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Sample records for neural crest-like human

  1. Generation of Neural Crest-Like Cells From Human Periodontal Ligament Cell-Derived Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Tomokiyo, Atsushi; Hynes, Kim; Ng, Jia; Menicanin, Danijela; Camp, Esther; Arthur, Agnes; Gronthos, Stan; Mark Bartold, Peter

    2017-02-01

    Neural crest cells (NCC) hold great promise for tissue engineering, however the inability to easily obtain large numbers of NCC is a major factor limiting their use in studies of regenerative medicine. Induced pluripotent stem cells (iPSC) are emerging as a novel candidate that could provide an unlimited source of NCC. In the present study, we examined the potential of neural crest tissue-derived periodontal ligament (PDL) iPSC to differentiate into neural crest-like cells (NCLC) relative to iPSC generated from a non-neural crest derived tissue, foreskin fibroblasts (FF). We detected high HNK1 expression during the differentiation of PDL and FF iPSC into NCLC as a marker for enriching for a population of cells with NCC characteristics. We isolated PDL iPSC- and FF iPSC-derived NCLC, which highly expressed HNK1. A high proportion of the HNK1-positive cell populations generated, expressed the MSC markers, whilst very few cells expressed the pluripotency markers or the hematopoietic markers. The PDL and FF HNK1-positive populations gave rise to smooth muscle, neural, glial, osteoblastic and adipocytic like cells and exhibited higher expression of smooth muscle, neural, and glial cell-associated markers than the PDL and FF HNK1-negative populations. Interestingly, the HNK1-positive cells derived from the PDL-iPSC exhibited a greater ability to differentiate into smooth muscle, neural, glial cells and adipocytes, than the HNK1-positive cells derived from the FF-iPSC. Our work suggests that HNK1-enriched NCLC from neural crest tissue-derived iPSC more closely resemble the phenotypic and functional hallmarks of NCC compared to the HNK1-low population and non-neural crest iPSC-derived NCLC. J. Cell. Physiol. 232: 402-416, 2017. © 2016 Wiley Periodicals, Inc.

  2. Trunk lateral cells are neural crest-like cells in the ascidian Ciona intestinalis: insights into the ancestry and evolution of the neural crest.

    Science.gov (United States)

    Jeffery, William R; Chiba, Takuto; Krajka, Florian Razy; Deyts, Carole; Satoh, Nori; Joly, Jean-Stéphane

    2008-12-01

    Neural crest-like cells (NCLC) that express the HNK-1 antigen and form body pigment cells were previously identified in diverse ascidian species. Here we investigate the embryonic origin, migratory activity, and neural crest related gene expression patterns of NCLC in the ascidian Ciona intestinalis. HNK-1 expression first appeared at about the time of larval hatching in dorsal cells of the posterior trunk. In swimming tadpoles, HNK-1 positive cells began to migrate, and after metamorphosis they were localized in the oral and atrial siphons, branchial gill slits, endostyle, and gut. Cleavage arrest experiments showed that NCLC are derived from the A7.6 cells, the precursors of trunk lateral cells (TLC), one of the three types of migratory mesenchymal cells in ascidian embryos. In cleavage arrested embryos, HNK-1 positive TLC were present on the lateral margins of the neural plate and later became localized adjacent to the posterior sensory vesicle, a staging zone for their migration after larval hatching. The Ciona orthologues of seven of sixteen genes that function in the vertebrate neural crest gene regulatory network are expressed in the A7.6/TLC lineage. The vertebrate counterparts of these genes function downstream of neural plate border specification in the regulatory network leading to neural crest development. The results suggest that NCLC and neural crest cells may be homologous cell types originating in the common ancestor of tunicates and vertebrates and support the possibility that a putative regulatory network governing NCLC development was co-opted to produce neural crest cells during vertebrate evolution.

  3. The quantum human central neural system.

    Science.gov (United States)

    Alexiou, Athanasios; Rekkas, John

    2015-01-01

    In this chapter we present Excess Entropy Production for human aging system as the sum of their respective subsystems and electrophysiological status. Additionally, we support the hypothesis of human brain and central neural system quantumness and we strongly suggest the theoretical and philosophical status of human brain as one of the unknown natural Dirac magnetic monopoles placed in the center of a Riemann sphere.

  4. Human Neural Cell-Based Biosensor

    Science.gov (United States)

    2013-05-28

    including incubation with factors such as SHH ) and proceed to Human Neural Progenitor Cells Dopaminergic Differentiation β-III Tubulin/TH...exposure in human embryonic stem cells. J Recept Signal Transduct Res. 2011 Jun;31(3):206-13. Gerwe BA, Angel PM, West FD, Hasneen K, Young A

  5. Neural networks of human nature and nurture

    Directory of Open Access Journals (Sweden)

    Daniel S. Levine

    2008-06-01

    Full Text Available Neural network methods have facilitated the unifi - cation of several unfortunate splits in psychology, including nature versus nurture. We review the contributions of this methodology and then discuss tentative network theories of caring behavior, of uncaring behavior, and of how the frontal lobes are involved in the choices between them. The implications of our theory are optimistic about the prospects of society to encourage the human potential for caring.

  6. Neural networks of human nature and nurture

    Directory of Open Access Journals (Sweden)

    Daniel S. Levine

    2009-11-01

    Full Text Available Neural network methods have facilitated the unification of several unfortunate splits in psychology, including nature versus nurture. We review the contributions of this methodology and then discuss tentative network theories of caring behavior, of uncaring behavior, and of how the frontal lobes are involved in the choices between them. The implications of our theory are optimistic about the prospects of society to encourage the human potential for caring.

  7. Effect of human neural progenitor cells on injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    XU Guang-hui; BAI Jin-zhu; CAI Qin-lin; LI Xiao-xia; LI Ling-song; SHEN Li

    2005-01-01

    Objective: To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats.Methods: Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan (BBB) locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry.Results: Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats.Conclusions: Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.

  8. Neural correlates of human body perception.

    Science.gov (United States)

    Aleong, Rosanne; Paus, Tomás

    2010-03-01

    The objective of this study was to investigate potential sex differences in the neural response to human bodies using fMRI carried out in healthy young adults. We presented human bodies in a block-design experiment to identify body-responsive regions of the brain, namely, extrastriate body area (EBA) and fusiform body area (FBA). In a separate event-related "adaptation" experiment, carried out in the same group of subjects, we presented sets of four human bodies of varying body size and shape. Varying levels of body morphing were introduced to assess the degree of morphing required for adaptation release. Analysis of BOLD signal in the block-design experiment revealed significant Sex x Hemisphere interactions in the EBA and the FBA responses to human bodies. Only women showed greater BOLD response to bodies in the right hemisphere compared with the left hemisphere for both EBA and FBA. The BOLD response in right EBA was higher in women compared with men. In the adaptation experiment, greater right versus left hemisphere response for EBA and FBA was also identified among women but not men. These findings are particularly novel in that they address potential sex differences in the lateralization of EBA and FBA responses to human body images. Although previous studies have found some degree of right hemisphere dominance in body perception, our results suggest that such a functional lateralization may differ between men and women.

  9. The neural basis of human tool use

    Directory of Open Access Journals (Sweden)

    Guy A Orban

    2014-04-01

    Full Text Available In this review, we propose that the neural basis for the spontaneous, diversified human tool use is an area devoted to the execution and observation of tool actions, located in the left anterior supramarginal gyrus (aSMG. The aSMG activation elicited by observing tool use is typical of human subjects, as macaques show no similar activation, even after an extensive training to use tools. The execution of tool actions, as well as their observation, requires the convergence upon aSMG of inputs from different parts of the dorsal and ventral visual streams. Non semantic features of the target object may be provided by the posterior parietal cortex (PPC for tool-object interaction, paralleling the well-known PPC input to AIP for hand-object interaction. Semantic information regarding tool identity, and knowledge of the typical manner of handling the tool, could be provided by inferior and middle regions of the temporal lobe. Somatosensory feedback and technical reasoning, as well as motor and intentional constraints also play roles during the planning of tool actions and consequently their signals likewise converge upon aSMG.We further propose that aSMG may have arisen though duplication of monkey AIP and invasion of the duplicate area by afferents from PPC providing distinct signals depending on the kinematics of the manipulative action. This duplication may have occurred when Homo Habilis or Homo Erectus emerged, generating the Oldowan or Acheulean Industrial complexes respectively. Hence tool use may have emerged during hominid evolution between bipedalism and language.We conclude that humans have two parietal systems involved in tool behavior: a biological circuit for grasping objects, including tools, and an artifactual system devoted specifically to tool use. Only the latter allows humans to understand the causal relationship between tool use and obtaining the goal, and is likely to be the basis of all technological developments.

  10. Know Your Place: Neural Processing of Social Hierarchy in Humans

    Science.gov (United States)

    Zink, Caroline F.; Tong, Yunxia; Chen, Qiang; Bassett, Danielle S.; Stein, Jason L.; Meyer-Lindenberg, Andreas

    2008-01-01

    Summary Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions were recruited related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health. PMID:18439411

  11. Evolution of Neural Controllers for Robot Navigation in Human Environments

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    Genci Capi

    2010-01-01

    Full Text Available Problem statement: In this study, we presented a novel vision-based learning approach for autonomous robot navigation. Approach: In our method, we converted the captured image in a binary one, which after the partition is used as the input of the neural controller. Results: The neural control system, which maps the visual information to motor commands, is evolved online using real robots. Conclusion/Recommendations: We showed that evolved neural networks performed well in indoor human environments. Furthermore, we compared the performance of neural controllers with an algorithmic vision based control method.

  12. Harmine stimulates proliferation of human neural progenitors

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    Dakic, Vanja; Maciel, Renata de Moraes; Drummond, Hannah; Nascimento, Juliana M.; Trindade, Pablo

    2016-01-01

    Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo. PMID:27957390

  13. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  14. Neural networks for perception human and machine perception

    CERN Document Server

    Wechsler, Harry

    1991-01-01

    Neural Networks for Perception, Volume 1: Human and Machine Perception focuses on models for understanding human perception in terms of distributed computation and examples of PDP models for machine perception. This book addresses both theoretical and practical issues related to the feasibility of both explaining human perception and implementing machine perception in terms of neural network models. The book is organized into two parts. The first part focuses on human perception. Topics on network model ofobject recognition in human vision, the self-organization of functional architecture in t

  15. Neural Correlates of the Cortisol Awakening Response in Humans

    OpenAIRE

    Boehringer, Andreas; Tost, Heike; Haddad, Leila; Lederbogen, Florian; Wüst, Stefan; Schwarz, Emanuel; Meyer-Lindenberg, Andreas

    2015-01-01

    The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (vox...

  16. Cloning and characterization of the neural isoforms of human dystonin

    Energy Technology Data Exchange (ETDEWEB)

    Brown, A.; Dalpe, G.; Mathieu, M.; Kothary, R. [Univ. of Montreal, Quebec (Canada)

    1995-10-10

    Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We have identified and cloned a gene encoded at the dt locus. The product of the dt gene, dystonin, is a neural isoform of a hemidesmosomal protein bullous pemphigoid antigen 1 (bpag1). To investigate the potential role of dystonin in human neuropathies, we have cloned the neural-specific 5{prime} exons of the human DT gene that together with the previously cloned BPAG1 sequences comprise human dystonin. The mouse and human dystonin genes demonstrate the same spectrum of alternatively spliced products, and the amino acid sequences of the neural-specific exons in the mouse and human genes are over 96% identical. 17 refs., 2 figs.

  17. Human Face Recognition Using Convolutional Neural Networks

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    Răzvan-Daniel Albu

    2009-10-01

    Full Text Available In this paper, I present a novel hybrid face recognition approach based on a convolutional neural architecture, designed to robustly detect highly variable face patterns. The convolutional network extracts successively larger features in a hierarchical set of layers. With the weights of the trained neural networks there are created kernel windows used for feature extraction in a 3-stage algorithm. I present experimental results illustrating the efficiency of the proposed approach. I use a database of 796 images of 159 individuals from Reims University which contains quite a high degree of variability in expression, pose, and facial details.

  18. High Accuracy Human Activity Monitoring using Neural network

    CERN Document Server

    Sharma, Annapurna; Chung, Wan-Young

    2011-01-01

    This paper presents the designing of a neural network for the classification of Human activity. A Triaxial accelerometer sensor, housed in a chest worn sensor unit, has been used for capturing the acceleration of the movements associated. All the three axis acceleration data were collected at a base station PC via a CC2420 2.4GHz ISM band radio (zigbee wireless compliant), processed and classified using MATLAB. A neural network approach for classification was used with an eye on theoretical and empirical facts. The work shows a detailed description of the designing steps for the classification of human body acceleration data. A 4-layer back propagation neural network, with Levenberg-marquardt algorithm for training, showed best performance among the other neural network training algorithms.

  19. DIFFERENCE FEATURE NEURAL NETWORK IN RECOGNITION OF HUMAN FACES

    Institute of Scientific and Technical Information of China (English)

    Chen Gang; Qi Feihu

    2001-01-01

    This article discusses vision recognition process and finds out that human recognizes objects not by their isolated features, but by their main difference features which people get by contrasting them. According to the resolving character of difference features for vision recognition, the difference feature neural network(DFNN) which is the improved auto-associative neural network is proposed.Using ORL database, the comparative experiment for face recognition with face images and the ones added Gaussian noise is performed, and the result shows that DFNN is better than the auto-associative neural network and it proves DFNN is more efficient.

  20. Directed Differentiation of Human Embryonic Stem Cells into Neural Progenitors.

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    Banda, Erin; Grabel, Laura

    2016-01-01

    A variety of protocols have been used to produce neural progenitors from human embryonic stem cells. We have focused on a monolayer culture approach that generates neural rosettes. To initiate differentiation, cells are plated in a serum-free nutrient-poor medium in the presence of a BMP inhibitor. Depending on the cell line used, additional growth factor inhibitors may be required to promote neural differentiation. Long-term culture and addition of the Notch inhibitor DAPT can promote terminal neuronal differentiation. Extent of differentiation is monitored using immunocytochemistry for cell type-specific markers.

  1. Generating trunk neural crest from human pluripotent stem cells

    OpenAIRE

    Miller Huang; Matthew L. Miller; McHenry, Lauren K.; Tina Zheng; Qiqi Zhen; Shirin Ilkhanizadeh; Conklin, Bruce R.; Bronner, Marianne E.; Weiss, William A.

    2016-01-01

    Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typi...

  2. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    Science.gov (United States)

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes. PMID:27212953

  3. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins.

    Science.gov (United States)

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  4. Pig Induced Pluripotent Stem Cell-Derived Neural Rosettes Parallel Human Differentiation Into Sensory Neural Subtypes.

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    Webb, Robin L; Gallegos-Cárdenas, Amalia; Miller, Colette N; Solomotis, Nicholas J; Liu, Hong-Xiang; West, Franklin D; Stice, Steven L

    2017-04-01

    The pig is the large animal model of choice for study of nerve regeneration and wound repair. Availability of porcine sensory neural cells would conceptually allow for analogous cell-based peripheral nerve regeneration in porcine injuries of similar severity and size to those found in humans. After recently reporting that porcine (or pig) induced pluripotent stem cells (piPSCs) differentiate into neural rosette (NR) structures similar to human NRs, here we demonstrate that pig NR cells could differentiate into neural crest cells and other peripheral nervous system-relevant cell types. Treatment with either bone morphogenetic protein 4 or fetal bovine serum led to differentiation into BRN3A-positive sensory cells and increased expression of sensory neuron TRK receptor gene family: TRKA, TRKB, and TRKC. Porcine sensory neural cells would allow determination of parallels between human and porcine cells in response to noxious stimuli, analgesics, and reparative mechanisms. In vitro differentiation of pig sensory neurons provides a novel model system for neural cell subtype specification and would provide a novel platform for the study of regenerative therapeutics by elucidating the requirements for innervation following injury and axonal survival.

  5. Senegenin promotes in vitro proliferation of human neural progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Fang Shi; Zhigang Liang; Zixuan Guo; Ran Li; Fen Yu; Zhanjun Zhang; Xuan Wang; Xiaomin Wang

    2011-01-01

    Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus.However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood.Cells from a ventral mesencephalon neural progenitor cell line (ReNcell VM) were utilized as models for pharmaceutical screening.The effects of various senegenin concentrations on cell proliferation were analyzed,demonstrating that high senegenin concentrations (5, 10, 50, and 100 pmo/L), particularly 50 pmol/L, significantly promoted proliferation of ReNcell VM cells.In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases.Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors.Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.

  6. Hand Gesture and Neural Network Based Human Computer Interface

    Directory of Open Access Journals (Sweden)

    Aekta Patel

    2014-06-01

    Full Text Available Computer is used by every people either at their work or at home. Our aim is to make computers that can understand human language and can develop a user friendly human computer interfaces (HCI. Human gestures are perceived by vision. The research is for determining human gestures to create an HCI. Coding of these gestures into machine language demands a complex programming algorithm. In this project, We have first detected, recognized and pre-processing the hand gestures by using General Method of recognition. Then We have found the recognized image’s properties and using this, mouse movement, click and VLC Media player controlling are done. After that we have done all these functions thing using neural network technique and compared with General recognition method. From this we can conclude that neural network technique is better than General Method of recognition. In this, I have shown the results based on neural network technique and comparison between neural network method & general method.

  7. A neural circuit encoding sexual preference in humans.

    OpenAIRE

    Poeppl, Timm B.; Langguth, Berthold; Rupprecht, Rainer; Laird, Angela R.; Eickhoff, Simon

    2016-01-01

    Sexual preference determines mate choice for reproduction and hence guarantees conservation of species in mammals. Despite this fundamental role in human behavior, current knowledge on its target-specific neurofunctional substrate is based on lesion studies and therefore limited. We used meta-analytic remodeling of neuroimaging data from 364 human subjects with diverse sexual interests during sexual stimulation to quantify neural regions associated with sexual preference manipulations. We fou...

  8. Apoptotic gene expression in the neural tube during early human embryonic development

    Institute of Scientific and Technical Information of China (English)

    Guifang Chen; Tiandong Li; Peipei Ding; Ping Yang; Xiao Zhang

    2011-01-01

    Neural tube development comprises neural induction,neural epithelial cell proliferation,and apoptosis,as well as migration of nerve cells.Too much or too little apoptosis leads to abnormal nervous system development.The present study analyzed expression and distribution of apoptotic-related factors,including Fas,FasL,and caspase-3,during human embryonic neural tube development.Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondriai-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development.Subsequently,Fas and FasL expression increased during embryonic development.The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways.Therefore,neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.

  9. Generating trunk neural crest from human pluripotent stem cells.

    Science.gov (United States)

    Huang, Miller; Miller, Matthew L; McHenry, Lauren K; Zheng, Tina; Zhen, Qiqi; Ilkhanizadeh, Shirin; Conklin, Bruce R; Bronner, Marianne E; Weiss, William A

    2016-01-27

    Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior "cranial" NCC form craniofacial bone, whereas solely posterior "trunk" NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages.

  10. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity.

    Science.gov (United States)

    Schwartz, Michael P; Hou, Zhonggang; Propson, Nicholas E; Zhang, Jue; Engstrom, Collin J; Santos Costa, Vitor; Jiang, Peng; Nguyen, Bao Kim; Bolin, Jennifer M; Daly, William; Wang, Yu; Stewart, Ron; Page, C David; Murphy, William L; Thomson, James A

    2015-10-01

    Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials and offer a cost-effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically defined polyethylene glycol hydrogels and cultured in serum-free medium to model cellular interactions within the developing brain. The precursors self-assembled into 3D neural constructs with diverse neuronal and glial populations, interconnected vascular networks, and ramified microglia. Replicate constructs were reproducible by RNA sequencing (RNA-Seq) and expressed neurogenesis, vasculature development, and microglia genes. Linear support vector machines were used to construct a predictive model from RNA-Seq data for 240 neural constructs treated with 34 toxic and 26 nontoxic chemicals. The predictive model was evaluated using two standard hold-out testing methods: a nearly unbiased leave-one-out cross-validation for the 60 training compounds and an unbiased blinded trial using a single hold-out set of 10 additional chemicals. The linear support vector produced an estimate for future data of 0.91 in the cross-validation experiment and correctly classified 9 of 10 chemicals in the blinded trial.

  11. Enhanced expression of FNDC5 in human embryonic stem cell-derived neural cells along with relevant embryonic neural tissues.

    Science.gov (United States)

    Ghahrizjani, Fatemeh Ahmadi; Ghaedi, Kamran; Salamian, Ahmad; Tanhaei, Somayeh; Nejati, Alireza Shoaraye; Salehi, Hossein; Nabiuni, Mohammad; Baharvand, Hossein; Nasr-Esfahani, Mohammad Hossein

    2015-02-25

    Availability of human embryonic stem cells (hESCs) has enhanced the capability of basic and clinical research in the context of human neural differentiation. Derivation of neural progenitor (NP) cells from hESCs facilitates the process of human embryonic development through the generation of neuronal subtypes. We have recently indicated that fibronectin type III domain containing 5 protein (FNDC5) expression is required for appropriate neural differentiation of mouse embryonic stem cells (mESCs). Bioinformatics analyses have shown the presence of three isoforms for human FNDC5 mRNA. To differentiate which isoform of FNDC5 is involved in the process of human neural differentiation, we have used hESCs as an in vitro model for neural differentiation by retinoic acid (RA) induction. The hESC line, Royan H5, was differentiated into a neural lineage in defined adherent culture treated by RA and basic fibroblast growth factor (bFGF). We collected all cell types that included hESCs, rosette structures, and neural cells in an attempt to assess the expression of FNDC5 isoforms. There was a contiguous increase in all three FNDC5 isoforms during the neural differentiation process. Furthermore, the highest level of expression of the isoforms was significantly observed in neural cells compared to hESCs and the rosette structures known as neural precursor cells (NPCs). High expression levels of FNDC5 in human fetal brain and spinal cord tissues have suggested the involvement of this gene in neural tube development. Additional research is necessary to determine the major function of FDNC5 in this process.

  12. Neural correlate of human reciprocity in social interactions.

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    Sakaiya, Shiro; Shiraito, Yuki; Kato, Junko; Ide, Hiroko; Okada, Kensuke; Takano, Kouji; Kansaku, Kenji

    2013-01-01

    Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions.

  13. Neural correlate of human reciprocity in social interactions

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    Shiro eSakaiya

    2013-12-01

    Full Text Available Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human and strategy (random, tit-for-tat in repeated prisoner’s dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate and theory of mind (ToM regions (i.e., ventromedial prefrontal cortex [VMPFC] and precuneus. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (deactivation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during

  14. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

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    Hayato Fukusumi

    2016-01-01

    Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  15. [Human pluripotent stem cell and neural differentiation].

    Science.gov (United States)

    Wataya, Takafumi; Muguruma, Keiko; Sasai, Yoshiki

    2008-10-01

    Recovery of lost brain function is an important issue in medical studies because neurons of the central nervous system (CNS) have poor potential for regeneration. Since few CNS diseases can be treated completely by medicines, regenerative therapy by using stem cells should be studied as a new type of therapeutic intervention. The efficacy of cell replacement therapy in Parkinson's disease has been well investigated. Several studies on fetal tissue transplantation have revealed that quantity and purity of transplanted cells are necessary for recovery of symptoms. SFEB (Serum-free floating culture of embryoid body-like aggregates) method is capable of inducing multi-potential CNS progenitors that can be steered to differentiate into region-specific tissues. On the basis of the existing knowledge of embryology, we have succeeded in the generating of various types of neurons such as telencephalic, cerebeller (Purkinje and granule cells), retinal (photoreceptor cells) and hypothalamic neurons. Application of this culture method to human ES (hES) cells is necessary for clinical purpose: however, poor survival of hES cells in SFEB culture might limit the possibility of using these cells for future medical applications. We found that a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, markedly diminished the dissociation-induced apoptosis of hES cells and enabled the cells to form aggregates in SFEB culture. For both mouse and human ES cells, SFEB culture is a favorable method that can generate large amounts of region-specific neurons. However, stem cell-based therapy continues to face several obstacles. It is important that researchers in the basic sciences and clinical medicine should discuss these problems together to overcome both scientific and ethical issues related to stem cells.

  16. Infrared neural stimulation of human spinal nerve roots in vivo.

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    Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

  17. Neural Signatures of Trust During Human-Automation Interactions

    Science.gov (United States)

    2016-04-01

    connectivity changes following explicit-memory training for face-name pairs in patients with mild cognitive impairment: a pilot study. Neurorehabil Neural...Descriptions Human: Mr. Steve Williams Mr. Steve Williams (Human) is a trained luggage screener, with extensive knowledge in identifying illegal imports... Extraversion 41.92 ± 3.37 40.42 ± 3.26 t = 1.11, p = .280 Openness 37.75 ± 3.60 36.92 ± 4.72 t = 0.49, p = .631 Agreeableness 38.67 ± 4.05 41.00

  18. Human -Computer Interface using Gestures based on Neural Network

    Directory of Open Access Journals (Sweden)

    Aarti Malik

    2014-10-01

    Full Text Available - Gestures are powerful tools for non-verbal communication. Human computer interface (HCI is a growing field which reduces the complexity of interaction between human and machine in which gestures are used for conveying information or controlling the machine. In the present paper, static hand gestures are utilized for this purpose. The paper presents a novel technique of recognizing hand gestures i.e. A-Z alphabets, 0-9 numbers and 6 additional control signals (for keyboard and mouse control by extracting various features of hand ,creating a feature vector table and training a neural network. The proposed work has a recognition rate of 99%. .

  19. Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair.

    Science.gov (United States)

    Tseng, Ting-Chen; Hsieh, Fu-Yu; Dai, Niann-Tzyy; Hsu, Shan-Hui

    2016-09-01

    Cell- and gene-based therapies have emerged as promising strategies for treating neurological diseases. The sources of neural stem cells are limited while the induced pluripotent stem (iPS) cells have risk of tumor formation. Here, we proposed the generation of self-renewable, multipotent, and neural lineage-related neural crest stem-like cells by chitosan substrate-mediated gene transfer of a single factor forkhead box D3 (FOXD3) for the use in neural repair. A simple, non-toxic, substrate-mediated method was applied to deliver the naked FOXD3 plasmid into human fibroblasts. The transfection of FOXD3 increased cell proliferation and up-regulated the neural crest marker genes (FOXD3, SOX2, and CD271), stemness marker genes (OCT4, NANOG, and SOX2), and neural lineage-related genes (Nestin, β-tubulin and GFAP). The expression levels of stemness marker genes and neural crest maker genes in the FOXD3-transfected fibroblasts were maintained until the fifth passage. The FOXD3 reprogrammed fibroblasts based on the new method significantly rescued the neural function of the impaired zebrafish. The chitosan substrate-mediated delivery of naked plasmid showed feasibility in reprogramming somatic cells. Particularly, the FOXD3 reprogrammed fibroblasts hold promise as an easily accessible cellular source with neural crest stem-like behavior for treating neural diseases in the future.

  20. Neural mechanisms of discourse comprehension: a human lesion study.

    Science.gov (United States)

    Barbey, Aron K; Colom, Roberto; Grafman, Jordan

    2014-01-01

    Discourse comprehension is a hallmark of human social behaviour and refers to the act of interpreting a written or spoken message by constructing mental representations that integrate incoming language with prior knowledge and experience. Here, we report a human lesion study (n = 145) that investigates the neural mechanisms underlying discourse comprehension (measured by the Discourse Comprehension Test) and systematically examine its relation to a broad range of psychological factors, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores obtained from these factors were submitted to voxel-based lesion-symptom mapping to elucidate their neural substrates. Stepwise regression analyses revealed that working memory and extraversion reliably predict individual differences in discourse comprehension: higher working memory scores and lower extraversion levels predict better discourse comprehension performance. Lesion mapping results indicated that these convergent variables depend on a shared network of frontal and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The observed findings motivate an integrative framework for understanding the neural foundations of discourse comprehension, suggesting that core elements of discourse processing emerge from a distributed network of brain regions that support specific competencies for executive and social function.

  1. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

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    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  2. Neural pattern in the human pollical distal phalanx.

    Science.gov (United States)

    Johnson, Richard K; Shrewsbury, Marvin M

    2005-09-01

    A morphological study of the neural pattern in the human ungual region of the pollical distal phalanx was carried out on eight male cadavers. The dissections showed a palmar neural arrangement consisting of four designated ungual nerves, two proximal and two distal, for each of the ulnar and radial palmar digital nerves at the lateral sides of the thumb. This neural configuration was associated with the compartmentalization of its ungual pulp, the difference between the type of sensory receptors within the ungual pulp, the overlapping of the tactile composition at the thumb tip, seen clinically after laceration of one of the palmar digital nerves, and the sensory supply to the nail bed in the dorsal portion of the thumb. The proximal ungual pulp compartment had a single proximal medial ungual nerve, which did not appear, as far as visually possible, to overlap at the midline of the proximal ungual pulp. In contrast, the distal ungual pulp compartment was supplied by a medial and a lateral ungual nerve, both of which did appear to overlap to their contralateral sides in the thumb tip. A single proximal dorsal sensory nerve branched dorsally from each of ulnar and radial palmar digital nerves at the level of the proximal ungual pulp to supply the nail bed on the dorsum of the thumb.

  3. Neural compensation within the human triceps surae during prolonged walking.

    Science.gov (United States)

    Cronin, Neil J; Peltonen, Jussi; Sinkjaer, Thomas; Avela, Janne

    2011-02-01

    During human walking, muscle activation strategies are approximately constant across consecutive steps over a short time, but it is unknown whether they are maintained over a longer duration. Prolonged walking may increase tendinous tissue (TT) compliance, which can influence neural activation, but the neural responses of individual muscles have not been investigated. This study investigated the hypothesis that muscle activity is up- or down-regulated in individual triceps surae muscles during prolonged walking. Thirteen healthy subjects walked on a treadmill for 60 min at 4.5 km/h, while triceps surae muscle activity, maximal muscle compound action potentials, and kinematics were recorded every 5 min, and fascicle lengths were estimated at the beginning and end of the protocol using ultrasound. After 1 h of walking, soleus activity increased by 9.3 ± 0.2% (P triceps surae muscles and that changes in muscle activation are generally mirrored by changes in muscle fascicle length. These findings also support the notion of muscle-specific changes in TT compliance after prolonged walking and highlight the ability of the CNS to maintain relatively constant movement patterns in spite of neuromechanical changes in individual muscles.

  4. Neural precursors derived from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    Peng Hongmei; Chen Gui'an

    2005-01-01

    Human embryonic stem (hES) cells provide a promising supply of specific cell types for transplantation therapy. We presented here the method to induce differentiation of purified neural precursors from hES cells, hES cells (Line PKU-1 and Line PKU-2) were cultured in suspension in bacteriological Petri dishes, which differentiated into cystic embryoid bodies (EBs).The EBs were then cultured in N2 medium containing bFGF in poly- L-lysine-coated tissue culture dishes for two weeks. The central, small cells with 2-3 short processes of the spreading outgrowth were isolated mechanically and replated. The resulting neurospheres were cultured in suspension for 10 days, then dissociated into single cell suspension with a Pasteur pipette and plated. Cells grew vigorously in an attached way and were passed every 4-5 days. Almost all the cells were proved nestin positive by immunostaining. Following withdrawal of bFGF, they differentiated into neurons expressing β-tubulin isotypeⅢ, GABA, serotonin and synaptophysin.Through induction of PDGF-AA, they differentiated into astrocytes expressing GFAP and oligodendrocytes expressing O4. The results showed that hES cells can differentiate into typical neural precursors expressing the specific marker nestin and capable of generating all three cell types of the central nervous system (CNS) in vitro.

  5. Neural decoding of expressive human movement from scalp electroencephalography (EEG

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    Zachery Ryan Hernandez

    2014-04-01

    Full Text Available Although efforts to characterize human movement through EEG have revealed neural activities unique to limb control that can be used to infer movement kinematics, it is still unknown the extent to which EEG can be used to discern the expressive qualities that influence such movements. In this study we used EEG and inertial sensors to record brain activity and movement of five skilled and certified Laban Movement Analysis (LMA dancers. Each dancer performed whole body functional movements of three Action types: movements devoid of expressive qualities ('Neutral', non-expressive movements while thinking about specific expressive qualities ('Think’, and enacted expressive movements ('Do'. The expressive movement qualities that were used in the 'Think' and 'Do' actions consisted of a sequence of eight Laban Efforts as defined by LMA - a notation system and language for describing, visualizing, interpreting and documenting all varieties of human movement. We used delta band (0.2 – 4 Hz EEG as input to a machine learning algorithm that computed locality-preserving Fisher’s discriminant analysis (LFDA for dimensionality reduction followed by Gaussian mixture models (GMMs to decode the type of Action. We also trained our LFDA-GMM models to classify all the possible combinations of Action Type and Laban Effort (giving a total of 17 classes. Classification accuracy rates were 59.4 ± 0.6% for Action Type and 88.2 ± 0.7% for Laban Effort Type. Ancillary analyses of the potential relations between the EEG and movement kinematics of the dancer's body, indicated that motion-related artifacts did not significantly influence our classification results. In summary, this research demonstrates that EEG has valuable information about the expressive qualities of movement. These results may have applications for advancing the understanding of the neural basis of expressive movements and for the development of neuroprosthetics to restore movements.

  6. Neural decoding of expressive human movement from scalp electroencephalography (EEG)

    Science.gov (United States)

    Cruz-Garza, Jesus G.; Hernandez, Zachery R.; Nepaul, Sargoon; Bradley, Karen K.; Contreras-Vidal, Jose L.

    2014-01-01

    Although efforts to characterize human movement through electroencephalography (EEG) have revealed neural activities unique to limb control that can be used to infer movement kinematics, it is still unknown the extent to which EEG can be used to discern the expressive qualities that influence such movements. In this study we used EEG and inertial sensors to record brain activity and movement of five skilled and certified Laban Movement Analysis (LMA) dancers. Each dancer performed whole body movements of three Action types: movements devoid of expressive qualities (“Neutral”), non-expressive movements while thinking about specific expressive qualities (“Think”), and enacted expressive movements (“Do”). The expressive movement qualities that were used in the “Think” and “Do” actions consisted of a sequence of eight Laban Effort qualities as defined by LMA—a notation system and language for describing, visualizing, interpreting and documenting all varieties of human movement. We used delta band (0.2–4 Hz) EEG as input to a machine learning algorithm that computed locality-preserving Fisher's discriminant analysis (LFDA) for dimensionality reduction followed by Gaussian mixture models (GMMs) to decode the type of Action. We also trained our LFDA-GMM models to classify all the possible combinations of Action Type and Laban Effort quality (giving a total of 17 classes). Classification accuracy rates were 59.4 ± 0.6% for Action Type and 88.2 ± 0.7% for Laban Effort quality Type. Ancillary analyses of the potential relations between the EEG and movement kinematics of the dancer's body, indicated that motion-related artifacts did not significantly influence our classification results. In summary, this research demonstrates that EEG has valuable information about the expressive qualities of movement. These results may have applications for advancing the understanding of the neural basis of expressive movements and for the development of

  7. Neural decoding of expressive human movement from scalp electroencephalography (EEG).

    Science.gov (United States)

    Cruz-Garza, Jesus G; Hernandez, Zachery R; Nepaul, Sargoon; Bradley, Karen K; Contreras-Vidal, Jose L

    2014-01-01

    Although efforts to characterize human movement through electroencephalography (EEG) have revealed neural activities unique to limb control that can be used to infer movement kinematics, it is still unknown the extent to which EEG can be used to discern the expressive qualities that influence such movements. In this study we used EEG and inertial sensors to record brain activity and movement of five skilled and certified Laban Movement Analysis (LMA) dancers. Each dancer performed whole body movements of three Action types: movements devoid of expressive qualities ("Neutral"), non-expressive movements while thinking about specific expressive qualities ("Think"), and enacted expressive movements ("Do"). The expressive movement qualities that were used in the "Think" and "Do" actions consisted of a sequence of eight Laban Effort qualities as defined by LMA-a notation system and language for describing, visualizing, interpreting and documenting all varieties of human movement. We used delta band (0.2-4 Hz) EEG as input to a machine learning algorithm that computed locality-preserving Fisher's discriminant analysis (LFDA) for dimensionality reduction followed by Gaussian mixture models (GMMs) to decode the type of Action. We also trained our LFDA-GMM models to classify all the possible combinations of Action Type and Laban Effort quality (giving a total of 17 classes). Classification accuracy rates were 59.4 ± 0.6% for Action Type and 88.2 ± 0.7% for Laban Effort quality Type. Ancillary analyses of the potential relations between the EEG and movement kinematics of the dancer's body, indicated that motion-related artifacts did not significantly influence our classification results. In summary, this research demonstrates that EEG has valuable information about the expressive qualities of movement. These results may have applications for advancing the understanding of the neural basis of expressive movements and for the development of neuroprosthetics to restore

  8. Secretome analysis of human oligodendrocytes derived from neural stem cells.

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    Woo Kyung Kim

    Full Text Available In this study, we investigated the secretome of human oligodendrocytes (F3.Olig2 cells generated from human neural stem cells by transduction with the gene encoding the Olig2 transcription factor. Using mRNA sequencing and protein cytokine arrays, we identified a number of biologically important secretory proteins whose expression has not been previously reported in oligodendrocytes. We found that F3.Olig2 cells secrete IL-6, PDGF-AA, GRO, GM-CSF, and M-CSF, and showed prominent expression of their corresponding receptors. Co-expression of ligands and receptors suggests that autocrine signaling loops may play important roles in both differentiation and maintenance of oligodendrocytes. We also found that F3.Olig2 cells secrete matrix metalloproteinases and matrix metalloproteinase-associated proteins associated with functional competence of oligodendrocytes. The results of our secretome analysis provide insights into the functional and molecular details of human oligodendrocytes. To the best of our knowledge, this is the first systematic analysis of the secretome of oligodendrocytes.

  9. Ultrastructure of human neural stem/progenitor cells and neurospheres

    Institute of Scientific and Technical Information of China (English)

    Yaodong Zhao; Tianyi Zhang; Qiang Huang; Aidong Wang; Jun Dong; Qing Lan; Zhenghong Qin

    2009-01-01

    BACKGROUND: Biological and morphological characteristics of neural stern/progenitor cells (NSPCs) have been widely investigated.OBJECTIVE: To explore the ultrastructure of human embryo-derived NSPCs and neurospheres cultivated in vitro using electron microscopy.DESIGN, TIME AND SETTING: A cell biology experiment was performed at the Brain Tumor Laboratory of Soochow University, and Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University between August 2007 and April 2008.MATERIALS: Human fetal brain tissue was obtained from an 8-week-old aborted fetus; serum-free Dulbecco's modified Eagle's medium/F12 culture medium was provided by Gibco, USA; scanning electron microscope was provided by Hitachi instruments, Japan; transmission electron microscope was provided by JEOL, Japan.METHODS: NSPCs were isolated from human fetal brain tissue and cultivated in serum-free Dulbecco's modified Eagle's medium/F12 culture medium. Cells were passaged every 5-7 days. After three passages, NSPCs were harvested and used for ultrastructural examination.MAIN OUTCOME MEASURES: Ultrastructural examination of human NSPCs and adjacent cells in neurospheres.RESULTS: Individual NSPCs were visible as spherical morphologies with rough surfaces under scanning electron microscope. Generally, they had large nuclei and little cytoplasm. Nuclei were frequently globular with large amounts of euchromatin and a small quantity of heterochromatin, and most NSPCs had only one nucleolus. The Golgi apparatus and endoplasmic reticulum were underdeveloped; however, autophagosomes were clearly visible. The neurospheres were made up of NSPCs and non-fixiform material inside. Between adjacent cells and at the cytoplasmic surface of apposed plasma membranes, there were vesicle-like structures. Some membrane boundaries with high permeabilities were observed between some contiguous NSPCs in neurospheres, possibly attributable to plasmalemmal fusion between adjacent cells.CONCLUSION: A large number

  10. Neural coding of movement direction in the healthy human brain.

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    Christopher D Cowper-Smith

    Full Text Available Neurophysiological studies in monkeys show that activity of neurons in primary cortex (M1, pre-motor cortex (PMC, and cerebellum varies systematically with the direction of reaching movements. These neurons exhibit preferred direction tuning, where the level of neural activity is highest when movements are made in the preferred direction (PD, and gets progressively lower as movements are made at increasing degrees of offset from the PD. Using a functional magnetic resonance imaging adaptation (fMRI-A paradigm, we show that PD coding does exist in regions of the human motor system that are homologous to those observed in non-human primates. Consistent with predictions of the PD model, we show adaptation (i.e., a lower level of the blood oxygen level dependent (BOLD time-course signal in M1, PMC, SMA, and cerebellum when consecutive wrist movements were made in the same direction (0° offset relative to movements offset by 90° or 180°. The BOLD signal in dorsolateral prefrontal cortex adapted equally in all movement offset conditions, mitigating against the possibility that the present results are the consequence of differential task complexity or attention to action in each movement offset condition.

  11. Functional integration of human neural precursor cells in mouse cortex.

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    Fu-Wen Zhou

    Full Text Available This study investigates the electrophysiological properties and functional integration of different phenotypes of transplanted human neural precursor cells (hNPCs in immunodeficient NSG mice. Postnatal day 2 mice received unilateral injections of 100,000 GFP+ hNPCs into the right parietal cortex. Eight weeks after transplantation, 1.21% of transplanted hNPCs survived. In these hNPCs, parvalbumin (PV-, calretinin (CR-, somatostatin (SS-positive inhibitory interneurons and excitatory pyramidal neurons were confirmed electrophysiologically and histologically. All GFP+ hNPCs were immunoreactive with anti-human specific nuclear protein. The proportions of PV-, CR-, and SS-positive cells among GFP+ cells were 35.5%, 15.7%, and 17.1%, respectively; around 15% of GFP+ cells were identified as pyramidal neurons. Those electrophysiologically and histological identified GFP+ hNPCs were shown to fire action potentials with the appropriate firing patterns for different classes of neurons and to display spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs. The amplitude, frequency and kinetic properties of sEPSCs and sIPSCs in different types of hNPCs were comparable to host cells of the same type. In conclusion, GFP+ hNPCs produce neurons that are competent to integrate functionally into host neocortical neuronal networks. This provides promising data on the potential for hNPCs to serve as therapeutic agents in neurological diseases with abnormal neuronal circuitry such as epilepsy.

  12. Neural mechanisms of perceptual grouping in human visual cortex

    Institute of Scientific and Technical Information of China (English)

    MAO Lihua; HAN Shihui; GUO Chunyan; JIANG Yi

    2004-01-01

    The current work examined neural substrates of perceptual grouping in human visual cortex using event-related potential (ERP) recording. Stimulus arrays consisted of local elements that were either evenly spaced (uniform stimuli) or grouped into columns or rows by proximity or color similarity (grouping stimuli). High-density ERPs were recorded while subjects identified orientations of perceptual groups in stimulus arrays that were presented randomly in one of the four quadrants of the visual field. Both uniform and grouping stimulus arrays elicited an early ERP component (C1), which peaked at about 70 ms after stimulus onset and changed its polarity as a function of stimulated elevations. Dipole modeling based on realistic- head boundary-element models revealed generators of the C1 component in the calcarine cortex. The C1 was modulated by perceptual grouping of local elements based on proximity, and this grouping effect was stronger in the upper than in the lower visual field. The findings provide ERP evidence for the engagement of human primary visual cortex in the early stage of perceptual grouping.

  13. Stage-specific roles of FGF2 signaling in human neural development.

    Science.gov (United States)

    Grabiec, Marta; Hříbková, Hana; Vařecha, Miroslav; Střítecká, Dana; Hampl, Aleš; Dvořák, Petr; Sun, Yuh-Man

    2016-09-01

    This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stem cell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes (a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cells with cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6(+)/Ki67(+) neural stem cells and the emergence of MAP2(+) neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo.

  14. 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.

  15. Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

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    Maucksch C

    2012-01-01

    Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

  16. Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

    Science.gov (United States)

    Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

    2016-05-01

    Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

  17. Neural correlates of human somatosensory integration in tinnitus

    NARCIS (Netherlands)

    Lanting, C. P.; de Kleine, E.; Eppinga, R. N.; van Dijk, P.

    2010-01-01

    Possible neural correlates of somatosensory modulation of tinnitus were assessed. Functional magnetic resonance imaging (fMRI) was used to investigate differences in neural activity between subjects that can modulate their tinnitus by jaw protrusion and normal hearing controls. We measured responses

  18. Neural response to emotional stimuli during experimental human endotoxemia.

    Science.gov (United States)

    Kullmann, Jennifer S; Grigoleit, Jan-Sebastian; Lichte, Philipp; Kobbe, Philipp; Rosenberger, Christina; Banner, Christina; Wolf, Oliver T; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Bingel, Ulrike; Forsting, Michael; Gizewski, Elke R; Schedlowski, Manfred

    2013-09-01

    Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects. In a double-blind, randomized crossover study, 18 healthy males received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline. Plasma levels of pro- and anti-inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood-oxygen-level dependent (BOLD) response during the presentation of aversive versus neutral pictures. Endotoxin administration induced pronounced transient increases in plasma levels of TNF-α, IL-1ra, IL-6, IL-10, and cortisol. Positive mood was decreased and state anxiety increased. In addition, activation of right inferior orbitofrontal cortex (OFC) in response to emotional visual stimuli was significantly increased in the LPS condition. Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation. These findings may have implications for the putative role of inflammatory processes in the pathophysiology of depression.

  19. Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal-Free Conditions.

    Science.gov (United States)

    Lukovic, Dunja; Diez Lloret, Andrea; Stojkovic, Petra; Rodríguez-Martínez, Daniel; Perez Arago, Maria Amparo; Rodriguez-Jimenez, Francisco Javier; González-Rodríguez, Patricia; López-Barneo, José; Sykova, Eva; Jendelova, Pavla; Kostic, Jelena; Moreno-Manzano, Victoria; Stojkovic, Miodrag; Bhattacharya, Shomi S; Erceg, Slaven

    2017-04-01

    Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal-free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic. Stem Cells Translational Medicine 2017;6:1217-1226.

  20. The in vitro myelin formation in neurospheres of human neural stem cells

    Institute of Scientific and Technical Information of China (English)

    杨立业; 郑佳坤; 刘相名; 惠国桢; 郭礼和

    2003-01-01

    Objective: To explore the culture conditions of human neural stem cells and to investigate the ultrastructure of neurospheres.Methods: The cells from the embryonic human cortices were mechanically dissociated. N2 medium was adapted to culture and expand the cells. The cells were identified by immunocytochemistry and EM was applied to examine the ultrastructure of neurospheres.Results: The neural stem cells from human embryonic brains were successfully cultured and formed typical neurospheres in suspension, and most of the cells expressed vimentin, which was a marker for neural progenitor cells, and the cells could differentiate into neurons, astrocytes and oligodendrocytes. In vitro myelin formation in neurospheres were observed at an early stage of culture.Conclusions: Human neural stem cells can be cultured from embryonic brains, can form the typical neurospheres in suspension in vitro and have the ability of myelinating, and may be potential source for transplantation in treating myelin disorders.

  1. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Science.gov (United States)

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  2. Methods for derivation of multipotent neural crest cells derived from human pluripotent stem cells

    Science.gov (United States)

    Avery, John; Dalton, Stephen

    2016-01-01

    Summary Multipotent, neural crest cells (NCCs) produce a wide-range of cell types during embryonic development. This includes melanocytes, peripheral neurons, smooth muscle cells, osteocytes, chondrocytes and adipocytes. The protocol described here allows for highly-efficient differentiation of human pluripotent stem cells to a neural crest fate within 15 days. This is accomplished under feeder-free conditions, using chemically defined medium supplemented with two small molecule inhibitors that block glycogen synthase kinase 3 (GSK3) and bone morphogenic protein (BMP) signaling. This technology is well-suited as a platform to understand in greater detail the pathogenesis of human disease associated with impaired neural crest development/migration. PMID:25986498

  3. Evolution of Neural Computations: Mantis Shrimp and Human Color Decoding

    National Research Council Canada - National Science Library

    Zaidi, Qasim; Marshall, Justin; Thoen, Hanne; Conway, Bevil R

    2014-01-01

    Mantis shrimp and primates both possess good color vision, but the neural implementation in the two species is very different, a reflection of the largely unrelated evolutionary lineages of these creatures...

