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Sample records for specific neural precursors

  1. Differentiation of Human Embryonic Stem Cells to Regional Specific Neural Precursors in Chemically Defined Medium Conditions

    Science.gov (United States)

    Erceg, Slaven; Laínez, Sergio; Ronaghi, Mohammad; Stojkovic, Petra; Pérez-Aragó, Maria Amparo; Moreno-Manzano, Victoria; Moreno-Palanques, Rubén; Planells-Cases, Rosa; Stojkovic, Miodrag

    2008-01-01

    Background Human embryonic stem cells (hESC) provide a unique model to study early events in human development. The hESC-derived cells can potentially be used to replace or restore different tissues including neuronal that have been damaged by disease or injury. Methodology and Principal Findings The cells of two different hESC lines were converted to neural rosettes using adherent and chemically defined conditions. The progenitor cells were exposed to retinoic acid (RA) or to human recombinant basic fibroblast growth factor (bFGF) in the late phase of the rosette formation. Exposing the progenitor cells to RA suppressed differentiation to rostral forebrain dopamine neural lineage and promoted that of spinal neural tissue including motor neurons. The functional characteristics of these differentiated neuronal precursors under both, rostral (bFGF) and caudalizing (RA) signals were confirmed by patch clamp analysis. Conclusions/Significance These findings suggest that our differentiation protocol has the capacity to generate region-specific and electrophysiologically active neurons under in vitro conditions without embryoid body formation, co-culture with stromal cells and without presence of cells of mesodermal or endodermal lineages. PMID:18461168

  2. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions.

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    Slaven Erceg

    Full Text Available BACKGROUND: Human embryonic stem cells (hESC provide a unique model to study early events in human development. The hESC-derived cells can potentially be used to replace or restore different tissues including neuronal that have been damaged by disease or injury. METHODOLOGY AND PRINCIPAL FINDINGS: The cells of two different hESC lines were converted to neural rosettes using adherent and chemically defined conditions. The progenitor cells were exposed to retinoic acid (RA or to human recombinant basic fibroblast growth factor (bFGF in the late phase of the rosette formation. Exposing the progenitor cells to RA suppressed differentiation to rostral forebrain dopamine neural lineage and promoted that of spinal neural tissue including motor neurons. The functional characteristics of these differentiated neuronal precursors under both, rostral (bFGF and caudalizing (RA signals were confirmed by patch clamp analysis. CONCLUSIONS/SIGNIFICANCE: These findings suggest that our differentiation protocol has the capacity to generate region-specific and electrophysiologically active neurons under in vitro conditions without embryoid body formation, co-culture with stromal cells and without presence of cells of mesodermal or endodermal lineages.

  3. Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification.

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    Hernández-Benítez, Reyna; Vangipuram, Sharada D; Ramos-Mandujano, Gerardo; Lyman, William D; Pasantes-Morales, Herminia

    2013-01-01

    Taurine is present at high concentrations in the fetal brain and is required for optimal brain development. Recent studies have reported that taurine causes increased proliferation of neural stem/progenitor neural cells (neural precursor cells, NPCs) obtained from embryonic and adult rodent brain. The present study is the first to show that taurine markedly increases cell numbers in cultures and neuronal generation from human NPCs (hNPCs). hNPCs obtained from 3 fetal brains (14-15 weeks of gestation) were cultured and expanded as neurospheres, which contained 76.3% nestin-positive cells. Taurine (5-20 mM) increased the number of hNPCs in culture, with maximal effect found at 10 mM and 4 days of culture. The taurine-induced increase ranged from 57 to 188% in the 3 brains examined. Taurine significantly enhanced the percentage of neurons formed from hNPCs under differentiating conditions, with increases ranging from 172 to 480% over controls without taurine. Taurine also increased the cell number and neuronal generation in cultures of the immortalized human cell line ReNcell VM. These results suggest that taurine has a positive influence on hNPC growth and neuronal formation. Copyright © 2013 S. Karger AG, Basel.

  4. Targeted deletion of Hand2 in enteric neural precursor cells affects its functions in neurogenesis, neurotransmitter specification and gangliogenesis, causing functional aganglionosis

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    Lei, Jun; Howard, Marthe J.

    2011-01-01

    Targeted deletion of the bHLH DNA-binding protein Hand2 in the neural crest, impacts development of the enteric nervous system (ENS), possibly by regulating the transition from neural precursor cell to neuron. We tested this hypothesis by targeting Hand2 deletion in nestin-expressing neural precursor (NEP) cells. The mutant mice showed abnormal ENS development, resulting in lethal neurogenic pseudo-obstruction. Neurogenesis of neurons derived from NEP cells identified a second nestin non-expressing neural precursor (NNEP) cell in the ENS. There was substantial compensation for the loss of neurons derived from the NEP pool by the NNEP pool but this was insufficient to abrogate the negative impact of Hand2 deletion. Hand2-mediated regulation of proliferation affected both neural precursor and neuron numbers. Differentiation of glial cells derived from the NEP cells was significantly decreased with no compensation from the NNEP pool of cells. Our data indicate differential developmental potential of NEPs and NNEPs; NNEPs preferentially differentiate as neurons, whereas NEPs give rise to both neurons and glial cells. Deletion of Hand2 also resulted in complete loss of NOS and VIP and a significant decrease in expression of choline acetyltransferase and calretinin, demonstrating a role for Hand2 in neurotransmitter specification and/or expression. Loss of Hand2 resulted in a marked disruption of the developing neural network, exemplified by lack of a myenteric plexus and extensive overgrowth of fibers. Thus, Hand2 is essential for neurogenesis, neurotransmitter specification and neural network patterning in the developing ENS. PMID:21989918

  5. A novel FoxD3 gene trap line reveals neural crest precursor movement and a role for FoxD3 in their specification.

    Science.gov (United States)

    Hochgreb-Hägele, Tatiana; Bronner, Marianne E

    2013-02-01

    Neural crest cells migrate extensively and contribute to diverse derivatives, including the craniofacial skeleton, peripheral neurons and glia, and pigment cells. Although several transgenic lines label neural crest subpopulations, few are suited for studying early events in neural crest development. Here, we present a zebrafish gene/protein trap line gt(foxd3-citrine)(ct110a) that expresses a Citrine fusion protein with FoxD3, a transcription factor expressed in premigratory and migrating neural crest cells. In this novel line, citrine expression exactly parallels endogenous foxd3 expression. High-resolution time-lapse imaging reveals the dynamic phases of precursor and migratory neural crest cell movements from the neural keel stage to times of active cell migration. In addition, Cre-recombination produces a variant line FoxD3-mCherry-pA whose homozygosis generates a FoxD3 mutant. Taking advantage of the endogenously regulated expression of FoxD3-mCherry fusion protein, we directly assess early effects of FoxD3 loss-of-function on specification and morphogenesis of dorsal root ganglia, craniofacial skeleton and melanophores. These novel lines provide new insights and useful new tools for studying specification, migration and differentiation of neural crest cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Cockayne syndrome b maintains neural precursor function.

