudes of rhythmic steady state bursts. Potential mechanisms for output enhancement were excitatory and inhibitory sensory feedback gains, excitatory and inhibitory interlimb coupling gains, and coupling geometry. We first simulated the simplest case, a single CPG, and then expanded the model to have two CPGs and lastly four CPGs. In the two and four CPG models, the lower limb CPGs did not receive supraspinal input such that the only mechanisms available for enhancing output were interlimb coupling gains and sensory feedback gains. Results In a two-CPG model with inhibitory sensory feedback gains, only excitatory gains of ipsilateral flexor-extensor/extensor-flexor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 26%. In a two-CPG model with excitatory sensory feedback gains, excitatory gains of contralateral flexor-flexor/extensor-extensor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 100%. However, within a given excitatory sensory feedback gain, enhancement due to excitatory interlimb gains could only reach levels up to 20%. Interconnecting four CPGs to have ipsilateral flexor-extensor/extensor-flexor coupling, contralateral flexor-flexor/extensor-extensor coupling, and bilateral flexor-extensor/extensor-flexor coupling could enhance

  12. Generalization performance of regularized neural network models

    DEFF Research Database (Denmark)

    Larsen, Jan; Hansen, Lars Kai

    1994-01-01

    Architecture optimization is a fundamental problem of neural network modeling. The optimal architecture is defined as the one which minimizes the generalization error. This paper addresses estimation of the generalization performance of regularized, complete neural network models. Regularization...

  13. voltage compensation using artificial neural network

    African Journals Online (AJOL)

    Offor Theophilos

    VOLTAGE COMPENSATION USING ARTIFICIAL NEURAL NETWORK: A CASE STUDY OF. RUMUOLA ... using artificial neural network (ANN) controller based dynamic voltage restorer (DVR). ... substation by simulating with sample of average voltage for Omerelu, Waterlines, Rumuola, Shell Industrial and Barracks.

  14. Plant Growth Models Using Artificial Neural Networks

    Science.gov (United States)

    Bubenheim, David

    1997-01-01

    In this paper, we descrive our motivation and approach to devloping models and the neural network architecture. Initial use of the artificial neural network for modeling the single plant process of transpiration is presented.

  15. Neural circulatory control in vasovagal syncope

    NARCIS (Netherlands)

    van Lieshout, J. J.; Wieling, W.; Karemaker, J. M.

    1997-01-01

    The orthostatic volume displacement associated with the upright position necessitates effective neural cardiovascular modulation. Neural control of cardiac chronotropy and inotropy, and vasomotor tone aims at maintaining venous return, thus opposing gravitational pooling of blood in the lower part

  16. Neural overlap in processing music and speech

    Science.gov (United States)

    Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

    2015-01-01

    Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

  17. The neural crest and neural crest cells: discovery and significance ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    such as sea urchins, flies, fish and humans. (ii) Embryos (and so larvae and adults) form by differentiation from these germ layers. (iii) Homologous structures in different animals arise from the same germ layers. The germ-layer theory exerted a profound influence on those claiming a neural crest — that is, an ectodermal.

  18. MEMBRAIN NEURAL NETWORK FOR VISUAL PATTERN RECOGNITION

    Directory of Open Access Journals (Sweden)

    Artur Popko

    2013-06-01

    Full Text Available Recognition of visual patterns is one of significant applications of Artificial Neural Networks, which partially emulate human thinking in the domain of artificial intelligence. In the paper, a simplified neural approach to recognition of visual patterns is portrayed and discussed. This paper is dedicated for investigators in visual patterns recognition, Artificial Neural Networking and related disciplines. The document describes also MemBrain application environment as a powerful and easy to use neural networks’ editor and simulator supporting ANN.

  19. Pathway Commons, a web resource for biological pathway data.

    Science.gov (United States)

    Cerami, Ethan G; Gross, Benjamin E; Demir, Emek; Rodchenkov, Igor; Babur, Ozgün; Anwar, Nadia; Schultz, Nikolaus; Bader, Gary D; Sander, Chris

    2011-01-01

    Pathway Commons (http://www.pathwaycommons.org) is a collection of publicly available pathway data from multiple organisms. Pathway Commons provides a web-based interface that enables biologists to browse and search a comprehensive collection of pathways from multiple sources represented in a common language, a download site that provides integrated bulk sets of pathway information in standard or convenient formats and a web service that software developers can use to conveniently query and access all data. Database providers can share their pathway data via a common repository. Pathways include biochemical reactions, complex assembly, transport and catalysis events and physical interactions involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims to collect and integrate all public pathway data available in standard formats. Pathway Commons currently contains data from nine databases with over 1400 pathways and 687,000 interactions and will be continually expanded and updated.

  20. Radioactive fallout and neural tube defects

    African Journals Online (AJOL)

    Nejat Akar

    2015-07-10

    Jul 10, 2015 ... Neural tube defects;. Anencephaly;. Spina bifida. Abstract Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate ... Neural tube defects, are one of the common congenital mal- formations ... ent cities of Turkey (˙Izmir/Aegean Region; Trabzon/Black Sea region ...

  1. Analysis of neural networks through base functions

    NARCIS (Netherlands)

    van der Zwaag, B.J.; Slump, Cornelis H.; Spaanenburg, L.

    Problem statement. Despite their success-story, neural networks have one major disadvantage compared to other techniques: the inability to explain comprehensively how a trained neural network reaches its output; neural networks are not only (incorrectly) seen as a "magic tool" but possibly even more

  2. Simplified LQG Control with Neural Networks

    DEFF Research Database (Denmark)

    Sørensen, O.

    1997-01-01

    A new neural network application for non-linear state control is described. One neural network is modelled to form a Kalmann predictor and trained to act as an optimal state observer for a non-linear process. Another neural network is modelled to form a state controller and trained to produce...

  3. Novel quantum inspired binary neural network algorithm

    Indian Academy of Sciences (India)

    In this paper, a quantum based binary neural network algorithm is proposed, named as novel quantum binary neural network algorithm (NQ-BNN). It forms a neural network structure by deciding weights and separability parameter in quantum based manner. Quantum computing concept represents solution probabilistically ...

  4. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    OpenAIRE

    Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain t...

  5. The neural basis of visual selective attention: a commentary on Harter and Aine.

    Science.gov (United States)

    Hillyard, S A; Mangun, G R

    1986-12-01

    Harter and Aine (1984) have proposed a 'neural specificity' model of visual selective attention, based primarily on evidence from recordings of event-related brain potentials (ERPs) in human subjects. In this framework, they consider ERP components elicited during visual-spatial attention to reflect selective neural processing in the tectopulvinar-partietal pathway, whereas selection of visual attributes such as pattern, color, and orientation is manifested by ERPs arising from the geniculostriate-inferotemporal projection system. The present article examines the empirical basis for anatomically-specific hypotheses and considers alternative explanations for the observed ERP changes during selective attention.

  6. Primers on molecular pathways--caspase pathway.

    Science.gov (United States)

    Lomberk, Gwen; Urrutia, Raul

    2009-01-01

    Apoptosis, or programmed cell death, is a physiological process of cellular autodestruction, or cell suicide. This process is strictly controlled in response to integrity of pro-death signaling and plays critical roles in development, maintenance of homeostasis and host defense in multicellular organisms. As pancreatologists, apoptosis plays a central role in the pancreas and its disease states, from diabetes to pancreatitis to pancreatic cancer. In pancreatic beta-cells, apoptotic cell death is involved in the pathogenesis of diabetes, as signals from death receptors and DNA damage have been widely accepted as being triggers of apoptosis in beta-cells. During acute pancreatitis, this common clinical condition is of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. However, recent research in this area has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In pancreatic cancer, various survival mechanisms have been shown to act in the prevention of cell death to result in promotion of tumor growth and metastasis. Thus, resistance of pancreatic cancer to apoptosis is the key factor preventing responses to therapies. Thus, it is for these reasons that in the current 'Primers on Molecular Pathways,' we take a closer look at the pathway cascade that is triggered during apoptosis. Copyright 2008 S. Karger AG, Basel and IAP.

  7. Degenerate coding in neural systems.

    Science.gov (United States)

    Leonardo, Anthony

    2005-11-01

    When the dimensionality of a neural circuit is substantially larger than the dimensionality of the variable it encodes, many different degenerate network states can produce the same output. In this review I will discuss three different neural systems that are linked by this theme. The pyloric network of the lobster, the song control system of the zebra finch, and the odor encoding system of the locust, while different in design, all contain degeneracies between their internal parameters and the outputs they encode. Indeed, although the dynamics of song generation and odor identification are quite different, computationally, odor recognition can be thought of as running the song generation circuitry backwards. In both of these systems, degeneracy plays a vital role in mapping a sparse neural representation devoid of correlations onto external stimuli (odors or song structure) that are strongly correlated. I argue that degeneracy between input and output states is an inherent feature of many neural systems, which can be exploited as a fault-tolerant method of reliably learning, generating, and discriminating closely related patterns.

  8. Optoelectronic Implementation of Neural Networks

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 9. Optoelectronic Implementation of Neural Networks - Use of Optics in Computing. R Ramachandran. General Article Volume 3 Issue 9 September 1998 pp 45-55. Fulltext. Click here to view fulltext PDF. Permanent link:

  9. Aphasia Classification Using Neural Networks

    DEFF Research Database (Denmark)

    Axer, H.; Jantzen, Jan; Berks, G.

    2000-01-01

    A web-based software model (http://fuzzy.iau.dtu.dk/aphasia.nsf) was developed as an example for classification of aphasia using neural networks. Two multilayer perceptrons were used to classify the type of aphasia (Broca, Wernicke, anomic, global) according to the results in some subtests...

  10. Memory Storage and Neural Systems.

    Science.gov (United States)

    Alkon, Daniel L.

    1989-01-01

    Investigates memory storage and molecular nature of associative-memory formation by analyzing Pavlovian conditioning in marine snails and rabbits. Presented is the design of a computer-based memory system (neural networks) using the rules acquired in the investigation. Reports that the artificial network recognized patterns well. (YP)

  11. Nanomaterial-enabled neural stimulation

    Directory of Open Access Journals (Sweden)

    Yongchen eWang

    2016-03-01

    Full Text Available Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed.

  12. Neural Control of the Circulation

    Science.gov (United States)

    Thomas, Gail D.

    2011-01-01

    The purpose of this brief review is to highlight key concepts about the neural control of the circulation that graduate and medical students should be expected to incorporate into their general knowledge of human physiology. The focus is largely on the sympathetic nerves, which have a dominant role in cardiovascular control due to their effects to…

  13. Classification using Bayesian neural nets

    NARCIS (Netherlands)

    J.C. Bioch (Cor); O. van der Meer; R. Potharst (Rob)

    1995-01-01

    textabstractRecently, Bayesian methods have been proposed for neural networks to solve regression and classification problems. These methods claim to overcome some difficulties encountered in the standard approach such as overfitting. However, an implementation of the full Bayesian approach to

  14. Vitamins and neural tube defects

    OpenAIRE

    Harris, Rodney

    1988-01-01

    The use of vitamin supplements by women around the time of conception was examined and compared in those having babies with neural tube defects, those with still births or some other type of malformation, and in women who had normal babies.

  15. Neural Mechanisms of Conceptual Relations

    Science.gov (United States)

    Lewis, Gwyneth A.

    2017-01-01

    An over-arching goal in neurolinguistic research is to characterize the neural bases of semantic representation. A particularly relevant goal concerns whether we represent features and events (a) together in a generalized semantic hub or (b) separately in distinct but complementary systems. While the left anterior temporal lobe (ATL) is strongly…

  16. Neural mechanisms for voice recognition

    NARCIS (Netherlands)

    Andics, A.V.; McQueen, J.M.; Petersson, K.M.; Gal, V.; Rudas, G.; Vidnyanszky, Z.

    2010-01-01

    We investigated neural mechanisms that support voice recognition in a training paradigm with fMRI. The same listeners were trained on different weeks to categorize the mid-regions of voice-morph continua as an individual's voice. Stimuli implicitly defined a voice-acoustics space, and training

  17. Non-invasive neural stimulation

    Science.gov (United States)

    Tyler, William J.; Sanguinetti, Joseph L.; Fini, Maria; Hool, Nicholas

    2017-05-01

    Neurotechnologies for non-invasively interfacing with neural circuits have been evolving from those capable of sensing neural activity to those capable of restoring and enhancing human brain function. Generally referred to as non-invasive neural stimulation (NINS) methods, these neuromodulation approaches rely on electrical, magnetic, photonic, and acoustic or ultrasonic energy to influence nervous system activity, brain function, and behavior. Evidence that has been surmounting for decades shows that advanced neural engineering of NINS technologies will indeed transform the way humans treat diseases, interact with information, communicate, and learn. The physics underlying the ability of various NINS methods to modulate nervous system activity can be quite different from one another depending on the energy modality used as we briefly discuss. For members of commercial and defense industry sectors that have not traditionally engaged in neuroscience research and development, the science, engineering and technology required to advance NINS methods beyond the state-of-the-art presents tremendous opportunities. Within the past few years alone there have been large increases in global investments made by federal agencies, foundations, private investors and multinational corporations to develop advanced applications of NINS technologies. Driven by these efforts NINS methods and devices have recently been introduced to mass markets via the consumer electronics industry. Further, NINS continues to be explored in a growing number of defense applications focused on enhancing human dimensions. The present paper provides a brief introduction to the field of non-invasive neural stimulation by highlighting some of the more common methods in use or under current development today.

  18. Neural networks and applications tutorial

    Science.gov (United States)

    Guyon, I.