  4. The human factor: behavioral and neural correlates of humanized perception in moral decision making.

    Directory of Open Access Journals (Sweden)

    Jasminka Majdandžić

    Full Text Available The extent to which people regard others as full-blown individuals with mental states ("humanization" seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim's perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition or not (Neutral condition. In subsequent moral dilemmas, participants had to decide about sacrificing these persons' lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC. Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others' perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more "human-like" persons acting against purely utilitarian decisions.

  5. Declined Neural Efficiency in Cognitively Stable Human Immunodeficiency Virus Patients

    Science.gov (United States)

    Ernst, Thomas; Yakupov, Renat; Nakama, Helenna; Crocket, Grace; Cole, Michael; Watters, Michael; Ricardo-Dukelow, Mary Lynn; Chang, Linda

    2009-01-01

    Objective To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)–infected and in HIV-seronegative control (SN) participants over a 1-year period. Methods Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations. Results Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. PMID:19334060

  6. Neural correlates of induced motion perception in the human brain.

    Science.gov (United States)

    Takemura, Hiromasa; Ashida, Hiroshi; Amano, Kaoru; Kitaoka, Akiyoshi; Murakami, Ikuya

    2012-10-10

    A physically stationary stimulus surrounded by a moving stimulus appears to move in the opposite direction. There are similarities between the characteristics of this phenomenon of induced motion and surround suppression of directionally selective neurons in the brain. Here, functional magnetic resonance imaging was used to investigate the link between the subjective perception of induced motion and cortical activity. The visual stimuli consisted of a central drifting sinusoid surrounded by a moving random-dot pattern. The change in cortical activity in response to changes in speed and direction of the central stimulus was measured. The human cortical area hMT+ showed the greatest activation when the central stimulus moved at a fast speed in the direction opposite to that of the surround. More importantly, the activity in this area was the lowest when the central stimulus moved in the same direction as the surround and at a speed such that the central stimulus appeared to be stationary. The results indicate that the activity in hMT+ is related to perceived speed modulated by induced motion rather than to physical speed or a kinetic boundary. Early visual areas (V1, V2, V3, and V3A) showed a similar pattern; however, the relationship to perceived speed was not as clear as that in hMT+. These results suggest that hMT+ may be a neural correlate of induced motion perception and play an important role in contrasting motion signals in relation to their surrounding context and adaptively modulating our motion perception depending on the spatial context.

  7. Human neural progenitor cells promote photoreceptor survival in retinal explants.

    Science.gov (United States)

    Englund-Johansson, Ulrica; Mohlin, Camilla; Liljekvist-Soltic, Ingela; Ekström, Per; Johansson, Kjell

    2010-02-01

    Different types of progenitor and stem cells have been shown to provide neuroprotection in animal models of photoreceptor degeneration. The present study was conducted to investigate whether human neural progenitor cells (HNPCs) have neuroprotective properties on retinal explants models with calpain- and caspase-3-dependent photoreceptor cell death. In the first experiments, HNPCs in a feeder layer were co-cultured for 6 days either with postnatal rd1 mouse or normal rat retinas. Retinal histological sections were used to determine outer nuclear layer (ONL) thickness, and to detect the number of photoreceptors with labeling for calpain activity, cleaved caspase-3 and TUNEL. The ONL thickness of co-cultured rat and rd1 retinas was found to be almost 10% and 40% thicker, respectively, compared to controls. Cell counts of calpain activity, cleaved caspase-3 and TUNEL labeled photoreceptors in both models revealed a 30-50% decrease when co-cultured with HNPCs. The results represent significant increases of photoreceptor survival in the co-cultured retinas. In the second experiments, for an identification of putative survival factors, or a combination of them, a growth factor profile was performed on conditioned medium. The relative levels of various growth factors were analyzed by densitometric measurements of growth factor array membranes. Following growth factors were identified as most potential survival factors; granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GMCSF), insulin-like growth factor II (IGF-II), neurotrophic factor 3 (NT-3), placental growth factor (PIGF), transforming growth factors (TGF-beta1 and TGF-beta2) and vascular endothelial growth factor (VEGF-D). HNPCs protect both against calpain- and caspase-3-dependent photoreceptor cell death in the rd1 mouse and against caspase-3-dependent photoreceptor cell death in normal rat retinas in vitro. The protective effect is possibly achieved by a variety of

  8. Erythropoietin and the effect of oxygen during proliferation and differentiation of human neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Frech Moritz J

    2010-12-01

    Full Text Available Abstract Background Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. In the present study, we explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process. Results In this study we demonstrate that differentiation of human fetal neural progenitor cells under hypoxic conditions results in an increased neurogenesis. In addition, expansion and proliferation under lowered oxygen conditions also increased neuronal differentiation, although proliferation rates were not altered compared to normoxic conditions. Erythropoietin partially mimicked these hypoxic effects, as shown by an increase of the metabolic activity during differentiation and protection of differentiated cells from apoptosis. Conclusion These results provide evidence that hypoxia promotes the differentiation of human fetal neural progenitor cells, and identifies the involvement of erythropoietin during differentiation as well as different cellular mechanisms underlying the induction of differentiation mediated by lowered oxygen levels.

  9. In our own image? Emotional and neural processing differences when observing human-human vs human-robot interactions.

    Science.gov (United States)

    Wang, Yin; Quadflieg, Susanne

    2015-11-01

    Notwithstanding the significant role that human-robot interactions (HRI) will play in the near future, limited research has explored the neural correlates of feeling eerie in response to social robots. To address this empirical lacuna, the current investigation examined brain activity using functional magnetic resonance imaging while a group of participants (n = 26) viewed a series of human-human interactions (HHI) and HRI. Although brain sites constituting the mentalizing network were found to respond to both types of interactions, systematic neural variation across sites signaled diverging social-cognitive strategies during HHI and HRI processing. Specifically, HHI elicited increased activity in the left temporal-parietal junction indicative of situation-specific mental state attributions, whereas HRI recruited the precuneus and the ventromedial prefrontal cortex (VMPFC) suggestive of script-based social reasoning. Activity in the VMPFC also tracked feelings of eeriness towards HRI in a parametric manner, revealing a potential neural correlate for a phenomenon known as the uncanny valley. By demonstrating how understanding social interactions depends on the kind of agents involved, this study highlights pivotal sub-routes of impression formation and identifies prominent challenges in the use of humanoid robots. © The Author (2015). Published by Oxford University Press.

  10. Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2015-01-01

    Full Text Available Human embryonic stem cells (hESCs are able to proliferate in vitro indefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs. hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, including NURR1, PITX3, and EN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.

  11. Measuring human emotions with modular neural networks and computer vision based applications

    Directory of Open Access Journals (Sweden)

    Veaceslav Albu

    2015-05-01

    Full Text Available This paper describes a neural network architecture for emotion recognition for human-computer interfaces and applied systems. In the current research, we propose a combination of the most recent biometric techniques with the neural networks (NN approach for real-time emotion and behavioral analysis. The system will be tested in real-time applications of customers' behavior for distributed on-land systems, such as kiosks and ATMs.

  12. 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.

  13. Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans.

    NARCIS (Netherlands)

    Hermans, E.J.; Ramsey, N.F.; Honk, J van

    2008-01-01

    BACKGROUND: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between

  14. Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception

    Science.gov (United States)

    Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness. PMID:28936171

  15. Neural Markers of Responsiveness to the Environment in Human Sleep

    DEFF Research Database (Denmark)

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai

    2016-01-01

    could be related to modulation in sleep depth. InREMsleep, however, this relationship was reversed.Wetherefore propose that, in REM sleep, endogenously generated processes compete with the processing of external input. Sleep can thus be seen as a self-regulated process in which external information can......Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed...... by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep...

  16. Evolution of neural computations: Mantis shrimp and human color decoding

    OpenAIRE

    Qasim Zaidi; Justin Marshall; Hanne Thoen; Conway, Bevil R.

    2014-01-01

    Mantis shrimp and primates both possess good color vision, but the neural implementation in the two species is very different, a reflection of the largely unrelated evolutionary lineages of these creatures. Mantis shrimp have scanning compound eyes with 12 classes of photoreceptors, and have evolved a system to decode color information at the front-end of the sensory stream. Primates have image-focusing eyes with three classes of cones, and decode color further along the visual-processing hie...

  17. Capacity of Human Dental Follicle Cells to Differentiate into Neural Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Shingo Kanao

    2017-01-01

    Full Text Available The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. Human dental follicle cells (hDFCs have the capacity to commit to differentiation into multiple cell types. Here we investigated the capacity of hDFCs to differentiate into neural cells and the efficiency of a two-step strategy involving floating neurosphere-like bodies for neural differentiation. Undifferentiated hDFCs showed a spindle-like morphology and were positive for neural markers such as nestin, β-III-tubulin, and S100β. The cellular morphology of several cells was neuronal-like including branched dendrite-like processes and neurites. Next, hDFCs were used for neurosphere formation in serum-free medium containing basic fibroblast growth factor, epidermal growth factor, and B27 supplement. The number of cells with neuronal-like morphology and that were strongly positive for neural markers increased with sphere formation. Gene expression of neural markers also increased in hDFCs with sphere formation. Next, gene expression of neural markers was examined in hDFCs during neuronal differentiation after sphere formation. Expression of Musashi-1 and Musashi-2, MAP2, GFAP, MBP, and SOX10 was upregulated in hDFCs undergoing neuronal differentiation via neurospheres, whereas expression of nestin and β-III-tubulin was downregulated. In conclusion, hDFCs may be another optimal source of neural/glial cells for cell-based therapies to treat neurological diseases.

  18. Adult human neural stem cell therapeutics: Currentdevelopmental status and prospect

    Institute of Scientific and Technical Information of China (English)

    Hyun Nam; Kee-Hang Lee; Do-Hyun Nam; Kyeung Min Joo

    2015-01-01

    Over the past two decades, regenerative therapies usingstem cell technologies have been developed for variousneurological diseases. Although stem cell therapy is anattractive option to reverse neural tissue damage and torecover neurological deficits, it is still under developmentso as not to show significant treatment effects in clinicalsettings. In this review, we discuss the scientific andclinical basics of adult neural stem cells (aNSCs), andtheir current developmental status as cell therapeuticsfor neurological disease. Compared with other typesof stem cells, aNSCs have clinical advantages, suchas limited proliferation, inborn differentiation potentialinto functional neural cells, and no ethical issues. Inspite of the merits of aNSCs, difficulties in the isolationfrom the normal brain, and in the in vitro expansion,have blocked preclinical and clinical study using aNSCs.However, several groups have recently developed noveltechniques to isolate and expand aNSCs from normaladult brains, and showed successful applications ofaNSCs to neurological diseases. With new technologiesfor aNSCs and their clinical strengths, previous hurdlesin stem cell therapies for neurological diseases could beovercome, to realize clinically efficacious regenerativestem cell therapeutics.

  19. An improved protocol that induces human embryonic stem cells to differentiate into neural cells in vitro.

    Science.gov (United States)

    Zhou, Jun-Mei; Chu, Jian-Xin; Chen, Xue-Jin

    2008-01-01

    Human embryonic stem (ES) cells have the capacity for self-renewal and are able to differentiate into any cell type. However, obtaining high-efficient neural differentiation from human ES cells remains a challenge. This study describes an improved 4-stage protocol to induce a human ES cell line derived from a Chinese population to differentiate into neural cells. At the first stage, embryonic bodies (EBs) were formed in a chemically-defined neural inducing medium rather than in traditional serum or serum-replacement medium. At the second stage, rosette-like structures were formed. At the third stage, the rosette-like structures were manually selected rather than enzymatically digested to form floating neurospheres. At the fourth stage, the neurospheres were further differentiated into neurons. The results show that, at the second stage, the rate of the formation of rosette-like structures from EBs induced by noggin was 88+/-6.32%, higher than that of retinoic acid 55+/-5.27%. Immunocytochemistry staining was used to confirm the neural identity of the cells. These results show a major improvement in obtaining efficient neural differentiation of human ES cells.

  20. Codevelopmental learning between human and humanoid robot using a dynamic neural-network model.

    Science.gov (United States)

    Tani, Jun; Nishimoto, Ryu; Namikawa, Jun; Ito, Masato

    2008-02-01

    This paper examines characteristics of interactive learning between human tutors and a robot having a dynamic neural-network model, which is inspired by human parietal cortex functions. A humanoid robot, with a recurrent neural network that has a hierarchical structure, learns to manipulate objects. Robots learn tasks in repeated self-trials with the assistance of human interaction, which provides physical guidance until the tasks are mastered and learning is consolidated within the neural networks. Experimental results and the analyses showed the following: 1) codevelopmental shaping of task behaviors stems from interactions between the robot and a tutor; 2) dynamic structures for articulating and sequencing of behavior primitives are self-organized in the hierarchically organized network; and 3) such structures can afford both generalization and context dependency in generating skilled behaviors.

  1. Comparison of different protocols for neural differentiation of human induced pluripotent stem cells.

    Science.gov (United States)

    Salimi, Ali; Nadri, Samad; Ghollasi, Marzieh; Khajeh, Khosro; Soleimani, Masoud

    2014-03-01

    Although embryonic stem cells (ESCs) have enormous potentials due to their pluripotency, their therapeutic use is limited by ethical, biological and safety issues. Compared to ESCs, induced pluripotent stem cells (iPSCs) can be obtained from mouse or human fibroblasts by reprogramming. Numerous studies have established many protocols for differentiation of human iPSCs (hiPSCs) into neural lineages. However, the low differentiation efficiency of such protocols motivates researchers to design new protocols for high yield differentiation. Herein, we compared neural differentiation potential of three induction media for conversion of hiPSCs into neural lineages. In this study, hiPSCs-derived embryoid bodies were plated on laminin coated dishes and were treated with three induction media including (1) bFGF, EGF (2) RA and (3) forskolin, IBMX. Immunofluorescence staining and quantitative real-time PCR (qPCR) analysis were used to detect the expression of neural genes and proteins. qPCR analysis showed that the expression of neural genes in differentiated hiPSCs in forskolin, IBMX supplemented media was significantly higher than undifferentiated cells and those in induction media containing bFGF, EGF or RA. In conclusion, our results indicated a successful establishment protocol with high efficiency for differentiation of hiPSCs into neural lineages.

  2. CXCR4 activation promotes differentiation of human embryonic stem cells to neural stem cells.

    Science.gov (United States)

    Zhang, Lijun; Hua, Qiuhong; Tang, Kaiyi; Shi, Changjie; Xie, Xin; Zhang, Ru

    2016-11-19

    G protein-coupled receptors (GPCRs) are involved in many fundamental cellular responses such as growth, death, movement, transcription and excitation. Their roles in human stem cell neural specialization are not well understood. In this study, we aimed to identify GPCRs that may play a role in the differentiation of human embryonic stem cells (hESCs) to neural stem cells (NSCs). Using a feeder-free hESC neural differentiation protocol, we found that the expression of several chemokine receptors changed dramatically during the hESC/NSC transition. Especially, the expression of CXCR4 increased approximately 50 folds in NSCs compared to the original hESCs. CXCR4 agonist SDF-1 promoted, whereas the antagonist AMD3100 delayed the neural induction process. In consistence with antagonizing CXCR4, knockdown of CXCR4 in hESCs also blocked the neural induction and cells with reduced CXCR4 were rarely positive for Nestin and Sox1-staining. Taken together, our results suggest that CXCR4 is involved in the neural induction process of hESC and it might be considered as a target to facilitate NSC production from hESCs in regenerative medicine.

  3. 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.

  4. Monitoring the differentiation and migration patterns of neural cells derived from human embryonic stem cells using a microfluidic culture system.

    Science.gov (United States)

    Lee, Nayeon; Park, Jae Woo; Kim, Hyung Joon; Yeon, Ju Hun; Kwon, Jihye; Ko, Jung Jae; Oh, Seung-Hun; Kim, Hyun Sook; Kim, Aeri; Han, Baek Soo; Lee, Sang Chul; Jeon, Noo Li; Song, Jihwan

    2014-06-01

    Microfluidics can provide unique experimental tools to visualize the development of neural structures within a microscale device, which is followed by guidance of neurite growth in the axonal isolation compartment. We utilized microfluidics technology to monitor the differentiation and migration of neural cells derived from human embryonic stem cells (hESCs). We co-cultured hESCs with PA6 stromal cells, and isolated neural rosette-like structures, which subsequently formed neurospheres in suspension culture. Tuj1-positive neural cells, but not nestin-positive neural precursor cells (NPCs), were able to enter the microfluidics grooves (microchannels), suggesting that neural cell-migratory capacity was dependent upon neuronal differentiation stage. We also showed that bundles of axons formed and extended into the microchannels. Taken together, these results demonstrated that microfluidics technology can provide useful tools to study neurite outgrowth and axon guidance of neural cells, which are derived from human embryonic stem cells.

  5. Seeing human: distinct and overlapping neural signatures associated with two forms of dehumanization.

    Science.gov (United States)

    Jack, Anthony I; Dawson, Abigail J; Norr, Megan E

    2013-10-01

    The process of dehumanization, or thinking of others as less than human, is a phenomenon with significant societal implications. According to Haslam's (2006) model, two concepts of humanness derive from comparing humans with either animals or machines: individuals may be dehumanized by likening them to either animals or machines, or humanized by emphasizing differences from animals or machines. Recent work in cognitive neuroscience emphasizes understanding cognitive processes in terms of interactions between distributed cortical networks. It has been found that reasoning about internal mental states is associated with activation of the default mode network (DMN) and deactivation of the task positive network (TPN); whereas reasoning about mechanical processes produces the opposite pattern. We conducted two neuroimaging studies. The first examined the neural bases of dehumanization and its relation to these two brain networks, using images and voice-over social narratives which either implicitly contrasted or implicitly likened humans to either animals or machines. The second study addressed a discrepancy between findings from the first study and prior work on the neural correlates of dehumanization: using a design similar to prior work we examined neural responses to pictures of humans, animals and machines, presented without any social context. In both studies, human and humanizing conditions were associated with relatively high activity in the DMN and relatively low activity in the TPN. However, the non-human and dehumanizing conditions deviated in different ways: they demonstrated more marked changes either in the DMN or in the TPN. Notably, differences between the animal dehumanizing and humanizing conditions were most evident in regions associated with mechanistic reasoning, not in the mentalizing network. Conjunction analysis of contrasts from both paradigms revealed that only one region was consistently more active when participants saw human, a medial

  6. Reward motivation accelerates the onset of neural novelty signals in humans to 85 milliseconds.

    Science.gov (United States)

    Bunzeck, Nico; Doeller, Christian F; Fuentemilla, Lluis; Dolan, Raymond J; Duzel, Emrah

    2009-08-11

    The neural responses that distinguish novel from familiar items in recognition memory tasks are remarkably fast in both humans and nonhuman primates. In humans, the earliest onsets of neural novelty effects emerge at about approximately 150-200 ms after stimulus onset. However, in recognition memory studies with nonhuman primates, novelty effects can arise at as early as 70-80 ms. Here, we address the possibility that this large species difference in onset latencies is caused experimentally by the necessity of using reward reinforcement to motivate the detection of novel or familiar items in nonhuman primates but not in humans. Via magnetoencephalography in humans, we show in two experiments that the onset of neural novelty signals is accelerated from approximately 200 ms to approximately 85 ms if correct recognition memory for either novel or familiar items is rewarded. Importantly, this acceleration is independent of whether the detection of the novel or the familiar scenes is rewarded. Furthermore, this early novelty effect contributed to memory retrieval because neural reward responses, which were contingent upon novelty detection, followed approximately 100 ms later. Thus, under the contextual influence of reward motivation, behaviorally relevant novelty signals emerge much faster than previously held possible in humans.

  7. ARTIFICIAL NEURAL NETWORK IN FACE DETECTION HUMAN ON DIGITAL IMAGE

    Directory of Open Access Journals (Sweden)

    Abdusamad Al-Marghilani

    2013-01-01

    Full Text Available Method itself is proposed to be formed by series of filters. Each filter is an independent method of detection and allows you to cut off quickly the regions that do not contain the face’s areas. For this purpose some of the different characteristics of the object are used in addition each subsequent part processes only promising areas of image which were obtained from the previous parts of the method. It has been tested by means of CMU/MIT test set. Analogy of speed and quality detection. There are two modifications to the classic use of neural networks in face detection. First the neural network only tests candidate regions for the face, thus dropping the search space. Secondly the window size is used in network scanning the input image is adaptive and depends on the size of the region of the candidate are implemented in Using Mat lab. The analysis of detection quality of a new method in comparison with the algorithm. The experimental results show that the proposed method the detection method, based on rectangular primitives, in quality. The proposed method, tested on a standard Test set, has surpassed all known methods in speed and quality of detection. Our approach without pre-treatment is not required because the normalization is enabled directly in the weights of the input network.

  8. Generation and properties of a new human ventral mesencephalic neural stem cell line

    DEFF Research Database (Denmark)

    Villa, Ana; Liste, Isabel; Courtois, Elise T

    2009-01-01

    Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro....... Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal...... derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing....

  9. Non-coding RNAs in pluripotency and neural differentiation of human pluripotent stem cells

    Science.gov (United States)

    Lukovic, Dunja; Moreno-Manzano, Victoria; Klabusay, Martin; Stojkovic, Miodrag; Bhattacharya, Shomi S.; Erceg, Slaven

    2014-01-01

    Several studies have demonstrated the important role of non-coding RNAs as regulators of posttranscriptional processes, including stem cells self-renewal and neural differentiation. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (ihPSCs) show enormous potential in regenerative medicine due to their capacity to differentiate to virtually any type of cells of human body. Deciphering the role of non-coding RNAs in pluripotency, self-renewal and neural differentiation will reveal new molecular mechanisms involved in induction and maintenances of pluripotent state as well as triggering these cells toward clinically relevant cells for transplantation. In this brief review we will summarize recently published studies which reveal the role of non-coding RNAs in pluripotency and neural differentiation of hESCs and ihPSC. PMID:24860598

  10. Application of structured support vector machine backpropagation to a convolutional neural network for human pose estimation.

    Science.gov (United States)

    Witoonchart, Peerajak; Chongstitvatana, Prabhas

    2017-08-01

    In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer. Thus, we obtain a new type of convolutional neural network called an Structured SVM convolutional neural network, which we applied to the human pose estimation problem. This new neural network can be used as the final layers in deep learning. Our method jointly learns the structural model parameters and the appearance model parameters. We implemented our method as a new layer in the existing Caffe library. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells

    Science.gov (United States)

    Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

    2016-01-01

    Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol’s effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event

  12. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  13. Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues.

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Sharma, Anil; Agirman, Gulistan; Rogister, Bernard; Foguenne, Jacques; Lallemend, François; Gothot, André; Wislet, Sabine

    2017-01-01

    Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow.

  14. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke;

    2011-01-01

    To investigate the feasibility of transplanting human neural progenitor cells (hNPCs) to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal ve...... that modulation of host immunity is likely necessary for prolonged xenograft survival in this model....

  15. The efficiency of expressing human neprilysin by using lentiviral vector transduction in neural stem cells

    Institute of Scientific and Technical Information of China (English)

    黄文

    2013-01-01

    Objective To study the transduction efficiency of expressing human neprilysin by using lentiviral(Lenti-NEP) in mouse embryonic neural stem cells(NSC) in vitro. Methods Primary NSC were harvested from C57BL/6J pregnant mouse at embryonic day

  16. Evolution of Neural Computations: Mantis Shrimp and Human Color Decoding

    Directory of Open Access Journals (Sweden)

    Qasim Zaidi

    2014-10-01

    Full Text Available Mantis shrimp and primates both possess good color vision, but the neural implementation in the two species is very different, a reflection of the largely unrelated evolutionary lineages of these creatures. Mantis shrimp have scanning compound eyes with 12 classes of photoreceptors, and have evolved a system to decode color information at the front-end of the sensory stream. Primates have image-focusing eyes with three classes of cones, and decode color further along the visual-processing hierarchy. Despite these differences, we report a fascinating parallel between the computational strategies at the color-decoding stage in the brains of stomatopods and primates. Both species appear to use narrowly tuned cells that support interval decoding color identification.

  17. Evolution of neural computations: Mantis shrimp and human color decoding.

    Science.gov (United States)

    Zaidi, Qasim; Marshall, Justin; Thoen, Hanne; Conway, Bevil R

    2014-01-01

    Mantis shrimp and primates both possess good color vision, but the neural implementation in the two species is very different, a reflection of the largely unrelated evolutionary lineages of these creatures. Mantis shrimp have scanning compound eyes with 12 classes of photoreceptors, and have evolved a system to decode color information at the front-end of the sensory stream. Primates have image-focusing eyes with three classes of cones, and decode color further along the visual-processing hierarchy. Despite these differences, we report a fascinating parallel between the computational strategies at the color-decoding stage in the brains of stomatopods and primates. Both species appear to use narrowly tuned cells that support interval decoding color identification.

  18. Defining properties of neural crest-derived progenitor cells from the apex of human developing tooth.

    Science.gov (United States)

    Degistirici, Ozer; Jaquiery, Claude; Schönebeck, Bodo; Siemonsmeier, Jürgen; Götz, Werner; Martin, Ivan; Thie, Michael

    2008-02-01

    The connective tissue of the human tooth arises from cells that are derived from the cranial neural crest and, thus, are termed as "ectomesenchymal cells." Here, cells being located in a pad-like tissue adjacent to the apex of the developing tooth, which we designated the third molar pad, were separated by the microexplant technique. When outgrowing from the explant, dental neural crest-derived progenitor cells (dNC-PCs) adhered to plastic, proliferated steadily, and displayed a fibroblast-like morphology. At the mRNA level, dNC-PCs expressed neural crest marker genes like Sox9, Snail1, Snail2, Twist1, Msx2, and Dlx6. Cytofluorometric analysis indicated that cells were positive for CD49d (alpha4 integrin), CD56 (NCAM), and PDGFRalpha, while negative for CD31, CD34, CD45, and STRO-1. dNC-PCs could be differentiated into neurogenic, chondrogenic, and osteogenic lineages and were shown to produce bone matrix in athymic mice. These results demonstrate that human third molar pad possesses neural crest-derived cells that represent multipotent stem/progenitor cells. As a rather large amount of dNC-PCs could be obtained from each single third molar, cells may be used to regenerate a wide range of tissues within the craniofacial region of humans.

  19. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?

    Science.gov (United States)

    Yoon, Hyung Ho; Min, Joongkee; Shin, Nari; Kim, Yong Hwan; Kim, Jin-Mo; Hwang, Yu-Shik; Suh, Jun-Kyo Francis; Hwang, Onyou; Jeon, Sang Ryong

    2013-05-05

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [(18)F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

  20. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?

    Institute of Scientific and Technical Information of China (English)

    Hyung Ho Yoon; Joongkee Min; Nari Shin; Yong Hwan Kim; Jin-Mo Kim; Yu-Shik Hwang; Jun-Kyo Francis Suh; Onyou Hwang; Sang Ryong Jeon

    2013-01-01

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18 F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

  1. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...... differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......-culture, large numbers of tyrosine hydroxylase (TH)-immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH-positive, contrasting a few TH-positive cells (

  2. Neural correlates of mental state decoding in human adults: an event-related potential study.

    Science.gov (United States)

    Sabbagh, Mark A; Moulson, Margaret C; Harkness, Kate L

    2004-04-01

    Successful negotiation of human social interactions rests on having a theory of mind - an understanding of how others' behaviors can be understood in terms of internal mental states, such as beliefs, desires, intentions, and emotions. A core theory-of-mind skill is the ability to decode others' mental states on the basis of observable information, such as facial expressions. Although several recent studies have focused on the neural correlates of reasoning about mental states, no research has addressed the question of what neural systems underlie mental state decoding. We used dense-array event-related potentials (ERP) to show that decoding mental states from pictures of eyes is associated with an N270-400 component over inferior frontal and anterior temporal regions of the right hemisphere. Source estimation procedures suggest that orbitofrontal and medial temporal regions may underlie this ERP effect. These findings suggest that different components of everyday theory-of-mind skills may rely on dissociable neural mechanisms.

  3. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    Science.gov (United States)

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G.; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-01-01

    Summary Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread. PMID:25418723

  4. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    Directory of Open Access Journals (Sweden)

    Usue Etxaniz

    2014-11-01

    Full Text Available Resident neural precursor cells (NPCs have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+ and perivascular (CD56− cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  5. Neural-competent cells of adult human dermis belong to the Schwann lineage.

    Science.gov (United States)

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-11-11

    Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  6. Human Inspired Self-developmental Model of Neural Network (HIM): Introducing Content/Form Computing

    Science.gov (United States)

    Krajíček, Jiří

    This paper presents cross-disciplinary research between medical/psychological evidence on human abilities and informatics needs to update current models in computer science to support alternative methods for computation and communication. In [10] we have already proposed hypothesis introducing concept of human information model (HIM) as cooperative system. Here we continue on HIM design in detail. In our design, first we introduce Content/Form computing system which is new principle of present methods in evolutionary computing (genetic algorithms, genetic programming). Then we apply this system on HIM (type of artificial neural network) model as basic network self-developmental paradigm. Main inspiration of our natural/human design comes from well known concept of artificial neural networks, medical/psychological evidence and Sheldrake theory of "Nature as Alive" [22].

  7. Neural speech recognition: continuous phoneme decoding using spatiotemporal representations of human cortical activity

    Science.gov (United States)

    Moses, David A.; Mesgarani, Nima; Leonard, Matthew K.; Chang, Edward F.

    2016-10-01

    Objective. The superior temporal gyrus (STG) and neighboring brain regions play a key role in human language processing. Previous studies have attempted to reconstruct speech information from brain activity in the STG, but few of them incorporate the probabilistic framework and engineering methodology used in modern speech recognition systems. In this work, we describe the initial efforts toward the design of a neural speech recognition (NSR) system that performs continuous phoneme recognition on English stimuli with arbitrary vocabulary sizes using the high gamma band power of local field potentials in the STG and neighboring cortical areas obtained via electrocorticography. Approach. The system implements a Viterbi decoder that incorporates phoneme likelihood estimates from a linear discriminant analysis model and transition probabilities from an n-gram phonemic language model. Grid searches were used in an attempt to determine optimal parameterizations of the feature vectors and Viterbi decoder. Main results. The performance of the system was significantly improved by using spatiotemporal representations of the neural activity (as opposed to purely spatial representations) and by including language modeling and Viterbi decoding in the NSR system. Significance. These results emphasize the importance of modeling the temporal dynamics of neural responses when analyzing their variations with respect to varying stimuli and demonstrate that speech recognition techniques can be successfully leveraged when decoding speech from neural signals. Guided by the results detailed in this work, further development of the NSR system could have applications in the fields of automatic speech recognition and neural prosthetics.

  8. Changes of neural markers expression during late neurogenic differentiation of human adipose-derived stem cells

    Science.gov (United States)

    Razavi, Shahnaz; Khosravizadeh, Zahra; Bahramian, Hamid; Kazemi, Mohammad

    2015-01-01

    Background: Different studies have been done to obtain sufficient number of neural cells for treatment of neurodegenerative diseases, spinal cord, and traumatic brain injury because neural stem cells are limited in central nerves system. Recently, several studies have shown that adipose-derived stem cells (ADSCs) are the appropriate source of multipotent stem cells. Furthermore, these cells are found in large quantities. The aim of this study was an assessment of proliferation and potential of neurogenic differentiation of ADSCs with passing time. Materials and Methods: Neurosphere formation was used for neural induction in isolated human ADSCs (hADSCs). The rate of proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and potential of neural differentiation of induced hADSCs was evaluated by immunocytochemical and real-time reverse transcription polymerase chain reaction analysis after 10 and 14 days post-induction. Results: The rate of proliferation of induced hADSCs increased after 14 days while the expression of nestin, glial fibrillary acidic protein, and microtubule-associated protein 2 was decreased with passing time during neurogenic differentiation. Conclusion: These findings showed that the proliferation of induced cells increased with passing time, but in early neurogenic differentiation of hADSCs, neural expression was higher than late of differentiation. Thus, using of induced cells in early differentiation may be suggested for in vivo application. PMID:26605238

  9. Derivation of Neural Precursor Cells from Human Embryonic Stem Cells for DNA Methylomic Analysis.

    Science.gov (United States)

    Roubal, Ivan; Park, Sun Joo; Kim, Yong

    2016-01-01

    Embryonic stem cells are self-renewing pluripotent cells with competency to differentiate into all three-germ lineages. Many studies have demonstrated the importance of genetic and epigenetic molecular mechanisms in the maintenance of self-renewal and pluripotency. Stem cells are under unique molecular and cellular regulations different from somatic cells. Proper regulation should be ensured to maintain their unique self-renewal and undifferentiated characteristics. Understanding key mechanisms in stem cell biology will be important for the successful application of stem cells for regenerative therapeutic medicine. More importantly practical use of stem cells will require our knowledge on how to properly direct and differentiate stem cells into the necessary type of cells. Embryonic stem cells and adult stem cells have been used as study models to unveil molecular and cellular mechanisms in various signaling pathways. They are especially beneficial to developmental studies where in vivo molecular/cellular study models are not available. We have derived neural stem cells from human embryonic stem cells as a model to study the effect of teratogen in neural development. We have tested commercial neural differentiation system and successfully derived neural precursor cells exhibiting key molecular features of neural stem cells, which will be useful for experimental application.

  10. On the nature and evolution of the neural bases of human language.

    Science.gov (United States)

    Lieberman, Philip

    2002-01-01

    The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

  11. On the nature and evolution of the neural bases of human language

    Science.gov (United States)

    Lieberman, Philip

    2002-01-01

    The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

  12. On the nature and evolution of the neural bases of human language

    Science.gov (United States)

    Lieberman, Philip

    2002-01-01

    The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

  13. Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

    Science.gov (United States)

    Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

    2017-07-01

    Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

  14. Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans

    Directory of Open Access Journals (Sweden)

    Chunyue Miao

    2016-10-01

    Full Text Available Neural tube defects (NTDs are severe malformations of the central nervous system caused by complex genetic and environmental factors. Among genes involved in NTD, cilia-related genes have been well defined and found to be essential for the completion of neural tube closure (NTC. We have carried out next-generation sequencing on target genes in 373 NTDs and 222 healthy controls, and discovered eight disease-specific rare mutations in cilia-related gene DNAAF1. DNAAF1 plays a central role in cytoplasmic preassembly of distinct dynein-arm complexes, and is expressed in some key tissues involved in neural system development, such as neural tube, floor plate, embryonic node, and brain ependyma epithelial cells in zebrafish and mouse. Therefore, we evaluated the expression and functions of mutations in DNAAF1 in transfected cells to analyze the potential correlation of these mutants to NTDs in humans. One rare frameshift mutation (p.Gln341Argfs*10 resulted in significantly diminished DNAAF1 protein expression, compared to the wild type. Another mutation, p.Lys231Gln, disrupted cytoplasmic preassembly of the dynein-arm complexes in cellular assay. Furthermore, results from NanoString assay on mRNA from NTD samples indicated that DNAAF1 mutants altered the expression level of NTC-related genes. Altogether, these findings suggest that the rare mutations in DNAAF1 may contribute to the susceptibility for NTDs in humans.

  15. Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

    Science.gov (United States)

    Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

    2015-09-15

    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

  16. Altered temporal dynamics of neural adaptation in the aging human auditory cortex.

    Science.gov (United States)

    Herrmann, Björn; Henry, Molly J; Johnsrude, Ingrid S; Obleser, Jonas

    2016-09-01

    Neural response adaptation plays an important role in perception and cognition. Here, we used electroencephalography to investigate how aging affects the temporal dynamics of neural adaptation in human auditory cortex. Younger (18-31 years) and older (51-70 years) normal hearing adults listened to tone sequences with varying onset-to-onset intervals. Our results show long-lasting neural adaptation such that the response to a particular tone is a nonlinear function of the extended temporal history of sound events. Most important, aging is associated with multiple changes in auditory cortex; older adults exhibit larger and less variable response magnitudes, a larger dynamic response range, and a reduced sensitivity to temporal context. Computational modeling suggests that reduced adaptation recovery times underlie these changes in the aging auditory cortex and that the extended temporal stimulation has less influence on the neural response to the current sound in older compared with younger individuals. Our human electroencephalography results critically narrow the gap to animal electrophysiology work suggesting a compensatory release from cortical inhibition accompanying hearing loss and aging.

  17. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  18. A Study for the Feature Selection to Identify GIEMSA-Stained Human Chromosomes Based on Artificial Neural Network

    Science.gov (United States)

    2007-11-02

    neural network (ANN) has been adopted for the human chromosome classification. It is important to select optimum features for training neural network...Many studies for computer-based chromosome analysis have shown that it is possible to classify chromosomes into 24 subgroups. In addition, artificial

  19. A three-dimensional human neural cell culture model of Alzheimer's disease.

    Science.gov (United States)

    Choi, Se Hoon; Kim, Young Hye; Hebisch, Matthias; Sliwinski, Christopher; Lee, Seungkyu; D'Avanzo, Carla; Chen, Hechao; Hooli, Basavaraj; Asselin, Caroline; Muffat, Julien; Klee, Justin B; Zhang, Can; Wainger, Brian J; Peitz, Michael; Kovacs, Dora M; Woolf, Clifford J; Wagner, Steven L; Tanzi, Rudolph E; Kim, Doo Yeon

    2014-11-13

    Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell

  20. Optimal Recognition Method of Human Activities Using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Oniga Stefan

    2015-12-01

    Full Text Available The aim of this research is an exhaustive analysis of the various factors that may influence the recognition rate of the human activity using wearable sensors data. We made a total of 1674 simulations on a publically released human activity database by a group of researcher from the University of California at Berkeley. In a previous research, we analyzed the influence of the number of sensors and their placement. In the present research we have examined the influence of the number of sensor nodes, the type of sensor node, preprocessing algorithms, type of classifier and its parameters. The final purpose is to find the optimal setup for best recognition rates with lowest hardware and software costs.

  1. The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

    Science.gov (United States)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

  2. Deep Neural Networks as a Computational Model for Human Shape Sensitivity

    Science.gov (United States)

    Op de Beeck, Hans P.

    2016-01-01

    Theories of object recognition agree that shape is of primordial importance, but there is no consensus about how shape might be represented, and so far attempts to implement a model of shape perception that would work with realistic stimuli have largely failed. Recent studies suggest that state-of-the-art convolutional ‘deep’ neural networks (DNNs) capture important aspects of human object perception. We hypothesized that these successes might be partially related to a human-like representation of object shape. Here we demonstrate that sensitivity for shape features, characteristic to human and primate vision, emerges in DNNs when trained for generic object recognition from natural photographs. We show that these models explain human shape judgments for several benchmark behavioral and neural stimulus sets on which earlier models mostly failed. In particular, although never explicitly trained for such stimuli, DNNs develop acute sensitivity to minute variations in shape and to non-accidental properties that have long been implicated to form the basis for object recognition. Even more strikingly, when tested with a challenging stimulus set in which shape and category membership are dissociated, the most complex model architectures capture human shape sensitivity as well as some aspects of the category structure that emerges from human judgments. As a whole, these results indicate that convolutional neural networks not only learn physically correct representations of object categories but also develop perceptually accurate representational spaces of shapes. An even more complete model of human object representations might be in sight by training deep architectures for multiple tasks, which is so characteristic in human development. PMID:27124699

  3. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  4. Signs of noise-induced neural degeneration in humans

    DEFF Research Database (Denmark)

    Holtegaard, Pernille; Olsen, Steen Østergaard

    2015-01-01

    Animal studies demonstrated that noise exposure causes a primary and selective loss of auditory-nerve fibres with low spontaneous firing rate. This neuronal impairment, if also present in humans, can be assumed to affect the processing of supra-threshold stimuli, especially in the presence...... thresholds within the “normal” range perform poorer, in terms of their speech recognition threshold in noise (SRTN), and (2) if auditory brainstem responses (ABR) reveal lower amplitude of wave I in the noise-exposed listeners. A test group of noise/music-exposed individuals and a control group were...

  5. Neural Dynamics Underlying Target Detection in the Human Brain

    Science.gov (United States)

    Bansal, Arjun K.; Madhavan, Radhika; Agam, Yigal; Golby, Alexandra; Madsen, Joseph R.

    2014-01-01

    Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses. PMID:24553944

  6. Human Neural Cells Transiently Express Reelin during Olfactory Placode Development.

    Directory of Open Access Journals (Sweden)

    M Cristina Antal

    Full Text Available Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS 15 to gestational week (GW 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed.

  7. Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures

    Directory of Open Access Journals (Sweden)

    V. Bleu Knight

    2017-01-01

    Full Text Available Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

  8. The neural code for face orientation in the human fusiform face area.

    Science.gov (United States)

    Ramírez, Fernando M; Cichy, Radoslaw M; Allefeld, Carsten; Haynes, John-Dylan

    2014-09-01

    Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA.

  9. Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures

    Science.gov (United States)

    Knight, V. Bleu

    2017-01-01

    Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

  10. Comparison of S-nitrosoglutathione- and staurosporine-induced apoptosis in human neural cells.

    Science.gov (United States)

    Sodja, Caroline; Ribecco-Lutkiewicz, Maria; Haukenfrers, Julie; Merchant, Fahar; Costain, Willard J; Bani-Yaghoub, Mahmud

    2014-12-01

    S-nitrosoglutathione (GSNO) is an endogenously produced S-nitrosylating compound that controls the function of various proteins. While a number of rodent cell lines have been used to study GSNO-induced apoptosis, the mechanisms of action remain to be evaluated in human cells and in parallel with other common apoptosis-inducing agents. In this study, we compared the pro-apoptotic effects of GSNO and staurosporine (STS) on human neural progenitors (NT2, hNP1) and neuroblasts (SH-SY5Y). We show that these cells exhibit comparable levels of susceptibility to GSNO- and STS-induced apoptotic cell death, as demonstrated by condensed nuclei and CASP3 activation. Mechanistic differences in apoptotic responses were observed as differential patterns of DNA fragmentation and levels of BAX, BCL-XL, CASP8, and p-ERK in response to GSNO and STS treatment. Mitochondrial membrane potential analysis revealed that NT2 and hNP1 cells, but not SH-SY5Y cells, undergo mitochondrial hyperpolarization in response to short-term exposure to STS prior to undergoing subsequent depolarization. This is the first study to report differences in apoptotic responses to GSNO and STS in 3 complementary human neural cell lines. Furthermore, these cells represent useful tools in cell pharmacological paradigms in which susceptibility to apoptosis-inducing agents needs to be assessed at different stages of neural cell fate commitment and differentiation.

  11. Delineating Neural Structures of Developmental Human Brains with Diffusion Tensor Imaging

    Directory of Open Access Journals (Sweden)

    Hao Huang

    2010-01-01

    Full Text Available The human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is a simple tubular structure. Revealing detailed anatomy at different stages of brain development not only aids in understanding this highly ordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. However, anatomical studies of human brain development during the fetal period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor imaging (DTI measures water diffusion to delineate the underlying neural structures. The high contrasts derived from DTI can be used to establish the brain atlas. With DTI tractography, coherent neural structures, such as white matter tracts, can be three-dimensionally reconstructed. The primary eigenvector of the diffusion tensor can be further explored to characterize microstructures in the cerebral wall of the developmental brains. In this mini-review, the application of DTI in order to reveal the structures of developmental fetal brains has been reviewed in the above-mentioned aspects. The fetal brain DTI provides a unique insight for delineating the neural structures in both macroscopic and microscopic levels. The resultant DTI database will provide structural guidance for the developmental study of human fetal brains in basic neuroscience, and reference standards for diagnostic radiology of premature newborns.

  12. Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells

    Science.gov (United States)

    Zhao, Zhu-ran; Yu, Wei-dong; Shi, Cheng; Liang, Rong; Chen, Xi; Feng, Xiao; Zhang, Xue; Mu, Qing; Shen, Huan; Guo, Jing-zhu

    2017-01-01

    Overexpression of receptor-interacting protein 140 (RIP140) promotes neuronal differentiation of N2a cells via extracellular regulated kinase 1/2 (ERK1/2) signaling. However, involvement of RIP140 in human neural differentiation remains unclear. We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells. Moreover, RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation, and positively correlated with the neural stem cell marker Nestin during later stages. Thus, ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

  13. Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells.

    Science.gov (United States)

    Zhao, Zhu-Ran; Yu, Wei-Dong; Shi, Cheng; Liang, Rong; Chen, Xi; Feng, Xiao; Zhang, Xue; Mu, Qing; Shen, Huan; Guo, Jing-Zhu

    2017-01-01

    Overexpression of receptor-interacting protein 140 (RIP140) promotes neuronal differentiation of N2a cells via extracellular regulated kinase 1/2 (ERK1/2) signaling. However, involvement of RIP140 in human neural differentiation remains unclear. We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells. Moreover, RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation, and positively correlated with the neural stem cell marker Nestin during later stages. Thus, ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

  14. Explaining neural signals in human visual cortex with an associative learning model.

    Science.gov (United States)

    Jiang, Jiefeng; Schmajuk, Nestor; Egner, Tobias

    2012-08-01

    "Predictive coding" models posit a key role for associative learning in visual cognition, viewing perceptual inference as a process of matching (learned) top-down predictions (or expectations) against bottom-up sensory evidence. At the neural level, these models propose that each region along the visual processing hierarchy entails one set of processing units encoding predictions of bottom-up input, and another set computing mismatches (prediction error or surprise) between predictions and evidence. This contrasts with traditional views of visual neurons operating purely as bottom-up feature detectors. In support of the predictive coding hypothesis, a recent human neuroimaging study (Egner, Monti, & Summerfield, 2010) showed that neural population responses to expected and unexpected face and house stimuli in the "fusiform face area" (FFA) could be well-described as a summation of hypothetical face-expectation and -surprise signals, but not by feature detector responses. Here, we used computer simulations to test whether these imaging data could be formally explained within the broader framework of a mathematical neural network model of associative learning (Schmajuk, Gray, & Lam, 1996). Results show that FFA responses could be fit very closely by model variables coding for conditional predictions (and their violations) of stimuli that unconditionally activate the FFA. These data document that neural population signals in the ventral visual stream that deviate from classic feature detection responses can formally be explained by associative prediction and surprise signals.

  15. Neural bases of personal and extrapersonal neglect in humans.

    Science.gov (United States)

    Committeri, Giorgia; Pitzalis, Sabrina; Galati, Gaspare; Patria, Fabiana; Pelle, Gina; Sabatini, Umberto; Castriota-Scanderbeg, Alessandro; Piccardi, Laura; Guariglia, Cecilia; Pizzamiglio, Luigi

    2007-02-01

    Human awareness of left space may be disrupted by cerebral lesions to the right hemisphere (hemispatial neglect). Current knowledge on the anatomical bases of this complex syndrome is based on the results of group studies that investigated primarily the best known aspect of the syndrome, which is visual neglect for near extrapersonal (or peripersonal) space. However, another component-neglect for personal space-is more often associated with, than double-dissociated from, extrapersonal neglect, especially, in chronic patients. The present investigation aimed at exploring the anatomical substrate of both extrapersonal and personal neglect by using different advanced methodological approaches to lesion-function correlation. Fifty-two right ischaemic patients were submitted to neuropsychological assessment and in-depth MRI evaluation. The borders of each patient's lesion were delimited onto its own high-resolution anatomical image and then submitted to an automated spatial normalization algorithm. Besides conventional lesion density plots and subtraction analysis, region-based statistical analyses were performed on percentage values of the lesioned tissue also using a new parcellation of the white matter (WM). Data were finally submitted to voxelwise statistical analysis using a recently proposed method (voxel-based lesion-symptom mapping). Results converged in showing that awareness of extrapersonal space is based on the integrity of a circuit of right frontal (ventral premotor cortex and middle frontal gyrus) and superior temporal regions, whereas awareness of personal space is rooted in right inferior parietal regions (supramarginal gyrus, post-central gyrus and especially the WM medial to them). Common but less crucial regions for both neglect sub-types were located in the temporo-peri-Sylvian cortex. We suggest that extrapersonal space awareness critically involves a ventral circuit recently described for the exogenous allocation and reorienting of attention in

  16. Consciousness: a neural capacity for objectivity, especially pronounced in humans.

    Science.gov (United States)

    Dijker, Anton J M

    2014-01-01

    Consciousness tends to be viewed either as subjective experience of sensations and feelings, or as perception and internal representation of objects. This paper argues that neither view sufficiently acknowledges that consciousness may refer to the brain's most adaptive property: its capacity to produce states of objectivity. It is proposed that this capacity relies on multiple sensorimotor networks for internally representing objects and their properties in terms of expectancies, as well as on motivational and motor mechanisms involved in exploration, play, and care for vulnerable living and non-living objects. States of objectivity are associated with a very special phenomenal aspect; the experience that subjective aspects are absent and one is "just looking" at the world as it really is and can be. However, these states are normally closely preceded and followed by (and tend to be combined or fused with) sensations and feelings which are caused by activation of sensory and motivational mechanisms. A capacity for objectivity may have evolved in different species and can be conceived as a common basis for other elusive psychological properties such as intelligence, conscience, and esthetic experience; all three linked to crucial behaviors in human evolution such as tool making, cooperation, and art. The brain's pervasive tendency to objectify may be responsible for wrongly equating consciousness with feelings and wrongly opposing it to well-learned or habitual ("unconscious") patterns of perception and behavior.