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    Sacco, Raffaele; Tamblyn, Laura; Rajakulendran, Nishani; Bralha, Fernando N; Tropepe, Vincent; Laposa, Rebecca R

    2013-02-01

    Neurodevelopmental defects are observed in the hereditary disorder Cockayne syndrome (CS). The gene most frequently mutated in CS, Cockayne Syndrome B (CSB), is required for the repair of bulky DNA adducts in transcribed genes during transcription-coupled nucleotide excision repair. CSB also plays a role in chromatin remodeling and mitochondrial function. The role of CSB in neural development is poorly understood. Here we report that the abundance of neural progenitors is normal in Csb(-/-) mice and the frequency of apoptotic cells in the neurogenic niche of the adult subependymal zone is similar in Csb(-/-) and wild type mice. Both embryonic and adult Csb(-/-) neural precursors exhibited defective self-renewal in the neurosphere assay. In Csb(-/-) neural precursors, self-renewal progressively decreased in serially passaged neurospheres. The data also indicate that Csb and the nucleotide excision repair protein Xpa preserve embryonic neural stem cell self-renewal after UV DNA damage. Although Csb(-/-) neural precursors do not exhibit altered neuronal lineage commitment after low-dose UV (1J/m(2)) in vitro, neurons differentiated in vitro from Csb(-/-) neural precursors that had been irradiated with 1J/m(2) UV exhibited defective neurite outgrowth. These findings identify a function for Csb in neural precursors. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Cell-specific precursor processing

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Bundgaard, Jens R

    2010-01-01

    in different cells and tissues therefore requires control of biogenesis and secretion in order to avoid interference with the function of a specific hormonal peptide from a particular endocrine cell. Several mechanisms are involved in such control, one of them being cell-specific processing of prohormones....... The following pages present four examples of such cell-specific processing and the implications of the phenomenon for the use of peptide hormones as markers of diseases. Notably, sick cells - not least the neoplastic cells - often process prohormones in a manner different from that of the normal endocrine cells....

  8. Culture of Mouse Neural Stem Cell Precursors

    OpenAIRE

    Currle, D. Spencer; Hu, Jia Sheng; Kolski-Andreaco, Aaron; Monuki, Edwin S.

    2007-01-01

    Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the...

  9. Restricted spontaneous in vitro differentiation and region-specific migration of long-term expanded fetal human neural precursor cells after transplantation into the adult rat brain.

    Science.gov (United States)

    Maciaczyk, Jaroslaw; Singec, Ilyas; Maciaczyk, Donata; Klein, Alexander; Nikkhah, Guido

    2009-09-01

    Human fetal neural stem/progenitor cells (hNSCs) are investigated for their potential as a cell source for cell-based therapies in neurodegenerative diseases. However, the limited availability of fetal tissue and insufficient understanding of the lineage-dependent pattern of survival, migration, and differentiation following engraftment are still unresolved issues. In the current study hNSCs derived from different brain regions were long-term expanded in vitro to yield proliferating neurospheres giving rise to neurons, astro-, and oligodendroglial cells and assessed for their potential for migration, differentiation, and anatomical integration following intracerebral grafting into rats. hNSCs isolated from neocortex, striatum, midbrain, and spinal cord (SC) proliferated following in vitro differentiation, and showed a significant decrease of newly formed neurons along the rostrocaudal axis of the developing central nervous system (CNS). Most of the mature neurons were positive for the neurotransmitter GABA. In vivo all cell types survived up to 9 weeks posttransplantation. Intrastriatally grafted hNSCs migrated extensively along white matter tracts reaching both rostral (forceps minor) and caudal (midbrain, cerebral peduncle) brain regions. The majority of migratory cells expressed the stem cell marker, nestin. A fraction of grafted cells acquired a neuronal phenotype expressing doublecortin, beta-III-tubulin, or GABA. These data demonstrate efficient in vitro propagation, region-specific long-term survival, long-distance migration, and neuronal differentiation of hNSCs after transplantation into the adult rat brain. The availability of a large pool of in vitro expanded nestin-positive cells offers the possibility for further ex vivo manipulations and the recruitment of different neuronal phenotypes for cell replacement strategies for CNS disorders.

  10. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse.

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    Leung, Kit-Yi; De Castro, Sandra C P; Savery, Dawn; Copp, Andrew J; Greene, Nicholas D E

    2013-09-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone.

  11. A Protocol for Isolation and Enriched Monolayer Cultivation of Neural Precursor Cells from Mouse Dentate Gyrus

    OpenAIRE

    Babu, Harish; Claasen, Jan-Hendrik; Kannan, Suresh; Rünker, Annette E.; Palmer, Theo; Kempermann, Gerd

    2011-01-01

    In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., 2007) to isolate neural precursor cells from the hippocampus of adult mice and maintain and propagate them as adherent monolayer cultures. The strategy is based on the use of Percoll density gradient centrifugation to enrich precursor cells from ...

  12. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus

    OpenAIRE

    Harish eBabu; Jan-Hendrik eClaasen; Jan-Hendrik eClaasen; Jan-Hendrik eClaasen; Suresh eKannan; Annette E. Rünker; Theo ePalmer; Gerd eKempermann; Gerd eKempermann

    2011-01-01

    In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons, PLoS One 2007, 2:e388) to isolate neural precursor cells from the hippocampus of adult mice and maintain and pro...

  13. Early Divergence of Central and Peripheral Neural Retina Precursors During Vertebrate Eye Development

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    Venters, Sara J.; Mikawa, Takashi; Hyer, Jeanette

    2015-01-01

    During development of the vertebrate eye, optic tissue is progressively compartmentalized into functionally distinct tissues. From the central to the peripheral optic cup, the original optic neuroepithelial tissue compartmentalizes, forming retina, ciliary body and iris. The retina can be further sub-divided into peripheral and central compartments, where the central domain is specialized for higher visual acuity, having a higher ratio and density of cone photoreceptors in most species. Classically, models depict a segregation of the early optic cup into only two domains, neural and non-neural. Recent studies, however, uncovered discrete precursors for central and peripheral retina in the optic vesicle, indicating that the neural retina cannot be considered as a single unit with homogeneous specification and development. Instead, central and peripheral retina may be subject to distinct developmental pathways that underlie their specialization. This review focuses on lineage relationships in the retina and revisits the historical context for segregation of central and peripheral retina precursors before overt eye morphogenesis. PMID:25329498

  14. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

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    Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  15. Precursors to numeracy in kindergartners with specific language impairment

    NARCIS (Netherlands)

    Kleemans, M.A.J.; Segers, P.C.J.; Verhoeven, L.T.W.

    2011-01-01

    The present study investigated to what extent children with specific language impairment (SLI) differ in their early numeracy skills, when compared to normal language achieving (NLA) children. It was also explored which precursors were related to the early numeracy skills in both groups. Sixty-one

  16. Lithium promotes neural precursor cell proliferation: evidence for the involvement of the non-canonical GSK-3β-NF-AT signaling

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    Qu Zhaoxia

    2011-05-01

    Full Text Available Abstract Lithium, a drug that has long been used to treat bipolar disorder and some other human pathogenesis, has recently been shown to stimulate neural precursor growth. However, the involved mechanism is not clear. Here, we show that lithium induces proliferation but not survival of neural precursor cells. Mechanistic studies suggest that the effect of lithium mainly involved activation of the transcription factor NF-AT and specific induction of a subset of proliferation-related genes. While NF-AT inactivation by specific inhibition of its upstream activator calcineurin antagonized the effect of lithium on the proliferation of neural precursor cells, specific inhibition of the NF-AT inhibitor GSK-3β, similar to lithium treatment, promoted neural precursor cell proliferation. One important function of lithium appeared to increase inhibitory phosphorylation of GSK-3β, leading to GSK-3β suppression and subsequent NF-AT activation. Moreover, lithium-induced proliferation of neural precursor cells was independent of its role in inositol depletion. These findings not only provide mechanistic insights into the clinical effects of lithium, but also suggest an alternative therapeutic strategy for bipolar disorder and other neural diseases by targeting the non-canonical GSK-3β-NF-AT signaling.