    1991-09-01

    The importance of neural networks has grown dramatically during this decade. While only a few years ago they were primarily of academic interest, now dozens of companies and many universities are investigating the potential use of these systems and products are beginning to appear. The idea of building a machine whose architecture is inspired by that of the brain has roots which go far back in history. Nowadays, technological advances of computers and the availability of custom integrated circuits, permit simulations of hundreds or even thousands of neurons. In conjunction, the growing interest in learning machines, non-linear dynamics and parallel computation spurred renewed attention in artificial neural networks. Many tentative applications have been proposed, including decision systems (associative memories, classifiers, data compressors and optimizers), or parametric models for signal processing purposes (system identification, automatic control, noise canceling, etc.). While they do not always outperform standard methods, neural network approaches are already used in some real world applications for pattern recognition and signal processing tasks. The tutorial is divided into six lectures, that where presented at the Third Graduate Summer Course on Computational Physics (September 3-7, 1990) on Parallel Architectures and Applications, organized by the European Physical Society: (1) Introduction: machine learning and biological computation. (2) Adaptive artificial neurons (perceptron, ADALINE, sigmoid units, etc.): learning rules and implementations. (3) Neural network systems: architectures, learning algorithms. (4) Applications: pattern recognition, signal processing, etc. (5) Elements of learning theory: how to build networks which generalize. (6) A case study: a neural network for on-line recognition of handwritten alphanumeric characters.

  19. Lingo-1 shRNA and Notch signaling inhibitor DAPT promote differentiation of neural stem/progenitor cells into neurons.

    Science.gov (United States)

    Wang, Jue; Ye, Zhizhong; Zheng, Shuhui; Chen, Luming; Wan, Yong; Deng, Yubin; Yang, Ruirui

    2016-03-01

    Determination of the exogenous factors that regulate differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes is an important step in the clinical therapy of spinal cord injury (SCI). The Notch pathway inhibits the differentiation of neural stem/progenitor cells and Lingo-1 is a strong negative regulator for myelination and axon growth. While Lingo-1 shRNA and N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-S-Phenylglycinet-butylester (DAPT), a Notch pathway inhibitor, have been used separately to help repair SCI, the results have been unsatisfactory. Here we investigated and elucidated the preliminary mechanism for the effect of Lingo-1 shRNA and DAPT on neural stem/progenitor cells differentiation. We found that neural stem/progenitor cells from E14 rat embryos expressed Nestin, Sox-2 and Lingo-1, and we optimized the transduction of neural stem/progenitor cells using lentiviral vectors encoding Lingo-1 shRNA. The addition of DAPT decreased the expression of Notch intracellular domain (NICD) as well as the downstream genes Hes1 and Hes5. Expression of NeuN, CNPase and GFAP in DAPT treated cells and expression of NeuN in Lingo-1 shRNA treated cells confirmed differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes. These results revealed that while Lingo-1 shRNA and Notch signaling inhibitor DAPT both promoted differentiation of neural stem cells into neurons, only DAPT was capable of driving neural stem/progenitor cells differentiation into oligodendrocytes and astrocytes. Since we were able to show that both Lingo-1 shRNA and DAPT could drive neural stem/progenitor cells differentiation, our data might aid the development of more effective SCI therapies using Lingo-1 shRNA and DAPT. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Neural Foundations of Creativity: A Systematic Review.

    Science.gov (United States)

    Mullen Raymond, Stephanie

    When considering the importance of the human cognitive function of creativity, we often overlook the fact that it is due to human creativity and to the constant search for new sensory stimuli that our world has, throughout the years, been one of innovation in every aspect of our existence -in the sciences, the humanities, and the arts. Almost everything that surrounds us is the result of human creativity, therefore it is not difficult to understand that although neuroscientific research has led to valuable perceptions into the probable underpinnings of this multifaceted ability, the precise neurological substrates that underlie creativity are yet to be determined. Despite the establishment of a strong link between creativity and divergent thinking, other brain networks have been implicated in this mental process. The following review underlines recent studies on the neural foundations of creativity. A comprehensive analysis of the upmost important facts will be presented, with emphasis on concepts, tests, and methods that have been used to study creativity, and how they have outlined a pathway to the key understanding of this unique human ability. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  1. Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Pan, Wei-Kang; Zheng, Bai-Jun; Wang, Huai-Jie [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

    2016-05-01

    A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin{sup +} cells decreased whilst the percentage of GFAP{sup +} cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. - Highlights: • Differences were identified between primary and daughter ENCCs. • Daughter ENCCs had reduced proliferation, migration and differentiation. • Daughter ENCCs also had increased apoptosis. • These altered characteristics warrant further investigation.

  2. Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro

    Directory of Open Access Journals (Sweden)

    Wei Cheng

    2015-03-01

    Full Text Available Background/Aims: There is interest in drugs and rehabilitation methods to enhance neurogenesis and improve neurological function after brain injury or degeneration. Resveratrol may enhance hippocampal neurogenesis and improve hippocampal atrophy in chronic fatigue mice and prenatally stressed rats. However, its effect and mechanism of neurogenesis after stroke is less well understood. Sonic hedgehog (Shh signaling is crucial for neurogenesis in the embryonic and adult brain, but relatively little is known about the role of Shh signaling in resveratrol-enhanced neurogenesis after stroke. Methods: Neural stem cells (NSCs before oxygen-glucose deprivation/reoxygenation (OGD/R in vitro were pretreated with resveratrol with or without cyclopamine. Survival and proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical staining. The expressions and activity of signaling proteins and mRNAs were detected by immunocytochemistry, Western blotting, and RT-PCR analysis. Results: Resveratrol significantly increased NSCs survival and proliferation in a concentration-dependent manner after OGD/R injury in vitro. At the same time, the expression of Patched-1, Smoothened (Smo, and Gli-1 proteins and mRNAs was upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a Smo inhibitor. Conclusion: Shh signaling mediates resveratrol to increase NSCs proliferation after OGD/R injury in vitro.

  3. Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology.

    Science.gov (United States)

    Masjkur, Jimmy; Poser, Steven W; Nikolakopoulou, Polyxeni; Chrousos, George; McKay, Ronald D; Bornstein, Stefan R; Jones, Peter M; Androutsellis-Theotokis, Andreas

    2016-02-01

    Loss of insulin-producing pancreatic islet β-cells is a hallmark of type 1 diabetes. Several experimental paradigms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these pathways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling pathways should not be seen as "on" or "off" but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play important roles. Thus, a pathway, once considered as "off" or "low" may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanonical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molecular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  4. The versatility of RhoA activities in neural differentiation.

    Science.gov (United States)

    Horowitz, Arie; Yang, Junning; Cai, Jingli; Iacovitti, Lorraine

    2017-01-26

    In this commentary we discuss a paper we published recently on the activities of the GTPase RhoA during neural differentiation of murine embryonic stem cells, and relate our findings to previous studies. We narrate how we found that RhoA impedes neural differentiation by inhibiting the production as well as the secretion of noggin, a soluble factor that antagonizes bone morphogenetic protein. We discuss how the questions we tried to address shaped the study, and how embryonic stem cells isolated from a genetically modified mouse model devoid of Syx, a RhoA-specific guanine exchange factor, were used to address them. We detail several signaling pathways downstream of RhoA that are hindered by the absence of Syx, and obstructed by retinoic acid, resulting in an increase of noggin production; we explain how the lower RhoA activity and, consequently, the sparser peri-junctional stress fibers in Syx -/- cells facilitated noggin secretion; and we report unpublished results showing that pharmacological inhibition of RhoA accelerates the neuronal differentiation of human embryonic stem cells. Finally, we identify signaling mechanisms in our recent study that warrant further study, and speculate on the possibility of manipulating RhoA signaling in combination with other pathways to drive the differentiation of neuronal subtypes.

  5. 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.

  6. Dynamic properties of cellular neural networks

    Directory of Open Access Journals (Sweden)

    Angela Slavova

    1993-01-01

    Full Text Available Dynamic behavior of a new class of information-processing systems called Cellular Neural Networks is investigated. In this paper we introduce a small parameter in the state equation of a cellular neural network and we seek for periodic phenomena. New approach is used for proving stability of a cellular neural network by constructing Lyapunov's majorizing equations. This algorithm is helpful for finding a map from initial continuous state space of a cellular neural network into discrete output. A comparison between cellular neural networks and cellular automata is made.

  7. Micro- and Nanotechnologies for Optical Neural Interfaces

    Science.gov (United States)

    Pisanello, Ferruccio; Sileo, Leonardo; De Vittorio, Massimo

    2016-01-01

    In last decade, the possibility to optically interface with the mammalian brain in vivo has allowed unprecedented investigation of functional connectivity of neural circuitry. Together with new genetic and molecular techniques to optically trigger and monitor neural activity, a new generation of optical neural interfaces is being developed, mainly thanks to the exploitation of both bottom-up and top-down nanofabrication approaches. This review highlights the role of nanotechnologies for optical neural interfaces, with particular emphasis on new devices and methodologies for optogenetic control of neural activity and unconventional methods for detection and triggering of action potentials using optically-active colloidal nanoparticles. PMID:27013939

  8. Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development.

    Science.gov (United States)

    Ramya, Seshadri; Shyamasundar, Sukanya; Bay, Boon Huat; Dheen, S Thameem

    2017-01-01

    Maternal diabetes is known to cause neural tube defects (NTDs) in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis. To address this, high throughput miRNA expression profiling in neural stem cells (NSCs) isolated from the forebrain of embryos from normal or streptozotocin-induced diabetic pregnancy was carried out. It is known that maternal diabetes results in fetal hypoglycemia/hyperglycemia or hypoxia. Hence, NSCs from embryos of control pregnant mice were exposed to low or high glucose or hypoxia in vitro. miRNA pathway analysis revealed distinct deregulation of several biological pathways, including axon guidance pathway, which are critical for brain development in NSCs exposed to different treatments. Among the differentially expressed miRNAs, the miRNA-30 family members which are predicted to target genes involved in brain development was upregulated in NSCs from embryos of diabetic pregnancy when compared to control. miRNA-30b was found to be upregulated while its target gene Sirtuin 1 (Sirt1), as revealed by luciferase assay, was down regulated in NSCs from embryos of diabetic pregnancy. Further, overexpression of miRNA-30b in NSCs, resulted in decreased expression of Sirt1 protein, and altered the neuron/glia ratio. On the other hand, siRNA mediated knockdown of Sirt1 in NSCs promoted astrogenesis, indicating that miRNA-30b alters lineage specification via Sirt1. Overall, these results suggest that maternal diabetes alters the genes involved in neural tube formation via

  9. Computational Graph Theoretical Model of the Zebrafish Sensorimotor Pathway

    Science.gov (United States)

    Peterson, Joshua M.; Stobb, Michael; Mazzag, Bori; Gahtan, Ethan

    2011-11-01

    Mapping the detailed connectivity patterns of neural circuits is a central goal of neuroscience and has been the focus of extensive current research [4, 3]. The best quantitative approach to analyze the acquired data is still unclear but graph theory has been used with success [3, 1]. We present a graph theoretical model with vertices and edges representing neurons and synaptic connections, respectively. Our system is the zebrafish posterior lateral line sensorimotor pathway. The goal of our analysis is to elucidate mechanisms of information processing in this neural pathway by comparing the mathematical properties of its graph to those of other, previously described graphs. We create a zebrafish model based on currently known anatomical data. The degree distributions and small-world measures of this model is compared to small-world, random and 3-compartment random graphs of the same size (with over 2500 nodes and 160,000 connections). We find that the zebrafish graph shows small-worldness similar to other neural networks and does not have a scale-free distribution of connections.

  10. Pathways to youth homelessness.

    Science.gov (United States)

    Martijn, Claudine; Sharpe, Louise

    2006-01-01

    Research documents high levels of psychopathology among homeless youth. Most research, however, has not distinguished between disorders that are present prior to homelessness and those that develop following homelessness. Hence whether psychological disorders are the cause or consequence of homelessness has not been established. The aim of this study is to investigate causal pathways to homelessness amongst currently homeless youth in Australia. The study uses a quasi-qualitative methodology to generate hypotheses for larger-scale research. High rates of psychological disorders were confirmed in the sample 35 homeless youth aged 14-25. The rates of psychological disorders at the point of homelessness were greater than in normative samples, but the rates of clinical disorder increased further once homeless. Further in-depth analyses were conducted to identify the temporal sequence for each individual with a view to establishing a set of causal pathways to homelessness and trajectories following homelessness that characterised the people in the sample. Five pathways to homelessness and five trajectories following homelessness were identified that accounted for the entire sample. Each pathway constituted a series of interactions between different factors similar to that described by Craig and Hodson (1998. Psychological Medicine, 28, 1379-1388) as "complex subsidiary pathways". The major findings were that (1) trauma is a common experience amongst homeless youth prior to homelessness and figured in the causal pathways to homelessness for over half of the sample; (2) once homeless, for the majority of youth there is an increase in the number of psychological diagnoses including drug and alcohol diagnoses; and (3) crime did not precede homelessness for all but one youth; however, following homelessness, involvement in criminal activity was common and became a distinguishing factor amongst youth. The implications of these findings for future research and service

  11. Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation.

    Science.gov (United States)

    Sullivan-Brown, Jessica L; Tandon, Panna; Bird, Kim E; Dickinson, Daniel J; Tintori, Sophia C; Heppert, Jennifer K; Meserve, Joy H; Trogden, Kathryn P; Orlowski, Sara K; Conlon, Frank L; Goldstein, Bob

    2016-01-01

    Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems. Copyright © 2016 by the Genetics Society of America.

  12. Neural retina identity is specified by lens-derived BMP signals.

    Science.gov (United States)

    Pandit, Tanushree; Jidigam, Vijay K; Patthey, Cedric; Gunhaga, Lena

    2015-05-15

    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity. © 2015. Published by The Company of Biologists Ltd.