  17. Consciousness: A neural capacity for objectivity, especially pronounced in humans

    Directory of Open Access Journals (Sweden)

    Anton J. M. Dijker

    2014-03-01

    Full Text Available Consciousness either tends to be viewed as subjective experience of sensations and feelings, or as perception and internal representation of objects. This paper argues that neither view sufficiently acknowledges that consciousness may refer to the brain’s most adaptive property: Its capacity to produce states of objectivity. It is proposed that this capacity relies on multiple sensorimotor networks for internally representing objects and their properties in terms of expectancies, as well as on motivational and motor mechanisms involved in exploration, play, and care for vulnerable living and nonliving objects. States of objectivity are associated with a very special phenomenal aspect; the experience that subjective aspects are absent and one is just looking at the world as it really is and can be. However, these states are normally closely preceded and followed by (and tend to be combined or fused with sensations and feelings which are caused by activation of sensory and motivational mechanisms. A capacity for objectivity may have evolved in different species and can be conceived as a common basis for other elusive psychological properties such as intelligence, conscience, and aesthetic experience; all three linked to crucial behaviors in human evolution such as tool making, cooperation, and art. The brain’s pervasive tendency to objectify may be responsible for wrongly equating consciousness with feelings and wrongly opposing it to well-learned or habitual (unconscious patterns of perception and behavior.

  18. Environmental layout complexity affects neural activity during navigation in humans.

    Science.gov (United States)

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation.

  19. Plasmid-based generation of induced neural stem cells from adult human fibroblasts

    Directory of Open Access Journals (Sweden)

    Philipp Capetian

    2016-10-01

    Full Text Available Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53. We employed a defined neural medium in combination with the neurotrophins bFGF, EGF and FGF4 for cultivation without the addition of small molecules. After reprogramming, cells demonstrated a temporary increase in the expression of endogenous Oct3/4. We obtained induced neural stem cells (iNSC 30 days after transfection. In contrast to previous results, plasmid vectors as well as a residual expression of reprogramming factors remained detectable in all cell lines. Cells showed a robust differentiation into neuronal (72% and glial cells (9% astrocytes, 6% oligodendrocytes. Despite the temporary increase of pluripotency-associated Oct3/4 expression during reprogramming, we did not detect pluripotent stem cells or non-neural cells in culture (except occasional residual fibroblasts. Neurons showed electrical activity and functional glutamatergic synapses. Our results demonstrate that reprogramming adult human fibroblasts to iNSC by plasmid vectors and basic neural medium without small molecules is possible and feasible. However, a full set of pluripotency-associated transcription factors may indeed result in the acquisition of a transient (at least partial pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside

  20. A wireless transmission neural interface system for unconstrained non-human primates

    Science.gov (United States)

    Fernandez-Leon, Jose A.; Parajuli, Arun; Franklin, Robert; Sorenson, Michael; Felleman, Daniel J.; Hansen, Bryan J.; Hu, Ming; Dragoi, Valentin

    2015-10-01

    Objective. Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. Approach. To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. Main results. We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. Significance. We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

  1. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation. PMID:26795421

  2. Neural and Synaptic Defects in slytherin a Zebrafish Model for Human Congenital Disorders of Glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Y Song; J Willer; P Scherer; J Panzer; A Kugath; E Skordalakes; R Gregg; G Willer; R Balice-Gordon

    2011-12-31

    Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent. We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.

  3. Generation and properties of a new human ventral mesencephalic neural stem cell line

    Energy Technology Data Exchange (ETDEWEB)

    Villa, Ana; Liste, Isabel; Courtois, Elise T.; Seiz, Emma G.; Ramos, Milagros [Center of Molecular Biology ' Severo Ochoa' , Autonomous University of Madrid-C.S.I.C., Campus Cantoblanco 28049-Madrid (Spain); Meyer, Morten [Department of Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Winslowparken 21,st, DK-500, Odense C (Denmark); Juliusson, Bengt; Kusk, Philip [NsGene A/S, Ballerup (Denmark); Martinez-Serrano, Alberto, E-mail: amserrano@cbm.uam.es [Center of Molecular Biology ' Severo Ochoa' , Autonomous University of Madrid-C.S.I.C., Campus Cantoblanco 28049-Madrid (Spain)

    2009-07-01

    Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal of growth factors, proliferation and expression of v-myc were dramatically reduced and the cells differentiated into astrocytes, oligodendrocytes and neurons. hVM1 cells yield a large number of dopaminergic neurons (about 12% of total cells are TH{sup +}) after differentiation, which also produce dopamine. In addition to proneural genes (NGN2, MASH1), differentiated cells show expression of several genuine mesencephalic dopaminergic markers such as: LMX1A, LMX1B, GIRK2, ADH2, NURR1, PITX3, VMAT2 and DAT, indicating that they retain their regional identity. Our data indicate that this cell line and its clonal derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing.

  4. Effect of Rat Schwann Cell Secretion on Proliferation and Differentiation of Human Neural Stem Cells

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To investigate the effect of rat Schwann cell secretion on the proliferation and differentiation of human embryonic neural stem cells (NSCs). Methods The samples were divided into three groups. In Group One, NSCs were cultured in DMED/F12 in which Schwann cells had grown for one day. In Group Two, NSCs and Schwann cells were co-cultured. In Group Three, NSCs were cultured in DMEM/F12. The morphology of NSCs was checked and b-tubulin, GalC, hoechst 33342 and GFAP labellings were detected. Results In Group One, all neural spheres were attached to the bottom and differentiated. The majority of them were b-tubulin positive while a few of cells were GFAP or GalC positive. In Group Two, neural spheres remained undifferentiatied and their proliferation was inhibited in places where Schwann cells were robust. In places where there were few Schwann cells, NSCs performed in a similar manner as in Group One. In Group Three, the cell growth state deteriorated day after day. On the 7th day, most NSCs died. Conclusion The secretion of rat Schwann cells has a growth supportive and differentiation-inducing effect on human NSCs.

  5. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  6. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    Science.gov (United States)

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy.

  7. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-22

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  8. Statistical control chart and neural network classification for improving human fall detection

    KAUST Repository

    Harrou, Fouzi

    2017-01-05

    This paper proposes a statistical approach to detect and classify human falls based on both visual data from camera and accelerometric data captured by accelerometer. Specifically, we first use a Shewhart control chart to detect the presence of potential falls by using accelerometric data. Unfortunately, this chart cannot distinguish real falls from fall-like actions, such as lying down. To bypass this difficulty, a neural network classifier is then applied only on the detected cases through visual data. To assess the performance of the proposed method, experiments are conducted on the publicly available fall detection databases: the University of Rzeszow\\'s fall detection (URFD) dataset. Results demonstrate that the detection phase play a key role in reducing the number of sequences used as input into the neural network classifier for classification, significantly reducing computational burden and achieving better accuracy.

  9. Neural Plasticity following Abacus Training in Humans: A Review and Future Directions

    Directory of Open Access Journals (Sweden)

    Yongxin Li

    2016-01-01

    Full Text Available The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact.

  10. Detection of some anaemia types in human blood smears using neural networks

    Science.gov (United States)

    Elsalamony, Hany A.

    2016-08-01

    The identification process based on measuring the level of haemoglobin and the classification of red blood cells using microscopic examination of blood smears is the principal way to diagnose anaemia. This paper presents a proposed algorithm for detecting some anaemia types like sickle and elliptocytosis and trying to count them with healthy ones in human red blood smears based on the circular Hough transform and some morphological tools. Some cells with unknown shapes (not platelets or white cells) also have been detected. The extracted data from the detection process has been analyzed by neural network. The experimental results have demonstrated high accuracy, and the proposed algorithm has achieved the highest detection of around 98.9% out of all the cells in 27 microscopic images. Effectiveness rates up to 100%, 98%, and 99.3% have been achieved by using neural networks for sickle, elliptocytosis and cells with unknown shapes, respectively.

  11. Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy

    Directory of Open Access Journals (Sweden)

    Emilio J Gualda

    2014-08-01

    Full Text Available The development of three dimensional cell cultures represents a big step for the better understanding of cell behavior and disease in a more natural like environment, providing not only single but multiple cell type interactions in a complex three dimensional matrix, highly resembling physiological conditions. Light sheet fluorescence microscopy is becoming an excellent tool for fast imaging of such three-dimensional biological structures. We demonstrate the potential of this technique for the imaging of human differentiated 3D neural aggregates in fixed and live samples, namely calcium imaging and cell death processes, showing the power of imaging modality compared with traditional microscopy. The combination of light sheet microscopy and 3D neural cultures will open the door to more challenging experiments involving drug testing at large scale as well as a better understanding of relevant biological processes in a more realistic environment.

  12. Neural Plasticity following Abacus Training in Humans: A Review and Future Directions.

    Science.gov (United States)

    Li, Yongxin; Chen, Feiyan; Huang, Wenhua

    2016-01-01

    The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact.

  13. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  14. Accelerometer signal-based human activity recognition using augmented autoregressive model coefficients and artificial neural nets.

    Science.gov (United States)

    Khan, A M; Lee, Y K; Kim, T S

    2008-01-01

    Automatic recognition of human activities is one of the important and challenging research areas in proactive and ubiquitous computing. In this work, we present some preliminary results of recognizing human activities using augmented features extracted from the activity signals measured using a single triaxial accelerometer sensor and artificial neural nets. The features include autoregressive (AR) modeling coefficients of activity signals, signal magnitude areas (SMA), and title angles (TA). We have recognized four human activities using AR coefficients (ARC) only, ARC with SMA, and ARC with SMA and TA. With the last augmented features, we have achieved the recognition rate above 99% for all four activities including lying, standing, walking, and running. With our proposed technique, real time recognition of some human activities is possible.

  15. Interplay between human microglia and neural stem/progenitor cells in an allogeneic co-culture model.

    Science.gov (United States)

    Liu, Jia; Hjorth, Erik; Zhu, Mingqin; Calzarossa, Cinzia; Samuelsson, Eva-Britt; Schultzberg, Marianne; Åkesson, Elisabet

    2013-11-01

    Experimental neural cell therapies, including donor neural stem/progenitor cells (NPCs) have been reported to offer beneficial effects on the recovery after an injury and to counteract inflammatory and degenerative processes in the central nervous system (CNS). The interplay between donor neural cells and the host CNS still to a large degree remains unclear, in particular in human allogeneic conditions. Here, we focused our studies on the interaction of human NPCs and microglia utilizing a co-culture model. In co-cultures, both NPCs and microglia showed increased survival and proliferation compared with mono-cultures. In the presence of microglia, a larger subpopulation of NPCs expressed the progenitor cell marker nestin, whereas a smaller group of NPCs expressed the neural markers polysialylated neural cell adhesion molecule, A2B5 and glial fibrillary acidic protein compared with NPC mono-cultures. Microglia thus hindered differentiation of NPCs. The presence of human NPCs increased microglial phagocytosis of latex beads. Furthermore, we observed that the expression of CD200 molecules on NPCs and the CD200 receptor protein on microglia was enhanced in co-cultures, whereas the release of transforming growth factor-β was increased suggesting anti-inflammatory features of the co-cultures. To conclude, the interplay between human allogeneic NPCs and microglia, significantly affected their respective proliferation and phenotype. Neural cell therapy including human donor NPCs may in addition to offering cell replacement, modulate host microglial phenotypes and functions to benefit neuroprotection and repair.

  16. Human facial neural activities and gesture recognition for machine-interfacing applications

    Directory of Open Access Journals (Sweden)

    Hamedi M

    2011-12-01

    Full Text Available M Hamedi1, Sh-Hussain Salleh2, TS Tan2, K Ismail2, J Ali3, C Dee-Uam4, C Pavaganun4, PP Yupapin51Faculty of Biomedical and Health Science Engineering, Department of Biomedical Instrumentation and Signal Processing, University of Technology Malaysia, Skudai, 2Centre for Biomedical Engineering Transportation Research Alliance, 3Institute of Advanced Photonics Science, Nanotechnology Research Alliance, University of Technology Malaysia (UTM, Johor Bahru, Malaysia; 4College of Innovative Management, Valaya Alongkorn Rajabhat University, Pathum Thani, 5Nanoscale Science and Engineering Research Alliance (N'SERA, Advanced Research Center for Photonics, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok, ThailandAbstract: The authors present a new method of recognizing different human facial gestures through their neural activities and muscle movements, which can be used in machine-interfacing applications. Human–machine interface (HMI technology utilizes human neural activities as input controllers for the machine. Recently, much work has been done on the specific application of facial electromyography (EMG-based HMI, which have used limited and fixed numbers of facial gestures. In this work, a multipurpose interface is suggested that can support 2–11 control commands that can be applied to various HMI systems. The significance of this work is finding the most accurate facial gestures for any application with a maximum of eleven control commands. Eleven facial gesture EMGs are recorded from ten volunteers. Detected EMGs are passed through a band-pass filter and root mean square features are extracted. Various combinations of gestures with a different number of gestures in each group are made from the existing facial gestures. Finally, all combinations are trained and classified by a Fuzzy c-means classifier. In conclusion, combinations with the highest recognition accuracy in each group are chosen. An average accuracy

  17. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liang [East Hospital, Tongji University School of Medicine, Shanghai (China); Dong, Chuanming [East Hospital, Tongji University School of Medicine, Shanghai (China); Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong (China); Sun, Chenxi; Ma, Rongjie; Yang, Danjing [East Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Hongwen, E-mail: hongwen_zhu@hotmail.com [Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin (China); Xu, Jun, E-mail: xunymc2000@yahoo.com [East Hospital, Tongji University School of Medicine, Shanghai (China)

    2015-08-21

    Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy.

  18. Generation of primitive neural stem cells from human fibroblasts using a defined set of factors

    Directory of Open Access Journals (Sweden)

    Takumi Miura

    2015-11-01

    Full Text Available In mice, leukemia inhibitory factor (LIF-dependent primitive neural stem cells (NSCs have a higher neurogenic potential than bFGF-dependent definitive NSCs. Therefore, expandable primitive NSCs are required for research and for the development of therapeutic strategies for neurological diseases. There is a dearth of suitable techniques for the generation of human long-term expandable primitive NSCs. Here, we have described a method for the conversion of human fibroblasts to LIF-dependent primitive NSCs using a strategy based on techniques for the generation of induced pluripotent stem cells (iPSCs. These LIF-dependent induced NSCs (LD-iNSCs can be expanded for >100 passages. Long-term cultured LD-iNSCs demonstrated multipotent neural differentiation potential and could generate motor neurons and dopaminergic neurons, as well as astrocytes and oligodendrocytes, indicating a high level of plasticity. Furthermore, LD-iNSCs easily reverted to human iPSCs, indicating that LD-iNSCs are in an intermediate iPSC state. This method may facilitate the generation of patient-specific human neurons for studies and treatment of neurodegenerative diseases.

  19. Continuous Timescale Long-Short Term Memory Neural Network for Human Intent Understanding

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    Zhibin Yu

    2017-08-01

    Full Text Available Understanding of human intention by observing a series of human actions has been a challenging task. In order to do so, we need to analyze longer sequences of human actions related with intentions and extract the context from the dynamic features. The multiple timescales recurrent neural network (MTRNN model, which is believed to be a kind of solution, is a useful tool for recording and regenerating a continuous signal for dynamic tasks. However, the conventional MTRNN suffers from the vanishing gradient problem which renders it impossible to be used for longer sequence understanding. To address this problem, we propose a new model named Continuous Timescale Long-Short Term Memory (CTLSTM in which we inherit the multiple timescales concept into the Long-Short Term Memory (LSTM recurrent neural network (RNN that addresses the vanishing gradient problem. We design an additional recurrent connection in the LSTM cell outputs to produce a time-delay in order to capture the slow context. Our experiments show that the proposed model exhibits better context modeling ability and captures the dynamic features on multiple large dataset classification tasks. The results illustrate that the multiple timescales concept enhances the ability of our model to handle longer sequences related with human intentions and hence proving to be more suitable for complex tasks, such as intention recognition.

  20. Sensitive periods for the functional specialization of the neural system for human face processing.

    Science.gov (United States)

    Röder, Brigitte; Ley, Pia; Shenoy, Bhamy H; Kekunnaya, Ramesh; Bottari, Davide

    2013-10-15

    The aim of the study was to identify possible sensitive phases in the development of the processing system for human faces. We tested the neural processing of faces in 11 humans who had been blind from birth and had undergone cataract surgery between 2 mo and 14 y of age. Pictures of faces and houses, scrambled versions of these pictures, and pictures of butterflies were presented while event-related potentials were recorded. Participants had to respond to the pictures of butterflies (targets) only. All participants, even those who had been blind from birth for several years, were able to categorize the pictures and to detect the targets. In healthy controls and in a group of visually impaired individuals with a history of developmental or incomplete congenital cataracts, the well-known enhancement of the N170 (negative peak around 170 ms) event-related potential to faces emerged, but a face-sensitive response was not observed in humans with a history of congenital dense cataracts. By contrast, this group showed a similar N170 response to all visual stimuli, which was indistinguishable from the N170 response to faces in the controls. The face-sensitive N170 response has been associated with the structural encoding of faces. Therefore, these data provide evidence for the hypothesis that the functional differentiation of category-specific neural representations in humans, presumably involving the elaboration of inhibitory circuits, is dependent on experience and linked to a sensitive period. Such functional specialization of neural systems seems necessary to archive high processing proficiency.

  1. Neural and non-neural control of skin blood flow during isometric handgrip exercise in the heat stressed human

    DEFF Research Database (Denmark)

    Shibasaki, M.; Rasmussen, P.; Secher, Niels H.

    2009-01-01

    During heat stress, isometric handgrip (IHG) exercise causes cutaneous vasoconstriction, but it remains controversial whether neural mechanisms are responsible for this observation. The objective of this study was to test the hypothesis that cutaneous vasoconstriction during IHG exercise in heat ...

  2. Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Katsutsugu Umeda

    2015-04-01

    Full Text Available Here we report the successful generation and long-term expansion of SOX9-expressing CD271+PDGFRα+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1−CD271hiPDGFRαloCD73− neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/transforming growth factorβ (TGFβ inhibitor and fibroblast growth factor (FGF. When “primed” with TGFβ, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. The ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages. They maintained normal karyotype for at least 10 passages and expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B, cranial mesenchyme (ALX1/3/4, and chondroprogenitors (SOX9, COL2A1 of neural crest origin (SOX8/9, NGFR, NES. Ectomesenchyme is a source of many craniofacial bone and cartilage structures. The method we describe for obtaining a large quantity of human ectomesenchymal cells will help to model craniofacial disorders in vitro and potentially provide cells for the repair of craniofacial damage.

  3. Highly efficient differentiation of neural precursors from human embryonic stem cells and benefits of transplantation after ischemic stroke in mice.

    Science.gov (United States)

    Drury-Stewart, Danielle; Song, Mingke; Mohamad, Osama; Guo, Ying; Gu, Xiaohuan; Chen, Dongdong; Wei, Ling

    2013-08-08

    Ischemic stroke is a leading cause of death and disability, but treatment options are severely limited. Cell therapy offers an attractive strategy for regenerating lost tissues and enhancing the endogenous healing process. In this study, we investigated the use of human embryonic stem cell-derived neural precursors as a cell therapy in a murine stroke model. Neural precursors were derived from human embryonic stem cells by using a fully adherent SMAD inhibition protocol employing small molecules. The efficiency of neural induction and the ability of these cells to further differentiate into neurons were assessed by using immunocytochemistry. Whole-cell patch-clamp recording was used to demonstrate the electrophysiological activity of human embryonic stem cell-derived neurons. Neural precursors were transplanted into the core and penumbra regions of a focal ischemic stroke in the barrel cortex of mice. Animals received injections of bromodeoxyuridine to track regeneration. Neural differentiation of the transplanted cells and regenerative markers were measured by using immunohistochemistry. The adhesive removal test was used to determine functional improvement after stroke and intervention. After 11 days of neural induction by using the small-molecule protocol, over 95% of human embryonic stem-derived cells expressed at least one neural marker. Further in vitro differentiation yielded cells that stained for mature neuronal markers and exhibited high-amplitude, repetitive action potentials in response to depolarization. Neuronal differentiation also occurred after transplantation into the ischemic cortex. A greater level of bromodeoxyuridine co-localization with neurons was observed in the penumbra region of animals receiving cell transplantation. Transplantation also improved sensory recovery in transplant animals over that in control animals. Human embryonic stem cell-derived neural precursors derived by using a highly efficient small-molecule SMAD inhibition

  4. Integrated Model of DNA Sequence Numerical Representation and Artificial Neural Network for Human Donor and Acceptor Sites Prediction

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    Mohammed Abo-Zahhad

    2014-07-01

    Full Text Available Human Genome Project has led to a huge inflow of genomic data. After the completion of human genome sequencing, more and more effort is being put into identification of splicing sites of exons and introns (donor and acceptor sites. These invite bioinformatics to analysis the genome sequences and identify the location of exon and intron boundaries or in other words prediction of splicing sites. Prediction of splice sites in genic regions of DNA sequence is one of the most challenging aspects of gene structure recognition. Over the last two decades, artificial neural networks gradually became one of the essential tools in bioinformatics. In this paper artificial neural networks with different numerical mapping techniques have been employed for building integrated model for splice site prediction in genes. An artificial neural network is trained and then used to find splice sites in human genes. A comparison between different mapping methods using trained neural network in terms of their precision in prediction of donor and acceptor sites will be presented in this paper. Training and measuring performance of neural network are carried out using sequences of the human genome (GRch37/hg19- chr21. Simulation results indicate that using Electron-Ion Interaction Potential numerical mapping method with neural network yields to the best performance in prediction.

  5. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  6. A comparison of epithelial and neural properties in progenitor cells derived from the adult human ciliary body and brain.

    Science.gov (United States)

    Moe, Morten C; Kolberg, Rebecca S; Sandberg, Cecilie; Vik-Mo, Einar; Olstorn, Havard; Varghese, Mercy; Langmoen, Iver A; Nicolaissen, Bjørn

    2009-01-01

    Cells isolated from the ciliary body (CB) of the adult human eye possess properties of retinal stem/progenitor cells and can be propagated as spheres in culture. As these cells are isolated from a non-neural epithelium which has neuroepithelial origin, they may have both epithelial and neural lineages. Since it is the properties of neural progenitor cells that are sought after in a future scenario of autotransplantation, we wanted to directly compare human CB spheres with neurospheres derived from the human subventricular zone (SVZ), which is the best characterized neural stem cell niche in the CNS of adults. The CB epithelium was dissected from donor eyes (n = 8). Biopsies from the ventricular wall were harvested during neurosurgery due to epilepsy (n = 7). CB and SVZ tissue were also isolated from Brown Norwegian rats. Dissociated single cells were cultivated in a sphere-promoting medium and passaged every 10-30 days. Fixed spheres were studied by immunohistochemistry, quantitative RT-PCR and scanning/transmission electron microscopy. We found that both CB and SVZ spheres contained a mixed population of cells embedded in extracellular matrix. CB spheres, in contrast to SVZ neurospheres, contained pigmented cells with epithelial morphology that stained for cytokeratins (3/12 + 19), were connected through desmosomes and tight-junctions and produced PEDF. Markers of neural progenitors (nestin, Sox-2, GFAP) were significantly lower expressed in human CB compared to SVZ spheres, and nestin positive cells in the CB spheres also contained pigment. There was higher expression of EGF and TGF-beta receptors in human CB spheres, and a comparative greater activation of the canonical Wnt pathway. These results indicate that adult human CB spheres contain progenitor cells with epithelial properties and limited expression of neural progenitor markers compared to CNS neurospheres. Further studies mapping the regulation between epithelial and neural properties in the adult human

  7. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  8. Cross-sectional study of the neural ossification centers of vertebrae C1-S5 in the human fetus.

    Science.gov (United States)

    Szpinda, Michał; Baumgart, Mariusz; Szpinda, Anna; Woźniak, Alina; Mila-Kierzenkowska, Celestyna

    2013-10-01

    An understanding of the normal evolution of the spine is of great relevance in the prenatal detection of spinal abnormalities. This study was carried out to estimate the length, width, cross-sectional area and volume of the neural ossification centers of vertebrae C1-S5 in the human fetus. Using the methods of CT (Biograph mCT), digital-image analysis (Osirix 3.9) and statistics (the one-way ANOVA test for paired data, the Kolmogorov-Smirnov test, Levene's test, Student's t test, the one-way ANOVA test for unpaired data with post hoc RIR Tukey comparisons) the size for the neural ossification centers throughout the spine in 55 spontaneously aborted human fetuses (27 males, 28 females) at ages of 17-30 weeks was studied. The neural ossification centers were visualized in the whole pre-sacral spine, in 74.5 % for S1, in 61.8 % for S2, in 52.7 % for S3, and in 12.7 % for S4. Neither male-female nor right-left significant differences in the size of neural ossification centers were found. The neural ossification centers were the longest within the cervical spine. The maximum values referred to the axis on the right, and to C5 vertebra on the left. There was a gradual decrease in length for the neural ossification centers of T1-S4 vertebrae. The neural ossification centers were the widest within the proximal thoracic spine and narrowed bi-directionally. The growth dynamics for CSA of neural ossification centers were found to parallel that of volume. The largest CSAs and volumes of neural ossification centers were found in the C3 vertebra, and decreased in the distal direction. The neural ossification centers show neither male-female nor right-left differences. The neural ossification centers are characterized by the maximum length for C2-C6 vertebrae, the maximum width for the proximal thoracic spine, and both the maximum cross-sectional area and volume for C3 vertebra. There is a sharp decrease in size of the neural ossification centers along the sacral spine. A

  9. Neural dynamics of reward probability coding: a Magnetoencephalographic study in humans

    Directory of Open Access Journals (Sweden)

    Julie eThomas

    2013-11-01

    Full Text Available Prediction of future rewards and discrepancy between actual and expected outcomes (prediction error are crucial signals for adaptive behavior. In humans, a number of fMRI studies demonstrated that reward probability modulates these two signals in a large brain network. Yet, the spatio-temporal dynamics underlying the neural coding of reward probability remains unknown. Here, using magnetoencephalography, we investigated the neural dynamics of prediction and reward prediction error computations while subjects learned to associate cues of slot machines with monetary rewards with different probabilities. We showed that event-related magnetic fields (ERFs arising from the visual cortex coded the expected reward value 155 ms after the cue, demonstrating that reward value signals emerge early in the visual stream. Moreover, a prediction error was reflected in ERF peaking 300 ms after the rewarded outcome and showing decreasing amplitude with higher reward probability. This prediction error signal was generated in a network including the anterior and posterior cingulate cortex. These findings pinpoint the spatio-temporal characteristics underlying reward probability coding. Together, our results provide insights into the neural dynamics underlying the ability to learn probabilistic stimuli-reward contingencies.

  10. Human Age Recognition by Electrocardiogram Signal Based on Artificial Neural Network

    Science.gov (United States)

    Dasgupta, Hirak

    2016-12-01

    The objective of this work is to make a neural network function approximation model to detect human age from the electrocardiogram (ECG) signal. The input vectors of the neural network are the Katz fractal dimension of the ECG signal, frequencies in the QRS complex, male or female (represented by numeric constant) and the average of successive R-R peak distance of a particular ECG signal. The QRS complex has been detected by short time Fourier transform algorithm. The successive R peak has been detected by, first cutting the signal into periods by auto-correlation method and then finding the absolute of the highest point in each period. The neural network used in this problem consists of two layers, with Sigmoid neuron in the input and linear neuron in the output layer. The result shows the mean of errors as -0.49, 1.03, 0.79 years and the standard deviation of errors as 1.81, 1.77, 2.70 years during training, cross validation and testing with unknown data sets, respectively.

  11. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

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    Alexandra Zirra

    2016-01-01

    Full Text Available Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

  12. Functional Magnetic Resonance Imaging for Imaging Neural Activity in the Human Brain: The Annual Progress

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

    Full Text Available Functional magnetic resonance imaging (fMRI is recently developed and applied to measure the hemodynamic response related to neural activity. The fMRI can not only noninvasively record brain signals without risks of ionising radiation inherent in other scanning methods, such as CT or PET scans, but also record signal from all regions of the brain, unlike EEG/MEG which are biased towards the cortical surface. This paper introduces the fundamental principles and summarizes the research progress of the last year for imaging neural activity in the human brain. Aims of functional analysis of neural activity from fMRI include biological findings, functional connectivity, vision and hearing research, emotional research, neurosurgical planning, pain management, and many others. Besides formulations and basic processing methods, models and strategies of processing technology are introduced, including general linear model, nonlinear model, generative model, spatial pattern analysis, statistical analysis, correlation analysis, and multimodal combination. This paper provides readers the most recent representative contributions in the area.

  13. Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain.

    Science.gov (United States)

    Kim, Hackjin; Shimojo, Shinsuke; O'Doherty, John P

    2006-07-01

    Avoidance learning poses a challenge for reinforcement-based theories of instrumental conditioning, because once an aversive outcome is successfully avoided an individual may no longer experience extrinsic reinforcement for their behavior. One possible account for this is to propose that avoiding an aversive outcome is in itself a reward, and thus avoidance behavior is positively reinforced on each trial when the aversive outcome is successfully avoided. In the present study we aimed to test this possibility by determining whether avoidance of an aversive outcome recruits the same neural circuitry as that elicited by a reward itself. We scanned 16 human participants with functional MRI while they performed an instrumental choice task, in which on each trial they chose from one of two actions in order to either win money or else avoid losing money. Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance.

  14. The neural processes underlying perceptual decision making in humans: recent progress and future directions.

    Science.gov (United States)

    Kelly, Simon P; O'Connell, Redmond G

    2015-01-01

    In the last two decades, animal neurophysiology research has made great strides towards explaining how the brain can enable adaptive action in the face of noisy sensory information. In particular, this work has identified neural signals that perform the role of a 'decision variable' which integrates sensory information in favor of a particular outcome up to an action-triggering threshold, consistent with long-standing predictions from mathematical psychology. This has provoked an intensive search for similar neural processes at work in the human brain. In this paper we review the progress that has been made in tracing the dynamics of perceptual decision formation in humans using functional imaging and electrophysiology. We highlight some of the limitations that non-invasive recording techniques place on our ability to make definitive judgments regarding the role that specific signals play in decision making. Finally, we provide an overview of our own work in this area which has focussed on two perceptual tasks - intensity change detection and motion discrimination - performed under continuous-monitoring conditions, and highlight the insights gained thus far. We show that through simple paradigm design features such as avoiding sudden intensity transients at evidence onset, a neural instantiation of the theoretical decision variable can be directly traced in the form of a centro-parietal positivity (CPP) in the standard event-related potential (ERP). We recapitulate evidence for the domain-general nature of the CPP process, being divorced from the sensory and motor requirements of the task, and re-plot data of both tasks highlighting this aspect as well as its relationship to decision outcome and reaction time. We discuss the implications of these findings for mechanistically principled research on normal and abnormal decision making in humans.

  15. Derivation of Neural Progenitors and Retinal Pigment Epithelium from Common Marmoset and Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Laughing Bear Torrez

    2012-01-01

    Full Text Available Embryonic and induced pluripotent stem cells (IPSCs derived from mammalian species are valuable tools for modeling human disease, including retinal degenerative eye diseases that result in visual loss. Restoration of vision has focused on transplantation of neural progenitor cells (NPCs and retinal pigmented epithelium (RPE to the retina. Here we used transgenic common marmoset (Callithrix jacchus and human pluripotent stem cells carrying the enhanced green fluorescent protein (eGFP reporter as a model system for retinal differentiation. Using suspension and subsequent adherent differentiation cultures, we observed spontaneous in vitro differentiation that included NPCs and cells with pigment granules characteristic of differentiated RPE. Retinal cells derived from human and common marmoset pluripotent stem cells provide potentially unlimited cell sources for testing safety and immune compatibility following autologous or allogeneic transplantation using nonhuman primates in early translational applications.

  16. Electrical stimulation of neural stem cells mediated by humanized carbon nanotube composite made with extracellular matrix protein.

    Science.gov (United States)

    Kam, Nadine Wong Shi; Jan, Edward; Kotov, Nicholas A

    2009-01-01

    One of the key challenges to engineering neural interfaces is to minimize their immune response toward implanted electrodes. One potential approach is to manufacture materials that bear greater structural resemblance to living tissues and by utilizing neural stem cells. The unique electrical and mechanical properties of carbon nanotubes make them excellent candidates for neural interfaces, but their adoption hinges on finding approaches for "humanizing" their composites. Here we demonstrated the fabrication of layer-by-layer assembled composites from single-walled carbon nanotubes (SWNTs) and laminin, which is an essential part of human extracellular matrix. Laminin-SWNT thin films were found to be conducive to neural stem cells (NSC) differentiation and suitable for their successful excitation. We observed extensive formation of functional neural network as indicated by the presence of synaptic connections. Calcium imaging of the NSCs revealed generation of action potentials upon the application of a lateral current through the SWNT substrate. These results indicate that the protein-SWNT composite can serve as materials foundation of neural electrodes with chemical structure better adapted with long-term integration with the neural tissue.

  17. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol.

    Science.gov (United States)

    Schulpen, Sjors H W; de Jong, Esther; de la Fonteyne, Liset J J; de Klerk, Arja; Piersma, Aldert H

    2015-04-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecular interaction of compounds with the neural differentiation process. Within the 11-day differentiation protocol of the assay, embryonic stem cells lost their pluripotency, evidenced by the reduced expression of stem cell markers Pou5F1 and Nanog. Moreover, stem cells differentiated into neural cells, with morphologically visible neural structures together with increased expression of neural differentiation-related genes such as βIII-tubulin, Map2, Neurogin1, Mapt and Reelin. Valproic acid (VPA) and carbamazepine (CBZ) exposure during hESTn differentiation led to concentration-dependent reduced expression of βIII-tubulin, Neurogin1 and Reelin. In parallel VPA caused an increased gene expression of Map2 and Mapt which is possibly related to the neural protective effect of VPA. These findings illustrate the added value of gene expression analysis for detecting compound specific effects in hESTn. Our findings were in line with and could explain effects observed in animal studies. This study demonstrates the potential of this assay protocol for mechanistic analysis of specific compound-induced inhibition of human neural cell differentiation.

  18. Human facial neural activities and gesture recognition for machine-interfacing applications.

    Science.gov (United States)

    Hamedi, M; Salleh, Sh-Hussain; Tan, T S; Ismail, K; Ali, J; Dee-Uam, C; Pavaganun, C; Yupapin, P P

    2011-01-01

    The authors present a new method of recognizing different human facial gestures through their neural activities and muscle movements, which can be used in machine-interfacing applications. Human-machine interface (HMI) technology utilizes human neural activities as input controllers for the machine. Recently, much work has been done on the specific application of facial electromyography (EMG)-based HMI, which have used limited and fixed numbers of facial gestures. In this work, a multipurpose interface is suggested that can support 2-11 control commands that can be applied to various HMI systems. The significance of this work is finding the most accurate facial gestures for any application with a maximum of eleven control commands. Eleven facial gesture EMGs are recorded from ten volunteers. Detected EMGs are passed through a band-pass filter and root mean square features are extracted. Various combinations of gestures with a different number of gestures in each group are made from the existing facial gestures. Finally, all combinations are trained and classified by a Fuzzy c-means classifier. In conclusion, combinations with the highest recognition accuracy in each group are chosen. An average accuracy >90% of chosen combinations proved their ability to be used as command controllers.

  19. The neural bases of crossmodal object recognition in non-human primates and rodents: a review.

    Science.gov (United States)

    Cloke, Jacob M; Jacklin, Derek L; Winters, Boyer D

    2015-05-15

    The ability to integrate information from different sensory modalities to form unique multisensory object representations is a highly adaptive cognitive function. Surprisingly, non-human animal studies of the neural substrates of this form of multisensory integration have been somewhat sparse until very recently, and this may be due in part to a relative paucity of viable testing methods. Here we review the historical development and use of various "crossmodal" cognition tasks for non-human primates and rodents, focusing on tests of "crossmodal object recognition", the ability to recognize an object across sensory modalities. Such procedures have great potential to elucidate the cognitive and neural bases of object representation as it pertains to perception and memory. Indeed, these studies have revealed roles in crossmodal cognition for various brain regions (e.g., prefrontal and temporal cortices) and neurochemical systems (e.g., acetylcholine). A recent increase in behavioral and physiological studies of crossmodal cognition in rodents augurs well for the future of this research area, which should provide essential information about the basic mechanisms of object representation in the brain, in addition to fostering a better understanding of the causes of, and potential treatments for, cognitive deficits in human diseases characterized by atypical multisensory integration.

  20. Integrating verbal and nonverbal communication in a dynamic neural field architecture for human-robot interaction

    Directory of Open Access Journals (Sweden)

    Estela Bicho

    2010-05-01

    Full Text Available How do humans coordinate their intentions, goals and motor behaviors when performing joint action tasks? Recent experimental evidence suggests that resonance processes in the observer's motor system are crucially involved in our ability to understand actions of others', to infer their goals and even to comprehend their action-related language. In this paper, we present a control architecture for human-robot collaboration that exploits this close perception-action linkage as a means to achieve more natural and efficient communication grounded in sensorimotor experiences. The architecture is formalized by a coupled system of dynamic neural fields representing a distributed network of neural populations that encode in their activation patterns goals, actions and shared task knowledge. We validate the verbal and non-verbal communication skills of the robot in a joint assembly task in which the human-robot team has to construct toy objects from their components. The experiments focus on the robot’s capacity to anticipate the user’s needs and to detect and communicate unexpected events that may occur during joint task execution.

  1. Inhibition of FGF signaling accelerates neural crest cell differentiation of human pluripotent stem cells.

    Science.gov (United States)

    Jaroonwitchawan, Thiranut; Muangchan, Pattamon; Noisa, Parinya

    2016-12-02

    Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, SU5402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST1, were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2α, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases.

  2. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene

    Institute of Scientific and Technical Information of China (English)

    CAI Pei-qiang; TANG Xun; LIN Yue-qiu; Oudega Martin; SUN Guang-yun; XU Lin; YANG Yun-kang; ZHOU Tian-hua

    2006-01-01

    Objective:To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs)mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI).Methods: Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3(NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot.Results: Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot.Conclusions: Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  3. A 3D human neural cell culture system for modeling Alzheimer’s disease

    Science.gov (United States)

    Kim, Young Hye; Choi, Se Hoon; D’Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Brüstle, Oliver; Tanzi, Rudolph E.; Kim, Doo Yeon

    2015-01-01

    Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks. PMID:26068894

  4. Gene expression profiling of human neural progenitor cells following the serum-induced astrocyte differentiation.

    Science.gov (United States)

    Obayashi, Shinya; Tabunoki, Hiroko; Kim, Seung U; Satoh, Jun-ichi

    2009-05-01

    Neural stem cells (NSC) with self-renewal and multipotent properties could provide an ideal cell source for transplantation to treat spinal cord injury, stroke, and neurodegenerative diseases. However, the majority of transplanted NSC and neural progenitor cells (NPC) differentiate into astrocytes in vivo under pathological environments in the central nervous system, which potentially cause reactive gliosis. Because the serum is a potent inducer of astrocyte differentiation of rodent NPC in culture, we studied the effect of the serum on gene expression profile of cultured human NPC to identify the gene signature of astrocyte differentiation of human NPC. Human NPC spheres maintained in the serum-free culture medium were exposed to 10% fetal bovine serum (FBS) for 72 h, and processed for analyzing on a Whole Human Genome Microarray of 41,000 genes, and the microarray data were validated by real-time RT-PCR. The serum elevated the levels of expression of 45 genes, including ID1, ID2, ID3, CTGF, TGFA, METRN, GFAP, CRYAB and CSPG3, whereas it reduced the expression of 23 genes, such as DLL1, DLL3, PDGFRA, SOX4, CSPG4, GAS1 and HES5. Thus, the serum-induced astrocyte differentiation of human NPC is characterized by a counteraction of ID family genes on Delta family genes. Coimmunoprecipitation analysis identified ID1 as a direct binding partner of a proneural basic helix-loop-helix (bHLH) transcription factor MASH1. Luciferase assay indicated that activation of the DLL1 promoter by MASH1 was counteracted by ID1. Bone morphogenetic protein 4 (BMP4) elevated the levels of ID1 and GFAP expression in NPC under the serum-free culture conditions. Because the serum contains BMP4, these results suggest that the serum factor(s), most probably BMP4, induces astrocyte differentiation by upregulating the expression of ID family genes that repress the proneural bHLH protein-mediated Delta expression in human NPC.

  5. Identification of TSS in the Human Genome Based on a RBF Neural Network

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Peng; Jie Chen; Li-Jun Cao; Ting-Ting Gao

    2006-01-01

    The identification of functional motifs in a DNA sequence is fundamentally a statistical pattern recognition problem. This paper introduces a new algorithm for the recognition of functional transcription start sites (TSSs) in human genome sequences, in which a RBF neural network is adopted, and an improved heuristic method for a 5-tuple feature viable construction, is proposed and implemented in two RBFPromoter and ImpRBFPromoter packages developed in Visual C++6.0. The algorithm is evaluated on several different test sequence sets. Compared with several other promoter recognition programs, this algorithm is proved to be more flexible, with stronger learning ability and higher accuracy.

  6. BrainCrafter: An investigation into human-based neural network engineering

    DEFF Research Database (Denmark)

    Piskur, J.; Greve, P.; Togelius, J.

    2015-01-01

    This paper presents the online application Brain-Crafter, in which users can manually build artificial neural networks (ANNs) to control a robot in a maze environment. Users can either start to construct networks from scratch or elaborate on networks created by other users. In particular, Brain......Crafter was designed to study how good we as humans are at building ANNs for control problems and if collaborating with other users can facilitate this process. The results in this paper show that (1) some users were in fact able to successfully construct ANNs that solve the navigation tasks, (2) collaboration between...

  7. Using convolutional neural networks for human activity classification on micro-Doppler radar spectrograms

    Science.gov (United States)

    Jordan, Tyler S.

    2016-05-01

    This paper presents the findings of using convolutional neural networks (CNNs) to classify human activity from micro-Doppler features. An emphasis on activities involving potential security threats such as holding a gun are explored. An automotive 24 GHz radar on chip was used to collect the data and a CNN (normally applied to image classification) was trained on the resulting spectrograms. The CNN achieves an error rate of 1.65 % on classifying running vs. walking, 17.3 % error on armed walking vs. unarmed walking, and 22 % on classifying six different actions.

  8. Mathematical Modeling and Evaluation of Human Motions in Physical Therapy Using Mixture Density Neural Networks

    Science.gov (United States)

    Vakanski, A; Ferguson, JM; Lee, S

    2016-01-01

    Objective The objective of the proposed research is to develop a methodology for modeling and evaluation of human motions, which will potentially benefit patients undertaking a physical rehabilitation therapy (e.g., following a stroke or due to other medical conditions). The ultimate aim is to allow patients to perform home-based rehabilitation exercises using a sensory system for capturing the motions, where an algorithm will retrieve the trajectories of a patient’s exercises, will perform data analysis by comparing the performed motions to a reference model of prescribed motions, and will send the analysis results to the patient’s physician with recommendations for improvement. Methods The modeling approach employs an artificial neural network, consisting of layers of recurrent neuron units and layers of neuron units for estimating a mixture density function over the spatio-temporal dependencies within the human motion sequences. Input data are sequences of motions related to a prescribed exercise by a physiotherapist to a patient, and recorded with a motion capture system. An autoencoder subnet is employed for reducing the dimensionality of captured sequences of human motions, complemented with a mixture density subnet for probabilistic modeling of the motion data using a mixture of Gaussian distributions. Results The proposed neural network architecture produced a model for sets of human motions represented with a mixture of Gaussian density functions. The mean log-likelihood of observed sequences was employed as a performance metric in evaluating the consistency of a subject’s performance relative to the reference dataset of motions. A publically available dataset of human motions captured with Microsoft Kinect was used for validation of the proposed method. Conclusion The article presents a novel approach for modeling and evaluation of human motions with a potential application in home-based physical therapy and rehabilitation. The described approach

  9. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Jun Yan

    2007-02-01

    Full Text Available BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major

  10. Three dimensional cellular microarray platform for human neural stem cell differentiation and toxicology

    Directory of Open Access Journals (Sweden)

    Luciana Meli

    2014-07-01

    Full Text Available We developed a three-dimensional (3D cellular microarray platform for the high-throughput (HT analysis of human neural stem cell (hNSC growth and differentiation. The growth of an immortalized hNSC line, ReNcell VM, was evaluated on a miniaturized cell culture chip consisting of 60 nl spots of cells encapsulated in alginate, and compared to standard 2D well plate culture conditions. Using a live/dead cell viability assay, we demonstrated that the hNSCs are able to expand on-chip, albeit with lower proliferation rates and viabilities than in conventional 2D culture platforms. Using an in-cell, on-chip immunofluorescence assay, which provides quantitative information on cellular levels of proteins involved in neural fate, we demonstrated that ReNcell VM can preserve its multipotent state during on-chip expansion. Moreover, differentiation of the hNSCs into glial progeny was achieved both off- and on-chip six days after growth factor removal, accompanied by a decrease in the neural progenitor markers. The versatility of the platform was further demonstrated by complementing the cell culture chip with a chamber system that allowed us to screen for differential toxicity of small molecules to hNSCs. Using this approach, we showed differential toxicity when evaluating three neurotoxic compounds and one antiproliferative compound, and the null effect of a non-toxic compound at relevant concentrations. Thus, our 3D high-throughput microarray platform may help predict, in vitro, which compounds pose an increased threat to neural development and should therefore be prioritized for further screening and evaluation.

  11. Stem Cells from Human Exfoliated Deciduous Tooth Exhibit Stromal-Derived Inducing Activity and Lead to Generation of Neural Crest Cells from Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Khadijeh Karbalaie

    2015-04-01

    Full Text Available Objective: The neural crest is a transient structure of early vertebrate embryos that generates neural crest cells (NCCs. These cells can migrate throughout the body and produce a diverse array of mature tissue types. Due to the ethical and technical problems surrounding the isolation of these early human embryo cells, researchers have focused on in vitro studies to produce NCCs and increase their knowledge of neural crest development. Materials and Methods: In this experimental study, we cultured human embryonic stem cells (hESCs on stromal stem cells from human exfoliated deciduous teeth (SHED for a two-week period. We used different approaches to characterize these differentiated cells as neural precursor cells (NPCs and NCCs. Results: In the first co-culture week, hESCs appeared as crater-like structures with marginal rosettes. NPCs derived from these structures expressed the early neural crest marker p75 in addition to numerous other genes associated with neural crest induction such as SNAIL, SLUG, PTX3 and SOX9. Flow cytometry analysis showed 70% of the cells were AP2/P75 positive. Moreover, the cells were able to self-renew, sustain multipotent differentiation potential, and readily form neurospheres in suspension culture. Conclusion: SHED, as an adult stem cell with a neural crest origin, has stromal-derived inducing activity (SDIA and can be used as an NCC inducer from hESCs. These cells provide an invaluable resource to study neural crest differentiation in both normal and disordered human neural crest development.

  12. Kinesin light chain 1 suppression impairs human embryonic stem cell neural differentiation and amyloid precursor protein metabolism.