  17. Enrichment of skin-derived neural precursor cells from dermal cell populations by altering culture conditions.

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    Bayati, Vahid; Gazor, Rohoullah; Nejatbakhsh, Reza; Negad Dehbashi, Fereshteh

    2016-01-01

    As stem cells play a critical role in tissue repair, their manipulation for being applied in regenerative medicine is of great importance. Skin-derived precursors (SKPs) may be good candidates for use in cell-based therapy as the only neural stem cells which can be isolated from an accessible tissue, skin. Herein, we presented a simple protocol to enrich neural SKPs by monolayer adherent cultivation to prove the efficacy of this method. To enrich neural SKPs from dermal cell populations, we have found that a monolayer adherent cultivation helps to increase the numbers of neural precursor cells. Indeed, we have cultured dermal cells as monolayer under serum-supplemented (control) and serum-supplemented culture, followed by serum free cultivation (test) and compared. Finally, protein markers of SKPs were assessed and compared in both experimental groups and differentiation potential was evaluated in enriched culture. The cells of enriched culture concurrently expressed fibronectin, vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors as compared to control culture. In addition, they possessed a multipotential capacity to differentiate into neurogenic, glial, adipogenic, osteogenic and skeletal myogenic cell lineages. It was concluded that serum-free adherent culture reinforced by growth factors have been shown to be effective on proliferation of skin-derived neural precursor cells (skin-NPCs) and drive their selective and rapid expansion.

  18. Embryonic cerebrospinal fluid activates neurogenesis of neural precursors within the subventricular zone of the adult mouse brain.

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    Carnicero, E; Alonso, M I; Carretero, R; Lamus, F; Moro, J A; de la Mano, A; Fernández, J M F; Gato, A

    2013-01-01

    There is a nondeveloped neurogenic potential in the adult mammalian brain, which could be the basis for neuroregenerative strategies. Many research efforts have been made to understand the control mechanisms which regulate the transition from a neural precursor to a neuron in the adult brain. Embryonic cerebrospinal fluid (CSF) is a complex fluid which has been shown to play a key role in neural precursor behavior during development, working as a powerful neurogenic inductor. We tested if the neurogenic properties of embryonic CSF are able to increase the neurogenic activity of neuronal precursors from the subventricular zone (SVZ) in the brains of adult mice. Our results show that mouse embryonic CSF significantly increases the neurogenic activity in precursor cells from adult brain SVZ. This intense neurogenic effect was specific for embryonic CSF and was not induced by adult CSF. Embryonic CSF is a powerful neurogenesis inductor in homologous neuronal precursors in the adult brain. This property of embryonic CSF could be a useful tool in neuroregeneration strategies.

  19. Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors: an involvement of astrocytes.

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    Shuken Boku

    Full Text Available Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG, which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP, we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI, a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA. These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.

  20. Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells.

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    Boku, Shuken; Nakagawa, Shin; Masuda, Takahiro; Nishikawa, Hiroyuki; Kato, Akiko; Toda, Hiroyuki; Song, Ning; Kitaichi, Yuji; Inoue, Takeshi; Koyama, Tsukasa

    2011-01-15

    Neurogenesis in the adult dentate gyrus (DG) is considered to be partly involved in the action of mood stabilizers. However, it remains unclear how mood stabilizers affect neural precursor cells in adult DG. We have established a culture system of adult rat DG-derived neural precursor cells (ADP) and have shown that lithium, a mood stabilizer, and dexamethasone, an agonist of glucocorticoid receptor, reciprocally regulate ADP proliferation. Neurogenesis constitutes not only proliferation of neural precursor cells but also apoptosis and differentiation. To develop further understanding of mood stabilizer effects on neural precursor cells in adult DG, we investigated and compared the effects of four common mood stabilizers-lithium, valproate, carbamazepine, and lamotrigine-on ADP proliferation, apoptosis, and differentiation. ADP proliferation, decreased by dexamethasone, was examined using Alamar Blue assay. Using TUNEL assay, ADP apoptosis induced by staurosporine was examined. The differentiated ADP induced by retinoic acid was characterized by immunostaining with anti-GFAP or anti-Tuj1 antibody. Lithium and valproate, but not carbamazepine and lamotrigine, recovered ADP proliferation decreased by dexamethasone. All four mood stabilizers decreased ADP apoptosis. Retinoic acid differentiated ADP into both neurons and astrocytes. Lithium and carbamazepine increased the ratio of neurons and decreased that of astrocytes. However, valproate and lamotrigine increased the ratio of astrocytes and decreased that of neurons. Therefore, these four stabilizers exhibited both common and differential effects on ADP proliferation, apoptosis, and differentiation. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Meninges harbor cells expressing neural precursor markers during development and adulthood

    Science.gov (United States)

    Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

    2015-01-01

    Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood. PMID:26483637

  2. Nestin-GFP Transgene Reveals Neural Precursor Cells in Adult Skeletal Muscle

    Science.gov (United States)

    Birbrair, Alexander; Wang, Zhong-Min; Messi, Maria Laura; Enikolopov, Grigori N.; Delbono, Osvaldo

    2011-01-01

    Background Therapy for neural lesions or degenerative diseases relies mainly on finding transplantable active precursor cells. Identifying them in peripheral tissues accessible for biopsy, outside the central nervous system, would circumvent the serious immunological and ethical concerns impeding cell therapy. Methodology/Principal Findings In this study, we isolated neural progenitor cells in cultured adult skeletal muscle from transgenic mice in which nestin regulatory elements control GFP expression. These cells also expressed the early neural marker Tuj1 and light and heavy neurofilament but not S100β, indicating that they express typical neural but not Schwann cell markers. GFP+/Tuj1+ cells were also negative for the endothelial and pericyte markers CD31 and α-smooth muscle actin, respectively. We established their a) functional response to glutamate in patch-clamp recordings; b) interstitial mesenchymal origin; c) replicative capacity; and d) the environment necessary for their survival after fluorescence-activated cell sorting. Conclusions/Significance We propose that the decline in nestin-GFP expression in muscle progenitor cells and its persistence in neural precursor cells in muscle cultures provide an invaluable tool for isolating a population of predifferentiated neural cells with therapeutic potential. PMID:21304812

  3. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Harish eBabu

    2011-07-01

    Full Text Available In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons, PLoS One 2007, 2:e388 to isolate neural precursor cells from the hippocampus of adult mice and maintain and propagate them as adherent monolayer cultures. The strategy is based on the use of Percoll density gradient centrifugation to enrich precursor cells from the micro-dissected dentate gyrus. Based on the expression of Nestin and Sox2, a culture-purity of more than 98% can be achieved. The cultures are expanded under serum-free conditions in Neurobasal A medium with addition of the mitogens EGF and FGF2 as well as the supplements Glutamax-1 and B27. Under differentiation conditions, the precursor cells reliably generate approximately 30% neurons with appropriate morphological, molecular and electrophysiological characteristics that might reflect granule cell properties as their in vivo counterpart. We also highlight potential modifications to the protocol.

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

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    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.

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

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    Michael Fatt

    2015-12-01

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

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

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    Hartung Hans-Peter

    2011-03-01

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

  7. 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.

  8. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus.

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    Babu, Harish; Claasen, Jan-Hendrik; Kannan, Suresh; Rünker, Annette E; Palmer, Theo; Kempermann, Gerd

    2011-01-01

    In vitro assays are valuable tools to study the characteristics of adult neural precursor cells under controlled conditions with a defined set of parameters. We here present a detailed protocol based on our previous original publication (Babu et al., 2007) to isolate neural precursor cells from the hippocampus of adult mice and maintain and propagate them as adherent monolayer cultures. The strategy is based on the use of Percoll density gradient centrifugation to enrich precursor cells from the micro-dissected dentate gyrus. Based on the expression of Nestin and Sox2, a culture-purity of more than 98% can be achieved. The cultures are expanded under serum-free conditions in Neurobasal A medium with addition of the mitogens Epidermal growth factor and Fibroblast growth factor 2 as well as the supplements Glutamax-1 and B27. Under differentiation conditions, the precursor cells reliably generate approximately 30% neurons with appropriate morphological, molecular, and electrophysiological characteristics that might reflect granule cell properties as their in vivo counterpart. We also highlight potential modifications to the protocol.