  13. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    This volume outlines key steps associated with the design, building, and testing of synthetic metabolic pathways for optimal cell factory performance and robustness, and illustrates how data-driven learning from these steps can be used for rational cost-effective engineering of cell factories...... topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  14. Spike Neural Models Part II: Abstract Neural Models

    OpenAIRE

    Johnson, Melissa G.; Chartier, Sylvain

    2018-01-01

    Neurons are complex cells that require a lot of time and resources to model completely. In spiking neural networks (SNN) though, not all that complexity is required. Therefore simple, abstract models are often used. These models save time, use less computer resources, and are easier to understand. This tutorial presents two such models: Izhikevich's model, which is biologically realistic in the resulting spike trains but not in the parameters, and the Leaky Integrate and Fire (LIF) model whic...

  15. Shaping the dynamics of a bidirectional neural interface.

    Directory of Open Access Journals (Sweden)

    Alessandro Vato

    Full Text Available Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices. The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device. Taken together, neural activity recording and microstimulation techniques allow us to embed a portion of the central nervous system within a closed-loop system, whose behavior emerges from the combined dynamical properties of its neural and artificial components. In this study we asked if it is possible to concurrently regulate this bidirectional brain-machine interaction so as to shape a desired dynamical behavior of the combined system. To this end, we followed a well-known biological pathway. In vertebrates, the communications between brain and limb mechanics are mediated by the spinal cord, which combines brain instructions with sensory information and organizes coordinated patterns of muscle forces driving the limbs along dynamically stable trajectories. We report the creation and testing of the first neural interface that emulates this sensory-motor interaction. The interface organizes a bidirectional communication between sensory and motor areas of the brain of anaesthetized rats and an external dynamical object with programmable properties. The system includes (a a motor interface decoding signals from a motor cortical area, and (b a sensory interface encoding the state of the external object into electrical stimuli to a somatosensory area. The interactions between brain activities and the state of the external object generate a family of trajectories converging upon a selected equilibrium point from arbitrary starting locations. Thus, the bidirectional interface establishes the possibility to specify not only a particular movement trajectory but an entire family of motions, which includes the prescribed reactions to unexpected

  16. Shaping the Dynamics of a Bidirectional Neural Interface

    Science.gov (United States)

    Vato, Alessandro; Semprini, Marianna; Maggiolini, Emma; Szymanski, Francois D.; Fadiga, Luciano; Panzeri, Stefano; Mussa-Ivaldi, Ferdinando A.

    2012-01-01

    Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices. The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device. Taken together, neural activity recording and microstimulation techniques allow us to embed a portion of the central nervous system within a closed-loop system, whose behavior emerges from the combined dynamical properties of its neural and artificial components. In this study we asked if it is possible to concurrently regulate this bidirectional brain-machine interaction so as to shape a desired dynamical behavior of the combined system. To this end, we followed a well-known biological pathway. In vertebrates, the communications between brain and limb mechanics are mediated by the spinal cord, which combines brain instructions with sensory information and organizes coordinated patterns of muscle forces driving the limbs along dynamically stable trajectories. We report the creation and testing of the first neural interface that emulates this sensory-motor interaction. The interface organizes a bidirectional communication between sensory and motor areas of the brain of anaesthetized rats and an external dynamical object with programmable properties. The system includes (a) a motor interface decoding signals from a motor cortical area, and (b) a sensory interface encoding the state of the external object into electrical stimuli to a somatosensory area. The interactions between brain activities and the state of the external object generate a family of trajectories converging upon a selected equilibrium point from arbitrary starting locations. Thus, the bidirectional interface establishes the possibility to specify not only a particular movement trajectory but an entire family of motions, which includes the prescribed reactions to unexpected perturbations. PMID

  17. Melanoblast development coincides with the late emerging cells from the dorsal neural tube in turtle Trachemys scripta.

    Science.gov (United States)

    Rice, Ritva; Cebra-Thomas, Judith; Haugas, Maarja; Partanen, Juha; Rice, David P C; Gilbert, Scott F

    2017-09-21

    Ectothermal reptiles have internal pigmentation, which is not seen in endothermal birds and mammals. Here we show that the development of the dorsal neural tube-derived melanoblasts in turtle Trachemys scripta is regulated by similar mechanisms as in other amniotes, but significantly later in development, during the second phase of turtle trunk neural crest emigration. The development of melanoblasts coincided with a morphological change in the dorsal neural tube between stages mature G15 and G16. The melanoblasts delaminated and gathered in the carapacial staging area above the neural tube at G16, and differentiated into pigment-forming melanocytes during in vitro culture. The Mitf-positive melanoblasts were not restricted to the dorsolateral pathway as in birds and mammals but were also present medially through the somites similarly to ectothermal anamniotes. This matched a lack of environmental barrier dorsal and lateral to neural tube and the somites that is normally formed by PNA-binding proteins that block entry to medial pathways. PNA-binding proteins may also participate in the patterning of the carapacial pigmentation as both the migratory neural crest cells and pigment localized only to PNA-free areas.

  18. Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation.

    Science.gov (United States)

    Mazemondet, Orianne; Hubner, Rayk; Frahm, Jana; Koczan, Dirk; Bader, Benjamin M; Weiss, Dieter G; Uhrmacher, Adelinde M; Frech, Moritz J; Rolfs, Arndt; Luo, Jiankai

    2011-12-01

    ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, in which the Wnt/β-catenin pathway is known to be involved. However, little is known about kinetic changes of this pathway in human neural progenitor cell differentiation. In the present study, we provide a quantitative profile of Wnt/β-catenin pathway dynamics showing its spatio-temporal regulation during ReNcell VM cell differentiation. We show first that T-cell factor dependent transcription can be activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands, pathway receptors and signaling molecules are temporally controlled, demonstrating changes related to differentiation stages. During the first three hours of differentiation the signaling molecules LRP6, Dvl2 and β-catenin are spatio-temporally regulated between distinct cellular compartments. From 24 h onward, components of the Wnt/β-catenin pathway are strongly activated and regulated as shown by mRNA up-regulation of Wnt ligands (Wnt5a and Wnt7a), receptors including Frizzled-2, -3, -6, -7, and -9, and co-receptors, and target genes including Axin2. This detailed temporal profile of the Wnt/β-catenin pathway is a first step to understand, control and to orientate, in vitro, human neural progenitor cell differentiation.

  19. Intermittent reductions in respiratory neural activity elicit spinal TNF-α-independent, atypical PKC-dependent inactivity-induced phrenic motor facilitation

    Science.gov (United States)

    Baertsch, Nathan A.

    2015-01-01

    In many neural networks, mechanisms of compensatory plasticity respond to prolonged reductions in neural activity by increasing cellular excitability or synaptic strength. In the respiratory control system, a prolonged reduction in synaptic inputs to the phrenic motor pool elicits a TNF-α- and atypical PKC-dependent form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although iPMF may be elicited by a prolonged reduction in respiratory neural activity, iPMF is more efficiently induced when reduced respiratory neural activity (neural apnea) occurs intermittently. Mechanisms giving rise to iPMF following intermittent neural apnea are unknown. The purpose of this study was to test the hypothesis that iPMF following intermittent reductions in respiratory neural activity requires spinal TNF-α and aPKC. Phrenic motor output was recorded in anesthetized and ventilated rats exposed to brief intermittent (5, ∼1.25 min), brief sustained (∼6.25 min), or prolonged sustained (30 min) neural apnea. iPMF was elicited following brief intermittent and prolonged sustained neural apnea, but not following brief sustained neural apnea. Unlike iPMF following prolonged neural apnea, spinal TNF-α was not required to initiate iPMF during intermittent neural apnea; however, aPKC was still required for its stabilization. These results suggest that different patterns of respiratory neural activity induce iPMF through distinct cellular mechanisms but ultimately converge on a similar downstream pathway. Understanding the diverse cellular mechanisms that give rise to inactivity-induced respiratory plasticity may lead to development of novel therapeutic strategies to treat devastating respiratory control disorders when endogenous compensatory mechanisms fail. PMID:25673781

  20. Kentucky Workforce Pathways Development

    Science.gov (United States)

    Coburn, Karen L.

    2017-01-01

    The purpose of the study was to determine whether the advent of healthcare information technology was a viable career pathway for the people of northeastern Kentucky. The qualitative study used the Delphi Method to conduct and examine interviews with nine experts in Kentucky's workforce development, economic development, education, and healthcare…

  1. Adverse outcome pathways

    DEFF Research Database (Denmark)

    Leist, Marcel; Ghallab, Ahmed; Graepel, Rabea

    2017-01-01

    , the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition...

  2. Pathways to School Success

    Science.gov (United States)

    University of Pittsburgh Office of Child Development, 2012

    2012-01-01

    In 2006, the University of Pittsburgh Office of Child Development began implementing a multi-year school readiness project in several area schools. Evidence from both research and the field point to several key elements that foster school readiness and create pathways to school success for all children. This paper presents components of a…

  3. Electrical stimulation superimposed on voluntary training can limit sensory integration in neural adaptations.

    Science.gov (United States)

    Paillard, Thierry

    2012-01-01

    P. Bezerra, S. Zhou, Z. Crowley, A. Davie, and R. Baglin (2011) suggested that the neural mechanisms responsible for steadiness improvement relate in particular to the discharge behavior of motor units and the practice and learning of skills rather than the strength gain after electromyostimulation superimposed over voluntary training. However, the afferent inputs are determining in control of the force level produced and thus contribute to ensure muscle steadiness. Hence, it is possible that electromyostimulation interferes in neurophysiological afference integration and prevents neural adaptations that enable improvement of the control of force (and then muscle steadiness) to occur. Therefore, the neural adaptations induced by electromyostimulation superimposed onto voluntary training should also be researched in relation to the sensory pathways.

  4. The human infant brain: A neural architecture able to learn language.

    Science.gov (United States)

    Dehaene-Lambertz, Ghislaine

    2017-02-01

    To understand the type of neural computations that may explain how human infants acquire their native language in only a few months, the study of their neural architecture is necessary. The development of brain imaging techniques has opened the possibilities of studying human infants without discomfort, and although these studies are still sparse, several characteristics are noticeable in the human infant's brain: first, parallel and hierarchical processing pathways are observed before intense exposure to speech with an efficient temporal coding in the left hemisphere and, second, frontal regions are involved from the start in infants' cognition. These observations are certainly not sufficient to explain language acquisition but illustrate a new approach that relies on a better description of infants' brain activity during linguistic tasks, which is compared to results in animals and human adults to clarify the neural bases of language in humans.

  5. Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation.

    Science.gov (United States)

    Kermer, Vanessa; Ritter, Mathias; Albuquerque, Boris; Leib, Christoph; Stanke, Matthias; Zimmermann, Herbert

    2010-11-26

    In the adult mammalian brain the subependymal layer of the lateral ventricles houses neural stem cells giving rise to young neurons migrating towards the olfactory bulb. The molecular cues controlling essential functions within the neurogenesis pathway such as proliferation, short and long distance migration, differentiation and functional integration are poorly understood. Neural progenitors in situ express the tissue nonspecific form of alkaline phosphatase (TNAP), a cell surface-located nonspecific phosphomonoesterase capable of hydrolyzing extracellular nucleotides. To gain insight into the functional role of TNAP in cultured multipotent neural stem cells we applied a knockdown protocol using RNA interference with shRNA and retroviral infection. We show that TNAP knockdown reduces cell proliferation and differentiation into neurons or oligodendrocytes. This effect is abrogated by addition of alkaline phosphatase to the culture medium. Our results suggest that TNAP is essential for NSC proliferation and differentiation in vitro and possibly also in vivo. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. The artist emerges: visual art learning alters neural structure and function.

    Science.gov (United States)

    Schlegel, Alexander; Alexander, Prescott; Fogelson, Sergey V; Li, Xueting; Lu, Zhengang; Kohler, Peter J; Riley, Enrico; Tse, Peter U; Meng, Ming

    2015-01-15

    How does the brain mediate visual artistic creativity? Here we studied behavioral and neural changes in drawing and painting students compared to students who did not study art. We investigated three aspects of cognition vital to many visual artists: creative cognition, perception, and perception-to-action. We found that the art students became more creative via the reorganization of prefrontal white matter but did not find any significant changes in perceptual ability or related neural activity in the art students relative to the control group. Moreover, the art students improved in their ability to sketch human figures from observation, and multivariate patterns of cortical and cerebellar activity evoked by this drawing task became increasingly separable between art and non-art students. Our findings suggest that the emergence of visual artistic skills is supported by plasticity in neural pathways that enable creative cognition and mediate perceptuomotor integration. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Evolutionary and Developmental Origins of the Cardiac Neural Crest: Building a Divided Outflow Tract

    Science.gov (United States)

    Keyte, Anna L.; Alonzo-Johnsen, Martha; Hutson, Mary R.

    2015-01-01

    The cardiac neural crest cells (CNCCs) have played an important role in the evolution and development of the vertebrate cardiovascular system: from reinforcement of the developing aortic arch arteries early in vertebrate evolution, to later orchestration of aortic arch artery remodeling into the great arteries of the heart, and finally outflow tract septation in amniotes. A critical element necessary for the evolutionary advent of outflow tract septation was the co-evolution of the cardiac neural crest cells with the second heart field. This review highlights the major transitions in vertebrate circulatory evolution, explores the evolutionary developmental origins of the CNCCs from the third stream cranial neural crest, and explores candidate signaling pathways in CNCC and outflow tract evolution drawn from our knowledge of DiGeorge Syndrome. PMID:25227322

  8. 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.