    Directory of Open Access Journals (Sweden)

    Rhiannon L Killian

    Full Text Available The etiology of sporadic Alzheimer disease (AD is largely unknown, although evidence implicates the pathological hallmark molecules amyloid beta (Aβ and phosphorylated Tau. Work in animal models suggests that altered axonal transport caused by Kinesin-1 dysfunction perturbs levels of both Aβ and phosphorylated Tau in neural tissues, but the relevance of Kinesin-1 dependent functions to the human disease is unknown. To begin to address this issue, we generated human embryonic stem cells (hESC expressing reduced levels of the kinesin light chain 1 (KLC1 Kinesin-1 subunit to use as a source of human neural cultures. Despite reduction of KLC1, undifferentiated hESC exhibited apparently normal colony morphology and pluripotency marker expression. Differentiated neural cultures derived from KLC1-suppressed hESC contained neural rosettes but further differentiation revealed obvious morphological changes along with reduced levels of microtubule-associated neural proteins, including Tau and less secreted Aβ, supporting the previously established connection between KLC1, Tau and Aβ. Intriguingly, KLC1-suppressed neural precursors (NPs, isolated using a cell surface marker signature known to identify cells that give rise to neurons and glia, unlike control cells, failed to proliferate. We suggest that KLC1 is required for normal human neural differentiation, ensuring proper metabolism of AD-associated molecules APP and Tau and for proliferation of NPs. Because impaired APP metabolism is linked to AD, this human cell culture model system will not only be a useful tool for understanding the role of KLC1 in regulating the production, transport and turnover of APP and Tau in neurons, but also in defining the essential function(s of KLC1 in NPs and their progeny. This knowledge should have important implications for human neurodevelopmental and neurodegenerative diseases.

  13. Classification of human activity on water through micro-Dopplers using deep convolutional neural networks

    Science.gov (United States)

    Kim, Youngwook; Moon, Taesup

    2016-05-01

    Detecting humans and classifying their activities on the water has significant applications for surveillance, border patrols, and rescue operations. When humans are illuminated by radar signal, they produce micro-Doppler signatures due to moving limbs. There has been a number of research into recognizing humans on land by their unique micro-Doppler signatures, but there is scant research into detecting humans on water. In this study, we investigate the micro-Doppler signatures of humans on water, including a swimming person, a swimming person pulling a floating object, and a rowing person in a small boat. The measured swimming styles were free stroke, backstroke, and breaststroke. Each activity was observed to have a unique micro-Doppler signature. Human activities were classified based on their micro-Doppler signatures. For the classification, we propose to apply deep convolutional neural networks (DCNN), a powerful deep learning technique. Rather than using conventional supervised learning that relies on handcrafted features, we present an alternative deep learning approach. We apply the DCNN, one of the most successful deep learning algorithms for image recognition, directly to a raw micro-Doppler spectrogram of humans on the water. Without extracting any explicit features from the micro-Dopplers, the DCNN can learn the necessary features and build classification boundaries using the training data. We show that the DCNN can achieve accuracy of more than 87.8% for activity classification using 5- fold cross validation.

  14. Protection of visual functions by human neural progenitors in a rat model of retinal disease.

    Directory of Open Access Journals (Sweden)

    David M Gamm

    Full Text Available BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90-100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative

  15. Neural mechanisms of human perceptual learning: electrophysiological evidence for a two-stage process.

    Science.gov (United States)

    Hamamé, Carlos M; Cosmelli, Diego; Henriquez, Rodrigo; Aboitiz, Francisco

    2011-04-26

    Humans and other animals change the way they perceive the world due to experience. This process has been labeled as perceptual learning, and implies that adult nervous systems can adaptively modify the way in which they process sensory stimulation. However, the mechanisms by which the brain modifies this capacity have not been sufficiently analyzed. We studied the neural mechanisms of human perceptual learning by combining electroencephalographic (EEG) recordings of brain activity and the assessment of psychophysical performance during training in a visual search task. All participants improved their perceptual performance as reflected by an increase in sensitivity (d') and a decrease in reaction time. The EEG signal was acquired throughout the entire experiment revealing amplitude increments, specific and unspecific to the trained stimulus, in event-related potential (ERP) components N2pc and P3 respectively. P3 unspecific modification can be related to context or task-based learning, while N2pc may be reflecting a more specific attentional-related boosting of target detection. Moreover, bell and U-shaped profiles of oscillatory brain activity in gamma (30-60 Hz) and alpha (8-14 Hz) frequency bands may suggest the existence of two phases for learning acquisition, which can be understood as distinctive optimization mechanisms in stimulus processing. We conclude that there are reorganizations in several neural processes that contribute differently to perceptual learning in a visual search task. We propose an integrative model of neural activity reorganization, whereby perceptual learning takes place as a two-stage phenomenon including perceptual, attentional and contextual processes.

  16. Neural mechanisms of human perceptual learning: electrophysiological evidence for a two-stage process.

    Directory of Open Access Journals (Sweden)

    Carlos M Hamamé

    Full Text Available BACKGROUND: Humans and other animals change the way they perceive the world due to experience. This process has been labeled as perceptual learning, and implies that adult nervous systems can adaptively modify the way in which they process sensory stimulation. However, the mechanisms by which the brain modifies this capacity have not been sufficiently analyzed. METHODOLOGY/PRINCIPAL FINDINGS: We studied the neural mechanisms of human perceptual learning by combining electroencephalographic (EEG recordings of brain activity and the assessment of psychophysical performance during training in a visual search task. All participants improved their perceptual performance as reflected by an increase in sensitivity (d' and a decrease in reaction time. The EEG signal was acquired throughout the entire experiment revealing amplitude increments, specific and unspecific to the trained stimulus, in event-related potential (ERP components N2pc and P3 respectively. P3 unspecific modification can be related to context or task-based learning, while N2pc may be reflecting a more specific attentional-related boosting of target detection. Moreover, bell and U-shaped profiles of oscillatory brain activity in gamma (30-60 Hz and alpha (8-14 Hz frequency bands may suggest the existence of two phases for learning acquisition, which can be understood as distinctive optimization mechanisms in stimulus processing. CONCLUSIONS/SIGNIFICANCE: We conclude that there are reorganizations in several neural processes that contribute differently to perceptual learning in a visual search task. We propose an integrative model of neural activity reorganization, whereby perceptual learning takes place as a two-stage phenomenon including perceptual, attentional and contextual processes.

  17. Classification of Human Emotion from Deap EEG Signal Using Hybrid Improved Neural Networks with Cuckoo Search

    Directory of Open Access Journals (Sweden)

    M. Sreeshakthy

    2016-01-01

    Full Text Available Department of Computer Science and Engineering,Anna University Regional Centre, Coimbatore, Indiam.sribtechit@gmail.comJ. PreethiDepartment of Computer Science and EngineeringAnna University Regional Centre, Coimbatore, Indiapreethi17j@yahoo.comEmotions are very important in human decision handling, interaction and cognitive process. In this paper describes that recognize the human emotions from DEAP EEG dataset with different kind of methods. Audio – video based stimuli is used to extract the emotions. EEG signal is divided into different bands using discrete wavelet transformation with db8 wavelet function for further process. Statistical and energy based features are extracted from the bands, based on the features emotions are classified with feed forward neural network with weight optimized algorithm like PSO. Before that the particular band has to be selected based on the training performance of neural networks and then the emotions are classified. In this experimental result describes that the gamma and alpha bands are provides the accurate classification result with average classification rate of 90.3% of using NNRBF, 90.325% of using PNN, 96.3% of using PSO trained NN, 98.1 of using Cuckoo trained NN. At last the emotions are classified into two different groups like valence and arousal. Based on that identifies the person normal and abnormal behavioral using classified emotion.

  18. ISOLATION AND EXPANSION OF HUMAN EMBRYONIC NEURAL STEM/PROGENITOR CELLS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective: To isolate, culture and identify human embryonic neural stem cells and to establish a practical passaging method. Method:The cerebral cortex cells were isolated from aborted embryos (11~13 weeks)by mechanical dissociation, and cultured in DMEM/F12 culture medium supplemented with N2 and growth factors for proliferation. Upon passaging, the neurospheres were pipetted gentlely to separate them into several cell masses and then grown in growth medium. The cells were grown in DMEM/F12 medium with serum (without growth factors) to induce differentiation. The stem cell, neuron, astrocyte and oligodendrocyte were identified by immunocytochemistry with antibodies to vimentin, MAP2, GFAP and GalC, respectively. Results:The primary cells grew together and formed neurospheres at 5th~7th day. They were all vimentin positive and could be passaged for at least 8passages. After passaging, the cell masses grew up and formed new neurospheres rapidly. These cells could differentiated into MAP2 ( + ), GFAP( + ) or GalC( + ) cells. Conclusion: The neural stem cells from human embryonic cerebral cortex have the capacity of proliferation and multi - differentiation in vitro. The passaging methods we used in this experiment were practical and convenient.

  19. Classification of Human Emotion from Deap EEG Signal Using Hybrid Improved Neural Networks with Cuckoo Search

    Directory of Open Access Journals (Sweden)

    M. Sreeshakthy

    2016-01-01

    Full Text Available Department of Computer Science and Engineering,Anna University Regional Centre, Coimbatore, Indiam.sribtechit@gmail.comJ. PreethiDepartment of Computer Science and EngineeringAnna University Regional Centre, Coimbatore, Indiapreethi17j@yahoo.comEmotions are very important in human decision handling, interaction and cognitive process. In this paper describes that recognize the human emotions from DEAP EEG dataset with different kind of methods. Audio – video based stimuli is used to extract the emotions. EEG signal is divided into different bands using discrete wavelet transformation with db8 wavelet function for further process. Statistical and energy based features are extracted from the bands, based on the features emotions are classified with feed forward neural network with weight optimized algorithm like PSO. Before that the particular band has to be selected based on the training performance of neural networks and then the emotions are classified. In this experimental result describes that the gamma and alpha bands are provides the accurate classification result with average classification rate of 90.3% of using NNRBF, 90.325% of using PNN, 96.3% of using PSO trained NN, 98.1 of using Cuckoo trained NN. At last the emotions are classified into two different groups like valence and arousal. Based on that identifies the person normal and abnormal behavioral using classified emotion.

  20. Noise-Induced Hearing Loss (NIHL Prediction in Humans Using a Modified Back Propagation Neural Network

    Directory of Open Access Journals (Sweden)

    Muhammad Zubair Rehman

    2011-01-01

    Full Text Available Noise-Induced Hearing Loss (NIHL has become a major source of health problem in industrial workers due to continuous exposure to high frequency sounds emitting from the machines. In the past, several studies have been carried-out to identify NIHL industrial workers. Unfortunately, these studies neglected some important factors that directly affect hearing ability in human. Artificial Neural Network (ANN provides very effective way to predict hearing loss in humans. However, the training process for an ANN required the designers to arbitrarily select parameters such as network topology, initial weights and biases, learning rate value, the activation function, value for gain in activation function and momentum. An improper choice of any of these parameters can result in slow convergence or even network paralysis, where the training process comes to a standstill or get stuck at local minima. Therefore, this current study focuses on proposing a new framework on using Gradient Descent Back Propagation Neural Network model with an improvement on the momentum value to identify the important factors that directly affect the hearing ability of industrial workers. Results from the prediction will be used in determining the environmental health hazards which affect the workers health.

  1. An Active Stereo Vision System Based on Neural Pathways of Human Binocular Motor System

    Institute of Scientific and Technical Information of China (English)

    Yu-zhang Gu; Makoto Sato; Xiao-lin Zhang

    2007-01-01

    An active stereo vision system based on a model of neural pathways of human binocular motor system is proposed. With this model, it is guaranteed that the two cameras of the active stereo vision system can keep their lines of sight fixed on the same target object during smooth pursuit. This feature is very important for active stereo vision systems, since not only 3D reconstruction needs the two cameras have an overlapping field of vision, but also it can facilitate the 3D reconstruction algorithm. To evaluate the effectiveness of the proposed method, some software simulations are done to demonstrate the same target tracking characteristic in a virtual environment apt to mistracking easily. Here, mistracking means two eyes track two different objects separately. Then the proposed method is implemented in our active stereo vision system to perform real tracking task in a laboratory scene where several persons walk self-determining. Before the proposed model is implemented in the system, mistracking occurred frequently. After it is enabled, mistracking never occurred. The result shows that the vision system based on neural pathways of human binocular motor system can reliably avoid mistracking.

  2. Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2017-06-01

    Full Text Available Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low to 500,000 (very high cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles.

  3. A hybrid neural network system for prediction and recognition of promoter regions in human genome

    Institute of Scientific and Technical Information of China (English)

    CHEN Chuan-bo; LI Tao

    2005-01-01

    This paper proposes a high specificity and sensitivity algorithm called PromPredictor for recognizing promoter regions in the human genome. PromPredictor extracts compositional features and CpG islands information from genomic sequence,feeding these features as input for a hybrid neural network system (HNN) and then applies the HNN for prediction. It combines a novel promoter recognition model, coding theory, feature selection and dimensionality reduction with machine learning algorithm.Evaluation on Human chromosome 22 was ~66% in sensitivity and ~48% in specificity. Comparison with two other systems revealed that our method had superior sensitivity and specificity in predicting promoter regions. PromPredictor is written in MATLAB and requires Matlab to run. PromPredictor is freely available at http://www.whtelecom.com/Prompredictor.htm.

  4. Reprogramming of adult human neural stem cells into induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    XIE Li-qian; SUN Hua-ping; WANG Tian; TANG Hai-liang; WANG Pu; ZHU Jian-hong; YAO Zheng-wei

    2013-01-01

    Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases,here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients.When combined with four factors (OCT3/4,SOX2,KLF4,and c-MYC),iPSCs colonies were successfully obtained.Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties,which include the ability to differentiate into all three germ layers both in vitro and in vivo.Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

  5. Xenotransplantation of Human Neural Progenitor Cells to the Subretinal Space of Nonimmunosuppressed Pigs

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    Karin Warfvinge

    2011-01-01

    Full Text Available To investigate the feasibility of transplanting human neural progenitor cells (hNPCs to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal vessels appeared normal without signs of exudation, bleeding, or subretinal elevation. Eyes were harvested at 10–28 days. H&E consistently showed mild retinal vasculitis, depigmentation of the RPE, and marked mononuclear cell infiltrate in the choroid adjacent to the site of transplantation. Human-specific antibodies revealed donor cells in the subretinal space at 10–13 days and smaller numbers within the retina on days 12 and 13, with evidence suggesting a limited degree of morphological integration; however, no cells remained at 4 weeks. The strong mononuclear cell reaction and loss of donor cells indicate that modulation of host immunity is likely necessary for prolonged xenograft survival in this model.

  6. Insights in spatio-temporal characterization of human fetal neural stem cells.

    Science.gov (United States)

    Martín-Ibáñez, Raquel; Guardia, Inés; Pardo, Mónica; Herranz, Cristina; Zietlow, Rike; Vinh, Ngoc-Nga; Rosser, Anne; Canals, Josep M

    2017-05-01

    Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum. We observed that, as fetal brain development proceeds, the number of neural precursors is diminished and post-mitotic cells are increased. In turn, primary cells obtained from older embryos are more sensitive to the dissociation process, their viability is diminished and they present lower proliferation ratios compared to younger embryos. However, independently of the developmental stage of derivation proliferation ratios were very low in all cases. Improvements in the expansion rates were achieved by mechanical, instead of enzymatic, dissociation of neurospheres but not by changes in the seeding densities. Regardless of the developmental stage, neurosphere cultures presented large variability in the viability and proliferation rates during the initial 3-4 passages, but stabilized achieving significant expansion rates at passage 5 to 6. This was true also for all brain regions except cerebellar derived cultures that did not expand. Interestingly, the brain region of hfNSC derivation influences the expansion potential, being forebrain, cortex and WGE derived cells the most expandable compared to cerebellar. Short term expansion partially compromised the regional identity of cortical but not WGE cultures. Nevertheless, both expanded cultures were

  7. Multimodal neural correlates of cognitive control in the Human Connectome Project.

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    Lerman-Sinkoff, Dov B; Sui, Jing; Rachakonda, Srinivas; Kandala, Sridhar; Calhoun, Vince D; Barch, Deanna M

    2017-08-31

    Cognitive control is a construct that refers to the set of functions that enable decision-making and task performance through the representation of task states, goals, and rules. The neural correlates of cognitive control have been studied in humans using a wide variety of neuroimaging modalities, including structural MRI, resting-state fMRI, and task-based fMRI. The results from each of these modalities independently have implicated the involvement of a number of brain regions in cognitive control, including dorsal prefrontal cortex, and frontal parietal and cingulo-opercular brain networks. However, it is not clear how the results from a single modality relate to results in other modalities. Recent developments in multimodal image analysis methods provide an avenue for answering such questions and could yield more integrated models of the neural correlates of cognitive control. In this study, we used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) to identify multimodal patterns of variation related to cognitive control. We used two independent cohorts of participants from the Human Connectome Project, each of which had data from four imaging modalities. We replicated the findings from the first cohort in the second cohort using both independent and predictive analyses. The independent analyses identified a component in each cohort that was highly similar to the other and significantly correlated with cognitive control performance. The replication by prediction analyses identified two independent components that were significantly correlated with cognitive control performance in the first cohort and significantly predictive of performance in the second cohort. These components identified positive relationships across the modalities in neural regions related to both dynamic and stable aspects of task control, including regions in both the frontal-parietal and cingulo-opercular networks, as well as regions

  8. Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury.

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    Daadi, Marcel M; Davis, Alexis S; Arac, Ahmet; Li, Zongjin; Maag, Anne-Lise; Bhatnagar, Rishi; Jiang, Kewen; Sun, Guohua; Wu, Joseph C; Steinberg, Gary K

    2010-03-01

    Hypoxic-ischemic (HI) brain injury in newborn infants represents a major cause of cerebral palsy, development delay, and epilepsy. Stem cell-based therapy has the potential to rescue and replace the ischemic tissue caused by HI and to restore function. However, the mechanisms by which stem cell transplants induce functional recovery are yet to be elucidated. In the present study, we sought to investigate the efficacy of human neural stem cells derived from human embryonic stem cells in a rat model of neonatal HI and the mechanisms enhancing brain repair. The human neural stem cells were genetically engineered for in vivo molecular imaging and for postmortem histological tracking. Twenty-four hours after the induction of HI, animals were grafted with human neural stem cells into the forebrain. Motor behavioral tests were performed the fourth week after transplantation. We used immunocytochemistry and neuroanatomical tracing to analyze neural differentiation, axonal sprouting, and microglia response. Treatment-induced changes in gene expression were investigated by microarray and quantitative polymerase chain reaction. Bioluminescence imaging permitted real time longitudinal tracking of grafted human neural stem cells. HI transplanted animals significantly improved in their use of the contralateral impeded forelimb and in the Rotorod test. The grafts showed good survival, dispersion, and differentiation. We observed an increase of uniformly distributed microglia cells in the grafted side. Anterograde neuroanatomical tracing demonstrated significant contralesional sprouting. Microarray analysis revealed upregulation of genes involved in neurogenesis, gliogenesis, and neurotrophic support. These results suggest that human neural stem cell transplants enhance endogenous brain repair through multiple modalities in response to HI.

  9. Preclinical Analysis of Fetal Human Mesencephalic Neural Progenitor Cell Lines: Characterization and Safety In Vitro and In Vivo.

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    Moon, Jisook; Schwarz, Sigrid C; Lee, Hyun-Seob; Kang, Jun Mo; Lee, Young-Eun; Kim, Bona; Sung, Mi-Young; Höglinger, Günter; Wegner, Florian; Kim, Jin Su; Chung, Hyung-Min; Chang, Sung Woon; Cha, Kwang Yul; Kim, Kwang-Soo; Schwarz, Johannes

    2016-09-02

    : We have developed a good manufacturing practice for long-term cultivation of fetal human midbrain-derived neural progenitor cells. The generation of human dopaminergic neurons may serve as a tool of either restorative cell therapies or cellular models, particularly as a reference for phenotyping region-specific human neural stem cell lines such as human embryonic stem cells and human inducible pluripotent stem cells. We cultivated 3 different midbrain neural progenitor lines at 10, 12, and 14 weeks of gestation for more than a year and characterized them in great detail, as well as in comparison with Lund mesencephalic cells. The whole cultivation process of tissue preparation, cultivation, and cryopreservation was developed using strict serum-free conditions and standardized operating protocols under clean-room conditions. Long-term-cultivated midbrain-derived neural progenitor cells retained stemness, midbrain fate specificity, and floorplate markers. The potential to differentiate into authentic A9-specific dopaminergic neurons was markedly elevated after prolonged expansion, resulting in large quantities of functional dopaminergic neurons without genetic modification. In restorative cell therapeutic approaches, midbrain-derived neural progenitor cells reversed impaired motor function in rodents, survived well, and did not exhibit tumor formation in immunodeficient nude mice in the short or long term (8 and 30 weeks, respectively). We conclude that midbrain-derived neural progenitor cells are a promising source for human dopaminergic neurons and suitable for long-term expansion under good manufacturing practice, thus opening the avenue for restorative clinical applications or robust cellular models such as high-content or high-throughput screening.

  10. Prospect of Human Pluripotent Stem Cell-Derived Neural Crest Stem Cells in Clinical Application

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    Qian Zhu

    2016-01-01

    Full Text Available Neural crest stem cells (NCSCs represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration.

  11. Prospect of Human Pluripotent Stem Cell-Derived Neural Crest Stem Cells in Clinical Application

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    Zhu, Qian; Lu, Qiqi; Gao, Rong

    2016-01-01

    Neural crest stem cells (NCSCs) represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration. PMID:28090209

  12. Human olfactory bulb neural stem cells mitigate movement disorders in a rat model of Parkinson's disease.

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    Marei, Hany E S; Lashen, Samah; Farag, Amany; Althani, Asmaa; Afifi, Nahla; A, Abd-Elmaksoud; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-07-01

    Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DA neurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide a therapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the human olfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, and provide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactory bulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFG-GFP-OBNSCs were transplanted into the striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eight weeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (25 ± 2.88%), neuron-like (52.63 ± 4.16%), and astrocyte -like (22.36 ± 1.56%) lineages, which we differentiated based on morphological and immunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in non-pharmacological behavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as a promising cell-based therapeutic strategy for Parkinson's disease. © 2014 Wiley Periodicals, Inc.

  13. STAT3 modulation to enhance motor neuron differentiation in human neural stem cells.

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    Rajalaxmi Natarajan

    Full Text Available Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3 plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs. In vitro hNSCs primed with fibroblast growth factor 2 (FGF2 exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF, which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.

  14. Human neural progenitors derived from integration-free iPSCs for SCI therapy

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    Ying Liu

    2017-03-01

    Full Text Available As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs provide great capability for tissue regeneration, particularly in spinal cord injury (SCI. However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

  15. Human neural stem cells alleviate Alzheimer-like pathology in a mouse model.

    Science.gov (United States)

    Lee, Il-Shin; Jung, Kwangsoo; Kim, Il-Sun; Lee, Haejin; Kim, Miri; Yun, Seokhwan; Hwang, Kyujin; Shin, Jeong Eun; Park, Kook In

    2015-08-21

    Alzheimer's disease (AD) is an inexorable neurodegenerative disease that commonly occurs in the elderly. The cognitive impairment caused by AD is associated with abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells (NSCs) are self-renewing, multipotential cells that differentiate into distinct neural cells. When transplanted into a diseased brain, NSCs repair and replace injured tissues after migration toward and engraftment within lesions. We investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs) that derived from an aborted human fetal telencephalon at 13 weeks of gestation. Cells were transplanted into the cerebral lateral ventricles of neuron-specific enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13 months of age. Implanted cells extensively migrated and engrafted, and some differentiated into neuronal and glial cells, although most hNSCs remained immature. The hNSC transplantation improved spatial memory in these mice, which also showed decreased tau phosphorylation and Aβ42 levels and attenuated microgliosis and astrogliosis. The hNSC transplantation reduced tau phosphorylation via Trk-dependent Akt/GSK3β signaling, down-regulated Aβ production through an Akt/GSK3β signaling-mediated decrease in BACE1, and decreased expression of inflammatory mediators through deactivation of microglia that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic plasticity and anti-apoptotic function via trophic supplies. Furthermore, the safety and feasibility of hNSC transplantation are supported. These findings demonstrate the hNSC transplantation modulates diverse AD pathologies and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data provide tangible preclinical evidence that human NSC transplantation could be a

  16. Defining the Role of Oxygen Tension in Human Neural Progenitor Fate

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    Yuan Xie

    2014-11-01

    Full Text Available Hypoxia augments human embryonic stem cell (hESC self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and hypoxia-inducible factor (HIF activity instead promote appropriate hESC differentiation. Through gain- and loss-of-function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate toward neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types.

  17. Genetic Programming Neural Networks: A Powerful Bioinformatics Tool for Human Genetics.

    Science.gov (United States)

    Ritchie, Marylyn D; Motsinger, Alison A; Bush, William S; Coffey, Christopher S; Moore, Jason H

    2007-01-01

    The identification of genes that influence the risk of common, complex disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. This challenge is partly due to the limitations of parametric statistical methods for detecting genetic effects that are dependent solely or partially on interactions. We have previously introduced a genetic programming neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of genetic and gene-environment combinations associated with disease risk. Previous empirical studies suggest GPNN has excellent power for identifying gene-gene and gene-environment interactions. The goal of this study was to compare the power of GPNN to stepwise logistic regression (SLR) and classification and regression trees (CART) for identifying gene-gene and gene-environment interactions. SLR and CART are standard methods of analysis for genetic association studies. Using simulated data, we show that GPNN has higher power to identify gene-gene and gene-environment interactions than SLR and CART. These results indicate that GPNN may be a useful pattern recognition approach for detecting gene-gene and gene-environment interactions in studies of human disease.

  18. High-frequency oscillations in distributed neural networks reveal the dynamics of human decision making

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    Adrian G Guggisberg

    2008-03-01

    Full Text Available We examine the relative timing of numerous brain regions involved in human decisions that are based on external criteria, learned information, personal preferences, or unconstrained internal considerations. Using magnetoencephalography (MEG and advanced signal analysis techniques, we were able to non-invasively reconstruct oscillations of distributed neural networks in the high-gamma frequency band (60–150 Hz. The time course of the observed neural activity suggested that two-alternative forced choice tasks are processed in four overlapping stages: processing of sensory input, option evaluation, intention formation, and action execution. Visual areas are activated fi rst, and show recurring activations throughout the entire decision process. The temporo-occipital junction and the intraparietal sulcus are active during evaluation of external values of the options, 250–500 ms after stimulus presentation. Simultaneously, personal preference is mediated by cortical midline structures. Subsequently, the posterior parietal and superior occipital cortices appear to encode intention, with different subregions being responsible for different types of choice. The cerebellum and inferior parietal cortex are recruited for internal generation of decisions and actions, when all options have the same value. Action execution was accompanied by activation peaks in the contralateral motor cortex. These results suggest that high-gamma oscillations as recorded by MEG allow a reliable reconstruction of decision processes with excellent spatiotemporal resolution.

  19. Plasticity of Corticospinal Neural Control after Locomotor Training in Human Spinal Cord Injury

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    Maria Knikou

    2012-01-01

    Full Text Available Spinal lesions substantially impair ambulation, occur generally in young and otherwise healthy individuals, and result in devastating effects on quality of life. Restoration of locomotion after damage to the spinal cord is challenging because axons of the damaged neurons do not regenerate spontaneously. Body-weight-supported treadmill training (BWSTT is a therapeutic approach in which a person with a spinal cord injury (SCI steps on a motorized treadmill while some body weight is removed through an upper body harness. BWSTT improves temporal gait parameters, muscle activation patterns, and clinical outcome measures in persons with SCI. These changes are likely the result of reorganization that occurs simultaneously in supraspinal and spinal cord neural circuits. This paper will focus on the cortical control of human locomotion and motor output, spinal reflex circuits, and spinal interneuronal circuits and how corticospinal control is reorganized after locomotor training in people with SCI. Based on neurophysiological studies, it is apparent that corticospinal plasticity is involved in restoration of locomotion after training. However, the neural mechanisms underlying restoration of lost voluntary motor function are not well understood and translational neuroscience research is needed so patient-orientated rehabilitation protocols to be developed.

  20. Effect of VEGF on Neural Differentiation of Human Embryonic Stem Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Shujie JIAO; Huifang XU; Jie XU; Yanqiang ZHAN; Suming ZHANG

    2009-01-01

    The effects of vascular endothelial growth factor (VEGF) on neural differentiation of human embryonic stem cells (hESCs) in vitro and the possible mechanism were observed. The hESCs lines,TJMU1 and TJMU2, were established and stored by our laboratory, hESCs differentiated into neuronal cells through embryonic body formation. In this induction process, hESCs were divided into three groups: group A, routine induction; group B, routine induction+10 ng/mL VEGF; group C, routine in-duction+10 ng/mL VEGF+10 ng/mL VEGFR2/Fc. OCT4, Nestin and GFAP in each group were de-tected by RT-PCR, and the cells expressing Nestin and GFAP were counted by immunofluorescence.The percentage of Nestin positive cells in group B was significantly higher than in groups A and C,while the percentage of GFAP positive cells in group B was significantly lower than in groups A and C (P0.05). It was concluded that VEGF, via VEGFR2, stimulated the neural differentiation of hESCs in vitro.

  1. Neural substrates of human facial expression of pleasant emotion induced by comic films: a PET Study.

    Science.gov (United States)

    Iwase, Masao; Ouchi, Yasuomi; Okada, Hiroyuki; Yokoyama, Chihiro; Nobezawa, Shuji; Yoshikawa, Etsuji; Tsukada, Hideo; Takeda, Masaki; Yamashita, Ko; Takeda, Masatoshi; Yamaguti, Kouzi; Kuratsune, Hirohiko; Shimizu, Akira; Watanabe, Yasuyoshi

    2002-10-01

    Laughter or smile is one of the emotional expressions of pleasantness with characteristic contraction of the facial muscles, of which the neural substrate remains to be explored. This currently described study is the first to investigate the generation of human facial expression of pleasant emotion using positron emission tomography and H(2)(15)O. Regional cerebral blood flow (rCBF) during laughter/smile induced by visual comics and the magnitude of laughter/smile indicated significant correlation in the bilateral supplementary motor area (SMA) and left putamen (P < 0.05, corrected), but no correlation in the primary motor area (M1). In the voluntary facial movement, significant correlation between rCBF and the magnitude of EMG was found in the face area of bilateral M1 and the SMA (P < 0.001, uncorrected). Laughter/smile, as opposed to voluntary movement, activated the visual association areas, left anterior temporal cortex, left uncus, and orbitofrontal and medial prefrontal cortices (P < 0.05, corrected), whereas voluntary facial movement generated by mimicking a laughing/smiling face activated the face area of the left M1 and bilateral SMA, compared with laughter/smile (P < 0.05, corrected). We demonstrated distinct neural substrates of emotional and volitional facial expression and defined cognitive and experiential processes of a pleasant emotion, laughter/smile.

  2. Controllability modulates the neural response to predictable but not unpredictable threat in humans.

    Science.gov (United States)

    Wood, Kimberly H; Wheelock, Muriah D; Shumen, Joshua R; Bowen, Kenton H; Ver Hoef, Lawrence W; Knight, David C

    2015-10-01

    Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

  3. Using human neural crest-derived progenitor cells to investigate osteogenesis: an in vitro study.

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    Degistirici, Ozer; Grabellus, Florian; Irsen, Stephan; Schmid, Kurt Werner; Thie, Michael

    2010-04-01

    Human tooth contains a distinct population of neural crest-derived progenitor cells (dNC-PCs) which are known to give rise to specialized daughter cells of an osteogenic lineage. We hypothesised that dNC-PCs could develop into neural crest-derived bone in a self-propagating and extracorporal culture system. Thus, we examined the three-dimensional structure obtained from osteogenic-stimulated dNC-PCs by morphological, biochemical and spectroscopic methods. After the onset of stimulation, cells formed a multilayer with outer cells covering the surface and inner cells secreting a hyaline matrix. With prolonged culture, multilayers contracted and formed a three-dimensional construct which subsequently converted to a calcified mass. Differentiation of progenitor cells was associated with apoptosis. Cell types which survived were smooth muscle actin-positive cells and bone-like cells. The expression of osteoblastic markers and the secretion of a collagenous matrix indicate that the bone cells had acquired their functional phenotype. Furthermore, these cells produced and secreted membrane-bound vesicles into the newly forming matrix. Consequently, an early biomineralized extracellular matrix was found with calcium phosphate deposits being associated with the newly formed collagen matrix framework. The molar calcium-phosphorus-ratio of the mineralized collagen indicated that amorphous calcium phosphate was present within this matrix. The data suggest that stimulated cultures of dNC-PCs are able to recapitulate some processes of the early phase of osteogenesis.

  4. Functional plasticity before the cradle: a review of neural functional imaging in the human fetus.

    Science.gov (United States)

    Anderson, Amy L; Thomason, Moriah E

    2013-11-01

    The organization of the brain is highly plastic in fetal life. Establishment of healthy neural functional systems during the fetal period is essential to normal growth and development. Across the last several decades, remarkable progress has been made in understanding the development of human fetal functional brain systems. This is largely due to advances in imaging methodologies. Fetal neuroimaging began in the 1950-1970's with fetal electroencephalography (EEG) applied during labor. Later, in the 1980's, magnetoencephalography (MEG) emerged as an effective approach for investigating fetal brain function. Most recently, functional magnetic resonance imaging (fMRI) has arisen as an additional powerful approach for examining fetal brain function. This review will discuss major developmental findings from fetal imaging studies such as the maturation of prenatal sensory system functions, functional hemispheric asymmetry, and sensory-driven neurodevelopment. We describe how with improved imaging and analysis techniques, functional imaging of the fetus has the potential to assess the earliest point of neural maturation and provide insight into the patterning and sequence of normal and abnormal brain development. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Convolutional Neural Network-Based Human Detection in Nighttime Images Using Visible Light Camera Sensors

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    Jong Hyun Kim

    2017-05-01

    Full Text Available Because intelligent surveillance systems have recently undergone rapid growth, research on accurately detecting humans in videos captured at a long distance is growing in importance. The existing research using visible light cameras has mainly focused on methods of human detection for daytime hours when there is outside light, but human detection during nighttime hours when there is no outside light is difficult. Thus, methods that employ additional near-infrared (NIR illuminators and NIR cameras or thermal cameras have been used. However, in the case of NIR illuminators, there are limitations in terms of the illumination angle and distance. There are also difficulties because the illuminator power must be adaptively adjusted depending on whether the object is close or far away. In the case of thermal cameras, their cost is still high, which makes it difficult to install and use them in a variety of places. Because of this, research has been conducted on nighttime human detection using visible light cameras, but this has focused on objects at a short distance in an indoor environment or the use of video-based methods to capture multiple images and process them, which causes problems related to the increase in the processing time. To resolve these problems, this paper presents a method that uses a single image captured at night on a visible light camera to detect humans in a variety of environments based on a convolutional neural network. Experimental results using a self-constructed Dongguk night-time human detection database (DNHD-DB1 and two open databases (Korea advanced institute of science and technology (KAIST and computer vision center (CVC databases, as well as high-accuracy human detection in a variety of environments, show that the method has excellent performance compared to existing methods.

  6. Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

    Science.gov (United States)

    Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine

    2009-05-01

    Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between

  7. Neural mechanisms of genetic risk for impulsivity and violence in humans.

    Science.gov (United States)

    Meyer-Lindenberg, Andreas; Buckholtz, Joshua W; Kolachana, Bhaskar; R Hariri, Ahmad; Pezawas, Lukas; Blasi, Giuseppe; Wabnitz, Ashley; Honea, Robyn; Verchinski, Beth; Callicott, Joseph H; Egan, Michael; Mattay, Venkata; Weinberger, Daniel R

    2006-04-18

    Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.

  8. Deep biomarkers of human aging: Application of deep neural networks to biomarker development.

    Science.gov (United States)

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-05-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis.

  9. Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Dana M. Cairns

    2016-09-01

    Full Text Available Limited availability of human neurons poses a significant barrier to progress in biological and preclinical studies of the human nervous system. Current stem cell-based approaches of neuron generation are still hindered by prolonged culture requirements, protocol complexity, and variability in neuronal differentiation. Here we establish stable human induced neural stem cell (hiNSC lines through the direct reprogramming of neonatal fibroblasts and adult adipose-derived stem cells. These hiNSCs can be passaged indefinitely and cryopreserved as colonies. Independently of media composition, hiNSCs robustly differentiate into TUJ1-positive neurons within 4 days, making them ideal for innervated co-cultures. In vivo, hiNSCs migrate, engraft, and contribute to both central and peripheral nervous systems. Lastly, we demonstrate utility of hiNSCs in a 3D human brain model. This method provides a valuable interdisciplinary tool that could be used to develop drug screening applications as well as patient-specific disease models related to disorders of innervation and the brain.

  10. Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Shirin FARIVAR*

    2015-01-01

    Full Text Available How to Cite This Article: : Farivar S, Mohamadzade Z, Shiari R, Fahimzad AR. Neural Differentiation of Human Umbilical CordMesenchymal Stem Cells by Cerebrospinal Fluid. . Iran J Child Neurol. 2015 Winter; 9(1:87-93.  Abstract Objective Wharton’s jelly (WJ is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF on neural differentiation of human WJ stem cells.Material & Methods The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2, and Glial Fibrillary Astrocytic Protein (GFAP for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR.Results Treatment with 100 and 200μg/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer.Conclusion RT-PCR showed that

  11. MicroRNAs as markers for neurally committed CD133+/CD34+ stem cells derived from human umbilical cord blood.

    Science.gov (United States)

    Hafizi, Maryam; Atashi, Amir; Bakhshandeh, Behnaz; Kabiri, Mahboubeh; Nadri, Samad; Hosseini, Reza Haji; Soleimani, Masoud

    2013-04-01

    Neural differentiation of the CD133+/CD34+ subpopulation of human umbilical cord blood stem cells was investigated, and neuro-miR (mir-9 and mir-124) expression was examined. An efficient induction protocol for neural differentiation of hematopoietic stem cells together with the exclusion of retinoic acid in this process was also studied. Transcription of some neural markers such as microtubule-associated protein-2, beta-tubulin III, and neuron-specific enolase was evaluated by real-time PCR, immunocytochemistry, and western blotting. Increased expression of neural indicators in the treated cells confirmed the appropriate neural differentiation, which supported the high efficiency of our defined neuronal induction protocol. Verified high expression of neuro-miRNAs along with neuronal specific proteins not only strengthens the regulatory role of miRNAs in determining stem cell fate but also introduces these miRNAs as novel indicators of neural differentiation. These data highlight the prominent therapeutic potential of hematopoietic stem cells for use in cell therapy of neurodegenerative diseases.

  12. Nature of the coupling between neural drive and force-generating capacity in the human quadriceps muscle.

    Science.gov (United States)

    Hug, François; Goupille, Clément; Baum, Daniel; Raiteri, Brent J; Hodges, Paul W; Tucker, Kylie

    2015-11-22

    The force produced by a muscle depends on both the neural drive it receives and several biomechanical factors. When multiple muscles act on a single joint, the nature of the relationship between the neural drive and force-generating capacity of the synergistic muscles is largely unknown. This study aimed to determine the relationship between the ratio of neural drive and the ratio of muscle force-generating capacity between two synergist muscles (vastus lateralis (VL) and vastus medialis (VM)) in humans. Twenty-one participants performed isometric knee extensions at 20 and 50% of maximal voluntary contractions (MVC). Myoelectric activity (surface electromyography (EMG)) provided an index of neural drive. Physiological cross-sectional area (PCSA) was estimated from measurements of muscle volume (magnetic resonance imaging) and muscle fascicle length (three-dimensional ultrasound imaging) to represent the muscles' force-generating capacities. Neither PCSA nor neural drive was balanced between VL and VM. There was a large (r = 0.68) and moderate (r = 0.43) correlation between the ratio of VL/VM EMG amplitude and the ratio of VL/VM PCSA at 20 and 50% of MVC, respectively. This study provides evidence that neural drive is biased by muscle force-generating capacity, the greater the force-generating capacity of VL compared with VM, the stronger bias of drive to the VL.

  13. Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells

    Directory of Open Access Journals (Sweden)

    Yannick Simonin

    2016-10-01

    Full Text Available The recent Zika virus (ZIKV epidemic has highlighted the poor knowledge on its physiopathology. Recent studies showed that ZIKV of the Asian lineage, responsible for this international outbreak, causes neuropathology in vitro and in vivo. However, two African lineages exist and the virus is currently found circulating in Africa. The original African strain was also suggested to be neurovirulent but its laboratory usage has been criticized due to its multiple passages. In this study, we compared the French Polynesian (Asian ZIKV strain to an African strain isolated in Central African Republic and show a difference in infectivity and cellular response between both strains in human neural stem cells and astrocytes. Consistently, this African strain led to a higher infection rate and viral production, as well as stronger cell death and anti-viral response. Our results highlight the need to better characterize the physiopathology and predict neurological impairment associated with African ZIKV.

  14. Cantorian Fractal Spacetime and Quantum-like Chaos in Neural Networks of the Human Brain

    CERN Document Server

    Selvam, A M

    1998-01-01

    The neural networks of the human brain act as very efficient parallel processing computers co-ordinating memory related responses to a multitude of input signals from sensory organs. Information storage, update and appropriate retrieval are controlled at the molecular level by the neuronal cytoskeleton which serves as the internal communication network within neurons. Information flow in the highly ordered parallel networks of the filamentous protein polymers which make up the cytoskeleton may be compared to atmospheric flows which exhibit long-range spatiotemporal correlations, i.e. long-term memory. Such long-range spatiotemporal correlations are ubiquitous to real world dynamical systems and is recently identified as signature of self-organized criticality or chaos. The signatures of self-organized criticality i.e. long-range temporal correlations have recently been identified in the electrical activity of the brain. A recently developed non-deterministic cell dynamical system model for atmospheric flows p...

  15. Interlimb coordination in human crawling reveals similarities in development and neural control with quadrupeds.

    Science.gov (United States)

    Patrick, Susan K; Noah, J Adam; Yang, Jaynie F

    2009-02-01

    The study of quadrupeds has furnished most of our understanding of mammalian locomotion. To allow a more direct comparison of coordination between the four limbs in humans and quadrupeds, we studied crawling in the human, a behavior that is part of normal human development and mechanically more similar to quadrupedal locomotion than is bipedal walking. Interlimb coordination during hands-and-knees crawling is compared between humans and quadrupeds and between human infants and adults. Mechanical factors were manipulated during crawling to understand the relative contributions of mechanics and neural control. Twenty-six infants and seven adults were studied. Video, force plate, and electrogoniometer data were collected. Belt speed of the treadmill, width of base, and limb length were manipulated in adults. Influences of unweighting and limb length were explored in infants. Infants tended to move diagonal limbs together (trot-like). Adults additionally moved ipsilateral limbs together (pace-like). At lower speeds, movements of the four limbs were more equally spaced in time, with no clear pairing of limbs. At higher speeds, running symmetrical gaits were never observed, although one adult galloped. Widening stance prevented adults from using the pace-like gait, whereas lengthening the hind limbs (hands-and-feet crawling) largely prevented the trot-like gait. Limb length and unweighting had no effect on coordination in infants. We conclude that human crawling shares features both with other primates and with nonprimate quadrupeds, suggesting similar underlying mechanisms. The greater restriction in coordination patterns used by infants suggests their nervous system has less flexibility.

  16. Neural Correlates of Vocal Production and Motor Control in Human Heschl's Gyrus.

    Science.gov (United States)

    Behroozmand, Roozbeh; Oya, Hiroyuki; Nourski, Kirill V; Kawasaki, Hiroto; Larson, Charles R; Brugge, John F; Howard, Matthew A; Greenlee, Jeremy D W

    2016-02-17

    The present study investigated how pitch frequency, a perceptually relevant aspect of periodicity in natural human vocalizations, is encoded in Heschl's gyrus (HG), and how this information may be used to influence vocal pitch motor control. We recorded local field potentials from multicontact depth electrodes implanted in HG of 14 neurosurgical epilepsy patients as they vocalized vowel sounds and received brief (200 ms) pitch perturbations at 100 Cents in their auditory feedback. Event-related band power responses to vocalizations showed sustained frequency following responses that tracked voice fundamental frequency (F0) and were significantly enhanced in posteromedial HG during speaking compared with when subjects listened to the playback of their own voice. In addition to frequency following responses, a transient response component within the high gamma frequency band (75-150 Hz) was identified. When this response followed the onset of vocalization, the magnitude of the response was the same for the speaking and playback conditions. In contrast, when this response followed a pitch shift, its magnitude was significantly enhanced during speaking compared with playback. We also observed that, in anterolateral HG, the power of high gamma responses to pitch shifts correlated with the magnitude of compensatory vocal responses. These findings demonstrate a functional parcellation of HG with neural activity that encodes pitch in natural human voice, distinguishes between self-generated and passively heard vocalizations, detects discrepancies between the intended and heard vocalization, and contains information about the resulting behavioral vocal compensations in response to auditory feedback pitch perturbations. The present study is a significant contribution to our understanding of sensor-motor mechanisms of vocal production and motor control. The findings demonstrate distinct functional parcellation of core and noncore areas within human auditory cortex on Heschl

  17. Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials.

    Science.gov (United States)

    Giusto, Elena; Donegà, Matteo; Cossetti, Chiara; Pluchino, Stefano

    2014-10-01

    Stem cell technology is a promising branch of regenerative medicine that is aimed at developing new approaches for the treatment of severely debilitating human diseases, including those affecting the central nervous system (CNS). Despite the increasing understanding of the mechanisms governing their biology, the application of stem cell therapeutics remains challenging. The initial idea that stem cell transplants work in vivo via the replacement of endogenous cells lost or damaged owing to disease has been challenged by accumulating evidence of their therapeutic plasticity. This new concept covers the remarkable immune regulatory and tissue trophic effects that transplanted stem cells exert at the level of the neural microenvironment to promote tissue healing via combination of immune modulatory and tissue protective actions, while retaining predominantly undifferentiated features. Among a number of promising candidate stem cell sources, neural stem/precursor cells (NPCs) are under extensive investigation with regard to their therapeutic plasticity after transplantation. The significant impact in vivo of experimental NPC therapies in animal models of inflammatory CNS diseases has raised great expectations that these stem cells, or the manipulation of the mechanisms behind their therapeutic impact, could soon be translated to human studies. This review aims to provide an update on the most recent evidence of therapeutically-relevant neuro-immune interactions following NPC transplants in animal models of multiple sclerosis, cerebral stroke and traumas of the spinal cord, and consideration of the forthcoming challenges related to the early translation of some of these exciting experimental outcomes into clinical medicines. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Micropatterned, clickable culture substrates enable in situ spatiotemporal control of human PSC-derived neural tissue morphology.

    Science.gov (United States)

    Knight, G T; Sha, J; Ashton, R S

    2015-03-28

    We describe a modular culture platform that enables spatiotemporal control of the morphology of 2D neural tissues derived from human pluripotent stem cells (hPSCs) by simply adding clickable peptides to the media. It should be widely applicable for elucidating how spatiotemporal changes in morphology and substrate biochemistry regulate tissue morphogenesis.

  19. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; de Jong, Esther; de la Fonteyne, Liset J. J.; de Klerk, Arja; Piersma, Aldert H.

    2015-01-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecu

  20. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; de Jong, Esther; de la Fonteyne, Liset J. J.; de Klerk, Arja; Piersma, Aldert H.

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the

  1. Distinct gene expression responses of two anticonvulsant drugs in a novel human embryonic stem cell based neural differentiation assay protocol

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; de Jong, Esther; de la Fonteyne, Liset J. J.; de Klerk, Arja; Piersma, Aldert H.

    2015-01-01

    Hazard assessment of chemicals and pharmaceuticals is increasingly gaining from knowledge about molecular mechanisms of toxic action acquired in dedicated in vitro assays. We have developed an efficient human embryonic stem cell neural differentiation test (hESTn) that allows the study of the molecu

  2. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jie Ting Zhang

    Full Text Available The biologic studies of human neural crest stem cells (hNCSCs are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs. For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

  3. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Science.gov (United States)

    Zhang, Jie Ting; Weng, Zhi Hui; Tsang, Kam Sze; Tsang, Lai Ling; Chan, Hsiao Chang; Jiang, Xiao Hua

    2016-01-01

    The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

  4. Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response.

    Science.gov (United States)

    Huang, Ke; Liu, PengFei; Li, Xiang; Chen, ShuBin; Wang, LiHui; Qin, Li; Su, ZhengHui; Huang, WenHao; Liu, Juli; Jia, Bei; Liu, Jie; Cai, JingLei; Pei, DuanQing; Pan, GuangJin

    2014-02-01

    The breakthrough development of induced pluripotent stem cells (iPSCs) raises the prospect of patient-specific treatment for many diseases through the replacement of affected cells. However, whether iPSC-derived functional cell lineages generate a deleterious immune response upon auto-transplantation remains unclear. In this study, we differentiated five human iPSC lines from skin fibroblasts and urine cells into neural progenitor cells (NPCs) and analyzed their immunogenicity. Through co-culture with autogenous peripheral blood mononuclear cells (PBMCs), we showed that both somatic cells and iPSC-derived NPCs do not stimulate significant autogenous PBMC proliferation. However, a significant immune reaction was detected when these cells were co-cultured with allogenous PBMCs. Furthermore, no significant expression of perforin or granzyme B was detected following stimulation of autogenous immune effector cells (CD3(+)CD8(-) T cells, CD3(+)CD8(+) T cells or CD3(-)CD56(+) NK cells) by NPCs in both PBMC and T cell co-culture systems. These results suggest that human iPSC-derived NPCs may not initiate an immune response in autogenous transplants, and thus set a base for further preclinical evaluation of human iPSCs.