  9. Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers

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    Kuzin Alexander

    2008-08-01

    Full Text Available Abstract Background The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers. Results Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS. Conclusion The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.

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

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

    2016-01-01

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

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

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    Loyal A Goff

    2009-09-01

    Full Text Available 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.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.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.

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

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    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.

  13. A study on precursors leading to geomagnetic storms using artificial neural network

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    Singh, Gaurav; Singh, A. K.

    2016-07-01

    Space weather prediction involves advance forecasting of the magnitude and onset time of major geomagnetic storms on Earth. In this paper, we discuss the development of an artificial neural network-based model to study the precursor leading to intense and moderate geomagnetic storms, following halo coronal mass ejection (CME) and related interplanetary (IP) events. IP inputs were considered within a 5-day time window after the commencement of storm. The artificial neural network (ANN) model training, testing and validation datasets were constructed based on 110 halo CMEs (both full and partial halo and their properties) observed during the ascending phase of the 24th solar cycle between 2009 and 2014. The geomagnetic storm occurrence rate from halo CMEs is estimated at a probability of 79%, by this model.

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

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    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.

  15. Neural correlates of specific musical anhedonia.

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    Martínez-Molina, Noelia; Mas-Herrero, Ernest; Rodríguez-Fornells, Antoni; Zatorre, Robert J; Marco-Pallarés, Josep

    2016-11-15

    Although music is ubiquitous in human societies, there are some people for whom music holds no reward value despite normal perceptual ability and preserved reward-related responses in other domains. The study of these individuals with specific musical anhedonia may be crucial to understand better the neural correlates underlying musical reward. Previous neuroimaging studies have shown that musically induced pleasure may arise from the interaction between auditory cortical networks and mesolimbic reward networks. If such interaction is critical for music-induced pleasure to emerge, then those individuals who do not experience it should show alterations in the cortical-mesolimbic response. In the current study, we addressed this question using fMRI in three groups of 15 participants, each with different sensitivity to music reward. We demonstrate that the music anhedonic participants showed selective reduction of activity for music in the nucleus accumbens (NAcc), but normal activation levels for a monetary gambling task. Furthermore, this group also exhibited decreased functional connectivity between the right auditory cortex and ventral striatum (including the NAcc). In contrast, individuals with greater than average response to music showed enhanced connectivity between these structures. Thus, our results suggest that specific musical anhedonia may be associated with a reduction in the interplay between the auditory cortex and the subcortical reward network, indicating a pivotal role of this interaction for the enjoyment of music.

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

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    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

  17. Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells.

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    Min-Jeong Kang

    2016-10-01

    Full Text Available Hippocalcin (Hpca is a neuronal calcium sensor protein expressed in the mammalian brain. However, its function in neural stem/precursor cells has not yet been studied. Here, we clarify the function of Hpca in astrocytic differentiation in hippocampal neural precursor cells (HNPCs. When we overexpressed Hpca in HNPCs in the presence or absence of bFGF, expression levels of nerve-growth factors such as neurotrophin-3 (NT-3, neurotrophin-4/5 (NT-4/5 and brain-derived neurotrophic factor (BDNF, together with the proneural basic helix loop helix (bHLH transcription factors neuroD and neurogenin 1 (ngn1, increased significantly. In addition, there was an increase in the number of cells expressing glial fibrillary acidic protein (GFAP, an astrocyte marker, and in dendrite outgrowth, indicating astrocytic differentiation of the HNPCs. Downregulation of Hpca by transfection with Hpca siRNA reduced expression of NT-3, NT-4/5, BDNF, neuroD and ngn1 as well as levels of GFAP protein. Furthermore, overexpression of Hpca increased the phosphorylation of STAT3 (Ser727, and this effect was abolished by treatment with a STAT3 inhibitor (S3I-201, suggesting that STAT3 (Ser727 activation is involved in Hpca-mediated astrocytic differentiation. As expected, treatment with Stat3 siRNA or STAT3 inhibitor caused a complete inhibition of astrogliogenesis induced by Hpca overexpression. Taken together, this is the first report to show that Hpca, acting through Stat3, has an important role in the expression of neurotrophins and proneural bHLH transcription factors, and that it is an essential regulator of astrocytic differentiation and dendrite outgrowth in HNPCs.

  18. Cadherin-11 regulates motility in normal cortical neural precursors and glioblastoma.

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    Jessica D Schulte

    Full Text Available Metastasizing tumor cells undergo a transformation that resembles a process in normal development when non-migratory epithelial cells modulate the expression of cytoskeletal and adhesion proteins to promote cell motility. Here we find a mesenchymal cadherin, Cadherin-11 (CDH11, is increased in cells exiting the ventricular zone (VZ neuroepithelium during normal cerebral cortical development. When overexpressed in cortical progenitors in vivo, CDH11 causes premature exit from the neuroepithelium and increased cell migration. CDH11 expression is elevated in human brain tumors, correlating with higher tumor grade and decreased patient survival. In glioblastoma, CDH11-expressing tumor cells can be found localized near tumor vasculature. Endothelial cells stimulate TGFβ signaling and CDH11 expression in glioblastoma cells. TGFβ promotes glioblastoma cell motility, and knockdown of CDH11 expression in primary human glioblastoma cells inhibits TGFβ-stimulated migration. Together, these findings show that Cadherin-11 can promote cell migration in neural precursors and glioblastoma cells and suggest that endothelial cells increase tumor aggressiveness by co-opting mechanisms that regulate normal neural development.

  19. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

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    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  20. Specificity of leaf mitochondrial and chloroplast processing systems for nuclear-encoded precursor proteins.

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    Whelan, J; Knorpp, C; Harmey, M A; Glaser, E

    1991-02-01

    The specificity of the mitochondrial and chloroplast processing enzymes for the nuclear-encoded precursor proteins was investigated. Mitochondrial precursor proteins of the Nicotiana plumbaginifolia and the Neurospora crassa beta subunits of F1-ATPase and the Neurospora Rieske FeS precursor protein were processed to the correct mature size by matrix extracts isolated from spinach leaves, yeast, rat liver and beef heart. The mitochondrial extracts failed to process chloroplast precursor proteins of the stromal small subunit of ribulose 1,5-bisphosphate carboxylase and the thylakoid 33 kDa protein of the oxygen-evolving complex. Both mitochondrial F1 beta precursors were specifically processed by a soluble stromal extract from chloroplasts. However, no processing of the Rieske FeS precursor protein was observed under the same conditions with the chloroplast extract. The cleavage of the mitochondrial F1 beta precursors by the chloroplast extract was shown to be sensitive to the metal chelators EDTA and ortho-phenanthroline. The cleavage site of the mitochondrial F1 beta precursor by the chloroplast soluble extract appears to be located at the N-terminus.

  1. Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function.

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    Stefano Pluchino

    Full Text Available BACKGROUND: The systemic injection of neural stem/precursor cells (NPCs provides remarkable amelioration of the clinico-pathological features of experimental autoimmune encephalomyelitis (EAE. This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains the immune modulatory capacity of transplanted NPCs. METHODOLOGY/PRINCIPAL FINDINGS: To achieve the exclusive targeting of the peripheral immune system, SJL mice with PLP-induced EAE were injected subcutaneously with NPCs and the treatment commenced prior to disease onset. NPC-injected EAE mice showed significant clinical improvement, as compared to controls. Exogenous NPCs lacking the expression of major neural antigens were reliably (and for long-term found at the level of draining lymph nodes, while establishing sophisticated anatomical interactions with lymph node cells. Importantly, injected NPCs were never found in organs other than lymph nodes, including the brain and the spinal cord. Draining lymph nodes from transplanted mice showed focal up-regulation of major developmental stem cell regulators, such as BMP-4, Noggin and Sonic hedgehog. In lymph nodes, injected NPCs hampered the activation of myeloid dendritic cells (DCs and steadily restrained the expansion of antigen-specific encephalitogenic T cells. Both ex vivo and in vitro experiments identified a novel highly NPC-specific-BMP-4-dependent-mechanism hindering the DC maturation. CONCLUSION/SIGNIFICANCE: The study described herein, identifies the first member of the TGF beta/BMP family of stem cell

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

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    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.