  9. Genetic attack on neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Naeh, Rivka; Kanter, Ido

    2006-03-01

    Different scaling properties for the complexity of bidirectional synchronization and unidirectional learning are essential for the security of neural cryptography. Incrementing the synaptic depth of the networks increases the synchronization time only polynomially, but the success of the geometric attack is reduced exponentially and it clearly fails in the limit of infinite synaptic depth. This method is improved by adding a genetic algorithm, which selects the fittest neural networks. The probability of a successful genetic attack is calculated for different model parameters using numerical simulations. The results show that scaling laws observed in the case of other attacks hold for the improved algorithm, too. The number of networks needed for an effective attack grows exponentially with increasing synaptic depth. In addition, finite-size effects caused by Hebbian and anti-Hebbian learning are analyzed. These learning rules converge to the random walk rule if the synaptic depth is small compared to the square root of the system size.

  10. Neural plasticity across the lifespan.

    Science.gov (United States)

    Power, Jonathan D; Schlaggar, Bradley L

    2017-01-01

    An essential feature of the brain is its capacity to change. Neuroscientists use the term 'plasticity' to describe the malleability of neuronal connectivity and circuitry. How does plasticity work? A review of current data suggests that plasticity encompasses many distinct phenomena, some of which operate across most or all of the lifespan, and others that operate exclusively in early development. This essay surveys some of the key concepts related to neural plasticity, beginning with how current patterns of neural activity (e.g., as you read this essay) come to impact future patterns of activity (e.g., your memory of this essay), and then extending this framework backward into more development-specific mechanisms of plasticity. WIREs Dev Biol 2017, 6:e216. doi: 10.1002/wdev.216 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  11. Neural Networks Methodology and Applications

    CERN Document Server

    Dreyfus, Gérard

    2005-01-01

    Neural networks represent a powerful data processing technique that has reached maturity and broad application. When clearly understood and appropriately used, they are a mandatory component in the toolbox of any engineer who wants make the best use of the available data, in order to build models, make predictions, mine data, recognize shapes or signals, etc. Ranging from theoretical foundations to real-life applications, this book is intended to provide engineers and researchers with clear methodologies for taking advantage of neural networks in industrial, financial or banking applications, many instances of which are presented in the book. For the benefit of readers wishing to gain deeper knowledge of the topics, the book features appendices that provide theoretical details for greater insight, and algorithmic details for efficient programming and implementation. The chapters have been written by experts ands seemlessly edited to present a coherent and comprehensive, yet not redundant, practically-oriented...

  12. Autonomic neural functions in space.

    Science.gov (United States)

    Mano, T

    2005-08-01

    Autonomic neural functions are important to regulate vital functions in the living body. There are different methods to evaluate indirectly and directly autonomic, sympathetic and parasympathetic, neural functions of human body. Among various methods, microneurography is a technique to evaluate directly sympathetic neural functions in humans. Using this technique sympathetic neural traffic leading to skeletal muscles (muscle sympathetic nerve activity; MSNA) can be recorded from human peripheral nerves in situ. MSNA plays essentially important roles to maintain blood pressure homeostasis against gravity. Orthostatic intolerance is an important problem as an autonomic dysfunction encountered after exposure of human beings to microgravity. There exist at least two different types of sympathetic neural responses, low and high responders to orthostatic stress in orthostatic hypotension seen in neurological disorders. To answer the question if post-spaceflight orthostatic intolerance is induced by low or high MSNA responses to orthostatic stress, MSNA was microneurographically recorded for the first time before, during and after spaceflight in 1998 under Neurolab international research project. The same activity has been recorded during and/or after ground-based short- and long-term simulations of microgravity. MSNA was rather enhanced on the 12(th) and 13(th) day of spaceflight and just after landing day. Postflight MSNA response to head-up tilt was well preserved in astronauts who were orthostatically well tolerant. MSNA was suppressed during short-term simulation of microgravity less than 2 hours but was enhanced after long-term simulation of microgravity more than 3 days. Orthostatic intolerance after exposure to long-term simulation of microgravity was associated with reduced MSNA response to orthostatic stress with impaired baroreflex functions. These findings obtained from MSNA recordings in subjects exposed to space as well as short- and long-term simulations of

  13. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

    DEFF Research Database (Denmark)

    Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida

    2012-01-01

    Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients ...

  14. 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice

    DEFF Research Database (Denmark)

    Wang, Yaoming; Zhao, Zhen; Rege, Sanket V

    2016-01-01

    profile in humans, 3K3A-APC has advanced to clinical trials as a neuroprotectant in ischemic stroke. Recently, 3K3A-APC has been shown to stimulate neuronal production by human neural stem and progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate-receptor 1-Akt pathway, which suggests...

  15. Adaptive Regularization of Neural Classifiers

    DEFF Research Database (Denmark)

    Andersen, Lars Nonboe; Larsen, Jan; Hansen, Lars Kai

    1997-01-01

    We present a regularization scheme which iteratively adapts the regularization parameters by minimizing the validation error. It is suggested to use the adaptive regularization scheme in conjunction with optimal brain damage pruning to optimize the architecture and to avoid overfitting. Furthermore......, we propose an improved neural classification architecture eliminating an inherent redundancy in the widely used SoftMax classification network. Numerical results demonstrate the viability of the method...

  16. Functional neural anatomy of talent.

    Science.gov (United States)

    Kalbfleisch, M Layne

    2004-03-01

    The terms gifted, talented, and intelligent all have meanings that suggest an individual's highly proficient or exceptional performance in one or more specific areas of strength. Other than Spearman's g, which theorizes about a general elevated level of potential or ability, more contemporary theories of intelligence are based on theoretical models that define ability or intelligence according to a priori categories of specific performance. Recent studies in cognitive neuroscience report on the neural basis of g from various perspectives such as the neural speed theory and the efficiency of prefrontal function. Exceptional talent is the result of interactions between goal-directed behavior and nonvolitional perceptual processes in the brain that have yet to be fully characterized and understood by the fields of psychology and cognitive neuroscience. Some developmental studies report differences in region-specific neural activation, recruitment patterns, and reaction times in subjects who are identified with high IQ scores according to traditional scales of assessment such as the WISC-III or Stanford-Binet. Although as cases of savants and prodigies illustrate, talent is not synonymous with high IQ. This review synthesizes information from the fields of psychometrics and gifted education, with findings from the neurosciences on the neural basis of intelligence, creativity, profiles of expert performers, cognitive function, and plasticity to suggest a paradigm for investigating talent as the maximal and productive use of either or both of one's high level of general intelligence or domain-specific ability. Anat Rec (Part B: New Anat) 277B:21-36, 2004. Copyright 2004 Wiley-Liss, Inc.

  17. Handbook on neural information processing

    CERN Document Server

    Maggini, Marco; Jain, Lakhmi

    2013-01-01

    This handbook presents some of the most recent topics in neural information processing, covering both theoretical concepts and practical applications. The contributions include:                         Deep architectures                         Recurrent, recursive, and graph neural networks                         Cellular neural networks                         Bayesian networks                         Approximation capabilities of neural networks                         Semi-supervised learning                         Statistical relational learning                         Kernel methods for structured data                         Multiple classifier systems                         Self organisation and modal learning                         Applications to ...

  18. Neural prostheses and brain plasticity

    Science.gov (United States)

    Fallon, James B.; Irvine, Dexter R. F.; Shepherd, Robert K.

    2009-12-01

    The success of modern neural prostheses is dependent on a complex interplay between the devices' hardware and software and the dynamic environment in which the devices operate: the patient's body or 'wetware'. Over 120 000 severe/profoundly deaf individuals presently receive information enabling auditory awareness and speech perception from cochlear implants. The cochlear implant therefore provides a useful case study for a review of the complex interactions between hardware, software and wetware, and of the important role of the dynamic nature of wetware. In the case of neural prostheses, the most critical component of that wetware is the central nervous system. This paper will examine the evidence of changes in the central auditory system that contribute to changes in performance with a cochlear implant, and discuss how these changes relate to electrophysiological and functional imaging studies in humans. The relationship between the human data and evidence from animals of the remarkable capacity for plastic change of the central auditory system, even into adulthood, will then be examined. Finally, we will discuss the role of brain plasticity in neural prostheses in general.

  19. Neural correlates of paediatric dysgraphia.

    Science.gov (United States)

    Van Hoorn, Jessika F; Maathuis, Carel G B; Hadders-Algra, Mijna

    2013-11-01

    Writing is an important skill that is related both to school performance and to psychosocial outcomes such as the child's self-esteem. Deficits in handwriting performance are frequently encountered in children with developmental coordination disorder. This review focuses on what is known about the neural correlates of atypical handwriting in children. Knowledge of the neural correlates is derived from studies using clinical case designs (e.g. lesion studies), studies using neuroimaging, and assessment of minor neurological dysfunction. The two functional imaging studies suggest a contribution of cortical areas and the cerebellum. The largest study indicated that cortical areas in all regions of the brain are involved (frontal, temporal, parietal, and occipital). The two lesion studies confirmed cerebellar involvement. The findings of the study on minor neurological dysfunction in children with writing problems correspond to the imaging results. The limited data on the neural substrate of paediatric dysgraphia suggest that at least a subset of the children with dysgraphia have dysfunctions in extensive supraspinal networks. In others, dysfunction may be restricted to either the cerebellum or specific cortical sites. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

  20. Three dimensional living neural networks

    Science.gov (United States)

    Linnenberger, Anna; McLeod, Robert R.; Basta, Tamara; Stowell, Michael H. B.

    2015-08-01

    We investigate holographic optical tweezing combined with step-and-repeat maskless projection micro-stereolithography for fine control of 3D positioning of living cells within a 3D microstructured hydrogel grid. Samples were fabricated using three different cell lines; PC12, NT2/D1 and iPSC. PC12 cells are a rat cell line capable of differentiation into neuron-like cells NT2/D1 cells are a human cell line that exhibit biochemical and developmental properties similar to that of an early embryo and when exposed to retinoic acid the cells differentiate into human neurons useful for studies of human neurological disease. Finally induced pluripotent stem cells (iPSC) were utilized with the goal of future studies of neural networks fabricated from human iPSC derived neurons. Cells are positioned in the monomer solution with holographic optical tweezers at 1064 nm and then are encapsulated by photopolymerization of polyethylene glycol (PEG) hydrogels formed by thiol-ene photo-click chemistry via projection of a 512x512 spatial light modulator (SLM) illuminated at 405 nm. Fabricated samples are incubated in differentiation media such that cells cease to divide and begin to form axons or axon-like structures. By controlling the position of the cells within the encapsulating hydrogel structure the formation of the neural circuits is controlled. The samples fabricated with this system are a useful model for future studies of neural circuit formation, neurological disease, cellular communication, plasticity, and repair mechanisms.

  1. Neural mechanisms of social dominance

    Directory of Open Access Journals (Sweden)

    Noriya eWatanabe

    2015-06-01

    Full Text Available In a group setting, individuals’ perceptions of their own level of dominance or of the dominance level of others, and the ability to adequately control their behavior based on these perceptions are crucial for living within a social environment. Recent advances in neural imaging and molecular technology have enabled researchers to investigate the neural substrates that support the perception of social dominance and the formation of a social hierarchy in humans. At the systems’ level, recent studies showed that dominance perception is represented in broad brain regions which include the amygdala, hippocampus, striatum, and various cortical networks such as the prefrontal, and parietal cortices. Additionally, neurotransmitter systems such as the dopaminergic and serotonergic systems, modulate and are modulated by the formation of the social hierarchy in a group. While these monoamine systems have a wide distribution and multiple functions, it was recently found that the Neuropeptide B/W contributes to the perception of dominance and is present in neurons that have a limited projection primarily to the amygdala. The present review discusses the specific roles of these neural regions and neurotransmitter systems in the perception of dominance and in hierarchy formation.

  2. Neural Correlates of Predictive Saccades.

    Science.gov (United States)

    Lee, Stephen M; Peltsch, Alicia; Kilmade, Maureen; Brien, Donald C; Coe, Brian C; Johnsrude, Ingrid S; Munoz, Douglas P

    2016-08-01

    Every day we generate motor responses that are timed with external cues. This phenomenon of sensorimotor synchronization has been simplified and studied extensively using finger tapping sequences that are executed in synchrony with auditory stimuli. The predictive saccade paradigm closely resembles the finger tapping task. In this paradigm, participants follow a visual target that "steps" between two fixed locations on a visual screen at predictable ISIs. Eventually, the time from target appearance to saccade initiation (i.e., saccadic RT) becomes predictive with values nearing 0 msec. Unlike the finger tapping literature, neural control of predictive behavior described within the eye movement literature has not been well established and is inconsistent, especially between neuroimaging and patient lesion studies. To resolve these discrepancies, we used fMRI to investigate the neural correlates of predictive saccades by contrasting brain areas involved with behavior generated from the predictive saccade task with behavior generated from a reactive saccade task (saccades are generated toward targets that are unpredictably timed). We observed striking differences in neural recruitment between reactive and predictive conditions: Reactive saccades recruited oculomotor structures, as predicted, whereas predictive saccades recruited brain structures that support timing in motor responses, such as the crus I of the cerebellum, and structures commonly associated with the default mode network. Therefore, our results were more consistent with those found in the finger tapping literature.

  3. Fuzzy neural networks: theory and applications

    Science.gov (United States)

    Gupta, Madan M.