  5. The Pavlovian craver: Neural and experiential correlates of single trial naturalistic food conditioning in humans.

    Science.gov (United States)

    Blechert, J; Testa, G; Georgii, C; Klimesch, W; Wilhelm, F H

    2016-05-01

    Present-day environments are replete with tempting foods and the current obesity pandemic speaks to humans' inability to adjust to this. Pavlovian processes may be fundamental to such hedonic overeating. However, a lack of naturalistic Pavlovian paradigms in humans makes translational research difficult and important parameters such as implicitness and acquisition speed are unknown. Here we present a novel naturalistic conditioning task: an image of a neutral object was conditioned to marzipan taste in a single trial procedure by asking the participant to eat the 'object' (made from marzipan). Relative to control objects, results demonstrate robust pre- to post-conditioning changes of both subjective ratings and early as well as late event related brain potentials, suggesting contributions of implicit (attentional) and explicit (motivational) processes. Naturalistic single-trial taste-appetitive conditioning is potent in humans and shapes attentional and motivational neural processes that might challenge self-regulation during exposure to tempting foods. Thus, appetitive conditioning processes might contribute to overweight and obesity.

  6. Tumor-specific gene therapy for pancreatic cancer using human neural stem cells encoding carboxylesterase.

    Science.gov (United States)

    Choi, Sung S; Yoon, Kichul; Choi, Seon-A; Yoon, Seung-Bin; Kim, Seung U; Lee, Hong J

    2016-11-15

    Advanced pancreatic cancer is one of the most lethal malignant human diseases lacking effective treatment. Its extremely low survival rate necessitates development of novel therapeutic approach. Human neural stem cells (NSCs) are known to have tumor-tropic effect. We genetically engineered them to express rabbit carboxyl esterase (F3.CE), which activates prodrug CPT-11(irinotecan) into potent metabolite SN-38. We found significant inhibition of the growth of BxPC3 human pancreatic cancer cell line in vitro by F3.CE in presence of CPT-11. Apoptosis was also markedly increased in BxPC3 cells treated with F3.CE and CPT-11. The ligand VEGF and receptor VEGF-1(Flt1) were identified to be the relevant tumor-tropic chemoattractant. We confirmed in vivo that in mice injected with BxPC3 on their skin, there was significant reduction of tumor size in those treated with both F3.CE and BxPC3 adjacent to the cancer mass. Administration of F3.CE in conjunction with CPT-11 could be a new possibility as an effective treatment regimen for patients suffering from advanced pancreatic cancer.

  7. Human GLUD2 glutamate dehydrogenase is expressed in neural and testicular supporting cells.

    Science.gov (United States)

    Spanaki, Cleanthe; Zaganas, Ioannis; Kleopa, Kleopas A; Plaitakis, Andreas

    2010-05-28

    Mammalian glutamate dehydrogenase (GDH) is an allosterically regulated enzyme that is expressed widely. Its activity is potently inhibited by GTP and thought to be controlled by the need of the cell for ATP. In addition to this housekeeping human (h) GDH1, humans have acquired (via a duplication event) a highly homologous isoenzyme (hGDH2) that is resistant to GTP. Although transcripts of GLUD2, the gene encoding hGDH2, have been detected in human neural and testicular tissues, data on the endogenous protein are lacking. Here, we developed an antibody specific for hGDH2 and used it to study human tissues. Western blot analyses revealed, to our surprise, that endogenous hGDH2 is more densely expressed in testis than in brain. At the subcellular level, hGDH2 localized to mitochondria. Study of testicular tissue using immunocytochemical and immunofluorescence methods revealed that the Sertoli cells were strongly labeled by our anti-hGDH2 antibody. In human cerebral cortex, a robust labeling of astrocytes was detected, with neurons showing faint hGDH2 immunoreactivity. Astrocytes and Sertoli cells are known to support neurons and germ cells, respectively, providing them with lactate that largely derives from the tricarboxylic acid cycle via conversion of glutamate to alpha-ketoglutarate (GDH reaction). As hGDH2 is not subject to GTP control, the enzyme is able to metabolize glutamate even when the tricarboxylic acid cycle generates GTP amounts sufficient to inactivate the housekeeping hGDH1 protein. Hence, the selective expression of hGDH2 by astrocytes and Sertoli cells may provide a significant biological advantage by facilitating metabolic recycling processes essential to the supportive role of these cells.

  8. Consonance and dissonance of musical chords: neural correlates in auditory cortex of monkeys and humans.

    Science.gov (United States)

    Fishman, Y I; Volkov, I O; Noh, M D; Garell, P C; Bakken, H; Arezzo, J C; Howard, M A; Steinschneider, M

    2001-12-01

    , AEPs recorded in the planum temporale do not display significant phase-locked activity, suggesting functional differentiation of auditory cortical regions in humans. These findings support the relevance of synchronous phase-locked neural ensemble activity in A1 for the physiological representation of sensory dissonance in humans and highlight the merits of complementary monkey/human studies in the investigation of neural substrates underlying auditory perception.

  9. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors

    DEFF Research Database (Denmark)

    Seminatore, Christine; Polentes, Jerome; Ellman, Ditte

    2010-01-01

    Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have...... analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors....

  10. Glycogen synthase kinase 3 (GSK3)-inhibitor SB216763 promotes the conversion of human umbilical cord mesenchymal stem cells into neural precursors in adherent culture.

    Science.gov (United States)

    Gao, Liyang; Zhao, Mingyan; Li, Peng; Kong, Junchao; Liu, Zhijun; Chen, Yonghua; Huang, Rui; Chu, Jiaqi; Quan, Juanhua; Zeng, Rong

    2017-01-01

    The ability to generate neural progenitor cells from human umbilical cord mesenchymal stem cells (hUC-MSCs) has provided an option to treat neurodegenerative diseases. To establish a method for this purpose, we characterized the early neural markers of hUC-MSCs-derived cells under different conditions. We found that neither the elimination of signals for alternative fate nor N2 supplement was sufficient to differentiate hUC-MSCs into neural precursor cells, but the GSK3 inhibitor SB216763 could promote an efficient neural commitment of hUC-MSCs. The results indicated that Wnt/β-catenin might play an important role during the early neural differentiation of hUC-MSCs. Here, we report a method for hUC-MSCs to commit efficiently into a neural fate within a short period of time. This protocol provides an efficient method for hUC-MSCs-based neural regeneration.

  11. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    Science.gov (United States)

    Secundo, Lavi

    , the correlation of ECoG activity to kinematic parameters of arm movement is context-dependent, an important constraint to consider in future development of BMI systems. The third chapter delves into a fundamental organizational principle of the primate motor system---cortical control of contralateral limb movements. However, ipsilateral motor areas also appear to play a role in the control of ipsilateral limb movements. Several studies in monkeys have shown that individual neurons in ipsilateral primary motor cortex (M1) may represent, on average, the direction of movements of the ipsilateral arm. Given the increasing body of evidence demonstrating that neural ensembles can reliably represent information with a high temporal resolution, here we characterize the distributed neural representation of ipsilateral upper limb kinematics in both monkey and man. In two macaque monkeys trained to perform center-out reaching movements, we found that the ensemble spiking activity in M1 could continuously represent ipsilateral limb position. We also recorded cortical field potentials from three human subjects and also consistently found evidence of a neural representation for ipsilateral movement parameters. Together, our results demonstrate the presence of a high-fidelity neural representation for ipsilateral movement and illustrates that it can be successfully incorporated into a brain-machine interface.

  12. The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans.

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    Ola Alsalman

    Full Text Available Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic

  13. The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans.

    Science.gov (United States)

    Alsalman, Ola; Ost, Jan; Vanspauwen, Robby; Blaivie, Catherine; De Ridder, Dirk; Vanneste, Sven

    2016-01-01

    Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic symptoms of vertigo

  14. Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles.

    Science.gov (United States)

    Baulch, Janet E; Craver, Brianna M; Tran, Katherine K; Yu, Liping; Chmielewski, Nicole; Allen, Barrett D; Limoli, Charles L

    2015-08-01

    Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC) exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO) and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively) in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS) was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut's ability to perform complex tasks during extended missions in deep space. Copyright © 2015 The Authors. Published by

  15. Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles

    Directory of Open Access Journals (Sweden)

    Janet E. Baulch

    2015-08-01

    Full Text Available Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut’s ability to perform complex tasks during extended missions in deep space.

  16. Interaction matters: A perceived social partner alters the neural processing of human speech.

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    Rice, Katherine; Redcay, Elizabeth

    2016-04-01

    Mounting evidence suggests that social interaction changes how communicative behaviors (e.g., spoken language, gaze) are processed, but the precise neural bases by which social-interactive context may alter communication remain unknown. Various perspectives suggest that live interactions are more rewarding, more attention-grabbing, or require increased mentalizing-thinking about the thoughts of others. Dissociating between these possibilities is difficult because most extant neuroimaging paradigms examining social interaction have not directly compared live paradigms to conventional "offline" (or recorded) paradigms. We developed a novel fMRI paradigm to assess whether and how an interactive context changes the processing of speech matched in content and vocal characteristics. Participants listened to short vignettes--which contained no reference to people or mental states--believing that some vignettes were prerecorded and that others were presented over a real-time audio-feed by a live social partner. In actuality, all speech was prerecorded. Simply believing that speech was live increased activation in each participant's own mentalizing regions, defined using a functional localizer. Contrasting live to recorded speech did not reveal significant differences in attention or reward regions. Further, higher levels of autistic-like traits were associated with altered neural specialization for live interaction. These results suggest that humans engage in ongoing mentalizing about social partners, even when such mentalizing is not explicitly required, illustrating how social context shapes social cognition. Understanding communication in social context has important implications for typical and atypical social processing, especially for disorders like autism where social difficulties are more acute in live interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Neural coding of cooperative vs. affective human interactions: 150 ms to code the action's purpose.

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    Alice Mado Proverbio

    Full Text Available The timing and neural processing of the understanding of social interactions was investigated by presenting scenes in which 2 people performed cooperative or affective actions. While the role of the human mirror neuron system (MNS in understanding actions and intentions is widely accepted, little is known about the time course within which these aspects of visual information are automatically extracted. Event-Related Potentials were recorded in 35 university students perceiving 260 pictures of cooperative (e.g., 2 people dragging a box or affective (e.g., 2 people smiling and holding hands interactions. The action's goal was automatically discriminated at about 150-170 ms, as reflected by occipito/temporal N170 response. The swLORETA inverse solution revealed the strongest sources in the right posterior cingulate cortex (CC for affective actions and in the right pSTS for cooperative actions. It was found a right hemispheric asymmetry that involved the fusiform gyrus (BA37, the posterior CC, and the medial frontal gyrus (BA10/11 for the processing of affective interactions, particularly in the 155-175 ms time window. In a later time window (200-250 ms the processing of cooperative interactions activated the left post-central gyrus (BA3, the left parahippocampal gyrus, the left superior frontal gyrus (BA10, as well as the right premotor cortex (BA6. Women showed a greater response discriminative of the action's goal compared to men at P300 and anterior negativity level (220-500 ms. These findings might be related to a greater responsiveness of the female vs. male MNS. In addition, the discriminative effect was bilateral in women and was smaller and left-sided in men. Evidence was provided that perceptually similar social interactions are discriminated on the basis of the agents' intentions quite early in neural processing, differentially activating regions devoted to face/body/action coding, the limbic system and the MNS.

  18. False memory for face in short-term memory and neural activity in human amygdala.

    Science.gov (United States)

    Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

    2014-12-03

    Human memory is often inaccurate. Similar to words and figures, new faces are often recognized as seen or studied items in long- and short-term memory tests; however, the neural mechanisms underlying this false memory remain elusive. In a previous fMRI study using morphed faces and a standard false memory paradigm, we found that there was a U-shaped response curve of the amygdala to old, new, and lure items. This indicates that the amygdala is more active in response to items that are salient (hit and correct rejection) compared to items that are less salient (false alarm), in terms of memory retrieval. In the present fMRI study, we determined whether the false memory for faces occurs within the short-term memory range (a few seconds), and assessed which neural correlates are involved in veridical and illusory memories. Nineteen healthy participants were scanned by 3T MRI during a short-term memory task using morphed faces. The behavioral results indicated that the occurrence of false memories was within the short-term range. We found that the amygdala displayed a U-shaped response curve to memory items, similar to those observed in our previous study. These results suggest that the amygdala plays a common role in both long- and short-term false memory for faces. We made the following conclusions: First, the amygdala is involved in detecting the saliency of items, in addition to fear, and supports goal-oriented behavior by modulating memory. Second, amygdala activity and response time might be related with a subject's response criterion for similar faces. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Foraging under competition: the neural basis of input-matching in humans.

    Science.gov (United States)

    Mobbs, Dean; Hassabis, Demis; Yu, Rongjun; Chu, Carlton; Rushworth, Matthew; Boorman, Erie; Dalgleish, Tim

    2013-06-01

    Input-matching is a key mechanism by which animals optimally distribute themselves across habitats to maximize net gains based on the changing input values of food supply rate and competition. To examine the neural systems that underlie this rule in humans, we created a continuous-input foraging task where subjects had to decide to stay or switch between two habitats presented on the left and right of the screen. The subject's decision to stay or switch was based on changing input values of reward-token supply rate and competition density. High density of competition or low-reward token rate was associated with decreased chance of winning. Therefore, subjects attempted to maximize their gains by switching to habitats that possessed low competition density and higher token rate. When it was increasingly disadvantageous to be in a habitat, we observed increased activity in brain regions that underlie preparatory motor actions, including the dorsal anterior cingulate cortex and the supplementary motor area, as well as the insula, which we speculate may be involved in the conscious urge to switch habitats. Conversely, being in an advantageous habitat is associated with activity in the reward systems, namely the striatum and medial prefrontal cortex. Moreover, amygdala and dorsal putamen activity steered interindividual preferences in competition avoidance and pursuing reward. Our results suggest that input-matching decisions are made as a net function of activity in a distributed set of neural systems. Furthermore, we speculate that switching behaviors are related to individual differences in competition avoidance and reward drive.

  20. Dynamical Integration of Language and Behavior in a Recurrent Neural Network for Human-Robot Interaction.

    Science.gov (United States)

    Yamada, Tatsuro; Murata, Shingo; Arie, Hiroaki; Ogata, Tetsuya

    2016-01-01

    To work cooperatively with humans by using language, robots must not only acquire a mapping between language and their behavior but also autonomously utilize the mapping in appropriate contexts of interactive tasks online. To this end, we propose a novel learning method linking language to robot behavior by means of a recurrent neural network. In this method, the network learns from correct examples of the imposed task that are given not as explicitly separated sets of language and behavior but as sequential data constructed from the actual temporal flow of the task. By doing this, the internal dynamics of the network models both language-behavior relationships and the temporal patterns of interaction. Here, "internal dynamics" refers to the time development of the system defined on the fixed-dimensional space of the internal states of the context layer. Thus, in the execution phase, by constantly representing where in the interaction context it is as its current state, the network autonomously switches between recognition and generation phases without any explicit signs and utilizes the acquired mapping in appropriate contexts. To evaluate our method, we conducted an experiment in which a robot generates appropriate behavior responding to a human's linguistic instruction. After learning, the network actually formed the attractor structure representing both language-behavior relationships and the task's temporal pattern in its internal dynamics. In the dynamics, language-behavior mapping was achieved by the branching structure. Repetition of human's instruction and robot's behavioral response was represented as the cyclic structure, and besides, waiting to a subsequent instruction was represented as the fixed-point attractor. Thanks to this structure, the robot was able to interact online with a human concerning the given task by autonomously switching phases.

  1. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun; Wang, Jing [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Chen, Guian [Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Fan, Dongsheng, E-mail: dsfan@yahoo.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Deng, Min, E-mail: dengmin1706@yahoo.com.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China)

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  2. P2X7 receptors mediate innate phagocytosis by human neural precursor cells and neuroblasts.

    Science.gov (United States)

    Lovelace, Michael D; Gu, Ben J; Eamegdool, Steven S; Weible, Michael W; Wiley, James S; Allen, David G; Chan-Ling, Tailoi

    2015-02-01

    During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68(+) microglia and astrocytes mediate phagocytosis during target-dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple-marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live-cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum-free environment, doublecortin(+) (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7(high) DCX(low) hNPCs and P2X7(high) DCX(high) neuroblasts, derived from primary cultures of human fetal telencephalon, phagocytosed targets including latex beads, apoptotic ReNcells, and apoptotic hNPC/neuroblasts. Pretreatment of neuroblasts and hNPCs with 1 mM adenosine triphosphate (ATP), 100 µM OxATP (P2X7 antagonist), or siRNA knockdown of P2X7 inhibited phagocytosis of these targets. Our results show that P2X7 functions as a scavenger receptor under serum-free conditions resembling those in early neurogenesis. This is the first demonstration that hNPCs and neuroblasts may participate in clearance of apoptotic corpses during pre target-dependent neurogenesis and mediate phagocytosis using P2X7 as a scavenger receptor.

  3. Dynamical Integration of Language and Behavior in a Recurrent Neural Network for Human--Robot Interaction

    Directory of Open Access Journals (Sweden)

    Tatsuro Yamada

    2016-07-01

    Full Text Available To work cooperatively with humans by using language, robots must not only acquire a mapping between language and their behavior but also autonomously utilize the mapping in appropriate contexts of interactive tasks online. To this end, we propose a novel learning method linking language to robot behavior by means of a recurrent neural network. In this method, the network learns from correct examples of the imposed task that are given not as explicitly separated sets of language and behavior but as sequential data constructed from the actual temporal flow of the task. By doing this, the internal dynamics of the network models both language--behavior relationships and the temporal patterns of interaction. Here, ``internal dynamics'' refers to the time development of the system defined on the fixed-dimensional space of the internal states of the context layer. Thus, in the execution phase, by constantly representing where in the interaction context it is as its current state, the network autonomously switches between recognition and generation phases without any explicit signs and utilizes the acquired mapping in appropriate contexts. To evaluate our method, we conducted an experiment in which a robot generates appropriate behavior responding to a human's linguistic instruction. After learning, the network actually formed the attractor structure representing both language--behavior relationships and the task's temporal pattern in its internal dynamics. In the dynamics, language--behavior mapping was achieved by the branching structure. Repetition of human's instruction and robot's behavioral response was represented as the cyclic structure, and besides, waiting to a subsequent instruction was represented as the fixed-point attractor. Thanks to this structure, the robot was able to interact online with a human concerning the given task by autonomously switching phases.

  4. In vivo tracking of human neural stem cells with 19F magnetic resonance imaging.

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    Philipp Boehm-Sturm

    Full Text Available BACKGROUND: Magnetic resonance imaging (MRI is a promising tool for monitoring stem cell-based therapy. Conventionally, cells loaded with ironoxide nanoparticles appear hypointense on MR images. However, the contrast generated by ironoxide labeled cells is neither specific due to ambiguous background nor quantitative. A strategy to overcome these drawbacks is (19F MRI of cells labeled with perfluorocarbons. We show here for the first time that human neural stem cells (NSCs, a promising candidate for clinical translation of stem cell-based therapy of the brain, can be labeled with (19F as well as detected and quantified in vitro and after brain implantation. METHODOLOGY/PRINCIPAL FINDINGS: Human NSCs were labeled with perfluoropolyether (PFPE. Labeling efficacy was assessed with (19F MR spectroscopy, influence of the label on cell phenotypes studied by immunocytochemistry. For in vitro MRI, NSCs were suspended in gelatin at varying densities. For in vivo experiments, labeled NSCs were implanted into the striatum of mice. A decrease of cell viability was observed directly after incubation with PFPE, which re-normalized after 7 days in culture of the replated cells. No label-related changes in the numbers of Ki67, nestin, GFAP, or βIII-tubulin+ cells were detected, both in vitro and on histological sections. We found that 1,000 NSCs were needed to accumulate in one image voxel to generate significant signal-to-noise ratio in vitro. A detection limit of ∼10,000 cells was found in vivo. The location and density of human cells (hunu+ on histological sections correlated well with observations in the (19F MR images. CONCLUSION/SIGNIFICANCE: Our results show that NSCs can be efficiently labeled with (19F with little effects on viability or proliferation and differentiation capacity. We show for the first time that (19F MRI can be utilized for tracking human NSCs in brain implantation studies, which ultimately aim for restoring loss of function after

  5. The Evaluation of Nerve Growth Factor Over Expression on Neural Lineage Specific Genes in Human Mesenchymal Stem Cells

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    Mortazavi Yousef

    2016-07-01

    Full Text Available Objective Treatment and repair of neurodegenerative diseases such as brain tumors, spinal cord injuries, and functional disorders, including Alzheimer’s disease, are challenging problems. A common treatment approach for such disorders involves the use of mesenchymal stem cells (MSCs as an alternative cell source to replace injured cells. However, use of these cells in hosts may potentially cause adverse outcomes such as tumorigenesis and uncontrolled differentiation. In attempt to generate mesenchymal derived neural cells, we have infected MSCs with recombinant lentiviruses that expressed nerve growth factor (NGF and assessed their neural lineage genes. Materials and Methods In this experimental study, we cloned the NGF gene sequence into a helper dependent lentiviral vector that contained the green fluorescent protein (GFP gene. The recombinant vector was amplified in DH5 bacterial cells. Recombinant viruses were generated in the human embryonic kidney 293 (HEK-293 packaging cell line with the helper vectors and analyzed under fluorescent microscopy. Bone marrow mesenchymal cells were infected by recombinant viruses for three days followed by assessment of neural differentiation. We evaluated expression of NGF through measurement of the NGF protein in culture medium by ELISA; neural specific genes were quantified by real-time polymerase chain reaction (PCR. Results We observed neural morphological changes after three days. Quantitative PCR showed that expressions of NESTIN, glial derived neurotrophic factor (GDNF, glial fibrillary acidic protein (GFAP and Microtubule-associated protein 2 (MAP2 genes increased following induction of NGF overexpression, whereas expressions of endogenous NGF and brain derived neural growth factor (BDNF genes reduced. Conclusion Ectopic expression of NGF can induce neurogenesis in MSCs. Direct injection of MSCs may cause tumorigenesis and an undesirable outcome. Therefore an alternative choice to overcome this

  6. The neural dynamics of reward value and risk coding in the human orbitofrontal cortex.

    Science.gov (United States)

    Li, Yansong; Vanni-Mercier, Giovanna; Isnard, Jean; Mauguière, François; Dreher, Jean-Claude

    2016-04-01

    The orbitofrontal cortex is known to carry information regarding expected reward, risk and experienced outcome. Yet, due to inherent limitations in lesion and neuroimaging methods, the neural dynamics of these computations has remained elusive in humans. Here, taking advantage of the high temporal definition of intracranial recordings, we characterize the neurophysiological signatures of the intact orbitofrontal cortex in processing information relevant for risky decisions. Local field potentials were recorded from the intact orbitofrontal cortex of patients suffering from drug-refractory partial epilepsy with implanted depth electrodes as they performed a probabilistic reward learning task that required them to associate visual cues with distinct reward probabilities. We observed three successive signals: (i) around 400 ms after cue presentation, the amplitudes of the local field potentials increased with reward probability; (ii) a risk signal emerged during the late phase of reward anticipation and during the outcome phase; and (iii) an experienced value signal appeared at the time of reward delivery. Both the medial and lateral orbitofrontal cortex encoded risk and reward probability while the lateral orbitofrontal cortex played a dominant role in coding experienced value. The present study provides the first evidence from intracranial recordings that the human orbitofrontal cortex codes reward risk both during late reward anticipation and during the outcome phase at a time scale of milliseconds. Our findings offer insights into the rapid mechanisms underlying the ability to learn structural relationships from the environment.

  7. Neural populations in human posteromedial cortex display opposing responses during memory and numerical processing

    Science.gov (United States)

    Foster, Brett L.; Dastjerdi, Mohammad; Parvizi, Josef

    2012-01-01

    Our understanding of the human default mode network derives primarily from neuroimaging data but its electrophysiological correlates remain largely unexplored. To address this limitation, we recorded intracranially from the human posteromedial cortex (PMC), a core structure of the default mode network, during various conditions of internally directed (e.g., autobiographical memory) as opposed to externally directed focus (e.g., arithmetic calculation). We observed late-onset (>400 ms) increases in broad high γ-power (70–180 Hz) within PMC subregions during memory retrieval. High γ-power was significantly reduced or absent when subjects retrieved self-referential semantic memories or responded to self-judgment statements, respectively. Conversely, a significant deactivation of high γ-power was observed during arithmetic calculation, the duration of which correlated with reaction time at the signal-trial level. Strikingly, at each recording site, the magnitude of activation during episodic autobiographical memory retrieval predicted the degree of suppression during arithmetic calculation. These findings provide important anatomical and temporal details—at the neural population level—of PMC engagement during autobiographical memory retrieval and address how the same populations are actively suppressed during tasks, such as numerical processing, which require externally directed attention. PMID:22949666

  8. Neural and cortisol responses during play with human and computer partners in children with autism.

    Science.gov (United States)

    Edmiston, Elliot Kale; Merkle, Kristen; Corbett, Blythe A

    2015-08-01

    Children with autism spectrum disorder (ASD) exhibit impairment in reciprocal social interactions, including play, which can manifest as failure to show social preference or discrimination between social and nonsocial stimuli. To explore mechanisms underlying these deficits, we collected salivary cortisol from 42 children 8-12 years with ASD or typical development during a playground interaction with a confederate child. Participants underwent functional MRI during a prisoner's dilemma game requiring cooperation or defection with a human (confederate) or computer partner. Search region of interest analyses were based on previous research (e.g. insula, amygdala, temporal parietal junction-TPJ). There were significant group differences in neural activation based on partner and response pattern. When playing with a human partner, children with ASD showed limited engagement of a social salience brain circuit during defection. Reduced insula activation during defection in the ASD children relative to TD children, regardless of partner type, was also a prominent finding. Insula and TPJ BOLD during defection was also associated with stress responsivity and behavior in the ASD group under playground conditions. Children with ASD engage social salience networks less than TD children during conditions of social salience, supporting a fundamental disturbance of social engagement. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

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    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  10. mRNA transfection of mouse and human neural stem cell cultures.

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    Samuel McLenachan

    Full Text Available The use of synthetic mRNA as an alternative gene delivery vector to traditional DNA-based constructs provides an effective method for inducing transient gene expression in cell cultures without genetic modification. Delivery of mRNA has been proposed as a safer alternative to viral vectors in the induction of pluripotent cells for regenerative therapies. Although mRNA transfection of fibroblasts, dendritic and embryonic stem cells has been described, mRNA delivery to neurosphere cultures has not been previously reported. Here we sought to establish an efficient method for delivering mRNA to primary neurosphere cultures. Neurospheres derived from the subventricular zone of adult mice or from human embryonic stem cells were transfected with EGFP mRNA by lipofection and electroporation. Transfection efficiency and expression levels were monitored by flow cytometry. Cell survival following transfection was examined using live cell counting and the MTT assay. Both lipofection and electroporation provided high efficiency transfection of neurospheres. In comparison with lipofection, electroporation resulted in increased transfection efficiencies, but lower expression per cell and shorter durations of expression. Additional rounds of lipofection renewed EGFP expression in neurospheres, suggesting this method may be suitable for reprogramming applications. In summary, we have developed a protocol for achieving high efficiency transfection rates in mouse and human neurosphere cell culture that can be applied for future studies of gene function studies in neural stem cells, such as defining efficient differentiation protocols for glial and neuronal linages.

  11. Putting the tritone paradox into context: insights from neural population decoding and human psychophysics.

    Science.gov (United States)

    Englitz, Bernhard; Akram, S; David, S V; Chambers, C; Pressnitzer, Daniel; Depireux, D; Fritz, J B; Shamma, Shihab A

    2013-01-01

    The context in which a stimulus occurs can influence its perception. We study contextual effects in audition using the tritone paradox, where a pair of complex (Shepard) tones separated by half an octave can be perceived as ascending or descending. While ambiguous in isolation, they are heard with a clear upward or downward change in pitch, when preceded by spectrally matched biasing sequences. We presented these biased Shepard pairs to awake ferrets and obtained neuronal responses from primary auditory cortex. Using dimensionality reduction from the neural population response, we decode the perceived pitch for each tone. The bias sequence is found to reliably shift the perceived pitch of the tones away from its central frequency. Using human psychophysics, we provide evidence that this shift in pitch is present in active human perception as well. These results are incompatible with the standard absolute distance decoder for Shepard tones, which would have predicted the bias to attract the tones. We propose a relative decoder that takes the stimulus history into account and is consistent with the present and other data sets.

  12. Micro-Doppler Based Classification of Human Aquatic Activities via Transfer Learning of Convolutional Neural Networks.

    Science.gov (United States)

    Park, Jinhee; Javier, Rios Jesus; Moon, Taesup; Kim, Youngwook

    2016-11-24

    Accurate classification of human aquatic activities using radar has a variety of potential applications such as rescue operations and border patrols. Nevertheless, the classification of activities on water using radar has not been extensively studied, unlike the case on dry ground, due to its unique challenge. Namely, not only is the radar cross section of a human on water small, but the micro-Doppler signatures are much noisier due to water drops and waves. In this paper, we first investigate whether discriminative signatures could be obtained for activities on water through a simulation study. Then, we show how we can effectively achieve high classification accuracy by applying deep convolutional neural networks (DCNN) directly to the spectrogram of real measurement data. From the five-fold cross-validation on our dataset, which consists of five aquatic activities, we report that the conventional feature-based scheme only achieves an accuracy of 45.1%. In contrast, the DCNN trained using only the collected data attains 66.7%, and the transfer learned DCNN, which takes a DCNN pre-trained on a RGB image dataset and fine-tunes the parameters using the collected data, achieves a much higher 80.3%, which is a significant performance boost.

  13. Micro-Doppler Based Classification of Human Aquatic Activities via Transfer Learning of Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Jinhee Park

    2016-11-01

    Full Text Available Accurate classification of human aquatic activities using radar has a variety of potential applications such as rescue operations and border patrols. Nevertheless, the classification of activities on water using radar has not been extensively studied, unlike the case on dry ground, due to its unique challenge. Namely, not only is the radar cross section of a human on water small, but the micro-Doppler signatures are much noisier due to water drops and waves. In this paper, we first investigate whether discriminative signatures could be obtained for activities on water through a simulation study. Then, we show how we can effectively achieve high classification accuracy by applying deep convolutional neural networks (DCNN directly to the spectrogram of real measurement data. From the five-fold cross-validation on our dataset, which consists of five aquatic activities, we report that the conventional feature-based scheme only achieves an accuracy of 45.1%. In contrast, the DCNN trained using only the collected data attains 66.7%, and the transfer learned DCNN, which takes a DCNN pre-trained on a RGB image dataset and fine-tunes the parameters using the collected data, achieves a much higher 80.3%, which is a significant performance boost.

  14. Experience Shapes the Development of Neural Substrates of Face Processing in Human Ventral Temporal Cortex.

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    Golarai, Golijeh; Liberman, Alina; Grill-Spector, Kalanit

    2017-02-01

    In adult humans, the ventral temporal cortex (VTC) represents faces in a reproducible topology. However, it is unknown what role visual experience plays in the development of this topology. Using functional magnetic resonance imaging in children and adults, we found a sequential development, in which the topology of face-selective activations across the VTC was matured by age 7, but the spatial extent and degree of face selectivity continued to develop past age 7 into adulthood. Importantly, own- and other-age faces were differentially represented, both in the distributed multivoxel patterns across the VTC, and also in the magnitude of responses of face-selective regions. These results provide strong evidence that experience shapes cortical representations of faces during development from childhood to adulthood. Our findings have important implications for the role of experience and age in shaping the neural substrates of face processing in the human VTC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Neural network analysis of the information content in population responses from human periodontal receptors

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    Edin, Benoni B.; Trulsson, Mats

    1992-07-01

    Understanding of the information processing in some sensory systems is hampered for several reasons. First, some of these systems may depend on several receptor types with different characteristics, and the crucial features of natural stimuli encoded by the receptors are rarely known with certainty. Second, the functional output of sensory processing is often not well defined. The human tooth is endowed with several types of sensory receptors. Among these, the mechanoreceptors located in the periodontal ligaments have been implicated in force encoding during chewing and biting. Individual receptors cannot, however, code unambiguously either the direction or the magnitude of the applied forces. Neuronal responses recorded in single human nerve fibers from periodontal receptors were fed to multi-layered feed-forward networks. The networks were trained with error back-propagation to identify specific features of the force stimuli that evoked the receptor responses. It was demonstrated that population responses in periodontal receptors contain information about both the point of attack and the direction of applied forces. It is concluded that networks may provide a powerful tool to investigate the information content in responses from biological receptor populations. As such, specific hypotheses with respect to information processing may be tested using neural networks also in sensory systems less well understood than, for instance, the visual system.

  16. Modeling activity-dependent plasticity in BCM spiking neural networks with application to human behavior recognition.

    Science.gov (United States)

    Meng, Yan; Jin, Yaochu; Yin, Jun

    2011-12-01

    Spiking neural networks (SNNs) are considered to be computationally more powerful than conventional NNs. However, the capability of SNNs in solving complex real-world problems remains to be demonstrated. In this paper, we propose a substantial extension of the Bienenstock, Cooper, and Munro (BCM) SNN model, in which the plasticity parameters are regulated by a gene regulatory network (GRN). Meanwhile, the dynamics of the GRN is dependent on the activation levels of the BCM neurons. We term the whole model "GRN-BCM." To demonstrate its computational power, we first compare the GRN-BCM with a standard BCM, a hidden Markov model, and a reservoir computing model on a complex time series classification problem. Simulation results indicate that the GRN-BCM significantly outperforms the compared models. The GRN-BCM is then applied to two widely used datasets for human behavior recognition. Comparative results on the two datasets suggest that the GRN-BCM is very promising for human behavior recognition, although the current experiments are still limited to the scenarios in which only one object is moving in the considered video sequences.

  17. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

    Science.gov (United States)

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

    2013-11-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  18. Tissue specific DNA methylation of CpG islands in normal human adult somatic tissues distinguishes neural from non-neural tissues.

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    Ghosh, Srimoyee; Yates, Allan J; Frühwald, Michael C; Miecznikowski, Jeffrey C; Plass, Christoph; Smiraglia, Dominic

    2010-08-16

    Although most CpG islands are generally thought to remain unmethylated in all adult somatic tissues, recent genome-wide approaches have found that some CpG islands have distinct methylation patterns in various tissues, with most differences being seen between germ cells and somatic tissues. Few studies have addressed this among human somatic tissues and fewer still have studied the same sets of tissues from multiple individuals. In the current study, we used Restriction Landmark Genomic Scanning to study tissue specific methylation patterns in a set of twelve human tissues collected from multiple individuals. We identified 34 differentially methylated CpG islands among these tissues, many of which showed consistent patterns in multiple individuals. Of particular interest were striking differences in CpG island methylation, not only among brain regions, but also between white and grey matter of the same region. These findings were confirmed for selected loci by quantitative bisulfite sequencing. Cluster analysis of the RLGS data indicated that several tissues clustered together, but the strongest clustering was in brain. Tissues from different brain regions clustered together, and, as a group, brain tissues were distinct from either mesoderm or endoderm derived tissues which demonstrated limited clustering. These data demonstrate consistent tissue specific methylation for certain CpG islands, with clear differences between white and grey matter of the brain. Furthermore, there was an overall pattern of tissue specifically methylated CpG islands that distinguished neural tissues from non-neural.

  19. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  20. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

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    Colleoni, Silvia, E-mail: silviacolleoni@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Galli, Cesare [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Dipartimento Clinico Veterinario, Universita di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Italy); Giannelli, Serena G. [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Armentero, Marie-Therese; Blandini, Fabio [Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson' s Disease, Neurological Institute C. Mondino, Via Mondino 2, 27100 Pavia (Italy); Broccoli, Vania, E-mail: broccoli.vania@hsr.it [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Lazzari, Giovanna, E-mail: giovannalazzari@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy)

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  1. Differentiation of Human Bone Marrow Stromal Cells into Neural-Like Cells Induced by Sodium Ferulate in vitro

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Zhifeng Deng; Xianliang Lai; Wei Tu

    2005-01-01

    Human marrow stromal cells (hMSCs) are multipotential stem cells, capable of differentiating into bone, cartilage,fat and muscle. Several recent reports demonstrated that hMSCs have been also differentiated into neural cells.However, only a few reported inducers are applicable for clinical use. This work is to explore the effects of sodium ferulate (SF) on differentiation of hMSCs into neural cells in vitro. We found that hMSCs could be induced to the cells with typical neural morphology when cultured with SF. The cells express neural proteins, such as nestin,neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP). About 30% of the hMSC-derived cells expressed nestin when cultured with SF for 3 h, but no expression was detected after 24 h. The percentages of positive cells for NSE or GFAP were about 67% and 39% separately at 6 h, and reached the plateau phage after treatment with SF for 3 days. The data suggest that SF can induce hMSCs to differentiate into neural-like cells in vitro.

  2. Gene expression profiling of embryonic human neural stem cells and dopaminergic neurons from adult human substantia nigra.

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    Hany E S Marei

    Full Text Available Neural stem cells (NSC with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN which are rich in dopaminergic (DA neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6% genes were up-regulated in the hENSC, 4116 (30.4% genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93% were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells.

  3. Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy.

    Science.gov (United States)

    Johnsen, Erik O; Frøen, Rebecca C; Albert, Réka; Omdal, Bente K; Sarang, Zsolt; Berta, András; Nicolaissen, Bjørn; Petrovski, Goran; Moe, Morten C

    2012-05-01

    In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial - and NSC-associated markers both after direct fixation and repetitive

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

    Science.gov (United States)

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

    2016-12-01

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

  5. Human Umbilical Cord Blood-Derived Neural Stem Cell Line as a Screening Model for Toxicity.

    Science.gov (United States)

    Patnaik, Rajashree; Padhy, Rabindra Nath

    2017-04-01

    The aim was to investigate whether a human neural stem cell (NSC) line derived from human umbilical cord blood (hUCB) can be used for toxicity study. Toxicity of both neurotoxic environmental xenobiotics, methyl mercury chloride (CH3HgCl), lead acetate (CH3COOPb), and chlorpyrifos (CP), and non-neurotoxic insecticide, dichlorvos, as well as non-neurotoxic drugs, theophylline and acetaminophen were assessed. Additionally, differentiation of neuronal and glial cell lines derived from hUCB was elucidated. It was observed that CH3HgCl was more toxic to human NSCs in comparison to CH3COOPb and CP. The minimum inhibitory concentration (MIC) value against NSCs was 3, 10, and 300 mg/L, in each staining process, acridine orange/ethidium bromide (AO/EB) staining, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay, and Hoechst staining, for CH3HgCl, CP, and CH3COOPb, respectively. CH3HgCl had the LC25 value as 10.0, 14.4, and 12.7 mg/L, by staining method mentioned in succession. CP had the LC25 value as 21.9, 23.7, and 18.4 mg/L; similarly, CH3COOPb had LC25 values, successively as 616.9, 719.2, and 890.3 mg/L. LC50 values ranged from 18.2 to 21.7 mg/L for CH3HgCl, 56.4 to 60.2 mg/L for CP, and 1000 to 1460.1 for CH3COOPb. Theophylline, acetaminophen, and dichlorvos had no impact on the viability of NSCs. This work justified that hUCB-NSC model can be used for toxicity study.

  6. Neural correlates of natural human echolocation in early and late blind echolocation experts.

    Directory of Open Access Journals (Sweden)

    Lore Thaler

    Full Text Available BACKGROUND: A small number of blind people are adept at echolocating silent objects simply by producing mouth clicks and listening to the returning echoes. Yet the neural architecture underlying this type of aid-free human echolocation has not been investigated. To tackle this question, we recruited echolocation experts, one early- and one late-blind, and measured functional brain activity in each of them while they listened to their own echolocation sounds. RESULTS: When we compared brain activity for sounds that contained both clicks and the returning echoes with brain activity for control sounds that did not contain the echoes, but were otherwise acoustically matched, we found activity in calcarine cortex in both individuals. Importantly, for the same comparison, we did not observe a difference in activity in auditory cortex. In the early-blind, but not the late-blind participant, we also found that the calcarine activity was greater for echoes reflected from surfaces located in contralateral space. Finally, in both individuals, we found activation in middle temporal and nearby cortical regions when they listened to echoes reflected from moving targets. CONCLUSIONS: These findings suggest that processing of click-echoes recruits brain regions typically devoted to vision rather than audition in both early and late blind echolocation experts.

  7. A reduction in ATP demand and mitochondrial activity with neural differentiation of human embryonic stem cells.

    Science.gov (United States)

    Birket, Matthew J; Orr, Adam L; Gerencser, Akos A; Madden, David T; Vitelli, Cathy; Swistowski, Andrzej; Brand, Martin D; Zeng, Xianmin

    2011-02-01

    Here, we have investigated mitochondrial biology and energy metabolism in human embryonic stem cells (hESCs) and hESC-derived neural stem cells (NSCs). Although stem cells collectively in vivo might be expected to rely primarily on anaerobic glycolysis for ATP supply, to minimise production of reactive oxygen species, we show that in vitro this is not so: hESCs generate an estimated 77% of their ATP through oxidative phosphorylation. Upon differentiation of hESCs into NSCs, oxidative phosphorylation declines both in absolute rate and in importance relative to glycolysis. A bias towards ATP supply from oxidative phosphorylation in hESCs is consistent with the expression levels of the mitochondrial gene regulators peroxisome-proliferator-activated receptor γ coactivator (PGC)-1α, PGC-1β and receptor-interacting protein 140 (RIP140) in hESCs when compared with a panel of differentiated cell types. Analysis of the ATP demand showed that the slower ATP turnover in NSCs was associated with a slower rate of most energy-demanding processes but occurred without a reduction in the cellular growth rate. This mismatch is probably explained by a higher rate of macromolecule secretion in hESCs, on the basis of evidence from electron microscopy and an analysis of conditioned media. Taken together, our developmental model provides an understanding of the metabolic transition from hESCs to more quiescent somatic cell types, and supports important roles for mitochondria and secretion in hESC biology.

  8. Cholinergic enhancement of visual attention and neural oscillations in the human brain.

    Science.gov (United States)

    Bauer, Markus; Kluge, Christian; Bach, Dominik; Bradbury, David; Heinze, Hans Jochen; Dolan, Raymond J; Driver, Jon

    2012-03-06

    Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Neural correlates of forward planning in a spatial decision task in humans

    Science.gov (United States)

    Simon, Dylan Alexander; Daw, Nathaniel D.

    2011-01-01

    Although reinforcement learning (RL) theories have been influential in characterizing the brain’s mechanisms for reward-guided choice, the predominant temporal difference (TD) algorithm cannot explain many flexible or goal-directed actions that have been demonstrated behaviorally. We investigate such actions by contrasting an RL algorithm that is model-based, in that it relies on learning a map or model of the task and planning within it, to traditional model-free TD learning. To distinguish these approaches in humans, we used fMRI in a continuous spatial navigation task, in which frequent changes to the layout of the maze forced subjects continually to relearn their favored routes, thereby exposing the RL mechanisms employed. We sought evidence for the neural substrates of such mechanisms by comparing choice behavior and BOLD signals to decision variables extracted from simulations of either algorithm. Both choices and value-related BOLD signals in striatum, though most often associated with TD learning, were better explained by the model-based theory. Further, predecessor quantities for the model-based value computation were correlated with BOLD signals in the medial temporal lobe and frontal cortex. These results point to a significant extension of both the computational and anatomical substrates for RL in the brain. PMID:21471389

  10. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-06-01

    Full Text Available Using a viral model of the demyelinating disease multiple sclerosis (MS, we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

  11. Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid

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    Elham Hashemi

    2017-01-01

    Full Text Available As the key producer of cerebrospinal fluid (CSF, the choroid plexus (CP provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2, as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.

  12. Further assessment of neuropathology in retinal explants and neuroprotection by human neural progenitor cells

    Science.gov (United States)

    Mohlin, Camilla; Liljekvist-Soltic, Ingela; Johansson, Kjell

    2011-10-01

    Explanted rat retinas show progressive photoreceptor degeneration that appears to be caspase-12-dependent. Decrease in photoreceptor density eventually affects the inner retina, particularly in the bipolar cell population. Explantation and the induced photoreceptor degeneration are accompanied by activation of Müller and microglia cells. The goal of this study was to determine whether the presence of a feeder layer of human neural progenitor cells (hNPCs) could suppress the degenerative and reactive changes in the explants. Immunohistochemical analyses showed considerable sprouting of rod photoreceptor axon terminals into the inner retina and reduced densities of cone and rod bipolar cells. Both sprouting and bipolar cell degenerations were significantly lower in retinas cultured with feeder layer cells compared to cultured controls. A tendency toward reduced microglia activation in the retinal layers was also noted in the presence of feeder layer cells. These results indicate that hNPCs or factors produced by them can limit the loss of photoreceptors and secondary injuries in the inner retina. The latter may be a consequence of disrupted synaptic arrangement.

  13. Assessment of human locomotion by using an insole measurement system and artificial neural networks.

    Science.gov (United States)

    Zhang, Kuan; Sun, Ming; Lester, D Kevin; Pi-Sunyer, F Xavier; Boozer, Carol N; Longman, Richard W

    2005-11-01

    A new method for measuring and characterizing free-living human locomotion is presented. A portable device was developed to objectively record and measure foot-ground contact information in every step for up to 24h. An artificial neural network (ANN) was developed to identify the type and intensity of locomotion. Forty subjects participated in the study. The subjects performed level walking, running, ascending and descending stairs at slow, normal and fast speeds determined by each subject, respectively. The device correctly identified walking, running, ascending and descending stairs (accuracy 98.78%, 98.33%, 97.33%, and 97.29% respectively) among different types of activities. It was also able to determine the speed of walking and running. The correlation between actual speed and estimated speed is 0.98, pwalking and running speed estimation is -0.050+/-0.747 km/h (mean +/- standard deviation). The study has shown the measurement of duration, frequency, type, and intensity of locomotion highly accurate using the new device and an ANN. It provides an alternative tool to the use of a gait lab to quantitatively study locomotion with high accuracy via a small, light and portable device, and to do so under free-living conditions for the clinical applications.

  14. Magnetically enhanced adeno-associated viral vector delivery for human neural stem cell infection.

    Science.gov (United States)

    Kim, Eunmi; Oh, Ji-Seon; Ahn, Ik-Sung; Park, Kook In; Jang, Jae-Hyung

    2011-11-01

    Gene therapy technology is a powerful tool to elucidate the molecular cues that precisely regulate stem cell fates, but developing safe vehicles or mechanisms that are capable of delivering genes to stem cells with high efficiency remains a challenge. In this study, we developed a magnetically guided adeno-associated virus (AAV) delivery system for gene delivery to human neural stem cells (hNSCs). Magnetically guided AAV delivery resulted in rapid accumulation of vectors on target cells followed by forced penetration of the vectors across the plasma membrane, ultimately leading to fast and efficient cellular transduction. To combine AAV vectors with the magnetically guided delivery, AAV was genetically modified to display hexa-histidine (6xHis) on the physically exposed loop of the AAV2 capsid (6xHis AAV), which interacted with nickel ions chelated on NTA-biotin conjugated to streptavidin-coated superparamagnetic iron oxide nanoparticles (NiStNPs). NiStNP-mediated 6xHis AAV delivery under magnetic fields led to significantly enhanced cellular transduction in a non-permissive cell type (i.e., hNSCs). In addition, this delivery method reduced the viral exposure times required to induce a high level of transduction by as much as to 2-10 min of hNSC infection, thus demonstrating the great potential of magnetically guided AAV delivery for numerous gene therapy and stem cell applications.