  3. Reprogramming fibroblasts to neural-precursor-like cells by structured overexpression of pallial patterning genes.

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    Raciti, Marilena; Granzotto, Marilena; Duc, Minh Do; Fimiani, Cristina; Cellot, Giada; Cherubini, Enrico; Mallamaci, Antonello

    2013-11-01

    In this study, we assayed the capability of four genes implicated in embryonic specification of the cortico-cerebral field, Foxg1, Pax6, Emx2 and Lhx2, to reprogramme mouse embryonic fibroblasts towards neural identities. Lentivirus-mediated, TetON-dependent overexpression of Pax6 and Foxg1 transgenes specifically activated the neural stem cell (NSC) reporter Sox1-EGFP in a substantial fraction of engineered cells. The efficiency of this process was enhanced up to ten times by simultaneous inactivation of Trp53 and co-administration of a specific drug mix inhibiting HDACs, H3K27-HMTase and H3K4m2-demethylase. Remarkably, a fraction of the reprogrammed population expressed other NSC markers and retained its new identity, even after switching off the reprogramming transgenes. When transferred into a pro-differentiative environment, Pax6/Foxg1-overexpressing cells activated the neuronal marker Tau-EGFP. Frequency of Tau-EGFP positive cells was almost doubled upon delayed delivery of Emx2 and Lhx2 transgenes. A further improvement of the neuron-like cell output was achieved by inhibition of the BMP and TGFβ pathways. Tau-EGFP positive cells were able to generate action potentials upon injection of depolarizing current pulses, further indicating their neuron-like phenotype. © 2013.

  4. Neural crest specification: tissues, signals, and transcription factors.

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    Rogers, C D; Jayasena, C S; Nie, S; Bronner, M E

    2012-01-01

    The neural crest is a transient population of multipotent and migratory cells unique to vertebrate embryos. Initially derived from the borders of the neural plate, these cells undergo an epithelial to mesenchymal transition to leave the central nervous system, migrate extensively in the periphery, and differentiate into numerous diverse derivatives. These include but are not limited to craniofacial cartilage, pigment cells, and peripheral neurons and glia. Attractive for their similarities to stem cells and metastatic cancer cells, neural crest cells are a popular model system for studying cell/tissue interactions and signaling factors that influence cell fate decisions and lineage transitions. In this review, we discuss the mechanisms required for neural crest formation in various vertebrate species, focusing on the importance of signaling factors from adjacent tissues and conserved gene regulatory interactions, which are required for induction and specification of the ectodermal tissue that will become neural crest. Copyright © 2011 Wiley Periodicals, Inc.

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

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    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.

  6. Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

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    Eisch Amelia

    2010-01-01

    Full Text Available Abstract Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ and the subgranular zone (SGZ. We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

  7. Plasma as a scaffold for regeneration of neural precursor cells after transplantation into rats with spinal cord injury.

    Science.gov (United States)

    Takenaga, Mitsuko; Ohta, Yuki; Tokura, Yukie; Hamaguchi, Akemi; Suzuki, Noboru; Nakamura, Masaya; Okano, Hideyuki; Igarashi, Rie

    2007-01-01

    The present study investigated whether plasma could be useful as a scaffold for cell transplantation in rats with spinal cord injury (SCI). Transplantation of cells with plasma promoted the recovery of SCI-induced motor dysfunction. Immunohistochemical analysis revealed that the grafted cells had differentiated into the neural lineage. When dissociated neural precursor cells were cultured with plasma, extensive neurite outgrowth was observed along with increased expression of p35 and NF68. Neural markers were also expressed by the cultured cells. Culture with plasma reduced thymidine incorporation, but promoted cell growth and increased the RNA contents. These findings suggest that the cells underwent differentiation into neurons in the presence of plasma. In conclusion, plasma could be a promising scaffold for cell transplantation therapy.

  8. Correction to: Cognitive and Linguistic Precursors to Early Literacy Achievement in Children With Specific Language Impairment

    NARCIS (Netherlands)

    Weerdenburg, M.W.C. van; Verhoeven, L.T.W.; Balkom, L.J.M. van; Bosman, A.M.T.

    2010-01-01

    An error appeared in the article "Cognitive and Linguistic Precursors to Early Literacy Achievement in Children With Specific Language Impairment" by van Weerdenburg et al., published in Scientific Studies of Reading 13(6), 484-507. It should be noted that the correct institution of affiliation for

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

    Roč. 11, č. 2016 (2016), s. 6267-6281 E-ISSN 1178-2013 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) 7F14057 Institutional support: RVO:68378041 ; RVO:61389013 ; RVO:68378271 Keywords : neural precursors * magnetic resonance imaging * cell differentiation Subject RIV: FH - Neurology; EB - Genetics ; Molecular Biology (FGU-C); CD - Macromolecular Chemistry (UMCH-V) Impact factor: 4.300, year: 2016

  10. Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus.

    Science.gov (United States)

    Mangale, Vrushali; Marro, Brett S; Plaisted, Warren C; Walsh, Craig M; Lane, Thomas E

    2017-11-01

    The present study examines the susceptibility of mouse induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) to infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Similar to NPCs derived from striatum of day 1 postnatal GFP-transgenic mice (GFP-NPCs), iPSC-derived NPCs (iPSC-NPCs) are able to differentiate into terminal neural cell types and express MHC class I and II in response to IFN-γ treatment. However, in contrast to postnatally-derived NPCs, iPSC-NPCs express low levels of carcinoembryonic antigen-cell adhesion molecule 1a (CEACAM1a), the surface receptor for JHMV, and are less susceptible to infection and virus-induced cytopathic effects. The relevance of this in terms of therapeutic application of NPCs resistant to viral infection is discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Culture, characterization and differentiation of neural precursors from the central nervous system of guinea pigs (Cavia porcellus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Erika Toledo da Fonseca

    Full Text Available Abstract: Potentially neurogenic areas were initially identified by incorporation of bromodeoxyuridine (BrdU in cells underlying the subventricular zone (SVZ of the lateral ventricles wall, hippocampus and olfactory bulbs of newborn guinea pigs. Neural precursors from the SVZ were cultured in suspension, generating neurospheres (NSFs, which, upon dissociation were able to generate new NSFs. Upon culture in the absence of growth factors, cells dissociated from NSFs displayed evidence for neural differentiation, giving rise to cells from neural lineage. Flow cytometry analysis for of NSFs-derived cells after differentiation revealed approximately 13.3% nestin positive, 5.5% Beta-III-tubulin positive, 9% GFAP positive and 7.8% mGalC positive. Functional assays by measurement of calcium influx upon gamma butiric amino acid (GABA and glutamate stimuli, revealed stimulation in differentiated cells, an indicator of neuronal differentiation. The ability of guinea pig SVZ cells to originate functional neurons in vitro is promising for research and towards a future use of neural stem cells in the therapy of neurological disorders.

  12. Artificial neural network approach for estimation of surface specific ...

    Indian Academy of Sciences (India)

    Microwave sensor MSMR (Multifrequency Scanning Microwave Radiometer) data onboard Oceansat-1 was used for retrieval of monthly averages of near surface specific humidity (a) and air temperature (a) by means of Artificial Neural Network (ANN). The MSMR measures the microwave radiances in 8 channels at ...