    1994-10-01

    During recent years, significant advances have been made in two distinct technological areas: fuzzy logic and computational neural networks. The theory of fuzzy logic provides a mathematical framework to capture the uncertainties associated with human cognitive processes, such as thinking and reasoning. It also provides a mathematical morphology to emulate certain perceptual and linguistic attributes associated with human cognition. On the other hand, the computational neural network paradigms have evolved in the process of understanding the incredible learning and adaptive features of neuronal mechanisms inherent in certain biological species. Computational neural networks replicate, on a small scale, some of the computational operations observed in biological learning and adaptation. The integration of these two fields, fuzzy logic and neural networks, have given birth to an emerging technological field -- fuzzy neural networks. Fuzzy neural networks, have the potential to capture the benefits of these two fascinating fields, fuzzy logic and neural networks, into a single framework. The intent of this tutorial paper is to describe the basic notions of biological and computational neuronal morphologies, and to describe the principles and architectures of fuzzy neural networks. Towards this goal, we develop a fuzzy neural architecture based upon the notion of T-norm and T-conorm connectives. An error-based learning scheme is described for this neural structure.

  4. PathwayAccess: CellDesigner plugins for pathway databases.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2010-09-15

    CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

  5. Assembling old tricks for new tasks: a neural model of instructional learning and control.

    Science.gov (United States)

    Huang, Tsung-Ren; Hazy, Thomas E; Herd, Seth A; O'Reilly, Randall C

    2013-06-01

    We can learn from the wisdom of others to maximize success. However, it is unclear how humans take advice to flexibly adapt behavior. On the basis of data from neuroanatomy, neurophysiology, and neuroimaging, a biologically plausible model is developed to illustrate the neural mechanisms of learning from instructions. The model consists of two complementary learning pathways. The slow-learning parietal pathway carries out simple or habitual stimulus-response (S-R) mappings, whereas the fast-learning hippocampal pathway implements novel S-R rules. Specifically, the hippocampus can rapidly encode arbitrary S-R associations, and stimulus-cued responses are later recalled into the basal ganglia-gated pFC to bias response selection in the premotor and motor cortices. The interactions between the two model learning pathways explain how instructions can override habits and how automaticity can be achieved through motor consolidation.

  6. Neural Acupuncture Unit: A New Concept for Interpreting Effects and Mechanisms of Acupuncture

    Science.gov (United States)

    Zhang, Zhang-Jin; Wang, Xiao-Min; McAlonan, Grainne M.

    2012-01-01

    When an acupuncture needle is inserted into a designated point on the body and mechanical or electrical stimulation is delivered, various neural and neuroactive components are activated. The collection of the activated neural and neuroactive components distributed in the skin, muscle, and connective tissues surrounding the inserted needle is defined as a neural acupuncture unit (NAU). The traditionally defined acupoints represent an anatomical landmark system that indicates local sites where NAUs may contain relatively dense and concentrated neural and neuroactive components, upon which acupuncture stimulation would elicit a more efficient therapeutic response. The NAU-based local mechanisms of biochemical and biophysical reactions play an important role in acupuncture-induced analgesia. Different properties of NAUs are associated with different components of needling sensation. There exist several central pathways to convey NAU-induced acupuncture signals, Electroacupuncture (EA) frequency-specific neurochemical effects are related to different peripheral and central pathways transmitting afferent signals from different frequency of NAU stimulation. More widespread and intense neuroimaging responses of brain regions to acupuncture may be a consequence of more efficient NAU stimulation modes. The introduction of the conception of NAU provides a new theoretical approach to interpreting effects and mechanisms of acupuncture in modern biomedical knowledge framework. PMID:22474503

  7. Neural interactions mediating conflict control and its training-induced plasticity.

    Science.gov (United States)

    Hu, Min; Wang, Xiangpeng; Zhang, Wenwen; Hu, Xueping; Chen, Antao

    2017-12-01

    Cognitive control is of great plasticity. Training programs targeted on improving it have been suggested to yield neural changes in the brain. However, until recently, the relationship between training-induced brain changes and improvements in cognitive control is still an open issue. Besides, although the literature has attributed the operation of cognitive control to interactions between large-scale networks, the neural pathways directly associated with it remain unclear. The current study aimed to examine these issues by focusing on conflict processing. In particular, we employed a training program with a randomized controlled design. The main findings were as follows: 1) In behavior, the training group showed reduced conflict effect after training, relative to the control group; 2) In the pretest stage, the behavioral conflict effect was negatively correlated with a number of neural pathways, including the connectivity from the cingulo-opercular network (CON) to the cerebellum and to sub-regions of the dorsal visual network; 3) increase in the connectivity strength of several network interactions, such as the connectivity from the CON to the cerebellum and to the primary visual network, was associated with behavioral gains; 4) there were also nonlinear correlations between behavioral and neural changes. These findings highlighted a critical role of the modulation of CON on other networks in mediating conflict processing and its plasticity, and raised the significance of investigating nonlinear relationship in the field of cognitive training. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Neural Mechanisms Underlying Musical Pitch Perception and Clinical Applications Including Developmental Dyslexia.

    Science.gov (United States)

    Yuskaitis, Christopher J; Parviz, Mahsa; Loui, Psyche; Wan, Catherine Y; Pearl, Phillip L

    2015-08-01

    Music production and perception invoke a complex set of cognitive functions that rely on the integration of sensorimotor, cognitive, and emotional pathways. Pitch is a fundamental perceptual attribute of sound and a building block for both music and speech. Although the cerebral processing of pitch is not completely understood, recent advances in imaging and electrophysiology have provided insight into the functional and anatomical pathways of pitch processing. This review examines the current understanding of pitch processing and behavioral and neural variations that give rise to difficulties in pitch processing, and potential applications of music education for language processing disorders such as dyslexia.

  9. Neural Mechanisms Underlying Musical Pitch Perception and Clinical Applications including Developmental Dyselxia

    Science.gov (United States)

    Yuskaitis, Christopher J.; Parviz, Mahsa; Loui, Psyche; Wan, Catherine Y.; Pearl, Phillip L.

    2017-01-01

    Music production and perception invoke a complex set of cognitive functions that rely on the integration of sensory-motor, cognitive, and emotional pathways. Pitch is a fundamental perceptual attribute of sound and a building block for both music and speech. Although the cerebral processing of pitch is not completely understood, recent advances in imaging and electrophysiology have provided insight into the functional and anatomical pathways of pitch processing. This review examines the current understanding of pitch processing, behavioral and neural variations that give rise to difficulties in pitch processing, and potential applications of music education for language processing disorders such as dyslexia. PMID:26092314

  10. Satellite image analysis using neural networks

    Science.gov (United States)

    Sheldon, Roger A.

    1990-01-01

    The tremendous backlog of unanalyzed satellite data necessitates the development of improved methods for data cataloging and analysis. Ford Aerospace has developed an image analysis system, SIANN (Satellite Image Analysis using Neural Networks) that integrates the technologies necessary to satisfy NASA's science data analysis requirements for the next generation of satellites. SIANN will enable scientists to train a neural network to recognize image data containing scenes of interest and then rapidly search data archives for all such images. The approach combines conventional image processing technology with recent advances in neural networks to provide improved classification capabilities. SIANN allows users to proceed through a four step process of image classification: filtering and enhancement, creation of neural network training data via application of feature extraction algorithms, configuring and training a neural network model, and classification of images by application of the trained neural network. A prototype experimentation testbed was completed and applied to climatological data.

  11. Neural plasticity of development and learning.

    Science.gov (United States)

    Galván, Adriana

    2010-06-01

    Development and learning are powerful agents of change across the lifespan that induce robust structural and functional plasticity in neural systems. An unresolved question in developmental cognitive neuroscience is whether development and learning share the same neural mechanisms associated with experience-related neural plasticity. In this article, I outline the conceptual and practical challenges of this question, review insights gleaned from adult studies, and describe recent strides toward examining this topic across development using neuroimaging methods. I suggest that development and learning are not two completely separate constructs and instead, that they exist on a continuum. While progressive and regressive changes are central to both, the behavioral consequences associated with these changes are closely tied to the existing neural architecture of maturity of the system. Eventually, a deeper, more mechanistic understanding of neural plasticity will shed light on behavioral changes across development and, more broadly, about the underlying neural basis of cognition. (c) 2010 Wiley-Liss, Inc.

  12. Neurosecurity: security and privacy for neural devices.

    Science.gov (United States)

    Denning, Tamara; Matsuoka, Yoky; Kohno, Tadayoshi

    2009-07-01

    An increasing number of neural implantable devices will become available in the near future due to advances in neural engineering. This discipline holds the potential to improve many patients' lives dramatically by offering improved-and in some cases entirely new-forms of rehabilitation for conditions ranging from missing limbs to degenerative cognitive diseases. The use of standard engineering practices, medical trials, and neuroethical evaluations during the design process can create systems that are safe and that follow ethical guidelines; unfortunately, none of these disciplines currently ensure that neural devices are robust against adversarial entities trying to exploit these devices to alter, block, or eavesdrop on neural signals. The authors define "neurosecurity"-a version of computer science security principles and methods applied to neural engineering-and discuss why neurosecurity should be a critical consideration in the design of future neural devices.

  13. Flexible and Organic Neural Interfaces: A Review

    Directory of Open Access Journals (Sweden)

    Nicolò Lago

    2017-12-01

    Full Text Available Neural interfaces are a fundamental tool to interact with neurons and to study neural networks by transducing cellular signals into electronics signals and vice versa. State-of-the-art technologies allow both in vivo and in vitro recording of neural activity. However, they are mainly made of stiff inorganic materials that can limit the long-term stability of the implant due to infection and/or glial scars formation. In the last decade, organic electronics is digging its way in the field of bioelectronics and researchers started to develop neural interfaces based on organic semiconductors, creating more flexible and conformable neural interfaces that can be intrinsically biocompatible. In this manuscript, we are going to review the latest achievements in flexible and organic neural interfaces for the recording of neuronal activity.

  14. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...... into the syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it....

  15. Rod-Shaped Neural Units for Aligned 3D Neural Network Connection.

    Science.gov (United States)

    Kato-Negishi, Midori; Onoe, Hiroaki; Ito, Akane; Takeuchi, Shoji

    2017-08-01

    This paper proposes neural tissue units with aligned nerve fibers (called rod-shaped neural units) that connect neural networks with aligned neurons. To make the proposed units, 3D fiber-shaped neural tissues covered with a calcium alginate hydrogel layer are prepared with a microfluidic system and are cut in an accurate and reproducible manner. These units have aligned nerve fibers inside the hydrogel layer and connectable points on both ends. By connecting the units with a poly(dimethylsiloxane) guide, 3D neural tissues can be constructed and maintained for more than two weeks of culture. In addition, neural networks can be formed between the different neural units via synaptic connections. Experimental results indicate that the proposed rod-shaped neural units are effective tools for the construction of spatially complex connections with aligned nerve fibers in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Person Movement Prediction Using Neural Networks

    OpenAIRE

    Vintan, Lucian; Gellert, Arpad; Petzold, Jan; Ungerer, Theo

    2006-01-01

    Ubiquitous systems use context information to adapt appliance behavior to human needs. Even more convenience is reached if the appliance foresees the user's desires and acts proactively. This paper proposes neural prediction techniques to anticipate a person's next movement. We focus on neural predictors (multi-layer perceptron with back-propagation learning) with and without pre-training. The optimal configuration of the neural network is determined by evaluating movement sequences of real p...

  17. Pediatric Nutritional Requirements Determination with Neural Networks

    OpenAIRE

    Karlık, Bekir; Ece, Aydın

    1998-01-01

    To calculate daily nutritional requirements of children, a computer program has been developed based upon neural network. Three parameters, daily protein, energy and water requirements, were calculated through trained artificial neural networks using a database of 312 children The results were compared with those of calculated from dietary requirements tables of World Health Organisation. No significant difference was found between two calculations. In conclusion, a simple neural network may ...

  18. Adaptive optimization and control using neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Mead, W.C.; Brown, S.K.; Jones, R.D.; Bowling, P.S.; Barnes, C.W.

    1993-10-22

    Recent work has demonstrated the ability of neural-network-based controllers to optimize and control machines with complex, non-linear, relatively unknown control spaces. We present a brief overview of neural networks via a taxonomy illustrating some capabilities of different kinds of neural networks. We present some successful control examples, particularly the optimization and control of a small-angle negative ion source.

  19. Initialization of multilayer forecasting artifical neural networks

    OpenAIRE

    Bochkarev, Vladimir V.; Maslennikova, Yulia S.

    2014-01-01

    In this paper, a new method was developed for initialising artificial neural networks predicting dynamics of time series. Initial weighting coefficients were determined for neurons analogously to the case of a linear prediction filter. Moreover, to improve the accuracy of the initialization method for a multilayer neural network, some variants of decomposition of the transformation matrix corresponding to the linear prediction filter were suggested. The efficiency of the proposed neural netwo...

  20. Texture Based Image Analysis With Neural Nets

    Science.gov (United States)

    Ilovici, Irina S.; Ong, Hoo-Tee; Ostrander, Kim E.

    1990-03-01

    In this paper, we combine direct image statistics and spatial frequency domain techniques with a neural net model to analyze texture based images. The resultant optimal texture features obtained from the direct and transformed image form the exemplar pattern of the neural net. The proposed approach introduces an automated texture analysis applied to metallography for determining the cooling rate and mechanical working of the materials. The results suggest that the proposed method enhances the practical applications of neural nets and texture extraction features.