  15. The Promotion of Human Neural Stem Cells Adhesion Using Bioinspired Poly(norepinephrine Nanoscale Coating

    Directory of Open Access Journals (Sweden)

    Minah Park

    2014-01-01

    Full Text Available The establishment of versatile biomaterial interfaces that can facilitate cellular adhesion is crucial for elucidating the cellular processes that occur on biomaterial surfaces. Furthermore, biomaterial interfaces can provide physical or chemical cues that are capable of stimulating cellular behaviors by regulating intracellular signaling cascades. Herein, a method of creating a biomimetic functional biointerface was introduced to enhance human neural stem cell (hNSC adhesion. The hNSC-compatible biointerface was prepared by the oxidative polymerization of the neurotransmitter norepinephrine, which generates a nanoscale organic thin layer, termed poly(norepinephrine (pNE. Due to its adhesive property, pNE resulted in an adherent layer on various substrates, and pNE-coated biointerfaces provided a highly favorable microenvironment for hNSCs, with no observed cytotoxicity. Only a 2-hour incubation of hNSCs was required to firmly attach the stem cells, regardless of the type of substrate. Importantly, the adhesive properties of pNE interfaces led to micropatterns of cellular attachment, thereby demonstrating the ability of the interface to organize the stem cells. This highly facile surface-modification method using a biomimetic pNE thin layer can be applied to a number of suitable materials that were previously not compatible with hNSC technology.

  16. Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells

    Directory of Open Access Journals (Sweden)

    Tetsuro Yasui

    2017-06-01

    Full Text Available Human neural precursor cells (hNPCs derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, we found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development. Thus, our findings shed further light on the molecular mechanisms regulating hNPC differentiation and provide attractive tools for the development of therapeutic strategies for treating astrocyte-mediated neurological disorders.

  17. Development of membrane ion channels during neural differentiation from human embryonic stem cells.

    Science.gov (United States)

    Mirsadeghi, Sara; Shahbazi, Ebrahim; Hemmesi, Katayoun; Nemati, Shiva; Baharvand, Hossein; Mirnajafi-Zadeh, Javad; Kiani, Sahar

    2017-09-09

    For human embryonic stem cells (hESCs) to differentiate into neurons, enormous changes has to occur leading to trigger action potential and neurotransmitter release. We attempt to determine the changes in expression of voltage gated channels (VGCs) and their electrophysiological properties during neural differentiation. The relative expressions of α-subunit of voltage gated potassium, sodium and calcium channels were characterized by qRT-PCR technique. Patch clamp recording was performed to characterize the electrophysiological properties of hESCs during their differentiation into neuron-like cells. Relative expression of α-subunit of channels changed significantly. 4-AP and TEA sensitive outward currents were observed in all stages, although TEA sensitive currents were recorded once in rosette structure. Nifedipine and QX314 sensitive inward currents were recorded only in neuron-like cells. K(+) currents were recorded in hESCs and rosette structure cells. Inward currents, sensitive to Nifedipine and QX314, were recorded in neuron-like cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Low oxygen alters mitochondrial function and response to oxidative stress in human neural progenitor cells

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    Yury M. Lages

    2015-12-01

    Full Text Available Oxygen concentration should be carefully regulated in all living tissues, beginning at the early embryonic stages. Unbalances in oxygen regulation can lead to cell death and disease. However, to date, few studies have investigated the consequences of variations in oxygen levels for fetal-like cells. Therefore, in the present work, human neural progenitor cells (NPCs derived from pluripotent stem cells grown in 3% oxygen (v/v were compared with NPCs cultured in 21% (v/v oxygen. Low oxygen concentrations altered the mitochondrial content and oxidative functions of the cells, which led to improved ATP production, while reducing generation of reactive oxygen species (ROS. NPCs cultured in both conditions showed no differences in proliferation and glucose metabolism. Furthermore, antioxidant enzymatic activity was not altered in NPCs cultured in 3% oxygen under normal conditions, however, when exposed to external agents known to induce oxidative stress, greater susceptibility to DNA damage was observed. Our findings indicate that the management of oxygen levels should be considered for in vitro models of neuronal development and drug screening.

  19. Effects of Silver Nanoparticles on Human and Rat Embryonic Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Fang eLiu

    2015-04-01

    Full Text Available Silver nano-particles (Ag-NPs are becoming increasingly prevalent in consumer products as antibacterial agents. The increased use of Ag NP-enhanced products will almost certainly increase environmental silver levels, resulting in increased exposures and the potential for increased adverse reactions including neurotoxic effects. In the present study, embryonic neural stem cells (NSCs from human and rat fetuses (gestational day-16 were used to determine whether Ag-NPs are capable of causing developmental neurotoxicity. The NSCs were cultured in serum free medium supplemented with appropriate growth factors. On the eighth day in vitro (DIV 8, the cells were exposed to Ag-NPs at concentrations of 1, 5, 10, and 20 µg/ml for 24 hours. The cultured cells then were characterized by NSC markers including nestin and SOX2 and a variety of assays were utilized to determine the effects of Ag-NPs on NSC proliferation and viability and the underlying mechanisms associated with these effects. The results indicate that mitochondrial viability (MTT metabolism was substantially attenuated and LDH release was increased significantly in a dose-dependent manner. Ag-NPs-induced neurotoxicity was further confirmed by up-regulated Bax protein expression, an increased number of TUNEL-positively stained cells, and elevated reactive oxygen species (ROS. NSC proliferation was also significantly decreased by Ag-NPs. Co-administration of acetyl-L-carnitine, an antioxidant agent, effectively blocked the adverse effects associated with Ag-NP exposure.

  20. Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.

    Science.gov (United States)

    Gao, Xiugong; Lin, Hsiuling; Ray, Radharaman; Ray, Prabhati

    2013-05-01

    Organophosphorus (OP) compounds represent an important group of chemical warfare nerve agents that remains a significant and constant military and civilian threat. OP compounds are considered acting primarily via cholinergic pathways by binding irreversibly to acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Many studies over the past years have suggested that other mechanisms of OP toxicity exist, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. Here we performed a microarray study in which cultured human neural cells were exposed to 0.1 or 10 μM of VX for 1 h. Global gene expression changes were analyzed 6, 24, and 72 h post exposure. Functional annotation and pathway analysis of the differentially expressed genes has revealed many genes, networks and canonical pathways that are related to nervous system development and function, or to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In particular, the neuregulin pathway impacted by VX exposure has important implications in many nervous system diseases including schizophrenia. These results provide useful information valuable in developing suitable antidotes for more effective prevention and treatment of, as well as in developing biomarkers for, VX-induced chronic neurotoxicity.

  1. Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells

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    Christopher J. Sontag

    2014-05-01

    Full Text Available The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how NSCs differentially respond to intact versus damaged CNS. Furthermore, single, terminal histological endpoints predominate, providing limited insight into the spatiotemporal dynamics of NSC engraftment and migration. We investigated the early and long-term engraftment dynamics of human CNS stem cells propagated as neurospheres (hCNS-SCns following transplantation into uninjured versus subacutely injured spinal cords of immunodeficient NOD-scid mice. We stereologically quantified engraftment, survival, proliferation, migration, and differentiation at 1, 7, 14, 28, and 98 days posttransplantation, and identified injury-dependent alterations. Notably, the injured microenvironment decreased hCNS-SCns survival, delayed and altered the location of proliferation, influenced both total and fate-specific migration, and promoted oligodendrocyte maturation.

  2. Human neural stem cell-induced endothelial morphogenesis requires autocrine/paracrine and juxtacrine signaling

    Science.gov (United States)

    Chou, Chung-Hsing; Modo, Michel

    2016-01-01

    Transplanted neural stem cells (NSC) interact with the host brain microenvironment. A neovascularization is commonly observed in the vicinity of the cell deposit, which is correlated with behavioral improvements. To elucidate the signaling mechanisms between human NSCs and endothelial cells (ECs), these were cocultured in an in vitro model in which NSC-induced endothelial morphogenesis produced a neurovascular environment. Soluble (autocrine/paracrine) and contact–mediated (juxtacrine) signaling molecules were evaluated for two conditionally immortalized fetal NSC lines derived from the cortical anlage (CTXOE03) and ganglionic eminence (STROC05), as well as an adult EC line (D3) derived from the cerebral microvasculature of a hippocampal biopsy. STROC05 were 4 times as efficient to induce endothelial morphogenesis compared to CTXOE03. The cascade of reciprocal interactions between NSCs and ECs in this process was determined by quantifying soluble factors, receptor mapping, and immunocytochemistry for extracellular matrix molecules. The mechanistic significance of these was further evaluated by pharmacological blockade. The sequential cell-specific regulation of autocrine/paracrine and juxtacrine signaling accounted for the differential efficiency of NSCs to induce endothelial morphogenesis. These in vitro studies shed new light on the reciprocal interactions between NSCs and ECs, which are pivotal for our mechanistic understanding of the efficacy of NSC transplantation. PMID:27374240

  3. Drive Control Scheme of Electric Power Assisted Wheelchair Based on Neural Network Learning of Human Wheelchair Operation Characteristics

    Science.gov (United States)

    Tanohata, Naoki; Seki, Hirokazu

    This paper describes a novel drive control scheme of electric power assisted wheelchairs based on neural network learning of human wheelchair operation characteristics. “Electric power assisted wheelchair” which enhances the drive force of the operator by employing electric motors is expected to be widely used as a mobility support system for elderly and disabled people. However, some handicapped people with paralysis of the muscles of one side of the body cannot maneuver the wheelchair as desired because of the difference in the right and left input force. Therefore, this study proposes a neural network learning system of such human wheelchair operation characteristics and a drive control scheme with variable distribution and assistance ratios. Some driving experiments will be performed to confirm the effectiveness of the proposed control system.

  4. Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects.

    Science.gov (United States)

    Bosoi, Ciprian M; Capra, Valeria; Allache, Redouane; Trinh, Vincent Quoc-Huy; De Marco, Patrizia; Merello, Elisa; Drapeau, Pierre; Bassuk, Alexander G; Kibar, Zoha

    2011-12-01

    The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure, and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified seven rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations.

  5. Comprehensive quantitative comparison of the membrane proteome and PTM-ome of human embryonic stem cells and neural stem cells

    DEFF Research Database (Denmark)

    Braga, Marcella Nunes de Melo; Schulz, Melanie; Jakobsen, Lene

    Introduction: Human embryonic stem cells (hESCs) can differentiate into all three germ layers and self-renew. Due to its ability to differentiate in vitro into human neural stem cells (hNSCs), which can further be differentiated into motor neurons and dopaminergic neurons, these cells are potential...... source for treatment of neurological diseases such as Parkinson´s disease. Membrane proteins are very important in cellular signaling and they are regulated by post-translational modifications such as phosphorylation and glycosylation. In order to obtain more information about important membrane proteins...... development and has been implicated in cell growth control. Neuronal cell adhesion molecule (NRCAM) is a sialylated glycoprotein upregulated in hNSCs. This protein is involved in several aspects of nervous system development, such as synaptogenesis. In addition, components of neural specific canonical...

  6. Enhanced dopaminergic differentiation of human neural stem cells by synergistic effect of Bcl-xL and reduced oxygen tension

    DEFF Research Database (Denmark)

    Krabbe, Christina; Courtois, Elise; Jensen, Pia

    2009-01-01

    Neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. Here we investigated the effect of the anti-apoptotic protein Bcl-x(L) and oxygen tension on dopaminergic...... differentiation and survival of a human ventral mesencephalic stem cell line (hVM1). hVM1 cells and a Bcl-x(L) over-expressing subline (hVMbcl-x(L)) were differentiated by sequential treatment with fibroblast growth factor-8, forskolin, sonic hedgehog, and glial cell line-derived neurotrophic factor. After 10...... was reduced in hVMbcl-x(L) cell cultures compared with control. We conclude that Bcl-x(L) and lowered oxygen tension act in concert to enhance dopaminergic differentiation and survival of human neural stem cells....

  7. A study on the possible involvement of the PAX3 gene in human neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Hol, F.A.; Hamel, B.C.J.; Geurds, M.P.A. [University Hospital Nijmegen (Netherlands)] [and others

    1994-09-01

    Neural tube defects (NTD) are congenital malformations of the central nervous system which are generally attributed to a combination of environmental and genetic factors. Recently, the molecular defect responsible for the phenotype of the Splotch mouse, a monogenic model system for NTD, was determined. A mutation disrupts the homeodomain of the gene for Pax3. In humans, mutations in the cognate gene for PAX3 can cause Waardenburg syndrome (WS), which is associated with NTD. Based on these findings, PAX3 can be regarded as a candidate gene for human NTD. To test this hypothesis we have screened the DNA of 39 familial and 70 sporadic NTD patients for mutations in the coding exons and flanking intron sequences of the PAX3 gene. SSC analysis revealed abnormal bands in exon 2, exon 5, exon 6 and exon 7 in different patients. A missense mutation was identified in exon 6 downstream from the homeodomain in several patients resulting in an amino acid substitution (Thr315Lys) in the protein. However, the same substitution was detected in unaffected controls suggesting no biological significance. Above shifts most likely represent polymorphisms that are irrelevant for NTD. A conspicuous SSC-band shift was observed in exon 5 of one familial patient with spina bifida. Sequencing revealed that the patient was heterozygous for a 5 bp deletion upstream of the homeodomain. The deletion causes a frameshift, which leads to premature termination of translation. Mild characteristics of WS were detected in several members of the family including the index patient. DNA analysis showed co-segregation of the mutation with these symptoms. Although PAX3 mutations can increase the penetrance of NTD in families with WS, our results show that their presence is not sufficient to cause NTD.

  8. Guided migration of neural stem cells derived from human embryonic stem cells by an electric field.

    Science.gov (United States)

    Feng, Jun-Feng; Liu, Jing; Zhang, Xiu-Zhen; Zhang, Lei; Jiang, Ji-Yao; Nolta, Jan; Zhao, Min

    2012-02-01

    Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF-stimulated and guided migration of hNSCs, we derived hNSCs from a well-established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho-kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases.

  9. Gold- and silver nanoparticles affect the growth characteristics of human embryonic neural precursor cells.

    Directory of Open Access Journals (Sweden)

    Erika Söderstjerna

    Full Text Available Rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of nanoparticles (NPs on human health and environment. NPs can be directly taken up by organs exposed, but also translocated to secondary organs, such as the central nervous system (CNS after systemic- or subcutaneous administration, or via the olfactory system. The CNS is particularly vulnerable during development and recent reports describe transport of NPs across the placenta and even into brain tissue using in vitro and in vivo experimental systems. Here, we investigated whether well-characterized commercial 20 and 80 nm Au- and AgNPs have an effect on human embryonic neural precursor cell (HNPC growth. After two weeks of NP exposure, uptake of NPs, morphological features and the amount of viable and dead cells, proliferative cells (Ki67 immunostaining and apoptotic cells (TUNEL assay, respectively, were studied. We demonstrate uptake of both 20 and 80 nm Au- and AgNPs respectively, by HNPCs during proliferation. A significant effect on the sphere size- and morphology was found for all cultures exposed to Au- and AgNPs. AgNPs of both sizes caused a significant increase in numbers of proliferating and apoptotic HNPCs. In contrast, only the highest dose of 20 nm AuNPs significantly affected proliferation, whereas no effect was seen on apoptotic cell death. Our data demonstrates that both Au- and AgNPs interfere with the growth profile of HNPCs, indicating the need of further detailed studies on the adverse effects of NPs on the developing CNS.

  10. Self-Organizing Neural Integration of Pose-Motion Features for Human Action Recognition

    Directory of Open Access Journals (Sweden)

    German Ignacio Parisi

    2015-06-01

    Full Text Available The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented towards human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR networks that obtain progressively generalized representations of sensory inputs and learn inherent spatiotemporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best 21 results for a public benchmark of domestic daily actions.

  11. Self-organizing neural integration of pose-motion features for human action recognition.

    Science.gov (United States)

    Parisi, German I; Weber, Cornelius; Wermter, Stefan

    2015-01-01

    The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented toward human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR) networks that obtain progressively generalized representations of sensory inputs and learn inherent spatio-temporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best results for a public benchmark of domestic daily actions.

  12. High-frequency neural activity and human cognition: past, present and possible future of intracranial EEG research

    Science.gov (United States)

    Lachaux, Jean-Philippe; Axmacher, Nikolai; Mormann, Florian; Halgren, Eric; Crone, Nathan E.

    2013-01-01

    Human intracranial EEG (iEEG) recordings are primarily performed in epileptic patients for presurgical mapping. When patients perform cognitive tasks, iEEG signals reveal high-frequency neural activities (HFA, between around 40 Hz and 150 Hz) with exquisite anatomical, functional and temporal specificity. Such HFA were originally interpreted in the context of perceptual or motor binding, in line with animal studies on gamma-band (‘40Hz’) neural synchronization. Today, our understanding of HFA has evolved into a more general index of cortical processing: task-induced HFA reveals, with excellent spatial and time resolution, the participation of local neural ensembles in the task-at-hand, and perhaps the neural communication mechanisms allowing them to do so. This review promotes the claim that studying HFA with iEEG provides insights into the neural bases of cognition that cannot be derived as easily from other approaches, such as fMRI. We provide a series of examples supporting that claim, drawn from studies on memory, language and default-mode networks, and successful attempts of real-time functional mapping. These examples are followed by several guidelines for HFA research, intended for new groups interested by this approach. Overall, iEEG research on HFA should play an increasing role in cognitive neuroscience in humans, because it can be explicitly linked to basic research in animals. We conclude by discussing the future evolution of this field, which might expand that role even further, for instance through the use of multi-scale electrodes and the fusion of iEEG with MEG and fMRI. PMID:22750156

  13. An externally head-mounted wireless neural recording device for laboratory animal research and possible human clinical use.

    Science.gov (United States)

    Yin, Ming; Li, Hao; Bull, Christopher; Borton, David A; Aceros, Juan; Larson, Lawrence; Nurmikko, Arto V

    2013-01-01

    In this paper we present a new type of head-mounted wireless neural recording device in a highly compact package, dedicated for untethered laboratory animal research and designed for future mobile human clinical use. The device, which takes its input from an array of intracortical microelectrode arrays (MEA) has ninety-seven broadband parallel neural recording channels and was integrated on to two custom designed printed circuit boards. These house several low power, custom integrated circuits, including a preamplifier ASIC, a controller ASIC, plus two SAR ADCs, a 3-axis accelerometer, a 48MHz clock source, and a Manchester encoder. Another ultralow power RF chip supports an OOK transmitter with the center frequency tunable from 3GHz to 4GHz, mounted on a separate low loss dielectric board together with a 3V LDO, with output fed to a UWB chip antenna. The IC boards were interconnected and packaged in a polyether ether ketone (PEEK) enclosure which is compatible with both animal and human use (e.g. sterilizable). The entire system consumes 17mA from a 1.2Ahr 3.6V Li-SOCl2 1/2AA battery, which operates the device for more than 2 days. The overall system includes a custom RF receiver electronics which are designed to directly interface with any number of commercial (or custom) neural signal processors for multi-channel broadband neural recording. Bench-top measurements and in vivo testing of the device in rhesus macaques are presented to demonstrate the performance of the wireless neural interface.

  14. Disabled-1 alternative splicing in human fetal retina and neural tumors.

    Directory of Open Access Journals (Sweden)

    Sachin Katyal

    Full Text Available BACKGROUND: The Reelin-Dab1 signaling pathway plays a critical role in the positioning of migrating neurons, dendrite formation and lamination in the developing central nervous system. We have previously identified two alternatively spliced forms of Dab1 in the developing chick retina: an early form, Dab1-E, expressed in retinal progenitor cells, and a late form, Dab1 or Dab1-L, expressed in amacrine and ganglion cells. Compared to Dab1-L, Dab1-E lacks two exons that encode two Src family kinase (SFK phosphorylation sites. PRINCIPAL FINDINGS: Both Dab1-L and Dab1-E-like transcripts were identified in human fetal retina. Expression of human Dab1-L in primary chick retinal cultures resulted in Reelin-mediated induction of SFK phosphorylation and formation of neurite-like processes. In contrast, human Dab1-E-expressing cells retained an undifferentiated morphology. The human Dab1 gene is located within a common fragile site, and it has been postulated that it may function as a tumor suppressor. Analysis of Dab1 splice forms in retinoblastoma and neuroblastoma tumor cells revealed relative enrichment of Dab1-L-like (includes exons 7 and 8 and Dab1-E-like (excludes exons 7 and 8 transcripts in retinoblastoma and neuroblastoma, respectively. Treatment of retinoblastoma cell line RB522A with Reelin resulted in increased tyrosine phosphorylation of Dab1. As Nova2 has previously been implicated in the exclusion of exons 9B and 9C in Dab1, we examined the expression of this splicing factor in neuroblastoma and retinoblastoma cell lines. Nova2 was only detected in neuroblastoma cells, suggesting a correlation between Nova2 expression and increased levels of Dab1-E-like splice forms in neuroblastoma. CONCLUSIONS: These results indicate that alternative splicing of Dab1 is conserved in avian and mammalian species, with Dab1-L driving SFK phosphorylation in both species. Dab1-E- and Dab-L-like isoforms are also expressed in childhood neural tumors, with

  15. Disabled-1 Alternative Splicing in Human Fetal Retina and Neural Tumors

    Science.gov (United States)

    Katyal, Sachin; Glubrecht, Darryl D.; Li, Lei; Gao, Zhihua; Godbout, Roseline

    2011-01-01

    Background The Reelin-Dab1 signaling pathway plays a critical role in the positioning of migrating neurons, dendrite formation and lamination in the developing central nervous system. We have previously identified two alternatively spliced forms of Dab1 in the developing chick retina: an early form, Dab1-E, expressed in retinal progenitor cells, and a late form, Dab1 or Dab1-L, expressed in amacrine and ganglion cells. Compared to Dab1-L, Dab1-E lacks two exons that encode two Src family kinase (SFK) phosphorylation sites. Principal Findings Both Dab1-L and Dab1-E-like transcripts were identified in human fetal retina. Expression of human Dab1-L in primary chick retinal cultures resulted in Reelin-mediated induction of SFK phosphorylation and formation of neurite-like processes. In contrast, human Dab1-E-expressing cells retained an undifferentiated morphology. The human Dab1 gene is located within a common fragile site, and it has been postulated that it may function as a tumor suppressor. Analysis of Dab1 splice forms in retinoblastoma and neuroblastoma tumor cells revealed relative enrichment of Dab1-L-like (includes exons 7 and 8) and Dab1-E-like (excludes exons 7 and 8) transcripts in retinoblastoma and neuroblastoma, respectively. Treatment of retinoblastoma cell line RB522A with Reelin resulted in increased tyrosine phosphorylation of Dab1. As Nova2 has previously been implicated in the exclusion of exons 9B and 9C in Dab1, we examined the expression of this splicing factor in neuroblastoma and retinoblastoma cell lines. Nova2 was only detected in neuroblastoma cells, suggesting a correlation between Nova2 expression and increased levels of Dab1-E-like splice forms in neuroblastoma. Conclusions These results indicate that alternative splicing of Dab1 is conserved in avian and mammalian species, with Dab1-L driving SFK phosphorylation in both species. Dab1-E- and Dab-L-like isoforms are also expressed in childhood neural tumors, with preferential enrichment

  16. EEG frequency tagging dissociates between neural processing of motion synchrony and human quality of multiple point-light dancers

    Science.gov (United States)

    Alp, Nihan; Nikolaev, Andrey R.; Wagemans, Johan; Kogo, Naoki

    2017-01-01

    Do we perceive a group of dancers moving in synchrony differently from a group of drones flying in-sync? The brain has dedicated networks for perception of coherent motion and interacting human bodies. However, it is unclear to what extent the underlying neural mechanisms overlap. Here we delineate these mechanisms by independently manipulating the degree of motion synchrony and the humanoid quality of multiple point-light displays (PLDs). Four PLDs moving within a group were changing contrast in cycles of fixed frequencies, which permits the identification of the neural processes that are tagged by these frequencies. In the frequency spectrum of the steady-state EEG we found two emergent frequency components, which signified distinct levels of interactions between PLDs. The first component was associated with motion synchrony, the second with the human quality of the moving items. These findings indicate that visual processing of synchronously moving dancers involves two distinct neural mechanisms: one for the perception of a group of items moving in synchrony and one for the perception of a group of moving items with human quality. We propose that these mechanisms underlie high-level perception of social interactions. PMID:28272421

  17. MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics

    National Research Council Canada - National Science Library

    Lawrence, Jean M; Singhal, Shweta; Bhatia, Bhairavi; Keegan, David J; Reh, Thomas A; Luthert, Philip J; Khaw, Peng T; Limb, Gloria Astrid

    2007-01-01

    .... We first reported the Müller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors...

  18. PSA-NCAM(+) neural precursor cells from human embryonic stem cells promote neural tissue integrity and behavioral performance in a rat stroke model.

    Science.gov (United States)

    Kim, Han-Soo; Choi, Seong-Mi; Yang, Wonsuk; Kim, Dae-Sung; Lee, Dongjin R; Cho, Sung-Rae; Kim, Dong-Wook

    2014-12-01

    Recently, cell-based therapy has been highlighted as an alternative to treating ischemic brain damage in stroke patients. The present study addresses the therapeutic potential of polysialic acid-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPC(PSA-NCAM+)) derived from human embryonic stem cells (hESCs) in a rat stroke model with permanent middle cerebral artery occlusion. Data showed that rats transplanted with NPC(PSA-NCAM+) are superior to those treated with phosphate buffered saline (PBS) or mesenchymal stem cells (MSCs) in behavioral performance throughout time points. In order to investigate its underlying events, immunohistochemical analysis was performed on rat ischemic brains treated with PBS, MSCs, and NPC(PSA-NCAM+). Unlike MSCs, NPC(PSA-NCAM+) demonstrated a potent immunoreactivity against human specific nuclei, doublecortin, and Tuj1 at day 26 post-transplantation, implying their survival, differentiation, and integration in the host brain. Significantly, NPC(PSA-NCAM+) evidently lowered the positivity of microglial ED-1 and astrocytic GFAP, suggesting a suppression of adverse glial activation in the host brain. In addition, NPC(PSA-NCAM+) elevated α-SMA(+) immunoreactivity and the expression of angiopoietin-1 indicating angiogenic stimulation in the host brain. Taken together, the current data demonstrate that transplanted NPC(PSA-NCAM+) preserve brain tissue with reduced infarct size and improve behavioral performance through actions encompassing anti-reactive glial activation and pro-angiogenic activity in a rat stroke model. In conclusion, the present findings support the potentiality of NPC(PSA-NCAM+) as the promising source in the development of cell-based therapy for neurological diseases including ischemic stroke.

  19. Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

    Directory of Open Access Journals (Sweden)

    Hong J Lee

    Full Text Available BACKGROUND: Intracerebral hemorrhage (ICH is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

  20. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  1. Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

    Directory of Open Access Journals (Sweden)

    Sanna Maria

    2006-02-01

    Full Text Available Abstract Background It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC. Cells were treated with: (1 TPA, forskolin, IBMX, FGF-1 or (2 retinoic acid and 2-mercaptoethanol (BME. Treatment (1 induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1 compared with treatment (2. In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.

  2. Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics

    Directory of Open Access Journals (Sweden)

    JFW Greiner

    2011-12-01

    Full Text Available Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

  3. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  4. Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

    Directory of Open Access Journals (Sweden)

    Palm Kaia

    2009-06-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression. Results In this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP. The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA. Conclusion Genomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity.

  5. HUMAN FACE RECOGNITION BY PSEUDO ZERNIKE MOMENT AND PROBABILISTIC NEURAL NETWORK

    Directory of Open Access Journals (Sweden)

    ESMAEEL FATEMI BEHBAHANI

    2011-07-01

    Full Text Available In this paper a new face recognition method has been introduced. By this method face features have been extracted by pseudo-Zernike moments (PZM.Then a probabilistic neural network has applied to classify thesemoments as feature vectors. Moment features are invariant under scaling, translation, rotation and reflection. Probabilistic Neural Networks have fast computational time. Results show that PZM of order of 14 with PNN have the best performance among all the moments

  6. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution. © 2015. Published by The Company of Biologists Ltd.

  7. Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors.

    Directory of Open Access Journals (Sweden)

    Loyal A Goff

    Full Text Available BACKGROUND: MicroRNAs are required for maintenance of pluripotency as well as differentiation, but since more microRNAs have been computationally predicted in genome than have been found, there are likely to be undiscovered microRNAs expressed early in stem cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: SOLiD ultra-deep sequencing identified >10(7 unique small RNAs from human embryonic stem cells (hESC and neural-restricted precursors that were fit to a model of microRNA biogenesis to computationally predict 818 new microRNA genes. These predicted genomic loci are associated with chromatin patterns of modified histones that are predictive of regulated gene expression. 146 of the predicted microRNAs were enriched in Ago2-containing complexes along with 609 known microRNAs, demonstrating association with a functional RISC complex. This Ago2 IP-selected subset was consistently expressed in four independent hESC lines and exhibited complex patterns of regulation over development similar to previously-known microRNAs, including pluripotency-specific expression in both hESC and iPS cells. More than 30% of the Ago2 IP-enriched predicted microRNAs are new members of existing families since they share seed sequences with known microRNAs. CONCLUSIONS/SIGNIFICANCE: Extending the classic definition of microRNAs, this large number of new microRNA genes, the majority of which are less conserved than their canonical counterparts, likely represent evolutionarily recent regulators of early differentiation. The enrichment in Ago2 containing complexes, the presence of chromatin marks indicative of regulated gene expression, and differential expression over development all support the identification of 146 new microRNAs active during early hESC differentiation.

  8. Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine.

    Science.gov (United States)

    Marutle, Amelia; Ohmitsu, Masao; Nilbratt, Mats; Greig, Nigel H; Nordberg, Agneta; Sugaya, Kiminobu

    2007-07-24

    In a previous study, we found that human neural stem cells (HNSCs) exposed to high concentrations of secreted amyloid-precursor protein (sAPP) in vitro differentiated into mainly astrocytes, suggesting that pathological alterations in APP processing during neurodegenerative conditions such as Alzheimer's disease (AD) may prevent neuronal differentiation of HNSCs. Thus, successful neuroplacement therapy for AD may require regulating APP expression to favorable levels to enhance neuronal differentiation of HNSCs. Phenserine, a recently developed cholinesterase inhibitor (ChEI), has been reported to reduce APP levels in vitro and in vivo. In this study, we found reductions of APP and glial fibrillary acidic protein (GFAP) levels in the hippocampus of APP23 mice after 14 days treatment with (+)-phenserine (25 mg/kg) lacking ChEI activity. No significant change in APP gene expression was detected, suggesting that (+)-phenserine decreases APP levels and reactive astrocytes by posttranscription regulation. HNSCs transplanted into (+)-phenserine-treated APP23 mice followed by an additional 7 days of treatment with (+)-phenserine migrated and differentiated into neurons in the hippocampus and cortex after 6 weeks. Moreover, (+)-phenserine significantly increased neuronal differentiation of implanted HNSCs in hippocampal and cortical regions of APP23 mice and in the CA1 region of control mice. These results indicate that (+)-phenserine reduces APP protein in vivo and increases neuronal differentiation of HNSCs. Combination use of HNSC transplantation and treatment with drugs such as (+)-phenserine that modulate APP levels in the brain may be a useful tool for understanding mechanisms regulating stem cell migration and differentiation during neurodegenerative conditions in AD.

  9. Mild hypoxia enhances proliferation and multipotency of human neural stem cells.

    Directory of Open Access Journals (Sweden)

    Guido Santilli

    Full Text Available BACKGROUND: Neural stem cells (NSCs represent an optimal tool for studies and therapy of neurodegenerative diseases. We recently established a v-myc immortalized human NSC (IhNSC line, which retains stem properties comparable to parental cells. Oxygen concentration is one of the most crucial environmental conditions for cell proliferation and differentiation both in vitro and in vivo. In the central nervous system, physiological concentrations of oxygen range from 0.55 to 8% oxygen. In particular, in the in the subventricular zone niche area, it's estimated to be 2.5 to 3%. METHODOLOGY/PRINCIPAL FINDINGS: We investigated in vitro the effects of 1, 2.5, 5, and 20% oxygen concentrations on IhNSCs both during proliferation and differentiation. The highest proliferation rate, evaluated through neurosphere formation assay, was obtained at 2.5 and 5% oxygen, while 1% oxygen was most noxious for cell survival. The differentiation assays showed that the percentages of beta-tubIII+ or MAP2+ neuronal cells and of GalC+ oligodendrocytes were significantly higher at 2.5% compared with 1, 5, or 20% oxygen at 17 days in vitro. Mild hypoxia (2.5 to 5% oxygen promoted differentiation into neuro-oligodendroglial progenitors as revealed by the higher percentage of MAP2+/Ki67+ and GalC+/Ki67+ residual proliferating progenitors, and enhanced the yield of GABAergic and slightly of glutamatergic neurons compared to 1% and 20% oxygen where a significant percentage of GFAP+/nestin+ cells were still present at 17 days of differentiation. CONCLUSIONS/SIGNIFICANCE: These findings raise the possibility that reduced oxygen levels occurring in neuronal disorders like cerebral ischemia transiently lead to NSC remaining in a state of quiescence. Conversely, mild hypoxia favors NSC proliferation and neuronal and oligodendroglial differentiation, thus providing an important advance and a useful tool for NSC-mediated therapy of ischemic stroke and neurodegenerative diseases like

  10. Comparison of gene expression regulation in mouse- and human embryonic stem cell assays during neural differentiation and in response to valproic acid exposure

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; Theunissen, Peter T.; Pennings, Jeroen L. A.; Piersma, Aldert H.

    2015-01-01

    Embryonic stem cell tests (EST) are considered promising alternative assays for developmental toxicity testing. Classical mouse derived assays (mEST) are being replaced by human derived assays (hEST), in view of their relevance for human hazard assessment. We have compared mouse and human neural EST

  11. Human neural stem cells: a model system for the study of Lesch-Nyhan disease neurological aspects.

    Science.gov (United States)

    Cristini, Silvia; Navone, Stefania; Canzi, Laura; Acerbi, Francesco; Ciusani, Emilio; Hladnik, Uros; de Gemmis, Paola; Alessandri, Giulio; Colombo, Augusto; Parati, Eugenio; Invernici, Gloria

    2010-05-15

    The study of Lesch-Nyhan-diseased (LND) human brain is crucial for understanding how mutant hypoxanthine-phosphoribosyltransferase (HPRT) might lead to neuronal dysfunction. Since LND is a rare, inherited disorder caused by a deficiency of the enzyme HPRT, human neural stem cells (hNSCs) that carry this mutation are a precious source for delineating the consequences of HPRT deficiency and for developing new treatments. In our study we have examined the effect of HPRT deficiency on the differentiation of neurons in hNSCs isolated from human LND fetal brain. We have examined the expression of a number of transcription factors essential for neuronal differentiation and marker genes involved in dopamine (DA) biosynthetic pathway. LND hNSCs demonstrate aberrant expression of several transcription factors and DA markers. HPRT-deficient dopaminergic neurons also demonstrate a striking deficit in neurite outgrowth. These results represent direct experimental evidence for aberrant neurogenesis in LND hNSCs and suggest developmental roles for other housekeeping genes in neurodevelopmental disease. Moreover, exposure of the LND hNSCs to retinoic acid medium elicited the generation of dopaminergic neurons. The lack of precise understanding of the neurological dysfunction in LND has precluded development of useful therapies. These results evidence aberrant neurogenesis in LND hNSCs and suggest a role for HPRT gene in neurodevelopment. These cells combine the peculiarity of a neurodevelopmental model and a human, neural origin to provide an important tool to investigate the pathophysiology of HPRT deficiency and more broadly demonstrate the utility of human neural stem cells for studying the disease and identifying potential therapeutics.

  12. Lymphotropic Virions Affect Chemokine Receptor-Mediated Neural Signaling and Apoptosis: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia

    Science.gov (United States)

    Zheng, Jialin; Ghorpade, Anuja; Niemann, Douglas; Cotter, Robin L.; Thylin, Michael R.; Epstein, Leon; Swartz, Jennifer M.; Shepard, Robin B.; Liu, Xiaojuan; Nukuna, Adeline; Gendelman, Howard E.

    1999-01-01

    Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis. PMID:10482576

  13. Dual small-molecule targeting of SMAD signaling stimulates human induced pluripotent stem cells toward neural lineages.

    Directory of Open Access Journals (Sweden)

    Methichit Wattanapanitch

    Full Text Available Incurable neurological disorders such as Parkinson's disease (PD, Huntington's disease (HD, and Alzheimer's disease (AD are very common and can be life-threatening because of their progressive disease symptoms with limited treatment options. To provide an alternative renewable cell source for cell-based transplantation and as study models for neurological diseases, we generated induced pluripotent stem cells (iPSCs from human dermal fibroblasts (HDFs and then differentiated them into neural progenitor cells (NPCs and mature neurons by dual SMAD signaling inhibitors. Reprogramming efficiency was improved by supplementing the histone deacethylase inhibitor, valproic acid (VPA, and inhibitor of p160-Rho associated coiled-coil kinase (ROCK, Y-27632, after retroviral transduction. We obtained a number of iPS colonies that shared similar characteristics with human embryonic stem cells in terms of their morphology, cell surface antigens, pluripotency-associated gene and protein expressions as well as their in vitro and in vivo differentiation potentials. After treatment with Noggin and SB431542, inhibitors of the SMAD signaling pathway, HDF-iPSCs demonstrated rapid and efficient differentiation into neural lineages. Six days after neural induction, neuroepithelial cells (NEPCs were observed in the adherent monolayer culture, which had the ability to differentiate further into NPCs and neurons, as characterized by their morphology and the expression of neuron-specific transcripts and proteins. We propose that our study may be applied to generate neurological disease patient-specific iPSCs allowing better understanding of disease pathogenesis and drug sensitivity assays.

  14. Analysis of G-banding in tumor cell lines derived from human neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Junhua Zou; Yanhui Li

    2006-01-01

    BACKGROUND: The application of neural stem cell (NSC) is restricted because of its tumorigenesis, and the possible pathogenesis needs investigation.OBJECTIVE: To compare the differences of chromosomal G-banding between human NSCs (hNSCs) derived tumor cell line and hNSCs derived normal cell lines.DESIGN: A randomized controlled observation.SETTING: Building of Anatomy, Peking University Health Science Center.MATERIALS: The hNSC lines and hNSC-derived tumor cell lines were provided by the Research Center of Stem Cells, Peking University; DMEM/F12 (1:1) medium, N2 additive, B27 additive epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were produced by GIBCO BRL Company (USA); fetal bovine serum by HYCLONE Company (USA).METHODS: The experiments were carried out in the Department of Genetics, Peking University Health Science Center from February 2003 to July 2004. Human fetal striatal NSCs were inoculated hypodermically on the right scapular of nude mice; Normal human fetal striatal NSCs were cultured to 5-8 passages as controls. Karyotyping was performed on the 5th passage of hNSC-derived tumor cells at 6 weeks after hN-SC transplantation into nude mice (T1) and tumor cells at 15 weeks after transplantation (T2). Metaphase chromosomes were examined with microscope, G-banding cytogenetic analysis and karyotyping were performed according to the Cytoscan Karyotyping FISH and CGH software system (United biotechnology USA Corporation).MAIN OUTCOME MEASURES: G-banded analytical results of human fetal striatal nerve stem cells derived tumor cell lines (T1 and T2) of metaphase chromosomes were observed.RESULTS: ① Chromosome analysis of hNSC-derived tumor cell lines 1 (T1): Twenty-five well-spread metaphases were randomly selected for analysis. The karyotypes were 64, XX (8, 32%); 65, XX (1, 4%); 67,XX (5, 20%); 68, XX (11, 44%). The modal number of chromosomes in this cell lines was 68, which were all hypotriploid. The analysis of 8 G

  15. Human epidermal neural crest stem cells as candidates for cell-based therapies, disease modeling, and drug discovery.

    Science.gov (United States)

    Sieber-Blum, Maya

    2014-09-01

    In this review article I explore the suitability of human epidermal neural crest stem cells (hEPI-NCSC) for translational medicine. hEPI-NCSC are multipotent somatic stem cells that are derived from the embryonic neural crest. hEPI-NCSC are located in the bulge of hair follicles where they persist postnatally and into adulthood. Because of their location in the hairy skin and their migratory behavior, hEPI-NCSC can be easily isolated as a highly pure population of stem cells without the need for purification. Furthermore they can be expanded ex vivo into millions of stem cells, they do not form tumors in vivo, and they can undergo directed differentiation into crest and noncrest-derived cell types of clinical relevance. Taken together, these characteristics make hEPI-NCSC attractive candidates for cell-based therapies, drug discovery, and disease modeling. © 2014 Wiley Periodicals, Inc.

  16. Comprehensive quantitative comparison of the membrane proteome, phosphoproteome, and sialiome of human embryonic and neural stem cells

    DEFF Research Database (Denmark)

    Melo-Braga, Marcella Nunes; Schulz, Melanie; Liu, Qiuyue;

    2014-01-01

    Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. Therefore, these cells have huge potential as source for treatment of neurological diseases. Membrane-associated proteins are very important......ESCs and NSCs as well as to investigate potential new markers for these two cell stages, we performed large-scale quantitative membrane-proteomic of hESCs and NSCs. This approach employed membrane purification followed by peptide dimethyl labeling and peptide enrichment to study the membrane subproteome as well...... in which 78% of phosphopeptides were identified with ≥99% confidence in site assignment and 1810 unique formerly sialylated N-linked glycopeptides. Several proteins were identified as significantly regulated in hESCs and NSC, including proteins involved in the early embryonic and neural development...

  17. Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin

    Directory of Open Access Journals (Sweden)

    Cho Hyong-Ho

    2010-04-01

    Full Text Available Abstract Background Adult mesenchymal stem cells (MSCs derived from adipose tissue have the capacity to differentiate into mesenchymal as well as endodermal and ectodermal cell lineage in vitro. We characterized the multipotent ability of human adipose tissue-derived stem cells (hADSCs as MSCs and investigated the neural differentiation potential of these cells. Results Human ADSCs from earlobe fat maintained self-renewing capacity and differentiated into adipocytes, osteoblasts, or chondrocytes under specific culture conditions. Following neural induction with bFGF and forskolin, hADSCs were differentiated into various types of neural cells including neurons and glia in vitro. In neural differentiated-hADSCs (NI-hADSCs, the immunoreactivities for neural stem cell marker (nestin, neuronal markers (Tuj1, MAP2, NFL, NFM, NFH, NSE, and NeuN, astrocyte marker (GFAP, and oligodendrocyte marker (CNPase were significantly increased than in the primary hADSCs. RT-PCR analysis demonstrated that the mRNA levels encoding for ABCG2, nestin, Tuj1, MAP2, NFL, NFM, NSE, GAP43, SNAP25, GFAP, and CNPase were also highly increased in NI-hADSCs. Moreover, NI-hADSCs acquired neuron-like functions characterized by the display of voltage-dependent tetrodotoxin (TTX-sensitive sodium currents, outward potassium currents, and prominent negative resting membrane potentials under whole-cell patch clamp recordings. Further examination by RT-PCR showed that NI-hADSCs expressed high level of ionic channel genes for sodium (SCN5A, potassium (MaxiK, Kv4.2, and EAG2, and calcium channels (CACNA1C and CACNA1G, which were expressed constitutively in the primary hADSCs. In addition, we demonstrated that Kv4.3 and Eag1, potassium channel genes, and NE-Na, a TTX-sensitive sodium channel gene, were highly induced following neural differentiation. Conclusions These combined results indicate that hADSCs have the same self-renewing capacity and multipotency as stem cells, and can be

  18. Electrical stimulation using conductive polymer polypyrrole promotes differentiation of human neural stem cells: a biocompatible platform for translational neural tissue engineering.

    Science.gov (United States)

    Stewart, Elise; Kobayashi, Nao R; Higgins, Michael J; Quigley, Anita F; Jamali, Sina; Moulton, Simon E; Kapsa, Robert M I; Wallace, Gordon G; Crook, Jeremy M

    2015-04-01

    Conductive polymers (CPs) are organic materials that hold great promise for biomedicine. Potential applications include in vitro or implantable electrodes for excitable cell recording and stimulation and conductive scaffolds for cell support and tissue engineering. In this study, we demonstrate the utility of electroactive CP polypyrrole (PPy) containing the anionic dopant dodecylbenzenesulfonate (DBS) to differentiate novel clinically relevant human neural stem cells (hNSCs). Electrical stimulation of PPy(DBS) induced hNSCs to predominantly β-III Tubulin (Tuj1) expressing neurons, with lower induction of glial fibrillary acidic protein (GFAP) expressing glial cells. In addition, stimulated cultures comprised nodes or clusters of neurons with longer neurites and greater branching than unstimulated cultures. Cell clusters showed a similar spatial distribution to regions of higher conductivity on the film surface. Our findings support the use of electrical stimulation to promote neuronal induction and the biocompatibility of PPy(DBS) with hNSCs and opens up the possibility of identifying novel mechanisms of fate determination of differentiating human stem cells for advanced in vitro modeling, translational drug discovery, and regenerative medicine.

  19. Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

    Directory of Open Access Journals (Sweden)

    James C K Lai

    2008-12-01

    Full Text Available James C K Lai1, Maria B Lai1, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Christopher K Daniels1, Solomon W Leung21Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, and Biomedical Research Institute; 2Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USAAbstract: The use of titanium dioxide (TiO2 in various industrial applications (eg, production of paper, plastics, cosmetics, and paints has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO2 nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO2 micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO nanoparticles were the most effective, TiO2 nanoparticles the second most effective, and magnesium oxide (MgO nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO2 micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.Keywords: cytotoxicity of titanium dioxide micro- and nanoparticles, cytotoxicity of zinc oxide and magnesium oxide nanoparticles, human neural cells

  20. Cultivation of human neural progenitor cells in a 3-dimensional self-assembling peptide hydrogel.

    Science.gov (United States)

    Liedmann, Andrea; Rolfs, Arndt; Frech, Moritz J

    2012-01-11

    technique like fluorescence microscopes able to take z-stacks of the specimen. Furthermore this kind of analysis is extremely time consuming. Here we demonstrate a method to release cells from the 3D-scaffolds for the later analysis e.g. by flow cytometry. In this protocol human neural progenitor cells (hNPCs) of the ReNcell VM cell line (Millipore USA) were cultured and differentiated in 3D-scaffolds consisting of PuraMatrix (PM) or PuraMatrix supplemented with laminin (PML). In our hands a PM-concentration of 0.25% was optimal for the cultivation of the cells, however the concentration might be adapted to other cell types. The released cells can be used for e.g. immunocytochemical studies and subsequently analysed by flow cytometry. This speeds up the analysis and more over, the obtained data rest upon a wider base, improving the reliability of the data.

  1. Neural correlates of consonance, dissonance, and the hierarchy of musical pitch in the human brainstem.

    Science.gov (United States)

    Bidelman, Gavin M; Krishnan, Ananthanarayan

    2009-10-21

    Consonant and dissonant pitch relationships in music provide the foundation of melody and harmony, the building blocks of Western tonal music. We hypothesized that phase-locked neural activity within the brainstem may preserve information relevant to these important perceptual attributes of music. To this end, we measured brainstem frequency-following responses (FFRs) from nonmusicians in response to the dichotic presentation of nine musical intervals that varied in their degree of consonance and dissonance. Neural pitch salience was computed for each response using temporally based autocorrelation and harmonic pitch sieve analyses. Brainstem responses to consonant intervals were more robust and yielded stronger pitch salience than those to dissonant intervals. In addition, the ordering of neural pitch salience across musical intervals followed the hierarchical arrangement of pitch stipulated by Western music theory. Finally, pitch salience derived from neural data showed high correspondence with behavioral consonance judgments (r = 0.81). These results suggest that brainstem neural mechanisms mediating pitch processing show preferential encoding of consonant musical relationships and, furthermore, preserve the hierarchical pitch relationships found in music, even for individuals without formal musical training. We infer that the basic pitch relationships governing music may be rooted in low-level sensory processing and that an encoding scheme that favors consonant pitch relationships may be one reason why such intervals are preferred behaviorally.