  13. Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.

    Science.gov (United States)

    Kimura-Yoshida, Chiharu; Mochida, Kyoko; Ellwanger, Kristina; Niehrs, Christof; Matsuo, Isao

    2015-06-01

    During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. Our results also demonstrated that canonical Wnt and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into SE or NE fates in accord with the progress of neural tube closure. Additionally, SE specification of the neural plate border via canonical Wnt signaling is directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose that the fate specification of uncommitted progenitors in the neural plate border by canonical Wnt signaling and its downstream effector Grhl3 is crucial for neural tube closure. This study implicates that failure in critical genetic factors controlling fate specification of progenitor cells in the neural plate border/neural fold coordinated with neural tube closure may be potential causes of human neural tube defects.

  14. Minocycline Directly Enhances the Self-Renewal of Adult Neural Precursor Cells.

    Science.gov (United States)

    Kuroda, Anri; Fuchigami, Takahiro; Fuke, Satoshi; Koyama, Natsu; Ikenaka, Kazuhiro; Hitoshi, Seiji

    2017-10-28

    Minocycline not only has antibacterial action but also produces a variety of pharmacological effects. It has drawn considerable attention as a therapeutic agent for symptoms caused by inflammation in many neurological disorders, leading to several clinical trials. Although some of these effects are mediated through its function of suppressing microglial activation, it is not clear whether minocycline acts on other cell types in the adult brain. In this study, we utilized a colony-forming neurosphere assay, in which neural stem cells (NSCs) clonally proliferate to form floating colonies, called neurospheres. We found that minocycline (at therapeutically relevant concentrations in cerebrospinal fluid) enhances the self-renewal capability of NSCs derived from the subependymal zone of adult mouse brain and facilitates their differentiation into oligodendrocytes. Importantly, these effects were independent of a suppression of microglial activation and were specifically observed with minocycline (among tetracycline derivatives). In addition, the size of the NSC population in the adult brain was increased when minocycline was infused into the lateral ventricle by an osmotic minipump in vivo. While precise molecular mechanisms of how minocycline alters the behavior of adult NSCs remain unknown, our data provide a basis for the clinical use of minocycline to treat neurodegenerative and demyelinating diseases.

  15. Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

    Directory of Open Access Journals (Sweden)

    Mohamed Ariff Iqbal

    2017-01-01

    Full Text Available In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.

  16. Differentiation of neurons from neural precursors generated in floating spheres from embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Forrester Jeff

    2009-09-01

    Full Text Available Abstract Background Neural differentiation of embryonic stem (ES cells is usually achieved by induction of ectoderm in embryoid bodies followed by the enrichment of neuronal progenitors using a variety of factors. Obtaining reproducible percentages of neural cells is difficult and the methods are time consuming. Results Neural progenitors were produced from murine ES cells by a combination of nonadherent conditions and serum starvation. Conversion to neural progenitors was accompanied by downregulation of Oct4 and NANOG and increased expression of nestin. ES cells containing a GFP gene under the control of the Sox1 regulatory regions became fluorescent upon differentiation to neural progenitors, and ES cells with a tau-GFP fusion protein became fluorescent upon further differentiation to neurons. Neurons produced from these cells upregulated mature neuronal markers, or differentiated to glial and oligodendrocyte fates. The neurons gave rise to action potentials that could be recorded after application of fixed currents. Conclusion Neural progenitors were produced from murine ES cells by a novel method that induced neuroectoderm cells by a combination of nonadherent conditions and serum starvation, in contrast to the embryoid body method in which neuroectoderm cells must be selected after formation of all three germ layers.

  17. Different mechanisms must be considered to explain the increase in hippocampal neural precursor cell proliferation by physical activity

    Directory of Open Access Journals (Sweden)

    Rupert W Overall

    2016-08-01

    Full Text Available The number of proliferating neural precursor cells in the adult hippocampus is strongly increased by physical activity. The mechanisms through which this behavioral stimulus induces cell proliferation, however, are not yet understood. In fact, even the mode of proliferation of the stem and progenitor cells is not exactly known. Evidence exists for several mechanisms including cell cycle shortening, reduced cell death and stem cell recruitment, but as yet no model can account for all observations. An appreciation of how the cells proliferate, however, is crucial to our ability to model the neurogenic process and predict its behavior in response to pro-neurogenic stimuli. In a recent study, we addressed modulation of the cell cycle length as one possible mode of regulation of precursor cell proliferation in running mice. Our results indicated that the observed increase in number of proliferating cells could not be explained through a shortening of the cell cycle. We must therefore consider other mechanisms by which physical activity leads to enhanced precursor cell proliferation. Here we review the evidence for and against several different hypotheses and discuss the implications for future research in the field.

  18. Impact of epitope specificity and precursor maturation in pro-B-type natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Goetze, J.P.; Dahlstrom, U.; Alehagen, U.

    2008-01-01

    the impact of epitope specificity and precursor maturation on plasma measurement of proBNP-derived peptides. METHODS: We compared 2 assays, N-terminal proBNP and proBNP 1-76, in a randomly collected set of human plasma specimens (n = 370). Additionally, we evaluated the clinical performance of 4 assays...... with different epitope specificities in a cohort of elderly patients presenting with symptoms associated with heart failure (n = 415). RESULTS: Comparison of N-terminal proBNP with proBNP 1-76 measurement in plasma revealed a high correlation on regression analysis (r(2) = 0.91, P

  19. Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos.

    Science.gov (United States)

    Chatfield, Jodie; O'Reilly, Marie-Anne; Bachvarova, Rosemary F; Ferjentsik, Zoltan; Redwood, Catherine; Walmsley, Maggie; Patient, Roger; Loose, Mathew; Johnson, Andrew D

    2014-06-01

    A common feature of development in most vertebrate models is the early segregation of the germ line from the soma. For example, in Xenopus and zebrafish embryos primordial germ cells (PGCs) are specified by germ plasm that is inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the commitment of cells to the germ line. How these disparate mechanisms of PGC specification evolved is unknown. Here, in order to identify the ancestral mechanism of PGC specification in vertebrates, we studied PGC specification in embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor. In the axolotl, PGCs develop within mesoderm, and classic studies have reported their induction from primitive ectoderm (animal cap). We used an axolotl animal cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The role of FGF was then confirmed in vivo. We also showed PGC induction by Brachyury, in the presence of BMP4. These conditions induced pluripotent mesodermal precursors that give rise to a variety of somatic cell types, in addition to PGCs. Irreversible restriction of the germ line did not occur until the mid-tailbud stage, days after the somatic germ layers are established. Before this, germline potential was maintained by MAP kinase signalling. We propose that this stochastic mechanism of PGC specification, from mesodermal precursors, is conserved in vertebrates. © 2014. Published by The Company of Biologists Ltd.

  20. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Directory of Open Access Journals (Sweden)

    Hui-Fang Chang

    Full Text Available We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz. The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  1. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Science.gov (United States)

    Chang, Hui-Fang; Lee, Ying-Shan; Tang, Tang K; Cheng, Ji-Yen

    2016-01-01

    We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  2. Learning speaker-specific characteristics with a deep neural architecture.