  1. Spina bifida and other neural tube defects.

    Science.gov (United States)

    Northrup, H; Volcik, K A

    2000-01-01

    NTDs, resulting from failure of the neural tube to close during the fourth week of embryogenesis, are the most common severely disabling birth defects in the United States, with a frequency of approximately 1 of every 2000 births. Neural tube malformations involving the spinal cord and vertebral arches are referred to as spina bifida, with severe types of spina bifida involving protrusion of the spinal cord and/or meninges through a defect in the vertebral arch. Depending on the level of the lesion, interruption of the spinal cord at the site of the spina bifida defect causes paralysis of the legs, incontinence of urine and feces, anesthesia of the skin, and abnormalities of the hips, knees, and feet. Two additional abnormalities often seen in children with spina bifida include hydrocephalus and the Arnold-Chiari type II malformation. Despite the physical and particular learning disabilities children with spina bifida must cope with, participation in individualized educational programs can allow these children to develop skills necessary for autonomy in adulthood. Advances in research to uncover the molecular basis of NTDs is enhanced by knowledge of the link between both the environmental and genetic factors involved in the etiology of NTDs. The most recent development in NTD research for disease-causing genes is the discovery of a genetic link to the most well-known environmental cause of neural tube malformation, folate deficiency in pregnant women. Nearly a decade ago, periconceptional folic acid supplementation was proven to decrease both the recurrence and occurrence of NTDs. The study of folate and its association with NTDs is an ongoing endeavor that has led to numerous studies of different genes involved in the folate metabolism pathway, including the most commonly studied thermolabile mutation (C677T) in the MTHFR gene. An additional focus for NTD research involves mouse models that exhibit both naturally occurring NTDs, as well as those created by

  2. Neural network architecture for cognitive navigation in dynamic environments.

    Science.gov (United States)

    Villacorta-Atienza, José Antonio; Makarov, Valeri A

    2013-12-01

    Navigation in time-evolving environments with moving targets and obstacles requires cognitive abilities widely demonstrated by even simplest animals. However, it is a long-standing challenging problem for artificial agents. Cognitive autonomous robots coping with this problem must solve two essential tasks: 1) understand the environment in terms of what may happen and how I can deal with this and 2) learn successful experiences for their further use in an automatic subconscious way. The recently introduced concept of compact internal representation (CIR) provides the ground for both the tasks. CIR is a specific cognitive map that compacts time-evolving situations into static structures containing information necessary for navigation. It belongs to the class of global approaches, i.e., it finds trajectories to a target when they exist but also detects situations when no solution can be found. Here we extend the concept of situations with mobile targets. Then using CIR as a core, we propose a closed-loop neural network architecture consisting of conscious and subconscious pathways for efficient decision-making. The conscious pathway provides solutions to novel situations if the default subconscious pathway fails to guide the agent to a target. Employing experiments with roving robots and numerical simulations, we show that the proposed architecture provides the robot with cognitive abilities and enables reliable and flexible navigation in realistic time-evolving environments. We prove that the subconscious pathway is robust against uncertainty in the sensory information. Thus if a novel situation is similar but not identical to the previous experience (because of, e.g., noisy perception) then the subconscious pathway is able to provide an effective solution.

  3. Clinical Pathway for Thyroidectomy.

    Science.gov (United States)

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

    Directory of Open Access Journals (Sweden)

    S.L. Cravo

    2011-09-01

    Full Text Available Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

  5. Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders.

    Directory of Open Access Journals (Sweden)

    Ileena Mitra

    2017-01-01

    Full Text Available Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies, we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02. We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10-16, with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway.

  6. Alzheimer disease: functional abnormalities in the dorsal visual pathway.

    LENUS (Irish Health Repository)

    Bokde, Arun L W

    2012-02-01

    PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

  7. DMPD: Antiviral innate immunity pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16474426 Antiviral innate immunity pathways. Seth RB, Sun L, Chen ZJ. Cell Res. 200...6 Feb;16(2):141-7. (.png) (.svg) (.html) (.csml) Show Antiviral innate immunity pathways. PubmedID 16474426 ...Title Antiviral innate immunity pathways. Authors Seth RB, Sun L, Chen ZJ. Publication Cell Res. 2006 Feb;16

  8. Suppressed expression of mitogen-activated protein kinases in hyperthermia induced defective neural tube.

    Science.gov (United States)

    Zhang, Tianliang; Leng, Zhaoting; Liu, Wenjing; Wang, Xia; Yan, Xue; Yu, Li

    2015-05-06

    Neural tube defects (NTDs) are common congenital malformations. Mitogen-activated protein kinases (MAPKs) pathway is involved in many physiological processes. HMGB1 has been showed closely associated with neurulation and NTDs induced by hyperthermia and could activate MAPKs pathway. Since hyperthermia caused increased activation of MAPKs in many systems, the present study aims to investigate whether HMGB1 contributes to hyperthermia induced NTDs through MAPKs pathway. The mRNA levels of MAPKs and HMGB1 between embryonic day 8.5 and 10 (E8.5-10) in hyperthermia induced defective neural tube were detected by real-time quantitative polymerase chain reaction (qPCR). By immunofluorescence and western blotting, the expressions of HMGB1 and phosphorylated MAPKs (ERK1/2, JNK and p38) in neural tubes after hyperthermia were studied. The mRNA levels of MAPKs and HMGB1, as well as the expressions of HMGB1 along with phosphorylated JNK, p38 and ERK, were downregulated in NTDs groups induced by hyperthermia compared with control. The findings suggested that HMGB1 may contribute to hyperthermia induced NTDs formation through decreased cell proliferation due to inhibited phosphorylated ERK1/2 MAPK. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Cognitive Control Signals for Neural Prosthetics

    National Research Council Canada - National Science Library

    S. Musallam; B. D. Corneil; B. Greger; H. Scherberger; R. A. Andersen

    2004-01-01

    Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external devices...

  10. NeuroMEMS: Neural Probe Microtechnologies

    Directory of Open Access Journals (Sweden)

    Sam Musallam

    2008-10-01

    Full Text Available Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimer’s, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultralong multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

  11. Neural repair in the adult brain

    Science.gov (United States)

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  12. Neural network based system for equipment surveillance

    Science.gov (United States)

    Vilim, R.B.; Gross, K.C.; Wegerich, S.W.

    1998-04-28

    A method and system are disclosed for performing surveillance of transient signals of an industrial device to ascertain the operating state. The method and system involves the steps of reading into a memory training data, determining neural network weighting values until achieving target outputs close to the neural network output. If the target outputs are inadequate, wavelet parameters are determined to yield neural network outputs close to the desired set of target outputs and then providing signals characteristic of an industrial process and comparing the neural network output to the industrial process signals to evaluate the operating state of the industrial process. 33 figs.

  13. Fuzzy neural network theory and application

    CERN Document Server

    Liu, Puyin

    2004-01-01

    This book systematically synthesizes research achievements in the field of fuzzy neural networks in recent years. It also provides a comprehensive presentation of the developments in fuzzy neural networks, with regard to theory as well as their application to system modeling and image restoration. Special emphasis is placed on the fundamental concepts and architecture analysis of fuzzy neural networks. The book is unique in treating all kinds of fuzzy neural networks and their learning algorithms and universal approximations, and employing simulation examples which are carefully designed to he

  14. Neural reflexes in inflammation and immunity

    National Research Council Canada - National Science Library

    Andersson, Ulf; Tracey, Kevin J

    2012-01-01

    .... Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals...

  15. Neural network optimization, components, and design selection

    Science.gov (United States)

    Weller, Scott W.

    1991-01-01

    Neural Networks are part of a revived technology which has received a lot of hype in recent years. As is apt to happen in any hyped technology, jargon and predictions make its assimilation and application difficult. Nevertheless, Neural Networks have found use in a number of areas, working on non-trivial and non-contrived problems. For example, one net has been trained to "read", translating English text into phoneme sequences. Other applications of Neural Networks include data base manipulation and the solving of routing and classification types of optimization problems. It was their use in optimization that got me involved with Neural Networks. As it turned out, "optimization" used in this context was somewhat misleading, because while some network configurations could indeed solve certain kinds of optimization problems, the configuring or "training" of a Neural Network itself is an optimization problem, and most of the literature which talked about Neural Nets and optimization in the same breath did not speak to my goal of using Neural Nets to help solve lens optimization problems. I did eventually apply Neural Network to lens optimization, and I will touch on those results. The application of Neural Nets to the problem of lens selection was much more successful, and those results will dominate this paper.

  16. Practical neural network recipies in C++

    CERN Document Server

    Masters

    2014-01-01

    This text serves as a cookbook for neural network solutions to practical problems using C++. It will enable those with moderate programming experience to select a neural network model appropriate to solving a particular problem, and to produce a working program implementing that network. The book provides guidance along the entire problem-solving path, including designing the training set, preprocessing variables, training and validating the network, and evaluating its performance. Though the book is not intended as a general course in neural networks, no background in neural works is assum

  17. Sequential neural models with stochastic layers

    DEFF Research Database (Denmark)

    Fraccaro, Marco; Sønderby, Søren Kaae; Paquet, Ulrich

    2016-01-01

    How can we efficiently propagate uncertainty in a latent state representation with recurrent neural networks? This paper introduces stochastic recurrent neural networks which glue a deterministic recurrent neural network and a state space model together to form a stochastic and sequential neural ...... the uncertainty in a latent path, like a state space model, we improve the state of the art results on the Blizzard and TIMIT speech modeling data sets by a large margin, while achieving comparable performances to competing methods on polyphonic music modeling....

  18. miR-430 regulates oriented cell division during neural tube development in zebrafish.

    Science.gov (United States)

    Takacs, Carter M; Giraldez, Antonio J

    2016-01-15

    MicroRNAs have emerged as critical regulators of gene expression. Originally shown to regulate developmental timing, microRNAs have since been implicated in a wide range of cellular functions including cell identity, migration and signaling. miRNA-430, the earliest expressed microRNA during zebrafish embryogenesis, is required to undergo morphogenesis and has previously been shown to regulate maternal mRNA clearance, Nodal signaling, and germ cell migration. The functions of miR-430 in brain morphogenesis, however, remain unclear. Herein we find that miR-430 instructs oriented cell divisions in the neural rod required for neural midline formation. Loss of miR-430 function results in mitotic spindle misorientation in the neural rod, failed neuroepithelial integration after cell division, and ectopic cell accumulation in the dorsal neural tube. We propose that miR-430, independently of canonical apicobasal and planar cell polarity (PCP) pathways, coordinates the stereotypical cell divisions that instruct neural tube morphogenesis. Copyright © 2015. Published by Elsevier Inc.

  19. Modeling anterior development in mice: diet as modulator of risk for neural tube defects.

    Science.gov (United States)

    Kappen, Claudia

    2013-11-01

    Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient-gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. © 2013 Wiley Periodicals, Inc.

  20. Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

    Directory of Open Access Journals (Sweden)

    Lauren J. Manderfield

    2014-12-01

    Full Text Available Loss of Pax3, a developmentally regulated transcription factor expressed in premigratory neural crest, results in severe developmental defects and embryonic lethality. Although Pax3 mutations produce profound phenotypes, the intrinsic transcriptional activation exhibited by Pax3 is surprisingly modest. We postulated the existence of transcriptional coactivators that function with Pax3 to mediate developmental functions. A high-throughput screen identified the Hippo effector proteins Taz and Yap65 as Pax3 coactivators. Synergistic coactivation of target genes by Pax3-Taz/Yap65 requires DNA binding by Pax3, is Tead independent, and is regulated by Hippo kinases Mst1 and Lats2. In vivo, Pax3 and Yap65 colocalize in the nucleus of neural crest progenitors in the dorsal neural tube. Neural crest deletion of Taz and Yap65 results in embryo-lethal neural crest defects and decreased expression of the Pax3 target gene, Mitf. These results suggest that Pax3 activity is regulated by the Hippo pathway and that Pax factors are Hippo effectors.

  1. Rare neural correlations implement robotic conditioning with delayed rewards and disturbances

    Directory of Open Access Journals (Sweden)

    Andrea eSoltoggio

    2013-04-01

    Full Text Available Neural conditioning associates cues and actions with following rewards. The environments in which robots operate, however, are pervaded by a variety of disturbing stimuli and uncertain timing. In particular, variable reward delays make it difficult to reconstruct which previous actions are responsible for following rewards. Such an uncertainty is handled by biological neural networks, but represents a challenge for computational models, suggesting the lack of a satisfactory theory for robotic neural conditioning. The present study demonstrates the use of rare neural correlations in making correct associations between rewards and previous cues or actions. Rare correlations are functional in selecting sparse synapses to be eligible for later weight updates if a reward occurs. The repetition of this process singles out the associating and reward-triggering pathways, and thereby copes with distal rewards. The neural network displays macro-level classical and operant conditioning, which is demonstrated in an interactive real-life human-robot interaction. The proposed mechanism models realistic conditioning in humans and animals and implements similar behaviours in neuro-robotic platforms.

  2. Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Taichi [Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Kondo, Natsuko [Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); Mori, Eiichiro [Department of Biology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Ken [Department of Biology, Ibaraki Prefectual University of Health Sciences, 4669-2 Ami, Ami-mati, Inasiki-gun, Ibaraki 300-0394 (Japan); Zdzienicka, Malgorzata Z. [Department of Molecular Cell Genetics, Collegium Medicum in Bydgoszcz, Nicolaus-Copernicus-University in Torun, ul. Sklodowskiej-Curie 9, 85-094 Bydgoszcz (Poland); Thompson, Larry H. [Biosciences and Biotechnology Division, L452, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551-0808 (United States); Helleday, Thomas [Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ (United Kingdom); Department of Genetics, Microbiology and Toxicology Stockholm University, SE-106 91 Stockholm (Sweden); Asada, Hideo [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); and others

    2011-01-07

    The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA{sup -/-}, FANCC{sup -/-}, FANCA{sup -/-}C{sup -/-}, FANCD2{sup -/-} and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs) were detected with an immunocytochemical {gamma}H2AX-staining assay. Although the sensitivity of FANCA{sup -/-}, FANCC{sup -/-} and FANCA{sup -/-}C{sup -/-} cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2{sup -/-} cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, {gamma}H2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. -- Research highlights: {yields} We examined to clarify the repair pathways of formaldehyde-induced DNA damage. Formaldehyde induces DNA double strand breaks (DSBs). {yields} DSBs are repaired through the Fanconi anemia (FA) repair pathway. {yields} This pathway is independent of the FA nuclear core complex. {yields} We also found that homologous recombination repair was induced by formaldehyde.