  2. Aging degrades the neural encoding of simple and complex sounds in the human brainstem.

    Science.gov (United States)

    Clinard, Christopher G; Tremblay, Kelly L

    2013-01-01

    Older adults, with or without normal peripheral hearing sensitivity, have difficulty understanding speech. This impaired speech perception may, in part, be due to desynchronization affecting the neural representation of acoustic features. Here we determine if phase-locked neural activity generating the brainstem frequency-following response (FFR) exhibits age-related desynchronization and how this degradation affects the neural representation of simple and complex sounds. The objectives of this study were to (1) characterize the effects of age on the neural representation of simple tones and complex consonant-vowel stimuli, (2) determine if sustained and transient components of the FFR are differentially affected by age, and (3) determine if the inability to encode a simple signal predicts degradation in representation for complex speech signals. Correlational. Thirty four adults (aged 22-77 yr) with hearing thresholds falling within normal limits. Stimuli used to evoke FFRs were 1000 Hz tone bursts as well as a consonant-vowel /da/ sound. The neural representation of simple (tone) and complex (/da/) stimuli declines with advancing age. Tone-FFR phase coherence decreased as chronological age increased. For the consonant-vowel FFRs, transient onset and offset response amplitudes were smaller, and offset responses were delayed with age. Sustained responses at the onset of vowel periodicity were prolonged in latency and smaller in amplitude as age increased. FFT amplitude of the consonant-vowel FFR fundamental frequency did not significantly decline with increasing age. The ability to encode a simple signal was related to degradation in the neural representation of a complex, speechlike sound. Tone-FFR phase coherence was significantly related to the later vowel response components but not the earlier vowel components. FFR components representing the tone and consonant-vowel /da/ stimulus were negatively affected by age, showing age-related reductions in response

  3. Coupling between mechanical and neural behaviour in the human first dorsal interosseous muscle.

    Science.gov (United States)

    Hudson, Anna L; Taylor, Janet L; Gandevia, Simon C; Butler, Jane E

    2009-02-15

    The neural drive to a muscle and its biomechanical properties determine the force at a joint. These factors may be centrally linked. We studied the relationship between the ability of first dorsal interosseous muscle (FDI) to generate index flexion force around the metacarpophalangeal joint and the neural drive it receives in a voluntary contraction. The role of FDI was assessed in two thumb postures, thumb 'down' (thumb abducted) and thumb 'up' (thumb extended), and at different thumb carpometacarpal angles. These postures were designed to change acutely the flexion moment arm for FDI. The flexion twitch force evoked by supramaximal stimulation of the ulnar nerve was measured in the two postures and the change in moment arm was assessed by ultrasonography. Subjects also made voluntary flexion contractions of the index finger of approximately 5 N in both postures during which neural drive to FDI and the long finger flexor muscles was measured using surface EMG. Recordings of FDI EMG were normalized to the maximal M wave. Five of the 15 subjects also had a radial nerve block to eliminate any co-contraction of the extensor muscles, and extensor muscle EMG was monitored in subjects without radial nerve block. Compared to thumb up, flexion twitch force was approximately 60% greater, and the flexion moment arm was approximately 50% greater with the thumb down. There was minimal effect of altered carpometacarpal angle on flexion twitch force for either thumb posture. During voluntary flexion contractions, normalized FDI EMG was approximately 28% greater with thumb down, compared to thumb up, with no consistent change in neural drive to the long flexors. Hence, the contribution of FDI to index finger flexion can be altered by changes in thumb position. This is linked to changes in neural drive to FDI such that neural drive increases when the mechanical contribution increases, and provides a central mechanism to produce efficient voluntary movements.

  4. SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells.

    Science.gov (United States)

    Klajn, A; Drakulic, D; Tosic, M; Pavkovic, Z; Schwirtlich, M; Stevanovic, M

    2014-11-01

    SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.

  5. Differentiation and tumorigenicity of neural stem cells from human cord blood mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Jing Xiang; Changming Wang; Jingzhou Wang

    2009-01-01

    BACKGROUND:Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissues and exhibit low immunogenicity.OBJECTIVE:To investigate isolation and in vitro cultivation methods of human cord blood MSCs,to observe expression of neural stem cell (NSC) marker mRNA under induction,and to detect tumorigenicity in animals.DESIGN,TIME AND SETTING:A cell biological,in vitro trial and a randomized,controlled,in vivo experiment were performed at the Department of Neurology,Daping Hospital at the Third Military Medical University of Chinese PLA from August 2006 to May 2008.MATERIALS:Umbilical cord blood was collected from full-term-delivery fetus at the Department of Gynecology and Obstetrics of DapJng Hospital,China.Eighteen BALB/C nu/nu nude mice were randomly assigned to three groups:back subcutaneous,cervical subcutaneous,and control,with 6 mice in each group.METHODS:Monocytes were isolated from heparinized human cord blood samples by density gradient centrifugation and then adherent cultivated in vitro to obtain MSC clones.After the cord blood MSCs were cultured for 7 days with nerve growth factor and retinoic acid to induce differentiation into NSCs,the cells (adjusted density of 1×10~7/mL) were prepared into cell suspension.In the back subcutaneous and cervical subcutaneous groups,nude mice were hypodermically injected with a 0.5-mL cell suspension into the back and cervical regions,respectively.In the control group,nude mice received a subcutaneous injection of 0.5 mL physiological saline into the back or cervical regions,respectively.MAIN OUTCOME MEASURES:Cellular morphology was observed by inverted microscopy,cultured cord blood MSCs were examined by flow cytometry,expression of nestin and musashi-1 mRNA was detected by reverse-transcriptase polymerase chain reaction prior to and after induction,and tumorigenicity following cord blood MSC transplantation was assayed by hematoxylin-eosin staining.RESULTS:Following adherent cultivation

  6. Three-dimensional normal human neural progenitor tissue-like assemblies: a model of persistent varicella-zoster virus infection.

    Directory of Open Access Journals (Sweden)

    Thomas J Goodwin

    Full Text Available Varicella-zoster virus (VZV is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP in tissue-like assemblies (TLAs, which can be successfully maintained for at least 180 days in three-dimensional (3D culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  7. Three-dimensional normal human neural progenitor tissue-like assemblies: a model of persistent varicella-zoster virus infection.

    Science.gov (United States)

    Goodwin, Thomas J; McCarthy, Maureen; Osterrieder, Nikolaus; Cohrs, Randall J; Kaufer, Benedikt B

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  8. Comparison of the neural differentiation potential of human mesenchymal stem cells from amniotic fluid and adult bone marrow.

    Science.gov (United States)

    Yan, Zhong-Jie; Hu, Yu-Qin; Zhang, Hong-Tian; Zhang, Peng; Xiao, Zong-Yu; Sun, Xin-Lin; Cai, Ying-Qian; Hu, Chang-Chen; Xu, Ru-Xiang

    2013-05-01

    Human mesenchymal stem cells (MSCs) are considered a promising tool for cell-based therapies of nervous system diseases. Bone marrow (BM) has been the traditional source of MSCs (BM-MSCs). However, there are some limitations for their clinical use, such as the decline in cell number and differentiation potential with age. Recently, amniotic fluid (AF)-derived MSCs (AF-MSCs) have been shown to express embryonic and adult stem cell markers, and can differentiate into cells of all three germ layers. In this study, we isolated AF-MSCs from second-trimester AF by limiting dilution and compared their proliferative capacity, multipotency, neural differentiation ability, and secretion of neurotrophins to those of BM-MSCs. AF-MSCs showed a higher proliferative capacity and more rapidly formed and expanded neurospheres compared to those of BM-MSCs. Both immunocytochemical and quantitative real-time PCR analyses demonstrated that AF-MSCs showed higher expression of neural stemness markers than those of BM-MSCs following neural stem cell (NSC) differentiation. Furthermore, the levels of brain-derived growth factor and nerve growth factor secreted by AF-MSCs in the culture medium were higher than those of BM-MSCs. In addition, AF-MSCs maintained a normal karyotype in long-term cultures after NSC differentiation and were not tumorigenic in vivo. Our findings suggest that AF-MSCs are a promising and safe alternative to BM-MSCs for therapy of nervous system diseases.

  9. Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer's Disease Phenotypes.

    Science.gov (United States)

    Raja, Waseem K; Mungenast, Alison E; Lin, Yuan-Ta; Ko, Tak; Abdurrob, Fatema; Seo, Jinsoo; Tsai, Li-Huei

    2016-01-01

    The dismal success rate of clinical trials for Alzheimer's disease (AD) motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cells (iPSCs) allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe. We report brain organoids that use pluripotent stem cells derived from AD patients and recapitulate AD-like pathologies such as amyloid aggregation, hyperphosphorylated tau protein, and endosome abnormalities. These pathologies are observed in an age-dependent manner in organoids derived from multiple familial AD (fAD) patients harboring amyloid precursor protein (APP) duplication or presenilin1 (PSEN1) mutation, compared to controls. The incidence of AD pathology was consistent amongst several fAD lines, which carried different mutations. Although these are complex assemblies of neural tissue, they are also highly amenable to experimental manipulation. We find that treatment of patient-derived organoids with β- and γ-secretase inhibitors significantly reduces amyloid and tau pathology. Moreover, these results show the potential of this model system to greatly increase the translatability of pre-clinical drug discovery in AD.

  10. Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population.

    Science.gov (United States)

    De Marco, Patrizia; Merello, Elisa; Piatelli, Gianluca; Cama, Armando; Kibar, Zoha; Capra, Valeria

    2014-08-01

    Neural Tube Defects (NTDs) are congenital malformations that involve failure of the neural tube closure during the early phases of development at any level of the rostro-caudal axis. The planar cell polarity (PCP) pathway is a highly conserved, noncanonical Wnt-Frizzled-Dishevelled signaling cascade, that was first identified in the fruit fly Drosophila. We are here reviewing the role of the PCP pathway genes in the etiology of human NTDs, updating the list of the rare and deleterious mutations identified so far. We report 50 rare nonsynonymous mutations of PCP genes in 54 patients having a pathogenic effect on the protein function. Thirteen mutations that have previously been reported as novel are now reported in public databases, although at very low frequencies. The mutations were private, mostly missense, and transmitted by a healthy parent. To date, no clear genotype-phenotype correlation has been possible to create. Even if PCP pathway genes are involved in the pathogenesis of neural tube defects, future studies will be necessary to better dissect the genetic causes underlying these complex malformations.

  11. Emotional expectations influence neural sensitivity to fearful faces in humans:An event-related potential study

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The present study tested whether neural sensitivity to salient emotional facial expressions was influenced by emotional expectations induced by a cue that validly predicted the expression of a subsequently presented target face. Event-related potentials (ERPs) elicited by fearful and neutral faces were recorded while participants performed a gender discrimination task under cued (‘expected’) and uncued (‘unexpected’) conditions. The behavioral results revealed that accuracy was lower for fearful compared with neutral faces in the unexpected condition, while accuracy was similar for fearful and neutral faces in the expected condition. ERP data revealed increased amplitudes in the P2 component and 200–250 ms interval for unexpected fearful versus neutral faces. By contrast, ERP responses were similar for fearful and neutral faces in the expected condition. These findings indicate that human neural sensitivity to fearful faces is modulated by emotional expectations. Although the neural system is sensitive to unpredictable emotionally salient stimuli, sensitivity to salient stimuli is reduced when these stimuli are predictable.

  12. Resolving the neural dynamics of visual and auditory scene processing in the human brain: a methodological approach

    Science.gov (United States)

    Teng, Santani

    2017-01-01

    In natural environments, visual and auditory stimulation elicit responses across a large set of brain regions in a fraction of a second, yielding representations of the multimodal scene and its properties. The rapid and complex neural dynamics underlying visual and auditory information processing pose major challenges to human cognitive neuroscience. Brain signals measured non-invasively are inherently noisy, the format of neural representations is unknown, and transformations between representations are complex and often nonlinear. Further, no single non-invasive brain measurement technique provides a spatio-temporally integrated view. In this opinion piece, we argue that progress can be made by a concerted effort based on three pillars of recent methodological development: (i) sensitive analysis techniques such as decoding and cross-classification, (ii) complex computational modelling using models such as deep neural networks, and (iii) integration across imaging methods (magnetoencephalography/electroencephalography, functional magnetic resonance imaging) and models, e.g. using representational similarity analysis. We showcase two recent efforts that have been undertaken in this spirit and provide novel results about visual and auditory scene analysis. Finally, we discuss the limits of this perspective and sketch a concrete roadmap for future research. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044019

  13. Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cell transplantation improves hypoxic-ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dengna Zhu; Yanjie Jia; Jun Wang; Boai Zhang; Guohui Niu; Yazhen Fan

    2011-01-01

    Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cells were transplanted into a hypoxic-ischemic neonatal rat model via the tail vein.BrdU-positive cells at day 7post-transplantation,as well as nestin-and neuron specific enolase-positive cells at day 14 wereincreased compared with those of the single neural stem cell transplantation group.In addition,theproportion of neuronal differentiation was enhanced.The genetically modified cell-transplanted ratsexhibited enhanced performance in correctly crossing a Y-maze and climbing an angled slope compared with those of the single neural stem cell transplantation group.These results showed that human insulin-like growth factor 1-transfected neural stem cell transplantation promotes therecovery of the learning,memory and motor functions in hypoxic-ischemic rats.

  14. Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies.

    Science.gov (United States)

    Fullana, M A; Harrison, B J; Soriano-Mas, C; Vervliet, B; Cardoner, N; Àvila-Parcet, A; Radua, J

    2016-04-01

    Classical Pavlovian fear conditioning remains the most widely employed experimental model of fear and anxiety, and continues to inform contemporary pathophysiological accounts of clinical anxiety disorders. Despite its widespread application in human and animal studies, the neurobiological basis of fear conditioning remains only partially understood. Here we provide a comprehensive meta-analysis of human fear-conditioning studies carried out with functional magnetic resonance imaging (fMRI), yielding a pooled sample of 677 participants from 27 independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from the authors of 13 of these studies. Our primary analyses demonstrate that human fear conditioning is associated with a consistent and robust pattern of neural activation across a hypothesized genuine network of brain regions resembling existing anatomical descriptions of the 'central autonomic-interoceptive network'. This finding is discussed with a particular emphasis on the neural substrates of conscious fear processing. Our associated meta-analysis of functional deactivations-a scarcely addressed dynamic in fMRI fear-conditioning studies-also suggests the existence of a coordinated brain response potentially underlying the 'safety signal' (that is, non-threat) processing. We attempt to provide an integrated summary on these findings with the view that they may inform ongoing studies of fear-conditioning processes both in healthy and clinical populations, as investigated with neuroimaging and other experimental approaches.

  15. An Efficient Feature Extraction Method with Pseudo-Zernike Moment in RBF Neural Network-Based Human Face Recognition System

    Directory of Open Access Journals (Sweden)

    Ahmadi Majid

    2003-01-01

    Full Text Available This paper introduces a novel method for the recognition of human faces in digital images using a new feature extraction method that combines the global and local information in frontal view of facial images. Radial basis function (RBF neural network with a hybrid learning algorithm (HLA has been used as a classifier. The proposed feature extraction method includes human face localization derived from the shape information. An efficient distance measure as facial candidate threshold (FCT is defined to distinguish between face and nonface images. Pseudo-Zernike moment invariant (PZMI with an efficient method for selecting moment order has been used. A newly defined parameter named axis correction ratio (ACR of images for disregarding irrelevant information of face images is introduced. In this paper, the effect of these parameters in disregarding irrelevant information in recognition rate improvement is studied. Also we evaluate the effect of orders of PZMI in recognition rate of the proposed technique as well as RBF neural network learning speed. Simulation results on the face database of Olivetti Research Laboratory (ORL indicate that the proposed method for human face recognition yielded a recognition rate of 99.3%.

  16. Induction of Neural Progenitor-Like Cells from Human Fibroblasts via a Genetic Material-Free Approach.

    Directory of Open Access Journals (Sweden)

    Fahimeh Mirakhori

    Full Text Available A number of studies generated induced neural progenitor cells (iNPCs from human fibroblasts by viral delivering defined transcription factors. However, the potential risks associated with gene delivery systems have limited their clinical use. We propose it would be safer to induce neural progenitor-like cells from human adult fibroblasts via a direct non-genetic alternative approach.Here, we have reported that seven rounds of TAT-SOX2 protein transduction in a defined chemical cocktail under a 3D sphere culture gradually morphed fibroblasts into neuroepithelial-like colonies. We were able to expand these cells for up to 20 passages. These cells could give rise to cells that expressed neurons and glia cell markers both in vitro and in vivo.These results show that our approach is beneficial for the genetic material-free generation of iNPCs from human fibroblasts where small chemical molecules can provide a valuable, viable strategy to boost and improve induction in a 3D sphere culture.

  17. Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2015-09-01

    Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

  18. The study of neural tube defects after the Human Genome Project and folic acid fortification of foods.

    Science.gov (United States)

    Graf, W D; Oleinik, O E

    2000-12-01

    The implementation of folic acid fortification will eliminate a proportion of neural tube defects (NTD). As a result, the etiologic and clinical profiles of the developmental disorder may both change. In the assessment of NTD as it evolves, the bioinformatics structure and content of the Human Genome Project will find vital application. One important development will be an enhanced understanding of the role of folic acid in global regulation of gene expression through epigenetic processes. In addition, bioinformatics will facilitate coordination of research in the basic sciences with clinical investigations to better define remaining etiologic factors.

  19. Differential neural activity patterns for spatial relations in humans: a MEG study.

    Science.gov (United States)

    Scott, Nicole M; Leuthold, Arthur; Sera, Maria D; Georgopoulos, Apostolos P

    2016-02-01

    Children learn the words for above-below relations earlier than for left-right relations, despite treating these equally well in a simple visual categorization task. Even as adults--conflicts in congruency, such as when a stimulus is depicted in a spatially incongruent manner with respect to salient global cues--can be challenging. Here we investigated the neural correlates of encoding and maintaining in working memory above-below and left-right relational planes in 12 adults using magnetoencephalography in order to discover whether above-below relations are represented by the brain differently than left-right relations. Adults performed perfectly on the task behaviorally, so any differences in neural activity were attributed to the stimuli's cognitive attributes. In comparing above-below to left-right relations during stimulus encoding, we found the greatest differences in neural activity in areas associated with space and movement. In comparing congruent to incongruent trials, we found the greatest differential activity in premotor areas. For both contrasts, brain areas involved in the encoding phase were also involved in the maintenance phase, which provides evidence that those brain areas are particularly important in representing the relational planes or congruency types throughout the trial. When comparing neural activity associated with the relational planes during working memory, additional right posterior areas were implicated, whereas the congruent-incongruent contrast implicated additional bilateral frontal and temporal areas. These findings are consistent with the hypothesis left-right relations are represented differently than above-below relations.

  20. A Neural Network Model of the Structure and Dynamics of Human Personality

    Science.gov (United States)

    Read, Stephen J.; Monroe, Brian M.; Brownstein, Aaron L.; Yang, Yu; Chopra, Gurveen; Miller, Lynn C.

    2010-01-01

    We present a neural network model that aims to bridge the historical gap between dynamic and structural approaches to personality. The model integrates work on the structure of the trait lexicon, the neurobiology of personality, temperament, goal-based models of personality, and an evolutionary analysis of motives. It is organized in terms of two…

  1. Review: Human Intracortical recording and neural decoding for brain-computer interfaces.

    Science.gov (United States)

    Brandman, David M; Cash, Sydney S; Hochberg, Leigh R

    2017-03-02

    Brain Computer Interfaces (BCIs) use neural information recorded from the brain for voluntary control of external devices. The development of BCI systems has largely focused on improving functional independence for individuals with severe motor impairments, including providing tools for communication and mobility. In this review, we describe recent advances in intracortical BCI technology and provide potential directions for further research.

  2. A Neural Network Model of the Structure and Dynamics of Human Personality

    Science.gov (United States)

    Read, Stephen J.; Monroe, Brian M.; Brownstein, Aaron L.; Yang, Yu; Chopra, Gurveen; Miller, Lynn C.

    2010-01-01

    We present a neural network model that aims to bridge the historical gap between dynamic and structural approaches to personality. The model integrates work on the structure of the trait lexicon, the neurobiology of personality, temperament, goal-based models of personality, and an evolutionary analysis of motives. It is organized in terms of two…

  3. Neural Signatures of Number Processing in Human Infants: Evidence for Two Core Systems Underlying Numerical Cognition

    Science.gov (United States)

    Hyde, Daniel C.; Spelke, Elizabeth S.

    2011-01-01

    Behavioral research suggests that two cognitive systems are at the foundations of numerical thinking: one for representing 1-3 objects in parallel and one for representing and comparing large, approximate numerical magnitudes. We tested for dissociable neural signatures of these systems in preverbal infants by recording event-related potentials…

  4. Leukemia inhibitory factor (LIF) enhances MAP2 + and HUC/D + neurons and influences neurite extension during differentiation of neural progenitors derived from human embryonic stem cells.

    Science.gov (United States)

    Leukemia Inhibitory Factor (L1F), a member of the Interleukin 6 cytokine family, has a role in differentiation of Human Neural Progenitor (hNP) cells in vitro. hNP cells, derived from Human Embryonic Stem (hES) cells, have an unlimited capacity for self-renewal in monolayer cultu...

  5. Leukemia inhibitory factor (LIF) enhances MAP2 + and HUC/D + neurons and influences neurite extension during differentiation of neural progenitors derived from human embryonic stem cells.

    Science.gov (United States)

    Leukemia Inhibitory Factor (L1F), a member of the Interleukin 6 cytokine family, has a role in differentiation of Human Neural Progenitor (hNP) cells in vitro. hNP cells, derived from Human Embryonic Stem (hES) cells, have an unlimited capacity for self-renewal in monolayer cultu...

  6. Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation

    Directory of Open Access Journals (Sweden)

    Bertrand P. Tseng

    2013-01-01

    Full Text Available Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs. We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS, reactive nitrogen species (RNS, nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

  7. Pluripotent stem cell-derived somatic stem cells as tool to study the role of microRNAs in early human neural development.

    Science.gov (United States)

    Roese-Koerner, B; Stappert, L; Koch, P; Brüstle, O; Borghese, L

    2013-06-01

    The in vitro differentiation of human pluripotent stem cells represents a convenient approach to generate large numbers of neural cells for basic and translational research. We recently described the derivation of homogeneous populations of long-term self-renewing neuroepithelial-like stem cells from human pluripotent stem cells (lt-NES® cells). These cells constitute a suitable source of neural stem cells for in vitro modelling of early human neural development. Recent evidence demonstrates that microRNAs are important regulators of stem cells and nervous system development. Studies in several model organisms suggest that microRNAs contribute to different stages of neurogenesis - from progenitor self-renewal to survival and function of differentiated neurons. However, the understanding of the impact of microRNA-based regulation in human neural development is still at its dawn. Here, we give an overview on the current state of microRNA biology in stem cells and neural development and examine the role of the neural-associated miR-124, miR- 125b and miR-9/9* in human lt-NES® cells. We show that overexpression of miR-124, as well as overexpression of miR-125b, impair lt-NES® cell self-renewal and induce differentiation into neurons. Overexpression of the miR-9/9* locus also impairs self-renewal of lt-NES® cells and supports their commitment to neuronal differentiation. A detailed examination revealed that overexpression of miR-9 promotes differentiation, while overexpression of miR-9* affects both proliferation and differentiation of lt-NES® cells. This work provides insights into the regulation of early human neuroepithelial cells by microRNAs and highlights the potential of controlling differentiation of human stem cells by modulating the expression of selected microRNAs.

  8. Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor

    Directory of Open Access Journals (Sweden)

    Ebrahim Shahbazi

    2016-04-01

    Full Text Available Direct conversion of somatic cells into neural stem cells (NSCs by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. In addition, the single-seeded induced NSCs were able to form NSC colonies with efficiency comparable with control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating, and attaining neural phenotypes after transplantation into neonatal mouse and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts.

  9. Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain.

    Science.gov (United States)

    Ramos-Gómez, Milagros; Seiz, Emma G; Martínez-Serrano, Alberto

    2015-03-05

    Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging. These findings support the use of commercial MNPs to track cells for short- and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.

  10. Tracking of iron-labeled human neural stem cells by magnetic resonance imaging in cell replacement therapy for Parkinson's disease.

    Science.gov (United States)

    Ramos-Gómez, Milagros; Martínez-Serrano, Alberto

    2016-01-01

    Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson's disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation, self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time.

  11. Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects

    Directory of Open Access Journals (Sweden)

    Natasha W. Hanners

    2016-06-01

    Full Text Available The recent Zika virus (ZIKV outbreak in the Western hemisphere is associated with severe pathology in newborns, including microcephaly and brain damage. The mechanisms underlying these outcomes are under intense investigation. Here, we show that a 2015 ZIKV isolate replicates in multiple cell types, including primary human fetal neural progenitors (hNPs. In immortalized cells, ZIKV is cytopathic and grossly rearranges endoplasmic reticulum membranes similar to other flaviviruses. In hNPs, ZIKV infection has a partial cytopathic phase characterized by cell rounding, pyknosis, and activation of caspase 3. Despite notable cell death, ZIKV did not activate a cytokine response in hNPs. This lack of cell intrinsic immunity to ZIKV is consistent with our observation that virus replication persists in hNPs for at least 28 days. These findings, supported by published fetal neuropathology, establish a proof-of-concept that neural progenitors in the developing human fetus can be direct targets of detrimental ZIKV-induced pathology.

  12. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  13. Comprehensive quantitative comparison of the membrane proteome and PTM-ome of human embryonic stem cells and neural stem cells

    DEFF Research Database (Denmark)

    Braga, Marcella Nunes de Melo; Schulz, Melanie; Jakobsen, Lene

    Introduction: Human embryonic stem cells (hESCs) can differentiate into all three germ layers and self-renew. Due to its ability to differentiate in vitro into human neural stem cells (hNSCs), which can further be differentiated into motor neurons and dopaminergic neurons, these cells are potential...... source for treatment of neurological diseases such as Parkinson´s disease. Membrane proteins are very important in cellular signaling and they are regulated by post-translational modifications such as phosphorylation and glycosylation. In order to obtain more information about important membrane proteins...... and modification sites involved in the differentiation of hESCs to hNSCs and also investigate potential new markers for two stages, we have performed a comprehensive mass-spectrometry-based quantitative proteomics and PTMomics study. Methods: The hESC and hNSC were subject to Na2CO3 and ultracentrifugation...

  14. Revocation of European patent for neural progenitors highlights patent challenges for inventions relating to human embryonic stem cells.

    Science.gov (United States)

    Rigby, Barbara

    2013-11-01

    Cells derived from human embryonic stem cells have great therapeutic potential. Patents are key to allowing companies that develop methods of generating such cells to recuperate their investment. However, in Europe, inventions relating to the use of human embryos for commercial purposes are excluded from patentability on moral grounds. The scope of this morality exclusion was recently tested before Germany's highest court and before the European Patent Office (EPO), with diverging results. The decision by the EPO's Opposition Division to revoke EP1040185 relating to neural precursors and methods for their generation has received a mixed reception. The decision has very recently been appealed, and the outcome of this Appeal should provide more definitive guidance on the scope of the morality exclusion.

  15. Comparative analysis of the expression of neural stem cell-associated genes during neocortex and retina development in human.

    Science.gov (United States)

    Verdiev, B I; Milyushina, L A; Podgornyi, O V; Poltavtseva, R A; Zinov'eva, R D; Sukhikh, G T; Aleksandrova, M A

    2013-02-01

    We compared the expression of Sox2, Oct4, Nanog, Pax6, Prox1 genes associated with plasticity of neural stem and progenitor cells during human neocortex and retina development and in cell cultures. At the analyzed stages of neurogenesis, Pax6 gene is expressed in the neocortex and retina at constant levels, the expression is by one order of magnitude higher in the retina. The dynamics of Sox2 and Pax6 expression in the neocortex was similar. The expression of Oct4 and Nanog genes during neurogenesis in the neocortex and human fetal retina reflects the existence of a high-plasticity cell pool. The dynamics of βIII-tubulin expression indicates that the retina develops more rapidly than the neocortex. Our experiments showed that genetically determined cell potencies typical of native cells are realized in primary cultures without specific stimulation.

  16. Phase locked neural activity in the human brainstem predicts preference for musical consonance.

    Science.gov (United States)

    Bones, Oliver; Hopkins, Kathryn; Krishnan, Ananthanarayan; Plack, Christopher J

    2014-05-01

    When musical notes are combined to make a chord, the closeness of fit of the combined spectrum to a single harmonic series (the 'harmonicity' of the chord) predicts the perceived consonance (how pleasant and stable the chord sounds; McDermott, Lehr, & Oxenham, 2010). The distinction between consonance and dissonance is central to Western musical form. Harmonicity is represented in the temporal firing patterns of populations of brainstem neurons. The current study investigates the role of brainstem temporal coding of harmonicity in the perception of consonance. Individual preference for consonant over dissonant chords was measured using a rating scale for pairs of simultaneous notes. In order to investigate the effects of cochlear interactions, notes were presented in two ways: both notes to both ears or each note to different ears. The electrophysiological frequency following response (FFR), reflecting sustained neural activity in the brainstem synchronised to the stimulus, was also measured. When both notes were presented to both ears the perceptual distinction between consonant and dissonant chords was stronger than when the notes were presented to different ears. In the condition in which both notes were presented to the both ears additional low-frequency components, corresponding to difference tones resulting from nonlinear cochlear processing, were observable in the FFR effectively enhancing the neural harmonicity of consonant chords but not dissonant chords. Suppressing the cochlear envelope component of the FFR also suppressed the additional frequency components. This suggests that, in the case of consonant chords, difference tones generated by interactions between notes in the cochlea enhance the perception of consonance. Furthermore, individuals with a greater distinction between consonant and dissonant chords in the FFR to individual harmonics had a stronger preference for consonant over dissonant chords. Overall, the results provide compelling evidence

  17. Efficient derivation of multipotent neural stem/progenitor cells from non-human primate embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Hiroko Shimada

    Full Text Available The common marmoset (Callithrix jacchus is a small New World primate that has been used as a non-human primate model for various biomedical studies. We previously demonstrated that transplantation of neural stem/progenitor cells (NS/PCs derived from mouse and human embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs promote functional locomotor recovery of mouse spinal cord injury models. However, for the clinical application of such a therapeutic approach, we need to evaluate the efficacy and safety of pluripotent stem cell-derived NS/PCs not only by xenotransplantation, but also allotransplantation using non-human primate models to assess immunological rejection and tumorigenicity. In the present study, we established a culture method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs. Marmoset ESC-derived neurospheres could be passaged repeatedly and showed sequential generation of neurons and astrocytes, similar to that of mouse ESC-derived NS/PCs, and gave rise to functional neurons as indicated by calcium imaging. Although marmoset ESC-derived NS/PCs could not differentiate into oligodendrocytes under default culture conditions, these cells could abundantly generate oligodendrocytes by incorporating additional signals that recapitulate in vivo neural development. Moreover, principal component analysis of microarray data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene expression profiles to those of fetal brain-derived NS/PCs by repeated passaging. Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate evaluation by allotransplantation of NS/PCs into non-human primate models, but are also applicable to analysis of iPSCs established from transgenic disease model marmosets.

  18. Origin-Dependent Neural Cell Identities in Differentiated Human iPSCs In Vitro and after Transplantation into the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Gunnar Hargus

    2014-09-01

    Full Text Available The differentiation capability of induced pluripotent stem cells (iPSCs toward certain cell types for disease modeling and drug screening assays might be influenced by their somatic cell of origin. Here, we have compared the neural induction of human iPSCs generated from fetal neural stem cells (fNSCs, dermal fibroblasts, or cord blood CD34+ hematopoietic progenitor cells. Neural progenitor cells (NPCs and neurons could be generated at similar efficiencies from all iPSCs. Transcriptomics analysis of the whole genome and of neural genes revealed a separation of neuroectoderm-derived iPSC-NPCs from mesoderm-derived iPSC-NPCs. Furthermore, we found genes that were similarly expressed in fNSCs and neuroectoderm, but not in mesoderm-derived iPSC-NPCs. Notably, these neural signatures were retained after transplantation into the cortex of mice and paralleled with increased survival of neuroectoderm-derived cells in vivo. These results indicate distinct origin-dependent neural cell identities in differentiated human iPSCs both in vitro and in vivo.

  19. Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and In Vitro Disease Modeling

    Directory of Open Access Journals (Sweden)

    May Shin Yap

    2015-01-01

    Full Text Available Human pluripotent stem cells (hPSCs derived from either blastocyst stage embryos (hESCs or reprogrammed somatic cells (iPSCs can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.

  20. Brain Consequences of Spinal Cord Injury with and without Neuropathic Pain: Translating Animal Models of Neuroinflammation onto Human Neural Networks and Back

    Science.gov (United States)

    2016-10-01

    injury with regards to alterations in brain network function and expression of activated microglia, both human patients and in an animal model...Z39.18 Brain Consequences of Spinal Cord Injury with and without Neuropathic Pain: Translating Animal Models of Neuroinflammation onto Human Neural...Specific Aim 2A: Define brain structural, diffusion and functional network changes in the SCI populations. Goal 1: Human PET-MR imaging of microglia

  1. Intermittent electrical stimuli for guidance of human mesenchymal stem cell lineage commitment towards neural-like cells on electroconductive substrates.

    Science.gov (United States)

    Thrivikraman, Greeshma; Madras, Giridhar; Basu, Bikramjit

    2014-08-01

    In the context of the role of multiple physical factors in dictating stem cell fate, the present paper demonstrates the effectiveness of the intermittently delivered external electric field stimulation towards switching the stem cell fate to specific lineage, when cultured in the absence of biochemical growth factors. In particular, our findings present the ability of human mesenchymal stem cells (hMSCs) to respond to the electric stimuli by adopting extended neural-like morphology on conducting polymeric substrates. Polyaniline (PANI) is selected as the model system to demonstrate this effect, as the electrical conductivity of the polymeric substrates can be systematically tailored over a broad range (10(-9) to 10 S/cm) from highly insulating to conducting by doping with varying concentrations (10(-5) to 1 m) of HCl. On the basis of the culture protocol involving the systematic delivery of intermittent electric field (dc) stimulation, the parametric window of substrate conductivity and electric field strength was established to promote significant morphological extensions, with minimal cellular damage. A time dependent morphological change in hMSCs with significant filopodial elongation was observed after 7 days of electrically stimulated culture. Concomitant with morphological changes, a commensurate increase in the expression of neural lineage commitment markers such as nestin and βIII tubulin was recorded from hMSCs grown on highly conducting substrates, as revealed from the mRNA expression analysis using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) as well as by immune-fluorescence imaging. Therefore, the present work establishes the key role of intermittent and systematic delivery of electric stimuli as guidance cues in promoting neural-like differentiation of hMSCs, when grown on electroconductive substrates.

  2. Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

    Directory of Open Access Journals (Sweden)

    Omer Ziv

    2015-10-01

    Full Text Available Neural stem cells (NSCs are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

  3. Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

    Science.gov (United States)

    Ziv, Omer; Zaritsky, Assaf; Yaffe, Yakey; Mutukula, Naresh; Edri, Reuven; Elkabetz, Yechiel

    2015-10-01

    Neural stem cells (NSCs) are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture) and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM)--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII) reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

  4. Flash photo stimulation of human neural stem cells on graphene/TiO2 heterojunction for differentiation into neurons

    Science.gov (United States)

    Akhavan, Omid; Ghaderi, Elham

    2013-10-01

    For the application of human neural stem cells (hNSCs) in neural regeneration and brain repair, it is necessary to stimulate hNSC differentiation towards neurons rather than glia. Due to the unique properties of graphene in stem cell differentiation, here we introduce reduced graphene oxide (rGO)/TiO2 heterojunction film as a biocompatible flash photo stimulator for effective differentiation of hNSCs into neurons. Using the stimulation, the number of cell nuclei on rGO/TiO2 increased by a factor of ~1.5, while on GO/TiO2 and TiO2 it increased only ~48 and 24%, respectively. Moreover, under optimum conditions of flash photo stimulation (10 mW cm-2 flash intensity and 15.0 mM ascorbic acid in cell culture medium) not only did the number of cell nuclei and neurons differentiated on rGO/TiO2 significantly increase (by factors of ~2.5 and 3.6), but also the number of glial cells decreased (by a factor of ~0.28). This resulted in a ~23-fold increase in the neural to glial cell ratio. Such highly accelerated differentiation was assigned to electron injection from the photoexcited TiO2 into the cells on the rGO through Ti-C and Ti-O-C bonds. The role of ascorbic acid, as a scavenger of the photoexcited holes, in flash photo stimulation was studied at various concentrations and flash intensities.

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

    Directory of Open Access Journals (Sweden)

    Mauricio R Delgado

    2011-05-01

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

  6. Neural differentiation of human embryonic stem cells as an in vitro tool for the study of the expression patterns of the neuronal cytoskeleton during neurogenesis.

    Science.gov (United States)

    Liu, Chao; Zhong, Yongwang; Apostolou, Andria; Fang, Shengyun

    2013-09-13

    The neural differentiation of human embryonic stem cells (ESCs) is a potential tool for elucidating the key mechanisms involved in human neurogenesis. Nestin and β-III-tubulin, which are cytoskeleton proteins, are marker proteins of neural stem cells (NSCs) and neurons, respectively. However, the expression patterns of nestin and β-III-tubulin in neural derivatives from human ESCs remain unclear. In this study, we found that neural progenitor cells (NPCs) derived from H9 cells express high levels of nestin and musashi-1. In contrast, β-III-tubulin was weakly expressed in a few NPCs. Moreover, in these cells, nestin formed filament networks, whereas β-III-tubulin was distributed randomly as small particles. As the differentiation proceeded, the nestin filament networks and the β-III-tubulin particles were found in both the cell soma and the cellular processes. Moreover, the colocalization of nestin and β-III-tubulin was found mainly in the cell processes and neurite-like structures and not in the cell soma. These results may aid our understanding of the expression patterns of nestin and β-III-tubulin during the neural differentiation of H9 cells.

  7. Cross-linguistic differences in the neural representation of human language: evidence from users of signed languages.

    Science.gov (United States)

    Corina, David P; Lawyer, Laurel A; Cates, Deborah

    2012-01-01

    Studies of deaf individuals who are users of signed languages have provided profound insight into the neural representation of human language. Case studies of deaf signers who have incurred left- and right-hemisphere damage have shown that left-hemisphere resources are a necessary component of sign language processing. These data suggest that, despite frank differences in the input and output modality of language, core left perisylvian regions universally serve linguistic function. Neuroimaging studies of deaf signers have generally provided support for this claim. However, more fine-tuned studies of linguistic processing in deaf signers are beginning to show evidence of important differences in the representation of signed and spoken languages. In this paper, we provide a critical review of this literature and present compelling evidence for language-specific cortical representations in deaf signers. These data lend support to the claim that the neural representation of language may show substantive cross-linguistic differences. We discuss the theoretical implications of these findings with respect to an emerging understanding of the neurobiology of language.

  8. Polychlorinated biphenyls disturb differentiation of normal human neural progenitor cells: clue for involvement of thyroid hormone receptors.

    Science.gov (United States)

    Fritsche, Ellen; Cline, Jason E; Nguyen, Ngoc-Ha; Scanlan, Thomas S; Abel, Josef

    2005-07-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental chemicals that accumulate in adipose tissues over the food chain. Epidemiologic studies have indicated that PCBs influence brain development. Children who are exposed to PCBs during development suffer from neuropsychologic deficits such as a lower full-scale IQ (intelligence quotient), reduced visual recognition memory, and attention and motor deficits. The mechanisms leading to these effects are not fully understood. It has been speculated that PCBs may affect brain development by interfering with thyroid hormone (TH) signaling. Because most of the data are from animal studies, we established a model using primary normal human neural progenitor (NHNP) cells to determine if PCBs interfere with TH-dependent neural differentiation. NHNP cells differentiate into neurons, astrocytes, and oligodendrocytes in culture, and they express a variety of drug metabolism enzymes and nuclear receptors. Like triiodothyronine (T3), treatment with the mono-ortho-substituted PCB-118 (2,3',4,4 ,5-pentachlorobiphenyl; 0.01-1 microM) leads to a dose-dependent increase of oligodendrocyte formation. This effect was congener specific, because the coplanar PCB-126 (3,3',4,4 ,5-pentachlorobiphenyl) had no effect. Similar to the T3 response, the PCB-mediated effect on oligodendrocyte formation was blocked by retinoic acid and the thyroid hormone receptor antagonist NH-3. These results suggest that PCB-118 mimics T3 action via the TH pathway.

  9. Automatic Recognition of Human Parasite Cysts on Microscopic Stools Images using Principal Component Analysis and Probabilistic Neural Network

    Directory of Open Access Journals (Sweden)

    Beaudelaire Saha Tchinda

    2015-09-01

    Full Text Available Parasites live in a host and get its food from or at the expensive of that host. Cysts represent a form of resistance and spread of parasites. The manual diagnosis of microscopic stools images is time-consuming and depends on the human expert. In this paper, we propose an automatic recognition system that can be used to identify various intestinal parasite cysts from their microscopic digital images. We employ image pixel feature to train the probabilistic neural networks (PNN. Probabilistic neural networks are suitable for classification problems. The main novelty is the use of features vectors extracted directly from the image pixel. For this goal, microscopic images are previously segmented to separate the parasite image from the background. The extracted parasite is then resized to 12x12 image features vector. For dimensionality reduction, the principal component analysis basis projection has been used. 12x12 extracted features were orthogonalized into two principal components variables that consist the input vector of the PNN. The PNN is trained using 540 microscopic images of the parasite. The proposed approach was tested successfully on 540 samples of protozoan cysts obtained from 9 kinds of intestinal parasites.

  10. Cross-linguistic differences in the neural representation of human language: evidence from users of signed languages.

    Directory of Open Access Journals (Sweden)

    David eCorina

    2013-01-01

    Full Text Available Studies of deaf individuals who are users of signed languages have provided profound insight into the neural representation of human language. Case studies of deaf signers who have incurred left- and right-hemisphere damage have shown that left-hemisphere resources are a necessary component of sign language processing. These data suggest that, despite frank differences in the input and output modality of language,; core left perisylvian regions universally serve linguistic function. Neuroimaging studies of deaf signers have generally provided support for this claim. However, more fine-tuned studies of linguistic processing in deaf signers are beginning to show evidence of important differences in the representation of signed and spoken languages. In this paper, we provide a critical review of this literature and present compelling evidence for language-specific cortical representations in deaf signers. These data lend support to the claim that the neural representation of language may show substantive cross-linguistic differences. We discuss the theoretical implications of these findings with respect to an emerging understanding of the neurobiology of language.

  11. Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

    Science.gov (United States)

    Zuo, Fu-Xing; Bao, Xin-Jie; Sun, Xi-Cai; Wu, Jun; Bai, Qing-Ran; Chen, Guo; Li, Xue-Yuan; Zhou, Qiang-Yi; Yang, Yuan-Fan; Shen, Qin; Wang, Ren-Zhi

    2015-11-05

    Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

  12. Involvement of NOS3 in RA-Induced neural differentiation of human NT2/D1 cells.

    Science.gov (United States)

    Jezierski, Anna; Deb-Rinker, Paromita; Sodja, Caroline; Walker, P Roy; Ly, Dao; Haukenfrers, Julie; Sandhu, Jagdeep K; Bani-Yaghoub, Mahmud; Sikorska, Marianna

    2012-12-01

    Nitric oxide (NO) plays a key role in neurogenesis as a regulator of cell proliferation and differentiation. NO is synthesized from the amino acid L-arginine by nitric oxide synthases (NOS1, NOS2, and NOS3), which are encoded by separate genes and display different tissue distributions. We used an in vitro model of RA-induced neural differentiation of NT2 cells to examine which of the three NO-synthesizing enzymes is involved in this process. The results revealed a transient induction of NOS3 (known as the constitutively expressed endothelial nitric oxide synthase; eNOS) during the time course of the RA treatment. The peak of gene expression and the nuclear presence of NOS3 protein coincided with cell cycle exit of NT2-derived neuronal precursors. The subsequent analysis of cytosine methylation and histone H3 acetylation of the human NOS3 5' regulatory sequences indicated that epigenetic modifications, especially upstream of the proximal promoter (-734 to -989, relative to exon 2 TSS at +1), were also taking place. NOS1 was expressed only in the differentiated neurons (NT2-N), whereas NOS2 was not expressed at all in this cellular model. Thus, a burst of NO production, possibly required to inhibit neural cell proliferation, was generated by the transient expression of NOS3. This pattern of gene expression, in turn, required epigenetic remodeling of its regulatory region. Copyright © 2012 Wiley Periodicals, Inc.

  13. Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE

    Directory of Open Access Journals (Sweden)

    Hassan Rafieemehr

    2015-11-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. The aim of this study was to investigate the neuroprotective effects of transplanted human umbilical cord blood mesenchymal stromal cells (UCB-MSC derived neural progenitor cell (MDNPC in EAE, an experimental model of MS. To initiate neuronal differentiation of UCB-MSCs, the pre-induction medium was removed and replaced with induction media containing retinoic acid, b FGF, h EGF, NGF, IBMX and ascorbic acid for one week. The expression of neural genes was examined in comparison to control group by real-time PCR assay. Then, experimental autoimmune encephalitis (EAE was induced using myelin oligodendrocyte glycoprotein (MOG, 35-55 peptides in 24 C57BL/6 mice. After induction, the mice were divided in four groups (n=6 as follows: healthy, PBS, UCB-MSCs and MDNPC, respectively. At the end of the study, disease status in all the groups was analyzed using hematoxylin-eosin (H&E staining of brain sections. We found that UCB-MSCs exhibit neuronal differentiation potential in vitro and transplanted MDNPC lowered clinical score and reduced CNS leukocyte infiltration compared to untreated mice. Our results showed that MDNPC from UCB may be a proper candidate for regenerative therapy in MS and other neurodegenerative diseases. 

  14. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    Science.gov (United States)

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model. ©AlphaMed Press.

  15. Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model.

    Science.gov (United States)

    Jensen, Matthew B; Yan, Hongmei; Krishnaney-Davison, Rajeev; Al Sawaf, Abdullah; Zhang, Su-Chun

    2013-05-01

    Although administration of various stem cells has shown promise in stroke models, neural stem cells (NSCs) derived from human induced pluripotent stem cells (iPSCs) have advantages over other cell types. We studied whether these cells could survive, differentiate, and improve stroke recovery in an ischemic stroke model. Human iPSCs were induced in vitro to an early NSC stage. One week after focal cerebral ischemia, 20 rats received cells or vehicle by intracerebral injection. Graft cell fate, infarct volume, and behavioral deficits were assessed. Graft cells were found in 8 of the transplanted rats (80%), with estimated mean graft cell numbers nearly double the amount transplanted 1 month later. Graft cells also expressed markers of NSCs in 5 rats (63%), neurons in all 8 rats (100%), rare astrocytes in 4 rats (50%), and signs of proliferation in 4 rats (50%), but no tumor formation was observed. Stroke volume and behavioral recovery were similar between the groups. To our knowledge, this is the first report of transplantation of NSCs derived from human iPSCs in a stroke model. Human iPSC-derived NSCs survived in the postischemic rat brain and appeared to differentiate, primarily into neurons. This cell transplantation approach for stroke appears to be feasible, but further optimization is needed. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells.

    Science.gov (United States)

    Tabata, Yoshikuni; Murai, Norio; Sasaki, Takeo; Taniguchi, Sachie; Suzuki, Shuichi; Yamazaki, Kazuto; Ito, Masashi

    2015-10-01

    Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology.

  17. Dissociable neural systems supporting knowledge about human character and appearance in ourselves and others.

    Science.gov (United States)

    Moran, Joseph M; Lee, Su Mei; Gabrieli, John D E

    2011-09-01

    Functional neuroimaging has identified a neural system comprising posterior cingulate (pCC) and medial prefrontal (mPFC) cortices that appears to mediate self-referential thought. It is unclear whether the two components of this system mediate similar or different psychological processes, and how specific this system is for self relative to others. In an fMRI study, we compared brain responses for evaluation of character (e.g., honest) versus appearance (e.g., svelte) for oneself, one's mother (a close other), and President Bush (a distant other). There was a double dissociation between dorsal mPFC, which was more engaged for character than appearance judgments, and pCC, which was more engaged for appearance than character judgments. A ventral region of mPFC was engaged for judgments involving one's own character and appearance, and one's mother's character, but not her appearance. A follow-up behavioral study indicated that participants rate their own character and appearance, and their mother's character, but not her appearance, as important in their self-concept. This suggests that ventral mPFC activation reflects its role in processing information relevant to the self, but not limited to the self. Thus, specific neural systems mediate specific aspects of thinking about character and appearance in oneself and in others.