    Science.gov (United States)

    Chen, Ke; Salman, Ahmad

    2011-11-01

    Speech signals convey various yet mixed information ranging from linguistic to speaker-specific information. However, most of acoustic representations characterize all different kinds of information as whole, which could hinder either a speech or a speaker recognition (SR) system from producing a better performance. In this paper, we propose a novel deep neural architecture (DNA) especially for learning speaker-specific characteristics from mel-frequency cepstral coefficients, an acoustic representation commonly used in both speech recognition and SR, which results in a speaker-specific overcomplete representation. In order to learn intrinsic speaker-specific characteristics, we come up with an objective function consisting of contrastive losses in terms of speaker similarity/dissimilarity and data reconstruction losses used as regularization to normalize the interference of non-speaker-related information. Moreover, we employ a hybrid learning strategy for learning parameters of the deep neural networks: i.e., local yet greedy layerwise unsupervised pretraining for initialization and global supervised learning for the ultimate discriminative goal. With four Linguistic Data Consortium (LDC) benchmarks and two non-English corpora, we demonstrate that our overcomplete representation is robust in characterizing various speakers, no matter whether their utterances have been used in training our DNA, and highly insensitive to text and languages spoken. Extensive comparative studies suggest that our approach yields favorite results in speaker verification and segmentation. Finally, we discuss several issues concerning our proposed approach.

  3. Neural crest specification by noncanonical Wnt signaling and PAR-1

    Science.gov (United States)

    Ossipova, Olga; Sokol, Sergei Y.

    2011-01-01

    Neural crest (NC) cells are multipotent progenitors that form at the neural plate border, undergo epithelial-mesenchymal transition and migrate to diverse locations in vertebrate embryos to give rise to many cell types. Multiple signaling factors, including Wnt proteins, operate during early embryonic development to induce the NC cell fate. Whereas the requirement for the Wnt/β-catenin pathway in NC specification has been well established, a similar role for Wnt proteins that do not stabilize β-catenin has remained unclear. Our gain- and loss-of-function experiments implicate Wnt11-like proteins in NC specification in Xenopus embryos. In support of this conclusion, modulation of β-catenin-independent signaling through Dishevelled and Ror2 causes predictable changes in premigratory NC. Morpholino-mediated depletion experiments suggest that Wnt11R, a Wnt protein that is expressed in neuroectoderm adjacent to the NC territory, is required for NC formation. Wnt11-like signals might specify NC by altering the localization and activity of the serine/threonine polarity kinase PAR-1 (also known as microtubule-associated regulatory kinase or MARK), which itself plays an essential role in NC formation. Consistent with this model, PAR-1 RNA rescues NC markers in embryos in which noncanonical Wnt signaling has been blocked. These experiments identify novel roles for Wnt11R and PAR-1 in NC specification and reveal an unexpected connection between morphogenesis and cell fate. PMID:22110058

  4. S100A6 (calcyclin) is a novel marker of neural stem cells and astrocyte precursors in the subgranular zone of the adult mouse hippocampus.

    Science.gov (United States)

    Yamada, Jun; Jinno, Shozo

    2014-01-01

    S100A6 (calcyclin), an EF-hand calcium binding protein, is considered to play various roles in the brain, for example, cell proliferation and differentiation, calcium homeostasis, and neuronal degeneration. In addition to some limbic nuclei, S100A6 is distributed in the rostral migratory stream, one of the major neurogenic niches of the adult brain. However, the potential involvement of S100A6 in adult neurogenesis remains unclear. In this study, we aimed to elucidate the role of S100A6 in the other major neurogenic niche, the subgranular zone of the dentate gyrus in the adult mouse hippocampus. Immunofluorescent multiple labeling showed that S100A6 was highly expressed in neural stem cells labeled by sex determining region Y-box 2, brain lipid-binding protein protein and glial fibrillary acidic protein. S100A6+ cells often extended a long process typical of radial glial morphology. In addition, S100A6 was found in some S100β+ astrocyte lineage cells. Interestingly, proliferating cell nuclear antigen was detected in a fraction of S100A6+/S100β+ cells. These cells were considered to be lineage-restricted astrocyte precursors maintaining mitotic potential. On the other hand, S100A6 was rarely seen in neural lineage cells labeled by T-box brain protein 2, doublecortin, calretinin and calbindin D28K. Cell fate-tracing experiment using BrdU showed that the majority of newly generated immature astrocytes were immunoreactive for S100A6, while mature astrocytes lacked S100A6 immunoreactivity. Administration of S100 protein inhibitor, trifluoperazine, caused a reduction in production of S100β+ astrocyte lineage cells, but had no impact on neurogenesis. Overall, our data provide the first evidence that S100A6 is a specific marker of neural stem cells and astrocyte precursors, and may be especially important for generation of astrocytes in the adult hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  5. Combined transplantation of neural precursor cells and olfactory ensheathing cells for the treatment of X-linked adrenoleukodystrophy in children

    Directory of Open Access Journals (Sweden)

    Yang H

    2017-04-01

    Full Text Available Hui Yang,1,* Yu Zhang,1,* Zhaoyan Wang,1 Wei Lu,1 Fang Liu,1 Xin Yu,2 Xiaoyan Zheng,1 Yinxiang Yang,1 Zuo Luan,1 Suqing Qu1 1Department of Pediatrics, 2Department of Neurological Surgery, Navy General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work. Abstract: Hematopoietic stem cell transplantation is only suitable for early-stage adrenoleukodystrophy (ALD. In this study, we observed the therapeutic efficacy of combined transplantation of neural precursor cells (NPCs and olfactory ensheathing cells (OECs on late-stage X-linked ALD in nine children who were admitted in our hospital between June 2009 and January 2014. Related patient information included onset time 3 months to 1 year, magnetic resonance imaging (MRI score 11.02±0.90, and neurologic function score 2–3. All patients received combined transplantation of NPCs and OECs by injection around the lateral angle of the frontotemporal–occipital lesion under MRI guidance. It was found that the visual function, sleep, and communication obstacles were improved significantly without evidence of disease progression in six (66.7% of the nine patients within 1 month after transplantation. In two of the six patients, the lesions became significantly smaller than before, although their MRI scores remained unchanged significantly. In addition, cell therapy did not induce any irreversible adverse event during the study period, indicating that combined transplantation of NPCs and OECs was safe and reliable, and could improve the clinical manifestations of ALD in children within a short time. Although this cell therapy was not able to halt the progression of the disease 1–3 months after transplantation, it could still be used as an early treatment and provide patients with more opportunities for hematopoietic stem cell transplantation, which is the only effective long-term treatment for X-linked ALD at present. The preliminary results from this study

  6. Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Soheila Karimi-Abdolrezaee

    Full Text Available The adult spinal cord harbours a population of multipotent neural precursor cells (NPCs with the ability to replace oligodendrocytes. However, despite this capacity, proliferation and endogenous remyelination is severely limited after spinal cord injury (SCI. In the post-traumatic microenvironment following SCI, endogenous spinal NPCs mainly differentiate into astrocytes which could contribute to astrogliosis that exacerbate the outcomes of SCI. These findings emphasize a key role for the post-SCI niche in modulating the behaviour of spinal NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans (CSPGs in the glial scar restrict the outcomes of NPC transplantation in SCI by reducing the survival, migration and integration of engrafted NPCs within the injured spinal cord. These inhibitory effects were attenuated by administration of chondroitinase (ChABC prior to NPC transplantation. Here, in a rat model of compressive SCI, we show that perturbing CSPGs by ChABC in combination with sustained infusion of growth factors (EGF, bFGF and PDGF-AA optimize the activation and oligodendroglial differentiation of spinal NPCs after injury. Four days following SCI, we intrathecally delivered ChABC and/or GFs for seven days. We performed BrdU incorporation to label proliferating cells during the treatment period after SCI. This strategy increased the proliferation of spinal NPCs, reduced the generation of new astrocytes and promoted their differentiation along an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC and GF treatments enhanced the response of non-neural cells by increasing the generation of new vascular endothelial cells and decreasing the number of proliferating macrophages/microglia after SCI. In conclusions, our data strongly suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is critical not only to promote endogenous oligodendrocyte replacement, but also to reverse

  7. Propofol at Clinically Relevant Concentrations Increases Neuronal Differentiation but Is Not Toxic to Hippocampal Neural Precursor Cells In Vitro

    Science.gov (United States)

    Sall, Jeffrey W.; Stratmann, Greg; Leong, Jason; Woodward, Elliott; Bickler, Philip E.