  3. Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity.

    Science.gov (United States)

    Escobedo, Noelia; Contreras, Osvaldo; Muñoz, Rosana; Farías, Marjorie; Carrasco, Héctor; Hill, Charlotte; Tran, Uyen; Pryor, Sophie E; Wessely, Oliver; Copp, Andrew J; Larraín, Juan

    2013-07-01

    Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2(Lp) compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2(Lp) mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2(Lp/+) enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2(Lp/+) embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2(Lp/Lp)) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos.

  4. Polarity-specific high-level information propagation in neural networks.

    Science.gov (United States)

    Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

    2014-01-01

    Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals.

  5. Cultured neural networks: Optimisation of patterned network adhesiveness and characterisation of their neural activity

    NARCIS (Netherlands)

    Rutten, Wim; Ruardij, T.G.; Marani, Enrico; Roelofsen, B.H.

    2006-01-01

    One type of future, improved neural interface is the "cultured probe"?. It is a hybrid type of neural information transducer or prosthesis, for stimulation and/or recording of neural activity. It would consist of a microelectrode array (MEA) on a planar substrate, each electrode being covered and

  6. Fast and automatic activation of an abstract representation of money in the human ventral visual pathway.

    Directory of Open Access Journals (Sweden)

    Catherine Tallon-Baudry

    Full Text Available Money, when used as an incentive, activates the same neural circuits as rewards associated with physiological needs. However, unlike physiological rewards, monetary stimuli are cultural artifacts: how are monetary stimuli identified in the first place? How and when does the brain identify a valid coin, i.e. a disc of metal that is, by social agreement, endowed with monetary properties? We took advantage of the changes in the Euro area in 2002 to compare neural responses to valid coins (Euros, Australian Dollars with neural responses to invalid coins that have lost all monetary properties (French Francs, Finnish Marks. We show in magneto-encephalographic recordings, that the ventral visual pathway automatically distinguishes between valid and invalid coins, within only ∼150 ms. This automatic categorization operates as well on coins subjects were familiar with as on unfamiliar coins. No difference between neural responses to scrambled controls could be detected. These results could suggest the existence of a generic, all-purpose neural representation of money that is independent of experience. This finding is reminiscent of a central assumption in economics, money fungibility, or the fact that a unit of money is substitutable to another. From a neural point of view, our findings may indicate that the ventral visual pathway, a system previously thought to analyze visual features such as shape or color and to be influenced by daily experience, could also able to use conceptual attributes such as monetary validity to categorize familiar as well as unfamiliar visual objects. The symbolic abilities of the posterior fusiform region suggested here could constitute an efficient neural substrate to deal with culturally defined symbols, independently of experience, which probably fostered money's cultural emergence and success.

  7. A neural network model of causative actions.

    Science.gov (United States)

    Lee-Hand, Jeremy; Knott, Alistair

    2015-01-01

    A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g., Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umiltà et al., 2008; Hommel, 2013). In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John smashes a cup, he brings about the event of the cup smashing. Other actions do not bring about such effects. For instance, if John grabs a cup, this action does not cause the cup to "do" anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organized into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognizes arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the "causative actions" circuit in our model can be identified with a motor pathway reported in other work, specializing in "functional" actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013).

  8. Autism as an adaptive common variant pathway for human brain development

    Directory of Open Access Journals (Sweden)

    Mark H. Johnson

    2017-06-01

    Full Text Available While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency. Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development.

  9. The LILARTI neural network system

    Energy Technology Data Exchange (ETDEWEB)

    Allen, J.D. Jr.; Schell, F.M.; Dodd, C.V.

    1992-10-01

    The material of this Technical Memorandum is intended to provide the reader with conceptual and technical background information on the LILARTI neural network system of detail sufficient to confer an understanding of the LILARTI method as it is presently allied and to facilitate application of the method to problems beyond the scope of this document. Of particular importance in this regard are the descriptive sections and the Appendices which include operating instructions, partial listings of program output and data files, and network construction information.

  10. Phantom limbs and neural plasticity.

    Science.gov (United States)

    Ramachandran, V S; Rogers-Ramachandran, D

    2000-03-01

    The study of phantom limbs has received tremendous impetus from recent studies linking changes in cortical topography with perceptual experience. Systematic psychophysical testing and functional imaging studies on patients with phantom limbs provide 2 unique opportunities. First, they allow us to demonstrate neural plasticity in the adult human brain. Second, by tracking perceptual changes (such as referred sensations) and changes in cortical topography in individual patients, we can begin to explore how the activity of sensory maps gives rise to conscious experience. Finally, phantom limbs also allow us to explore intersensory effects and the manner in which the brain constructs and updates a "body image" throughout life.

  11. Neural processing of natural sounds.

    Science.gov (United States)

    Theunissen, Frédéric E; Elie, Julie E

    2014-06-01

    We might be forced to listen to a high-frequency tone at our audiologist's office or we might enjoy falling asleep with a white-noise machine, but the sounds that really matter to us are the voices of our companions or music from our favourite radio station. The auditory system has evolved to process behaviourally relevant natural sounds. Research has shown not only that our brain is optimized for natural hearing tasks but also that using natural sounds to probe the auditory system is the best way to understand the neural computations that enable us to comprehend speech or appreciate music.

  12. Optical implementation of neural networks

    Science.gov (United States)

    Yu, Francis T. S.; Guo, Ruyan

    2002-12-01

    An adaptive optical neuro-computing (ONC) using inexpensive pocket size liquid crystal televisions (LCTVs) had been developed by the graduate students in the Electro-Optics Laboratory at The Pennsylvania State University. Although this neuro-computing has only 8×8=64 neurons, it can be easily extended to 16×20=320 neurons. The major advantages of this LCTV architecture as compared with other reported ONCs, are low cost and the flexibility to operate. To test the performance, several neural net models are used. These models are Interpattern Association, Hetero-association and unsupervised learning algorithms. The system design considerations and experimental demonstrations are also included.

  13. Neural Nets for Scene Analysis

    Science.gov (United States)

    1992-09-01

    decision boundaries produced for the arificial database when prototypes are Se- feature 1 lected from reduced training set. ly selected from the 383...CLASSIFIER HIT MISS MOPOGIA CORRELATION LOW-LEVEL VISION IVARL&MCE NEURAL NE. (O D ILER) SE CORRELATION REUCE ETC.(OR I F RS)DI4ENSIONAIM AND TRAINING...A) = J11’, + tOi2Z2 + 61311’ (4) SPE Vol. 1608 mitalwg’t Robots and Coniutef Vision X (991)/501 - "X,, ,v ) X 1112 1P Pa P2 P2 .. 2 33 CL AS INPUT

  14. Pansharpening by Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Giuseppe Masi

    2016-07-01

    Full Text Available A new pansharpening method is proposed, based on convolutional neural networks. We adapt a simple and effective three-layer architecture recently proposed for super-resolution to the pansharpening problem. Moreover, to improve performance without increasing complexity, we augment the input by including several maps of nonlinear radiometric indices typical of remote sensing. Experiments on three representative datasets show the proposed method to provide very promising results, largely competitive with the current state of the art in terms of both full-reference and no-reference metrics, and also at a visual inspection.

  15. Neural networks and perceptual learning

    Science.gov (United States)

    Tsodyks, Misha; Gilbert, Charles

    2005-01-01

    Sensory perception is a learned trait. The brain strategies we use to perceive the world are constantly modified by experience. With practice, we subconsciously become better at identifying familiar objects or distinguishing fine details in our environment. Current theoretical models simulate some properties of perceptual learning, but neglect the underlying cortical circuits. Future neural network models must incorporate the top-down alteration of cortical function by expectation or perceptual tasks. These newly found dynamic processes are challenging earlier views of static and feedforward processing of sensory information. PMID:15483598

  16. Optimization with Potts Neural Networks

    Science.gov (United States)

    Söderberg, Bo

    The Potts Neural Network approach to non-binary discrete optimization problems is described. It applies to problems that can be described as a set of elementary `multiple choice' options. Instead of the conventional binary (Ising) neurons, mean field Potts neurons, having several available states, are used to describe the elementary degrees of freedom of such problems. The dynamics consists of iterating the mean field equations with annealing until convergence. Due to its deterministic character, the method is quite fast. When applied to problems of Graph Partition and scheduling types, it produces very good solutions also for problems of considerable size.

  17. Pathways with PathWhiz.

    Science.gov (United States)

    Pon, Allison; Jewison, Timothy; Su, Yilu; Liang, Yongjie; Knox, Craig; Maciejewski, Adam; Wilson, Michael; Wishart, David S

    2015-07-01

    PathWhiz (http://smpdb.ca/pathwhiz) is a web server designed to create colourful, visually pleasing and biologically accurate pathway diagrams that are both machine-readable and interactive. As a web server, PathWhiz is accessible from almost any place and compatible with essentially any operating system. It also houses a public library of pathways and pathway components that can be easily viewed and expanded upon by its users. PathWhiz allows users to readily generate biologically complex pathways by using a specially designed drawing palette to quickly render metabolites (including automated structure generation), proteins (including quaternary structures, covalent modifications and cofactors), nucleic acids, membranes, subcellular structures, cells, tissues and organs. Both small-molecule and protein/gene pathways can be constructed by combining multiple pathway processes such as reactions, interactions, binding events and transport activities. PathWhiz's pathway replication and propagation functions allow for existing pathways to be used to create new pathways or for existing pathways to be automatically propagated across species. PathWhiz pathways can be saved in BioPAX, SBGN-ML and SBML data exchange formats, as well as PNG, PWML, HTML image map or SVG images that can be viewed offline or explored using PathWhiz's interactive viewer. PathWhiz has been used to generate over 700 pathway diagrams for a number of popular databases including HMDB, DrugBank and SMPDB. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during Embryonic Stem Cell Neural Differentiation.

    Science.gov (United States)

    Xi, Jiajie; Wu, Yukang; Li, Guoping; Ma, Li; Feng, Ke; Guo, Xudong; Jia, Wenwen; Wang, Guiying; Yang, Guang; Li, Ping; Kang, Jiuhong

    2017-08-08

    During gastrulation, the neuroectoderm cells form the neural tube and neural crest. The nervous system contains significantly more microRNAs than other tissues, but the role of microRNAs in controlling the differentiation of neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural differentiation systems, we found that miR-29b was upregulated in NTE cells and downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE cells and inhibited their differentiation into NCCs. Accordingly, the inhibition of miR-29b significantly inhibited the differentiation of NTE cells. A mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a) to regulate neural differentiation. Moreover, miR-29b mediated the function of Pou3f1, a critical neural transcription factor. Therefore, our study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated the determination of cell fate. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2013-08-01

    Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.

  20. Chromosome 7 and 19 trisomy in cultured human neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Dhruv Sareen

    Full Text Available BACKGROUND: Stem cell expansion and differentiation is the foundation of emerging cell therapy technologies. The potential applications of human neural progenitor cells (hNPCs are wide ranging, but a normal cytogenetic profile is important to avoid the risk of tumor formation in clinical trials. FDA approved clinical trials are being planned and conducted for hNPC transplantation into the brain or spinal cord for various neurodegenerative disorders. Although human embryonic stem cells (hESCs are known to show recurrent chromosomal abnormalities involving 12 and 17, no studies have revealed chromosomal abnormalities in cultured hNPCs. Therefore, we investigated frequently occurring chromosomal abnormalities in 21 independent fetal-derived hNPC lines and the possible mechanisms triggering such aberrations. METHODS AND FINDINGS: While most hNPC lines were karyotypically normal, G-band karyotyping and fluorescent in situ hybridization (FISH analyses revealed the emergence of trisomy 7 (hNPC(+7 and trisomy 19 (hNPC(+19, in 24% and 5% of the lines, respectively. Once detected, subsequent passaging revealed emerging dominance of trisomy hNPCs. DNA microarray and immunoblotting analyses demonstrate epidermal growth factor receptor (EGFR overexpression in hNPC(+7 and hNPC(+19 cells. We observed greater levels of telomerase (hTERT, increased proliferation (Ki67, survival (TUNEL, and neurogenesis (beta(III-tubulin in hNPC(+7 and hNPC(+19, using respective immunocytochemical markers. However, the trisomy lines underwent replicative senescence after 50-60 population doublings and never showed neoplastic changes. Although hNPC(+7 and hNPC(+19 survived better after xenotransplantation into the rat striatum, they did not form malignant tumors. Finally, EGF deprivation triggered a selection of trisomy 7 cells in a diploid hNPC line. CONCLUSIONS: We report that hNPCs are susceptible to accumulation of chromosome 7 and 19 trisomy in long-term cell culture. These

  1. Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor proliferation and apical constriction during mouse brain development.