  18. Neural adaptation to silence in the human auditory cortex: a magnetoencephalographic study.

    Science.gov (United States)

    Okamoto, Hidehiko; Kakigi, Ryusuke

    2014-01-01

    Previous studies demonstrated that a decrement in the N1m response, a major deflection in the auditory evoked response, with sound repetition was mainly caused by bottom-up driven neural refractory periods following brain activation due to sound stimulations. However, it currently remains unknown whether this decrement occurs with a repetition of silences, which do not induce refractoriness. In the present study, we investigated decrements in N1m responses elicited by five repetitive silences in a continuous pure tone and by five repetitive pure tones in silence using magnetoencephalography. Repetitive sound stimulation differentially affected the N1m decrement in a sound type-dependent manner; while the N1m amplitude decreased from the 1st to the 2nd pure tone and remained constant from the 2nd to the 5th pure tone in silence, a gradual decrement was observed in the N1m amplitude from the 1st to the 5th silence embedded in a continuous pure tone. Our results suggest that neural refractoriness may mainly cause decrements in N1m responses elicited by trains of pure tones in silence, while habituation, which is a form of the implicit learning process, may play an important role in the N1m source strength decrements elicited by successive silences in a continuous pure tone.

  19. Cell-surface marker signatures for the isolation of neural stem cells, glia and neurons derived from human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Shauna H Yuan

    Full Text Available BACKGROUND: Neural induction of human pluripotent stem cells often yields heterogeneous cell populations that can hamper quantitative and comparative analyses. There is a need for improved differentiation and enrichment procedures that generate highly pure populations of neural stem cells (NSC, glia and neurons. One way to address this problem is to identify cell-surface signatures that enable the isolation of these cell types from heterogeneous cell populations by fluorescence activated cell sorting (FACS. METHODOLOGY/PRINCIPAL FINDINGS: We performed an unbiased FACS- and image-based immunophenotyping analysis using 190 antibodies to cell surface markers on naïve human embryonic stem cells (hESC and cell derivatives from neural differentiation cultures. From this analysis we identified prospective cell surface signatures for the isolation of NSC, glia and neurons. We isolated a population of NSC that was CD184(+/CD271(-/CD44(-/CD24(+ from neural induction cultures of hESC and human induced pluripotent stem cells (hiPSC. Sorted NSC could be propagated for many passages and could differentiate to mixed cultures of neurons and glia in vitro and in vivo. A population of neurons that was CD184(-/CD44(-/CD15(LOW/CD24(+ and a population of glia that was CD184(+/CD44(+ were subsequently purified from cultures of differentiating NSC. Purified neurons were viable, expressed mature and subtype-specific neuronal markers, and could fire action potentials. Purified glia were mitotic and could mature to GFAP-expressing astrocytes in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: These findings illustrate the utility of immunophenotyping screens for the identification of cell surface signatures of neural cells derived from human pluripotent stem cells. These signatures can be used for isolating highly pure populations of viable NSC, glia and neurons by FACS. The methods described here will enable downstream studies that require consistent and defined neural

  20. Combined effect of pulsed electromagnetic field and sound wave on In vitro and In vivo neural differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Choi, Yun-Kyong; Urnukhsaikhan, Enerelt; Yoon, Hee-Hoon; Seo, Young-Kwon; Cho, Hyunjin; Jeong, Jong-Seob; Kim, Soo-Chan; Park, Jung-Keug

    2017-01-01

    Biophysical wave stimulus has been used as an effective tool to promote cellular maturation and differentiation in the construction of engineered tissue. Pulsed electromagnetic fields (PEMFs) and sound waves have been selected as effective stimuli that can promote neural differentiation. The aim of this study was to investigate the synergistic effect of PEMFs and sound waves on the neural differentiation potential in vitro and in vivo using human bone marrow mesenchymal stem cells (hBM-MSCs). In vitro, neural-related genes in hBM-MSCs were accelerated by the combined exposure to both waves more than by individual exposure to PEMFs or sound waves. The combined wave also up-regulated the expression of neural and synaptic-related proteins in a three-dimensional (3-D) culture system through the phosphorylation of extracellular signal-related kinase. In a mouse model of photochemically induced ischemia, exposure to the combined wave reduced the infarction volume and improved post-injury behavioral activity. These results indicate that a combined stimulus of biophysical waves, PEMFs and sound can enhance and possibly affect the differentiation of MSCs into neural cells. Our study is meaningful for highlighting the potential of combined wave for neurogenic effects and providing new therapeutic approaches for neural cell therapy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:201-211, 2017. © 2016 American Institute of Chemical Engineers.

  1. Potential for cell therapy in Parkinson's disease using genetically programmed human embryonic stem cell-derived neural progenitor cells.

    Science.gov (United States)

    Ambasudhan, Rajesh; Dolatabadi, Nima; Nutter, Anthony; Masliah, Eliezer; Mckercher, Scott R; Lipton, Stuart A

    2014-08-15

    Neural transplantation is a promising strategy for restoring dopaminergic dysfunction and modifying disease progression in Parkinson's disease (PD). Human embryonic stem cells (hESCs) are a potential resource in this regard because of their ability to provide a virtually limitless supply of homogenous dopaminergic progenitors and neurons of appropriate lineage. The recent advances in developing robust cell culture protocols for directed differentiation of hESCs to near pure populations of ventral mesencephalic (A9-type) dopaminergic neurons has heightened the prospects for PD cell therapy. Here, we focus our review on current state-of-the-art techniques for harnessing hESC-based strategies toward development of a stem cell therapeutic for PD. Importantly, we also briefly describe a novel genetic-programming approach that may address many of the key challenges that remain in the field and that may hasten clinical translation. © 2014 Wiley Periodicals, Inc.

  2. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy.

  3. Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation

    NARCIS (Netherlands)

    H.E.S. Marei (Hany); A. Althani (Asmaa); N. Afifi (Nahla); A. Abd-Elmaksoud (Ahmed); C. Bernardini (Camilla); F. Michetti (Fabrizio); M. Barba (Marta); M. Pescatori (Mario); G. Maira (Giulio); E. Paldino (Emanuela); L. Manni (Luigi); P. Casalbore (Patrizia); C. Cenciarelli (Carlo)

    2013-01-01

    textabstractThe adult human olfactory bulb neural stem/progenitor cells (OBNC/PC) are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, h

  4. Neural differentiation of the human neuroblastoma cell line IMR32 induces production of a thyrotropin-releasing hormone-like peptide

    NARCIS (Netherlands)

    J.M.M. Rondeel (Jan); W. Klootwijk (Willem); E. Linkels; W.J. de Greef (W.); T.J. Visser (Theo)

    1994-01-01

    textabstractThe human neuroblastoma cell line IMR32 produces and secretes substantial amounts of TRH-immunoreactivity (TRH-IR) as measured with radioimmunoassay (RIA) using the nonspecific antiserum 4319. It was found that synthesis of TRH-IR is dependent on neural differentiation: under serum-free

  5. Pyrolysed 3D-Carbon Scaffolds Induce Spontaneous Differentiation of Human Neural Stem Cells and Facilitate Real-Time Dopamine Detection

    NARCIS (Netherlands)

    Amato, Letizia; Heiskanen, Arto; Caviglia, Claudia; Shah, Fozia; Zor, Kinga; Skolimowski, Maciej; Madou, Marc; Gammelgaard, Lauge; Hansen, Rasmus; Seiz, Emma G.; Ramos, Milagros; Ramos Moreno, Tania; Martinez-Serrano, Alberto; Keller, Stephan S.; Emneus, Jenny

    2014-01-01

    Structurally patterned pyrolysed three-dimensional carbon scaffolds (p3D-carbon) are fabricated and applied for differentiation of human neural stem cells (hNSCs) developed for cell replacement therapy and sensing of released dopamine. In the absence of differentiation factors (DF) the pyrolysed car

  6. Visual gravity cues in the interpretation of biological movements: neural correlates in humans.

    Science.gov (United States)

    Maffei, Vincenzo; Indovina, Iole; Macaluso, Emiliano; Ivanenko, Yuri P; A Orban, Guy; Lacquaniti, Francesco

    2015-01-01

    Our visual system takes into account the effects of Earth gravity to interpret biological motion (BM), but the neural substrates of this process remain unclear. Here we measured functional magnetic resonance (fMRI) signals while participants viewed intact or scrambled stick-figure animations of walking, running, hopping, and skipping recorded at normal or reduced gravity. We found that regions sensitive to BM configuration in the occipito-temporal cortex (OTC) were more active for reduced than normal gravity but with intact stimuli only. Effective connectivity analysis suggests that predictive coding of gravity effects underlies BM interpretation. This process might be implemented by a family of snapshot neurons involved in action monitoring. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Differentiation of Equine Mesenchymal Stromal Cells into Cells of Neural Lineage: Potential for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Claudia Cruz Villagrán

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSCs are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses.

  8. The neural basis of temporal individuation and its capacity limits in the human brain.

    Science.gov (United States)

    Naughtin, Claire K; Tamber-Rosenau, Benjamin J; Dux, Paul E

    2014-02-01

    Individuation refers to individuals' use of spatial and temporal properties to register an object as a distinct perceptual event relative to other stimuli. Although behavioral studies have examined both spatial and temporal individuation, neuroimaging investigations of individuation have been restricted to the spatial domain and at relatively late stages of information processing. In this study we used univariate and multivoxel pattern analyses of functional magnetic resonance imaging data to identify brain regions involved in individuating temporally distinct visual items and the neural consequences that arise when this process reaches its capacity limit (repetition blindness, RB). First, we found that regional patterns of blood oxygen level-dependent activity in a large group of brain regions involved in "lower-level" perceptual and "higher-level" attentional/executive processing discriminated between instances where repeated and nonrepeated stimuli were successfully individuated, conditions that placed differential demands on temporal individuation. These results could not be attributed to repetition suppression, stimulus or response factors, task difficulty, regional activation differences, other capacity-limited processes, or artifacts in the data or analyses. Consistent with the global workplace model of consciousness, this finding suggests that temporal individuation is supported by a distributed set of brain regions, rather than a single neural correlate. Second, conditions that reflect the capacity limit of individuation (instances of RB) modulated the amplitude, rather than spatial pattern, of activity in the left hemisphere premotor cortex. This finding could not be attributed to response conflict/ambiguity and likely reflects a candidate brain region underlying the capacity-limited process that gives rise to RB.

  9. Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

    Directory of Open Access Journals (Sweden)

    Florian Wegner

    Full Text Available BACKGROUND: Human fetal midbrain-derived neural progenitor cells (NPCs may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+-K(+-Cl(- co-transporter 1 (NKCC1-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. CONCLUSIONS/SIGNIFICANCE: These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.

  10. Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects.

    Science.gov (United States)

    Yang, Xue-Yan; Zhou, Xiang-Yu; Wang, Qing Qing; Li, Hong; Chen, Ying; Lei, Yun-Ping; Ma, Xiao-Hang; Kong, Pan; Shi, Yan; Jin, Li; Zhang, Ting; Wang, Hong-Yan

    2013-08-01

    Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations in the planar cell polarity (PCP) pathway genes had been implicated in the pathogenesis of NTDs in both the mouse model and in human cohorts. Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis. In this study, we found four rare missense heterozygous SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, and p.Ala1251Gly) in NTDs cases that were absent in all controls. Among them, p.Phe227Ser and p.Phe682Leu affected its protein stability and physical interaction with VANGL2. Three variants (p.Phe227Ser, p.Arg1248Gln, and p.Ala1251Gly) were demonstrated to affect VANGL2 subcellular localization in cultured cells. Further functional analysis in the zebrafish including overexpression and dosage-dependent rescue study suggested that these four mutations all displayed loss-of-function effects compared with wild-type SEC24B. Our study demonstrated that functional mutations in SEC24B might contribute to the etiology of a subset of human NTDs and further expanded our knowledge of the role of PCP pathway-related genes in the pathogenesis of human NTDs.

  11. Human fetal striatum-derived neural stem (NS) cells differentiate to mature neurons in vitro and in vivo.

    Science.gov (United States)

    Monni, Emanuela; Cusulin, Carlo; Cavallaro, Maurizio; Lindvall, Olle; Kokaia, Zaal

    2014-01-01

    Clonogenic neural stem (NS) cell lines grown in adherent cultures have previously been established from embryonic stem cells and fetal and adult CNS in rodents and from human fetal brain and spinal cord. Here we describe the isolation of a new cell line from human fetal striatum (hNS cells). These cells showed properties of NS cells in vitro such as monolayer growth, high proliferation rate and expression of radial glia markers. The hNS cells expressed an early neuronal marker while being in the proliferative state. Under appropriate conditions, the hNS cells were efficiently differentiated to neurons, and after 4 weeks about 50% of the cells were βIII tubulin positive. They also expressed the mature neuronal marker NeuN and markers of neuronal subtypes, GABA, calbindin, and DARPP32. After intrastriatal implantation into newborn rats, the hNS cells survived and many of them migrated outside the transplant core into the surrounding tissue. A high percentage of cells in the grafts expressed the neuroblast marker DCX, indicating their neurogenic potential, and some of the cells differentiated to NeuN+ mature neurons. The human fetal striatum-derived NS cell line described here should be a useful tool for studies on cell replacement strategies in models of the striatal neuronal loss occurring in Huntington's disease and stroke.

  12. Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

    Science.gov (United States)

    Wegner, Florian; Kraft, Robert; Busse, Kathy; Härtig, Wolfgang; Ahrens, Jörg; Leffler, Andreas; Dengler, Reinhard; Schwarz, Johannes

    2012-01-01

    Human fetal midbrain-derived neural progenitor cells (NPCs) may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A) receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1)-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.

  13. Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

    Science.gov (United States)

    Emgård, Mia; Piao, Jinghua; Aineskog, Helena; Liu, Jia; Calzarossa, Cinzia; Odeberg, Jenny; Holmberg, Lena; Samuelsson, Eva-Britt; Bezubik, Bartosz; Vincent, Per Henrik; Falci, Scott P; Seiger, Åke; Åkesson, Elisabet; Sundström, Erik

    2014-03-01

    To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

  14. From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium.

    Science.gov (United States)

    Reichman, Sacha; Terray, Angélique; Slembrouck, Amélie; Nanteau, Céline; Orieux, Gaël; Habeler, Walter; Nandrot, Emeline F; Sahel, José-Alain; Monville, Christelle; Goureau, Olivier

    2014-06-10

    Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease.

  15. 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…

  16. 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…

  17. In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133

    DEFF Research Database (Denmark)

    Barraud, Perrine; Stott, Simon; Møllgård, Kjeld;

    2007-01-01

    The stage-specific embryonic antigen 4 (SSEA4) is commonly used as a cell surface marker to identify the pluripotent human embryonic stem (ES) cells. Immunohistochemistry on human embryonic central nervous system revealed that SSEA4 is detectable in the early neuroepithelium, and its expression d...

  18. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

    Science.gov (United States)

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole; Perrier, Anselme L; Humbert, Sandrine

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.

  19. 人类外显记忆脑机制研究进展%The Neural Mechanisms of Human Explicit Memory Formation

    Institute of Scientific and Technical Information of China (English)

    程灶火; 王力

    2002-01-01

    The fMRI and ERPs have played important role s in understanding neura l mechanisms of human memory. Recent studies have revealed that distinct regions in medial temporal and prefrontal areas exhibit more neural activity during suc cessful than unsuccessful memory formation. The results from different studies s uggest that relational and non-relational memories are mediated by distinct sub- regions in medial temporal and prefrontal cortex and there are extensive interac tions between them in a parallel and bi-directional fashions. Emotionally arousi ng events enhance neural activity in amygdala, which in turn may modulate proces sing in other brain regions responsible for declarative memory formation.

  20. Artificial Brain Based on Credible Neural Circuits in a Human Brain

    CERN Document Server

    Burger, John Robert

    2010-01-01

    Neurons are individually translated into simple gates to plan a brain with human psychology and intelligence. State machines, assumed previously learned in subconscious associative memory are shown to enable equation solving and rudimentary thinking using nanoprocessing within short term memory.

  1. Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles.

    Science.gov (United States)

    Bible, Ellen; Qutachi, Omar; Chau, David Y S; Alexander, Morgan R; Shakesheff, Kevin M; Modo, Michel

    2012-10-01

    Replacing the tissue lost after a stroke potentially provides a new neural substrate to promote recovery. However, significant neurobiological and biotechnological challenges need to be overcome to make this possibility into a reality. Human neural stem cells (hNSCs) can differentiate into mature brain cells, but require a structural support that retains them within the cavity and affords the formation of a de novo tissue. Nevertheless, in our previous work, even after a week, this primitive tissue is void of a vasculature that could sustain its long-term viability. Therefore, tissue engineering strategies are required to develop a vasculature. Vascular endothelial growth factor (VEGF) is known to promote the proliferation and migration of endothelial cells during angio- and arteriogenesis. VEGF by itself here did not affect viability or differentiation of hNSCs, whereas growing cells on poly(D,L-lactic acid-co-glycolic acid) (PLGA) microparticles, with or without VEGF, doubled astrocytic and neuronal differentiation. Secretion of a burst and a sustained delivery of VEGF from the microparticles in vivo attracted endothelial cells from the host into this primitive tissue and in parts established a neovasculature, whereas in other parts endothelial cells were merely interspersed with hNSCs. There was also evidence of a hypervascularization indicating that further work will be required to establish an adequate level of vascularization. It is therefore possible to develop a putative neovasculature within de novo tissue that is forming inside a tissue cavity caused by a stroke. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. The effect of exogenous cortisol during sleep on the behavioral and neural correlates of emotional memory consolidation in humans.

    Science.gov (United States)

    van Marle, Hein J F; Hermans, Erno J; Qin, Shaozheng; Overeem, Sebastiaan; Fernández, Guillén

    2013-09-01

    A host of animal work demonstrates that the retention benefit for emotionally aversive over neutral memories is regulated by glucocorticoid action during memory consolidation. Particularly, glucocorticoids may affect systems-level processes that promote the gradual reorganization of emotional memory traces. These effects remain largely uninvestigated in humans. Therefore, in this functional magnetic resonance imaging study we administered hydrocortisone during a polysomnographically monitored night of sleep directly after healthy volunteers studied negative and neutral pictures in a double-blind, placebo-controlled, between-subjects design. The following evening memory consolidation was probed during a recognition memory test in the MR scanner by assessing the difference in brain activity associated with memory for the consolidated items studied before sleep and new, unconsolidated items studied shortly before test (remote vs. recent memory paradigm). Hydrocortisone administration resulted in elevated cortisol levels throughout the experimental night with no group difference at recent encoding or test. Behaviorally, we showed that cortisol enhanced the difference between emotional and neutral consolidated memory, effectively prioritizing emotional memory consolidation. On a neural level, we found that cortisol reduced amygdala reactivity related to the retrieval of these same consolidated, negative items. These findings show that cortisol administration during first post-encoding sleep had a twofold effect on the first 24h of emotional memory consolidation. While cortisol prioritized recognition memory for emotional items, it reduced reactivation of the neural circuitry underlying emotional responsiveness during retrieval. These findings fit recent theories on emotional depotentiation following consolidation during sleep, although future research should establish the sleep-dependence of this effect. Moreover, our data may shed light on mechanisms underlying

  3. A Hybrid Neural Network Approach for Kinematic Modeling of a Novel 6-UPS Parallel Human-Like Mastication Robot

    Directory of Open Access Journals (Sweden)

    Hadi Kalani

    2016-04-01

    Full Text Available Introduction we aimed to introduce a 6-universal-prismatic-spherical (UPS parallel mechanism for the human jaw motion and theoretically evaluate its kinematic problem. We proposed a strategy to provide a fast and accurate solution to the kinematic problem. The proposed strategy could accelerate the process of solution-finding for the direct kinematic problem by reducing the number of required iterations in order to reach the desired accuracy level. Materials and Methods To overcome the direct kinematic problem, an artificial neural network and third-order Newton-Raphson algorithm were combined to provide an improved hybrid method. In this method, approximate solution was presented for the direct kinematic problem by the neural network. This solution could be considered as the initial guess for the third-order Newton-Raphson algorithm to provide an answer with the desired level of accuracy. Results The results showed that the proposed combination could help find a approximate solution and reduce the execution time for the direct kinematic problem, The results showed that muscular actuations showed periodic behaviors, and the maximum length variation of temporalis muscle was larger than that of masseter and pterygoid muscles. By reducing the processing time for solving the direct kinematic problem, more time could be devoted to control calculations.. In this method, for relatively high levels of accuracy, the number of iterations and computational time decreased by 90% and 34%, respectively, compared to the conventional Newton method. Conclusion The present analysis could allow researchers to characterize and study the mastication process by specifying different chewing patterns (e.g., muscle displacements.

  4. EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Tingting Liu

    2017-02-01

    Full Text Available Background/Aims: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs. This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs in vitro. Methods: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. Results: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. Conclusion: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases.

  5. Cerebrospinal fluid derived from progressive multiple sclerosis patients promotes neuronal and oligodendroglial differentiation of human neural precursor cells in vitro.

    Science.gov (United States)

    Cristofanilli, M; Cymring, B; Lu, A; Rosenthal, H; Sadiq, S A

    2013-10-10

    In the adult CNS, tissue-specific germinal niches, such as the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus, contain multipotent neural precursor cells (NPCs) with the capacity to self-renew and differentiate into functional brain cells (i.e. neurons, astrocytes or oligodendrocytes). Due to their intrinsic plasticity, NPCs can be considered an essential part of the cellular mechanism(s) by which the CNS tries to repair itself after an injury. In inflammatory CNS disorders, such as multiple sclerosis (MS), neurogenesis and gliogenesis occur as part of an 'intrinsic' self-repair process. However, full and long-lasting repair in progressive MS is not achieved. Recent data suggest that endogenous NPCs, while trying to repair the damaged CNS in MS, may become the target of the disease itself. It is possible that factors produced during MS, like CNS-infiltrating blood-borne inflammatory mononuclear cells, reactive CNS-resident cells, and humoral mediators, can alter the physiological properties of NPCs, ultimately impairing their ability to promote neural regeneration. Here, we investigate the effect of cerebrospinal fluid (CSF) derived from primary progressive (PPMS) and secondary progressive (SPMS) MS patients (CSF-MS) on the survival, proliferation, and differentiation of commercially available human embryonic-derived NPCs named ENStem-A. We found that PPMS derived CSF markedly reduced the proliferation of ENStem-A and increased their differentiation toward neuronal and oligodendroglial cells, compared to control CSF. Similar but less striking results were seen when ENstem-A were treated with SPMS derived CSF. Our findings suggest that in both SPMS and PPMS the CNS milieu, as determined by extrapolation from CSF findings, may stimulate the endogenous pool of NPCs to differentiate into neurons and oligodendrocytes.

  6. Exploring the Role of Spatial Frequency Information during Neural Emotion Processing in Human Infants

    Directory of Open Access Journals (Sweden)

    Sarah Jessen

    2017-10-01

    Full Text Available Enhanced attention to fear expressions in adults is primarily driven by information from low as opposed to high spatial frequencies contained in faces. However, little is known about the role of spatial frequency information in emotion processing during infancy. In the present study, we examined the role of low compared to high spatial frequencies in the processing of happy and fearful facial expressions by using filtered face stimuli and measuring event-related brain potentials (ERPs in 7-month-old infants (N = 26. Our results revealed that infants’ brains discriminated between emotional facial expressions containing high but not between expressions containing low spatial frequencies. Specifically, happy faces containing high spatial frequencies elicited a smaller Nc amplitude than fearful faces containing high spatial frequencies and happy and fearful faces containing low spatial frequencies. Our results demonstrate that already in infancy spatial frequency content influences the processing of facial emotions. Furthermore, we observed that fearful facial expressions elicited a comparable Nc response for high and low spatial frequencies, suggesting a robust detection of fearful faces irrespective of spatial frequency content, whereas the detection of happy facial expressions was contingent upon frequency content. In summary, these data provide new insights into the neural processing of facial emotions in early development by highlighting the differential role played by spatial frequencies in the detection of fear and happiness.

  7. Identifying environmental risk factors for human neural tube defects before and after folic acid supplementation

    Directory of Open Access Journals (Sweden)

    Li Xinhu

    2009-10-01

    Full Text Available Abstract Background Birth defects are a major cause of infant mortality and disability in many parts of the world. Neural tube defects (NTDs are one of the most common types of birth defects. In 2001, the Chinese population and family planning commission initiated a national intervention program for the prevention of birth defects. A key step in the program was the introduction of folic acid supplementation. Of interest in the present study was to determine whether folic acid supplementation has the same protective effect on NTDs under various geographical and socioeconomic conditions within the Chinese population and the nature in which the influence of environmental factors varied after folic acid supplementation. Methods In this study, Heshun was selected as the region of interest as a surrogate for helping to answer some of the questions raised in this study on the impact of the intervention program. Spatial filtering in combination with GIS software was used to detect annual potential clusters from 1998 to 2005 in Heshun, and Kruskal-wallis test and multivariate regression were applied to identify the environmental risk factors for NTDs among various regions. Results In 1998, a significant (p Conclusion This suggests that the government needs to adapt the intervention measures according to local conditions. More attention needs to be paid to the poor and to people living in areas near coal mines.

  8. Prediction of human skin permeability using artificial neural network (ANN)modeling

    Institute of Scientific and Technical Information of China (English)

    Long-jian CHEN; Guo-ping LIAN; Lu-jia HAN

    2007-01-01

    Aim: To develop an artificial neural network (ANN) model for predicting skin permeability (log Kp) of new chemical entities. Methods: A large dataset of 215experimental data points was compiled from the literature. The dataset was subdi-vided into 5 subsets and 4 of them were used to train and validate an ANN model.The same 4 datasets were also used to build a multiple linear regression (MLR)model. The remaining dataset was then used to test the 2 models. Abraham descriptors were employed as inputs into the 2 models. Model predictions were compared with the experimental results. In addition, the relationship between log Kp and Abraham descriptors were investigated. Results: The regression re-sults of the MLR model were n=215, determination coefficient (R2)=0.699, mean square error (MSE)=0.243, and F=493.556. The ANN model gave improved results with n=215, R2=0.832, MSE=0.136, and F=1050.653. The ANN model suggests that the relationship between log Kp and Abraham descriptors is non-linear. Conclusion:The study suggests that Abraham descriptors may be used to predict skin permeability, and the ANN model gives improved prediction of skin permeability.

  9. Neural correlates of radial frequency trajectory perception in the human brain.

    Science.gov (United States)

    Gorbet, Diana J; Wilkinson, Frances; Wilson, Hugh R

    2014-01-10

    Radial frequency (RF) motion trajectories are visual stimuli that consist of a difference of Gaussians moving along a closed trajectory defined by a sinusoidal variation of the radius relative to a circular path. In the current study, multivoxel fMRI analyses demonstrated that spatial patterns of activity in visual regions V2, V3, and MT can predict RF motion trajectory shape regardless of whether an observer can behaviorally identify the shape or not. This result suggests that processing in these regions is concerned with local properties of the trajectories and not directly linked with a conscious percept of global trajectory shape. Whole-brain analyses show that RF motion trajectories also evoke premotor and posterior parietal cortical activity that may be a neural correlate of shape recognizability. Further, comparisons with activity evoked by static versions of the RF shapes reveal cue-invariant processing in regions of the posterior parietal and occipitotemporal cortices. Interestingly, the RF motion trajectories evoke patterns of dorsal visual stream cortical activity typical of visually guided movement preparation or action observation, suggesting that these stimuli may be processed as potential motor actions rather than as purely visual experiences.

  10. Data-driven automated acoustic analysis of human infant vocalizations using neural network tools

    Science.gov (United States)

    Warlaumont, Anne S.; Oller, D. Kimbrough; Buder, Eugene H.; Dale, Rick; Kozma, Robert

    2010-01-01

    Acoustic analysis of infant vocalizations has typically employed traditional acoustic measures drawn from adult speech acoustics, such as f0, duration, formant frequencies, amplitude, and pitch perturbation. Here an alternative and complementary method is proposed in which data-derived spectrographic features are central. 1-s-long spectrograms of vocalizations produced by six infants recorded longitudinally between ages 3 and 11 months are analyzed using a neural network consisting of a self-organizing map and a single-layer perceptron. The self-organizing map acquires a set of holistic, data-derived spectrographic receptive fields. The single-layer perceptron receives self-organizing map activations as input and is trained to classify utterances into prelinguistic phonatory categories (squeal, vocant, or growl), identify the ages at which they were produced, and identify the individuals who produced them. Classification performance was significantly better than chance for all three classification tasks. Performance is compared to another popular architecture, the fully supervised multilayer perceptron. In addition, the network’s weights and patterns of activation are explored from several angles, for example, through traditional acoustic measurements of the network’s receptive fields. Results support the use of this and related tools for deriving holistic acoustic features directly from infant vocalization data and for the automatic classification of infant vocalizations. PMID:20370038

  11. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.

    Science.gov (United States)

    Marei, Hany E S; Farag, Amany; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Lashen, Samah; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-01-01

    In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF. © 2014 Wiley Periodicals, Inc.

  12. 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......Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A......-APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models...

  13. Functional effects of cannabinoids during dopaminergic specification of human neural precursors derived from induced pluripotent stem cells.

    Science.gov (United States)

    Stanslowsky, Nancy; Jahn, Kirsten; Venneri, Anna; Naujock, Maximilian; Haase, Alexandra; Martin, Ulrich; Frieling, Helge; Wegner, Florian

    2016-03-30

    Among adolescents cannabis is one of the most widely used illicit drugs. In adolescence brain development continues, characterized by neuronal maturation and synaptic plasticity. The endocannabinoid system plays an important role during brain development by modulating neuronal function and neurogenesis. Changes in endocannabinoid signaling by Δ(9) -tetrahydrocannabinol (THC), the psychoactive component of cannabis, might therefore lead to neurobiological changes influencing brain function and behavior. We investigated the functional maturation and dopaminergic specification of human cord blood-derived induced pluripotent stem cell (hCBiPSC)-derived small molecule neural precursor cells (smNPCs) after cultivation with the endogenous cannabinoid anandamide (AEA) and the exogenous THC, both potent agonists at the cannabinoid 1 receptor (CB1 R). Higher dosages of 10-μM AEA or THC significantly decreased functionality of neurons, indicated by reduced ion currents and synaptic activity. A lower concentration of 1-μM THC had no marked effect on neuronal and dopaminergic maturation, while 1-μM AEA significantly enhanced the frequency of synaptic activity. As there were no significant effects on DNA methylation in promotor regions of genes important for neuronal function, these cannabinoid actions seem to be mediated by another than this epigenetic mechanism. Our data suggest that there are concentration-dependent actions of cannabinoids on neuronal function in vitro indicating neurotoxic, dysfunctional effects of 10-μM AEA and THC during human neurogenesis.

  14. Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants.

    Science.gov (United States)

    Nyffeler, Johanna; Karreman, Christiaan; Leisner, Heidrun; Kim, Yong Jun; Lee, Gabsang; Waldmann, Tanja; Leist, Marcel

    2017-01-01

    Migration of neural crest cells (NCCs) is one of the pivotal processes of human fetal development. Malformations arise if NCC migration and differentiation are impaired genetically or by toxicants. In the currently available test systems for migration inhibition of NCC (MINC), the manual generation of a cell-free space results in extreme operator dependencies, and limits throughput. Here a new test format was established. The assay avoids scratching by plating cells around a commercially available circular stopper. Removal of the stopper barrier after cell attachment initiates migration. This microwell-based circular migration zone NCC function assay (cMINC) was further optimized for toxicological testing of human pluripotent stem cell (hPSC)-derived NCCs. The challenge of obtaining data on viability and migration by automated image processing was addressed by developing a freeware. Data on cell proliferation were obtained by labelling replicating cells, and by careful assessment of cell viability for each experimental sample. The role of cell proliferation as an experimental confounder was tested experimentally by performing the cMINC in the presence of the proliferation-inhibiting drug cytosine arabinoside (AraC), and by a careful evaluation of mitotic events over time. Data from these studies led to an adaptation of the test protocol, so that toxicant exposure was limited to 24 h. Under these conditions, a prediction model was developed that allows classification of toxicants as either inactive, leading to unspecific cytotoxicity, or specifically inhibiting NC migration at non-cytotoxic concentrations.

  15. Isolation of neural progenitor cells from the human adult subventricular zone based on expression of the cell surface marker CD271.

    Science.gov (United States)

    van Strien, Miriam E; Sluijs, Jacqueline A; Reynolds, Brent A; Steindler, Dennis A; Aronica, Eleonora; Hol, Elly M

    2014-04-01

    Neural progenitor cells (NPCs) in the subventricular zone (SVZ) hold promise for future therapy for neurodegenerative disorders, because the stimulation of adult neurogenesis could potentially restore the function of degenerating neurons and glia. To obtain more knowledge on these NPCs, we developed a method to specifically isolate NPCs from postmortem adult human brains based on the expression of the specific human adult neural stem/progenitor cell marker glial fibrillary acidic protein δ (GFAPδ). An extensive immunophenotyping analysis for cell surface markers resulted in the observation that CD271 was limited to the SVZ-derived GFAPδ-positive cells. CD271(+) cells developed into neurospheres and could be differentiated into astrocytes, neurons, and oligodendrocytes. We are the first to show that a pure population of NPCs can be isolated from the adult human SVZ, which is highly instrumental for developing future therapies based on stimulating endogenous SVZ neurogenesis.

  16. Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks

    Directory of Open Access Journals (Sweden)

    Heikki Kiiski

    2013-05-01

    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC-derived neural cells could be cultured in human cerebrospinal fluid (CSF in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  17. Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks.

    Science.gov (United States)

    Kiiski, Heikki; Aänismaa, Riikka; Tenhunen, Jyrki; Hagman, Sanna; Ylä-Outinen, Laura; Aho, Antti; Yli-Hankala, Arvi; Bendel, Stepani; Skottman, Heli; Narkilahti, Susanna

    2013-06-15

    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  18. Distributed neural signatures of natural audiovisual speech and music in the human auditory cortex.

    Science.gov (United States)

    Salmi, Juha; Koistinen, Olli-Pekka; Glerean, Enrico; Jylänki, Pasi; Vehtari, Aki; Jääskeläinen, Iiro P; Mäkelä, Sasu; Nummenmaa, Lauri; Nummi-Kuisma, Katarina; Nummi, Ilari; Sams, Mikko

    2016-12-06

    During a conversation or when listening to music, auditory and visual information are combined automatically into audiovisual objects. However, it is still poorly understood how specific type of visual information shapes neural processing of sounds in lifelike stimulus environments. Here we applied multi-voxel pattern analysis to investigate how naturally matching visual input modulates supratemporal cortex activity during processing of naturalistic acoustic speech, singing and instrumental music. Bayesian logistic regression classifiers with sparsity-promoting priors were trained to predict whether the stimulus was audiovisual or auditory, and whether it contained piano playing, speech, or singing. The predictive performances of the classifiers were tested by leaving one participant at a time for testing and training the model using the remaining 15 participants. The signature patterns associated with unimodal auditory stimuli encompassed distributed locations mostly in the middle and superior temporal gyrus (STG/MTG). A pattern regression analysis, based on a continuous acoustic model, revealed that activity in some of these MTG and STG areas were associated with acoustic features present in speech and music stimuli. Concurrent visual stimulus modulated activity in bilateral MTG (speech), lateral aspect of right anterior STG (singing), and bilateral parietal opercular cortex (piano). Our results suggest that specific supratemporal brain areas are involved in processing complex natural speech, singing, and piano playing, and other brain areas located in anterior (facial speech) and posterior (music-related hand actions) supratemporal cortex are influenced by related visual information. Those anterior and posterior supratemporal areas have been linked to stimulus identification and sensory-motor integration, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The neural system that bridges reward and cognition in humans: An fMRI study

    Science.gov (United States)

    Pochon, J. B.; Levy, R.; Fossati, P.; Lehericy, S.; Poline, J. B.; Pillon, B.; Le Bihan, D.; Dubois, B.

    2002-01-01

    We test the hypothesis that motivational and cognitive processes are linked by a specific neural system to reach maximal efficiency. We studied six normal subjects performing a working memory paradigm (n-back tasks) associated with different levels of monetary reward during an fMRI session. The study showed specific brain activation in relation with changes in both the cognitive loading and the reward associated with task performance. First, the working memory tasks activated a network including the dorsolateral prefrontal cortex [Brodmann area (BA) 9/46] and, in addition, in the lateral frontopolar areas (BA 10), but only in the more demanding condition (3-back task). This result suggests that lateral prefrontal areas are organized in a caudo-rostral continuum in relation with the increase in executive requirement. Second, reward induces an increased activation in the areas already activated by working memory processing and in a supplementary region, the medial frontal pole (BA 10), regardless of the level of cognitive processing. It is postulated that the latter region plays a specific role in monitoring the reward value of ongoing cognitive processes. Third, we detected areas where the signal decreases (ventral-BA 11/47 and subgenual prefrontal cortices) in relation with both the increase of cognitive demand and the reward. The deactivation may represent an emotional gating aimed at inhibiting adverse emotional signals to maximize the level of performance. Taken together, these results suggest a balance between increasing activity in cortical cognitive areas and decreasing activity in the limbic and paralimbic structures during ongoing higher cognitive processing. PMID:11960021

  20. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

    Science.gov (United States)

    Levine, Benjamin D.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Zuckerman, Julie H.; Diedrich, Andre; Biaggioni, Italo; Ray, Chester A.; Smith, Michael L.; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Mano, Tadaaki; Zhang, Rong; Iwasaki, Kenichi; Lane, Lynda D.; Buckey, Jay C Jr; Cooke, William H.; Baisch, Friedhelm J.; Eckberg, Dwain L.; Blomqvist, C. Gunnar

    2002-01-01

    Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

  1. An overview of neural function and feedback control in human communication.

    Science.gov (United States)

    Hood, L J

    1998-01-01

    The speech and hearing mechanisms depend on accurate sensory information and intact feedback mechanisms to facilitate communication. This article provides a brief overview of some components of the nervous system important for human communication and some electrophysiological methods used to measure cortical function in humans. An overview of automatic control and feedback mechanisms in general and as they pertain to the speech motor system and control of the hearing periphery is also presented, along with a discussion of how the speech and auditory systems interact.

  2. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells].

    Science.gov (United States)

    Dupin, Elisabeth

    2011-01-01

    expression. This review considers the issue of whether neural crest-derived lineages are endowed with some phenotypic plasticity. Emphasis is put on the ability of pigment cells and Schwann cells to dedifferentiate and reprogram their fate in vitro. To address this question, we have studied the clonal progeny of differentiated Schwann cells and melanocytes after their isolation from the sciatic nerve and the back skin of quail embryos, respectively. When stimulated to proliferate in vitro in the presence of endothelin-3, both cell types were able to dedifferentiate and produce alternative neural crest-derived cell lineages. Individual Schwann cells isolated by FACS, using a glial-specific surface marker, gave rise in culture to pigment cells and myofibroblasts/smooth muscle cells. Treatment of the cultures with endothelin-3 was required for Schwann cell conversion into melanocytes, which involved acquisition of multipotency. Moreover, Schwann cell plasticity could also be induced in vivo: following transplantation into the branchial arch of a young chick host embryo, dedifferentiating Schwann cells were able to integrate the forming head structures of the host and, specifically, to contribute smooth muscle cells to the wall of cranial blood vessels. We also analyzed the in vitro behavior of individual pigment cells obtained by microdissection and enzymatic treatment of quail epidermis at embryonic and hatching stages. In single cell cultures treated with endothelin-3, pigment cells strongly proliferated while rapidly dedifferentiating into unpigmented cells, leading to the formation of large colonies that comprised glial cells and myofibroblasts in addition to melanocytes. By serially subcloning these primary colonies, we could efficiently propagate a bipotent glial-melanocytic precursor that is generated in the progeny of the melanocytic founder. These data therefore suggest that pigment cells have the ability to revert back to the state of self-renewing neural crest-like

  3. Task-dependent spatial distribution of neural activation pattern in human rectus femoris muscle.

    Science.gov (United States)

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2012-04-01

    Compartmentalization of skeletal muscle by multiple motor nerve branches, named as neuromuscular compartment (NMC), has been demonstrated in animals as well as humans. While different functional roles among individual NMCs were reported in the animal studies, no studies have clarified the region-specific functional role within a muscle related with NMCs arrangement in human skeletal muscle. It was reported that the rectus femoris (RF) muscle is innervated by two nerve branches attached at proximal and distal parts of the muscle. The purpose of the present study is to clarify the possible region-specific functional role in the human RF muscle. Multi-channel surface electromyography (SEMG) were recorded from the RF muscle by using 128 electrodes during two different submaximal isometric contractions that the muscle contributes, i.e. isometric knee extension and hip flexion, at 20%, 40%, 60% and 80% of maximal voluntary contraction (MVC). Results indicated that the central locus activation for the amplitude map of SEMG during hip flexion located at more proximal region compared with that during knee extension. Significant higher normalized root mean square (RMS) values were observed at the proximal region during the hip flexion in comparison to those at middle and distal regions at 60% and 80% of MVC (pMVC (p<0.05). The results of the present study suggest possible region-specific functional role in the human RF muscle.

  4. Oral texture influences the neural processing of ortho- and retronasal odors in humans

    NARCIS (Netherlands)

    Iannilli, E.; Bult, J.H.F.; Roudnitzky, N.; Gerber, J.; Wijk, de R.A.; Hummel, T.

    2014-01-01

    Eating implies mutual interactions between different senses. In the present work we aimed at studying relations between food texture and food odor, using both psychophysical and imaging techniques. Eighteen right-handed healthy human subjects participated to both behavioral and fMRI sessions. Fresh,

  5. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke;

    2011-01-01

    vessels appeared normal without signs of exudation, bleeding, or subretinal elevation. Eyes were harvested at 10-28 days. H&E consistently showed mild retinal vasculitis, depigmentation of the RPE, and marked mononuclear cell infiltrate in the choroid adjacent to the site of transplantation. Human...

  6. Using artificial neural networks for the transformation of human body postures based on landmarks

    NARCIS (Netherlands)

    Zhang, B.

    2005-01-01

    Designers, engineers and ergonomists are seeking to exploit the opportunities offered by the 3D anthropometric technologies. These technologies make 3D measurements possible and provide us with a more detailed description of human body in comparison with the traditional 1D or 2D data processing. In

  7. Neural Correlates of Species-Typical Illogical Cognitive Bias in Human Inference

    Science.gov (United States)

    Ogawa, Akitoshi; Yamazaki, Yumiko; Ueno, Kenichi; Cheng, Kang; Iriki, Atsushi

    2010-01-01

    The ability to think logically is a hallmark of human intelligence, yet our innate inferential abilities are marked by implicit biases that often lead to illogical inference. For example, given AB ("if A then B"), people frequently but fallaciously infer the inverse, BA. This mode of inference, called symmetry, is logically invalid because,…

  8. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain.

    Science.gov (United States)

    Kosi, Nina; Alić, Ivan; Kolačević, Matea; Vrsaljko, Nina; Jovanov Milošević, Nataša; Sobol, Margarita; Philimonenko, Anatoly; Hozák, Pavel; Gajović, Srećko; Pochet, Roland; Mitrečić, Dinko

    2015-02-09

    The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

    Directory of Open Access Journals (Sweden)

    Kee Hang Lee

    Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  10. Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats

    Institute of Scientific and Technical Information of China (English)

    LIANG Peng; JIN Lian-hong; LIANG Tao; LIU En-zhong; ZHAO Shi-guang

    2006-01-01

    Background Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord.Methods NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n=15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group,NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA.Results NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P< 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P< 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression

  11. MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics.

    Science.gov (United States)

    Lawrence, Jean M; Singhal, Shweta; Bhatia, Bhairavi; Keegan, David J; Reh, Thomas A; Luthert, Philip J; Khaw, Peng T; Limb, Gloria Astrid

    2007-08-01

    Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown that Müller cells exhibit progenitor characteristics in the postnatal chick and rat retinae, their progenitor-like role in developed human retina is unknown. We first reported the Müller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors. Since immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. Cells were grown as adherent monolayers, responded to epidermal growth factor, and could be expanded indefinitely without growth factors under normal culture conditions. They could be frozen and thawed without losing their characteristics. In the presence of extracellular matrix and fibroblast growth factor-2 or retinoic acid, they acquired neural morphology, formed neurospheres, and expressed neural stem cell markers including betaIII tubulin, Sox2, Pax6, Chx10, and Notch 1. They also expressed markers of postmitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into the subretinal space of dystrophic Royal College of Surgeons rats or neonatal Lister hooded rats, immortalized cells migrated into the retina, where they expressed various markers of retinal neurons. These observations indicate that adult human neural retina harbors a population of cells that express both Müller glial and stem cell markers and suggest that these cells may have potential use for cell-based therapies to restore retinal function. Disclosure of potential conflicts of interest is found at the end of this article.

  12. Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

    Science.gov (United States)

    Simeral, J. D.; Kim, S.-P.; Black, M. J.; Donoghue, J. P.; Hochberg, L. R.

    2011-04-01

    The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point

  13. Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of Parkinson's disease.

    Science.gov (United States)

    Gonzalez, Rodolfo; Garitaonandia, Ibon; Crain, Andrew; Poustovoitov, Maxim; Abramihina, Tatiana; Noskov, Alexander; Jiang, Chuan; Morey, Robert; Laurent, Louise C; Elsworth, John D; Snyder, Evan Y; Redmond, D Eugene; Semechkin, Ruslan

    2015-01-01

    Recent studies indicate that human pluripotent stem cell (PSC)-based therapies hold great promise in Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying viable human embryos and can be used to generate an unlimited supply of neural stem cells for transplantation. Here we evaluate for the first time the safety and engraftment of human parthenogenetic stem cell-derived neural stem cells (hpNSCs) in two animal models: 6-hydroxydopamine (6-OHDA)-lesioned rodents and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates (NHPs). In both rodents and nonhuman primates, we observed successful engraftment and higher dopamine levels in hpNSC-transplanted animals compared to vehicle control animals, without any adverse events. These results indicate that hpNSCs are safe, well tolerated, and could potentially be a source for cell-based therapies in PD.

  14. Long-term neural and physiological phenotyping of a single human.

    Science.gov (United States)

    Poldrack, Russell A; Laumann, Timothy O; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M; Gordon, Evan; Snyder, Abraham Z; Adeyemo, Babatunde; Petersen, Steven E; Glahn, David C; Reese Mckay, D; Curran, Joanne E; Göring, Harald H H; Carless, Melanie A; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A; Frick, Laurie; Marcotte, Edward M; Mumford, Jeanette A

    2015-12-09

    Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders.

  15. Social-network complexity in humans is associated with the neural response to social information.

    Science.gov (United States)

    Dziura, Sarah L; Thompson, James C

    2014-11-01

    Humans have evolved to thrive in large and complex social groups, and it is likely that this increase in group complexity has come with a greater need to decode and respond to complex and uncertain communicatory signals. In this functional MRI study, we examined whether complexity of social networks in humans is related to the functioning of brain regions key to the perception of basic, nonverbal social stimuli. Greater activation to biological than to scrambled motion in the right posterior superior temporal sulcus (pSTS) and right amygdala were positively correlated with the diversity of social-network roles. In the pSTS, in particular, this association was not due to a relationship between network diversity and network size. These findings suggest that increased functioning of brain regions involved in decoding social signals might facilitate the detection and decoding of subtle signals encountered in varied social settings.

  16. How social is error observation? The neural mechanisms underlying the observation of human and machine errors.

    Science.gov (United States)

    Desmet, Charlotte; Deschrijver, Eliane; Brass, Marcel

    2014-04-01

    Recently, it has been shown that the medial prefrontal cortex (MPFC) is involved in error execution as well as error observation. Based on this finding, it has been argued that recognizing each other's mistakes might rely on motor simulation. In the current functional magnetic resonance imaging (fMRI) study, we directly tested this hypothesis by investigating whether medial prefrontal activity in error observation is restricted to situations that enable simulation. To this aim, we compared brain activity related to the observation of errors that can be simulated (human errors) with brain activity related to errors that cannot be simulated (machine errors). We show that medial prefrontal activity is not only restricted to the observation of human errors but also occurs when observing errors of a machine. In addition, our data indicate that the MPFC reflects a domain general mechanism of monitoring violations of expectancies.

  17. Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study

    Science.gov (United States)

    2015-07-30

    network contains 29 distinct brain regions, spread over all four lobes of the cerebral hemisphere (with substantial inter-hemispheric asymmetry), along...human face). Another cluster in near the occipito- parietal junction, and includes the following regions: posterior intrapietal sulcus (IPSp...other in the medial aspect of the frontal lobe , are active when the subjects correctly decide that the scene in question does NOT contain a camouflaged

  18. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness.

    Science.gov (United States)

    Maslin, M R D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J

    2015-10-01

    Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.