    Science.gov (United States)

    Badouel, Caroline; Zander, Mark A; Liscio, Nicole; Bagherie-Lachidan, Mazdak; Sopko, Richelle; Coyaud, Etienne; Raught, Brian; Miller, Freda D; McNeill, Helen

    2015-08-15

    Mammalian brain development requires coordination between neural precursor proliferation, differentiation and cellular organization to create the intricate neuronal networks of the adult brain. Here, we examined the role of the atypical cadherins Fat1 and Fat4 in this process. We show that mutation of Fat1 in mouse embryos causes defects in cranial neural tube closure, accompanied by an increase in the proliferation of cortical precursors and altered apical junctions, with perturbations in apical constriction and actin accumulation. Similarly, knockdown of Fat1 in cortical precursors by in utero electroporation leads to overproliferation of radial glial precursors. Fat1 interacts genetically with the related cadherin Fat4 to regulate these processes. Proteomic analysis reveals that Fat1 and Fat4 bind different sets of actin-regulating and junctional proteins. In vitro data suggest that Fat1 and Fat4 form cis-heterodimers, providing a mechanism for bringing together their diverse interactors. We propose a model in which Fat1 and Fat4 binding coordinates distinct pathways at apical junctions to regulate neural progenitor proliferation, neural tube closure and apical constriction. © 2015. Published by The Company of Biologists Ltd.

  2. NeuralWISP: A Wirelessly Powered Neural Interface With 1-m Range.

    Science.gov (United States)

    Yeager, D J; Holleman, J; Prasad, R; Smith, J R; Otis, B P

    2009-12-01

    We present the NeuralWISP, a wireless neural interface operating from far-field radio-frequency RF energy. The NeuralWISP is compatible with commercial RF identification readers and operates at a range up to 1 m. It includes a custom low-noise, low-power amplifier integrated circuit for processing the neural signal and an analog spike detection circuit for reducing digital computational requirements and communications bandwidth. Our system monitors the neural signal and periodically transmits the spike density in a user-programmable time window. The entire system draws an average 20 muA from the harvested 1.8-V supply.

  3. Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13bhnn stems from abnormal Shh signaling

    Science.gov (United States)

    Horner, Vanessa L.; Caspary, Tamara

    2011-01-01

    In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals cooperate to specify neurons involved in sensation. Several signaling pathways, including Shh, rely on primary cilia in vertebrates. In this study, we used a mouse mutant with abnormal cilia, Arl13bhnn, to study the relationship between cilia, cell signaling, and neural tube patterning. Alr13bhnn mutants have abnormal ventral neural tube patterning due to disrupted Shh signaling; in addition, dorsal patterning defects occur, but the cause of these is unknown. Here we show that the Arl13bhnn dorsal patterning defects result from abnormal BMP signaling. In addition, we find that Wnt ligands are abnormally expressed in Arl13bhnn mutants; surprisingly, however, downstream Wnt signaling is normal. We demonstrate that Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression, indicating that the abnormal Shh signaling environment in Arl13bhnn embryos indirectly causes dorsal defects. PMID:21539826

  4. Neural network modeling of emotion

    Science.gov (United States)

    Levine, Daniel S.

    2007-03-01

    This article reviews the history and development of computational neural network modeling of cognitive and behavioral processes that involve emotion. The exposition starts with models of classical conditioning dating from the early 1970s. Then it proceeds toward models of interactions between emotion and attention. Then models of emotional influences on decision making are reviewed, including some speculative (not and not yet simulated) models of the evolution of decision rules. Through the late 1980s, the neural networks developed to model emotional processes were mainly embodiments of significant functional principles motivated by psychological data. In the last two decades, network models of these processes have become much more detailed in their incorporation of known physiological properties of specific brain regions, while preserving many of the psychological principles from the earlier models. Most network models of emotional processes so far have dealt with positive and negative emotion in general, rather than specific emotions such as fear, joy, sadness, and anger. But a later section of this article reviews a few models relevant to specific emotions: one family of models of auditory fear conditioning in rats, and one model of induced pleasure enhancing creativity in humans. Then models of emotional disorders are reviewed. The article concludes with philosophical statements about the essential contributions of emotion to intelligent behavior and the importance of quantitative theories and models to the interdisciplinary enterprise of understanding the interactions of emotion, cognition, and behavior.

  5. Clustering: a neural network approach.

    Science.gov (United States)

    Du, K-L

    2010-01-01

    Clustering is a fundamental data analysis method. It is widely used for pattern recognition, feature extraction, vector quantization (VQ), image segmentation, function approximation, and data mining. As an unsupervised classification technique, clustering identifies some inherent structures present in a set of objects based on a similarity measure. Clustering methods can be based on statistical model identification (McLachlan & Basford, 1988) or competitive learning. In this paper, we give a comprehensive overview of competitive learning based clustering methods. Importance is attached to a number of competitive learning based clustering neural networks such as the self-organizing map (SOM), the learning vector quantization (LVQ), the neural gas, and the ART model, and clustering algorithms such as the C-means, mountain/subtractive clustering, and fuzzy C-means (FCM) algorithms. Associated topics such as the under-utilization problem, fuzzy clustering, robust clustering, clustering based on non-Euclidean distance measures, supervised clustering, hierarchical clustering as well as cluster validity are also described. Two examples are given to demonstrate the use of the clustering methods.

  6. Imaging Posture Veils Neural Signals

    Directory of Open Access Journals (Sweden)

    Robert T Thibault

    2016-10-01

    Full Text Available Whereas modern brain imaging often demands holding body positions incongruent with everyday life, posture governs both neural activity and cognitive performance. Humans commonly perform while upright; yet, many neuroimaging methodologies require participants to remain motionless and adhere to non-ecological comportments within a confined space. This inconsistency between ecological postures and imaging constraints undermines the transferability and generalizability of many a neuroimaging assay.Here we highlight the influence of posture on brain function and behavior. Specifically, we challenge the tacit assumption that brain processes and cognitive performance are comparable across a spectrum of positions. We provide an integrative synthesis regarding the increasingly prominent influence of imaging postures on autonomic function, mental capacity, sensory thresholds, and neural activity. Arguing that neuroimagers and cognitive scientists could benefit from considering the influence posture wields on both general functioning and brain activity, we examine existing imaging technologies and the potential of portable and versatile imaging devices (e.g., functional near infrared spectroscopy. Finally, we discuss ways that accounting for posture may help unveil the complex brain processes of everyday cognition.

  7. Use of spatiotemporal templates for pathway discrimination in peripheral nerve recordings: a simulation study

    Science.gov (United States)

    Koh, Ryan G. L.; Nachman, Adrian I.; Zariffa, José

    2017-02-01

    Objective. Extraction of information from the peripheral nervous system can provide control signals in neuroprosthetic applications. However, the ability to selectively record from different pathways within peripheral nerves is limited. We investigated the integration of spatial and temporal information for pathway discrimination in peripheral nerves using measurements from a multi-contact nerve cuff electrode. Approach. Spatiotemporal templates were established for different neural pathways of interest, and used to obtain tailored matched filters for each of these pathways. Simulated measurements of compound action potentials propagating through the nerve in different test cases were used to evaluate classification accuracy, percentage of missed spikes, and ability to reconstruct the original firing rates of the neural pathways. Main results. The mean Pearson correlation coefficients between the original firing rates and estimated firing rates over all tests cases was found to be 0.832  ±  0.161, 0.421  ±  0.145, 0.481  ±  0.340 for our algorithm, Bayesian spatial filters, and velocity selective recordings respectively. Significance. The proposed method shows that the spatiotemporal templates were able to provide more robust spike detection and reliable pathway discrimination than these existing algorithms.

  8. Radiation Behavior of Analog Neural Network Chip

    Science.gov (United States)

    Langenbacher, H.; Zee, F.; Daud, T.; Thakoor, A.

    1996-01-01

    A neural network experiment conducted for the Space Technology Research Vehicle (STRV-1) 1-b launched in June 1994. Identical sets of analog feed-forward neural network chips was used to study and compare the effects of space and ground radiation on the chips. Three failure mechanisms are noted.

  9. 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 ...

  10. Neural network approach to parton distributions fitting

    CERN Document Server

    Piccione, Andrea; Forte, Stefano; Latorre, Jose I.; Rojo, Joan; Piccione, Andrea; Rojo, Joan

    2006-01-01

    We will show an application of neural networks to extract information on the structure of hadrons. A Monte Carlo over experimental data is performed to correctly reproduce data errors and correlations. A neural network is then trained on each Monte Carlo replica via a genetic algorithm. Results on the proton and deuteron structure functions, and on the nonsinglet parton distribution will be shown.

  11. NEURAL METHODS FOR THE FINANCIAL PREDICTION

    Directory of Open Access Journals (Sweden)

    Jerzy Balicki

    2016-06-01

    Full Text Available Artificial neural networks can be used to predict share investment on the stock market, assess the reliability of credit client or predicting banking crises. Moreover, this paper discusses the principles of cooperation neural network algorithms with evolutionary method, and support vector machines. In addition, a reference is made to other methods of artificial intelligence, which are used in finance prediction.

  12. Self-organization of neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Clark, J.W.; Winston, J.V.; Rafelski, J.

    1984-05-14

    The plastic development of a neural-network model operating autonomously in discrete time is described by the temporal modification of interneuronal coupling strengths according to momentary neural activity. A simple algorithm (brainwashing) is found which, applied to nets with initially quasirandom connectivity, leads to model networks with properties conducive to the simulation of memory and learning phenomena. 18 references, 2 figures.

  13. Medical image analysis with artificial neural networks.

    Science.gov (United States)

    Jiang, J; Trundle, P; Ren, J

    2010-12-01

    Given that neural networks have been widely reported in the research community of medical imaging, we provide a focused literature survey on recent neural network developments in computer-aided diagnosis, medical image segmentation and edge detection towards visual content analysis, and medical image registration for its pre-processing and post-processing, with the aims of increasing awareness of how neural networks can be applied to these areas and to provide a foundation for further research and practical development. Representative techniques and algorithms are explained in detail to provide inspiring examples illustrating: (i) how a known neural network with fixed structure and training procedure could be applied to resolve a medical imaging problem; (ii) how medical images could be analysed, processed, and characterised by neural networks; and (iii) how neural networks could be expanded further to resolve problems relevant to medical imaging. In the concluding section, a highlight of comparisons among many neural network applications is included to provide a global view on computational intelligence with neural networks in medical imaging. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Cockayne syndrome b maintains neural precursor function.

    Science.gov (United States)

    Sacco, Raffaele; Tamblyn, Laura; Rajakulendran, Nishani; Bralha, Fernando N; Tropepe, Vincent; Laposa, Rebecca R

    2013-02-01

    Neurodevelopmental defects are observed in the hereditary disorder Cockayne syndrome (CS). The gene most frequently mutated in CS, Cockayne Syndrome B (CSB), is required for the repair of bulky DNA adducts in transcribed genes during transcription-coupled nucleotide excision repair. CSB also plays a role in chromatin remodeling and mitochondrial function. The role of CSB in neural development is poorly understood. Here we report that the abundance of neural progenitors is normal in Csb(-/-) mice and the frequency of apoptotic cells in the neurogenic niche of the adult subependymal zone is similar in Csb(-/-) and wild type mice. Both embryonic and adult Csb(-/-) neural precursors exhibited defective self-renewal in the neurosphere assay. In Csb(-/-) neural precursors, self-renewal progressively decreased in serially passaged neurospheres. The data also indicate that Csb and the nucleotide excision repair protein Xpa preserve embryonic neural stem cell self-renewal after UV DNA damage. Although Csb(-/-) neural precursors do not exhibit altered neuronal lineage commitment after low-dose UV (1J/m(2)) in vitro, neurons differentiated in vitro from Csb(-/-) neural precursors that had been irradiated with 1J/m(2) UV exhibited defective neurite outgrowth. These findings identify a function for Csb in neural precursors. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Hidden neural networks: application to speech recognition

    DEFF Research Database (Denmark)

    Riis, Søren Kamaric

    1998-01-01

    We evaluate the hidden neural network HMM/NN hybrid on two speech recognition benchmark tasks; (1) task independent isolated word recognition on the Phonebook database, and (2) recognition of broad phoneme classes in continuous speech from the TIMIT database. It is shown how hidden neural networks...

  16. Genetic Algorithm Optimized Neural Networks Ensemble as ...

    African Journals Online (AJOL)

    Improvements in neural network calibration models by a novel approach using neural network ensemble (NNE) for the simultaneous spectrophotometric multicomponent analysis are suggested, with a study on the estimation of the components of an antihypertensive combination, namely, atenolol and losartan potassium.

  17. Neural Networks for Non-linear Control

    DEFF Research Database (Denmark)

    Sørensen, O.

    1994-01-01

    This paper describes how a neural network, structured as a Multi Layer Perceptron, is trained to predict, simulate and control a non-linear process.......This paper describes how a neural network, structured as a Multi Layer Perceptron, is trained to predict, simulate and control a non-linear process....

  18. Application of Neural Networks for Energy Reconstruction

    CERN Document Server

    Damgov, Jordan

    2002-01-01

    The possibility to use Neural Networks for reconstruction ofthe energy deposited in the calorimetry system of the CMS detector is investigated. It is shown that using feed-forward neural network, good linearity, Gaussian energy distribution and good energy resolution can be achieved. Significant improvement of the energy resolution and linearity is reached in comparison with other weighting methods for energy reconstruction.

  19. Neural Network to Solve Concave Games

    OpenAIRE

    Zixin Liu; Nengfa Wang

    2014-01-01

    The issue on neural network method to solve concave games is concerned. Combined with variational inequality, Ky Fan inequality, and projection equation, concave games are transformed into a neural network model. On the basis of the Lyapunov stable theory, some stability results are also given. Finally, two classic games’ simulation results are given to illustrate the theoretical results.

  20. Recognizing changing seasonal patterns using neural networks

    NARCIS (Netherlands)

    Ph.H.B.F. Franses (Philip Hans); G. Draisma (Gerrit)

    1997-01-01

    textabstractIn this paper we propose a graphical method based on an artificial neural network model to investigate how and when seasonal patterns in macroeconomic time series change over time. Neural networks are useful since the hidden layer units may become activated only in certain seasons or