    2012-01-01

    Background Propofol in the early postnatal period has been shown to cause brain cell death. One proposed mechanism for cognitive dysfunction after anesthesia is alteration of neural stem cell function and neurogenesis. We examined the effect of propofol on neural precursor or stem cells (NPCs) grown in vitro. Methods Hippocampal derived NPCs from postnatal day 2 rats were exposed to propofol or to Diprivan. NPCs were then analyzed for bromodeoxyuridine incorporation to measure proliferation. Cell death was measured by lactate dehydrogenase release. Immunocytochemistry was used to evaluate the expression of neuronal and glial markers in differentiating NPCs exposed to propofol. Results Propofol dose dependently increases the release of lactate dehydrogenase from NPCs under both proliferating and differentiating conditions at supraclinical concentrations (> 7.1μM). Both Diprivan and propofol had the same effect on NPCs. Propofol mediated release of lactate dehydrogenase is not inhibited by blocking the γ-aminobutyric acid type A receptor or extracellular calcium influx and is not mediated by caspase-3/7. Direct γ-aminobutyric acid type A receptor activation did not have the same effect. In differentiating NPCs 6 h of propofol at 2.1 μM increased the number neurons but not glial cells 4 days later. Increased neuronal differentiation was not blocked by Bicuculline. Conclusions Only supraclinical concentrations of propofol or Diprivan kill NPCs in culture by a non-γ-aminobutyric acid type A, noncaspase 3 mechanism. Clinically relevant doses of propofol increase neuronal fate choice by a non-γ-aminobutyric acid type A mechanism. PMID:23001052

  8. Specific Inhibition of β-Secretase Processing of the Alzheimer Disease Amyloid Precursor Protein.

    Science.gov (United States)

    Ben Halima, Saoussen; Mishra, Sabyashachi; Raja, K Muruga Poopathi; Willem, Michael; Baici, Antonio; Simons, Kai; Brüstle, Oliver; Koch, Philipp; Haass, Christian; Caflisch, Amedeo; Rajendran, Lawrence

    2016-03-08

    Development of disease-modifying therapeutics is urgently needed for treating Alzheimer disease (AD). AD is characterized by toxic β-amyloid (Aβ) peptides produced by β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP). β-secretase inhibitors reduce Aβ levels, but mechanism-based side effects arise because they also inhibit β-cleavage of non-amyloid substrates like Neuregulin. We report that β-secretase has a higher affinity for Neuregulin than it does for APP. Kinetic studies demonstrate that the affinities and catalytic efficiencies of β-secretase are higher toward non-amyloid substrates than toward APP. We show that non-amyloid substrates are processed by β-secretase in an endocytosis-independent manner. Exploiting this compartmentalization of substrates, we specifically target the endosomal β-secretase by an endosomally targeted β-secretase inhibitor, which blocked cleavage of APP but not non-amyloid substrates in many cell systems, including induced pluripotent stem cell (iPSC)-derived neurons. β-secretase inhibitors can be designed to specifically inhibit the Alzheimer process, enhancing their potential as AD therapeutics without undesired side effects. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Vesicular glutamate transporters play a role in neuronal differentiation of cultured SVZ-derived neural precursor cells.

    Directory of Open Access Journals (Sweden)

    Eduardo H Sánchez-Mendoza

    Full Text Available The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs and excitatory amino acid transporters (EAATs in controlling adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ-derived neural precursor cells (NPCs. Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes. In expression analyses we show that VGLUT1 and VGLUT2 are preferentially expressed by cultured SVZ-derived doublecortin+ neuroblasts, while VGLUT3 is found on GFAP+ glial cells. In cultured NPCs, inhibition of VGLUT by Evans Blue increased the mRNA level of neuronal markers doublecortin, B3T and MAP2, elevated the number of NPCs expressing doublecortin protein and promoted the number of cells with morphological appearance of branched neurons, suggesting that VGLUT function prevents neuronal differentiation of NPCs. This survival- and differentiation-promoting effect of Evans blue was corroborated by increased AKT phosphorylation and reduced MAPK phosphorylation. Thus, under physiological conditions, VGLUT1-3 inhibition, and thus decreased glutamate exocytosis, may promote neuronal differentiation of NPCs.

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

    Directory of Open Access Journals (Sweden)

    Lü He-Zuo

    2009-10-01

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

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

    Science.gov (United States)

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

    2009-09-01

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

  12. Skin-Derived Precursor Cells Promote Angiogenesis and Stimulate Proliferation of Endogenous Neural Stem Cells after Cerebral Infarction

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    Duo Mao

    2015-01-01

    Full Text Available Stroke is one of the most common diseases that caused high mortality and has become burden to the health care systems. Stem cell transplantation has shown therapeutic effect in ameliorating ischemic damage after cerebral artery occlusion mainly due to their neurogenesis, immune regulation, or effects on the plasticity, proliferation, and survival of host cells. Recent studies demonstrated that skin-derived precursor cells (SKPs could promote central nervous system regeneration in spinal cord injury model or the neonatal peripheral neuron. Here, we investigated the therapeutic potential of SKPs in a rat model of cerebral ischemia. SKPs were isolated, expanded, and transplanted into rat cortex and striatum after transient middle cerebral artery occlusion. Our results revealed that SKPs transplantation could improve the behavioral measures of neurological deficit. Moreover, immunohistology confirmed that SKPs could secrete basic FGF and VEGF in the ischemic region and further markedly increase the proliferation of endogenous nestin+ and βIII-tubulin+ neural stem cells. Furthermore, increased angiogenesis induced by SKPs was observed by vWF and α-SMA staining. These data suggest that SKPs induced endogenous neurogenesis and angiogenesis and protected neuron from hypoxic-ischemic environment. In conclusion, SKPs transplantation may be a promising approach in treatment of stroke.

  13. Probing Coagulation Behavior of Individual Aluminum Species for Removing Corresponding Disinfection Byproduct Precursors: The Role of Specific Ultraviolet Absorbance.

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    He Zhao

    Full Text Available Coagulation behavior of aluminum chloride and polyaluminum chloride (PACl for removing corresponding disinfection byproduct (DBP precursors was discussed in this paper. CHCl3, bromine trihalomethanes (THM-Br, dichloroacetic acid (DCAA and trichloroacetic acid (TCAA formation potential yields were correlated with specific ultraviolet absorbance (SUVA values in different molecular weight (MW fractions of humic substances (HS, respectively. Correlation analyses and principal component analysis were performed to examine the relationships between SUVA and different DBP precursors. To acquire more structural characters of DBP precursors and aluminum speciation, freeze-dried precipitates were analyzed by fourier transform infrared (FTIR and C 1s, Al 2p X-ray photoelectron spectroscopy (XPS. The results indicated that TCAA precursors (no MW limits, DCAA and CHCl3 precursors in low MW fractions (MW30 kDa were preferentially removed by PACl coagulation with preformed Al13 species at pH 5.0. Additionally, for DCAA precursors in high MW fractions (MW>30 kDa with relatively low aromatic content and more carboxylic structures, the greatest removal occurred at pH 6.0 through PACl coagulation with aggregated Al13 species.

  14. The role of the N-methyl-D-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells.

    Science.gov (United States)

    Taylor, Chanel J; He, RongQiao; Bartlett, Perry F

    2014-04-01

    New neurons are continuously generated from resident pools of neural stem and precursor cells (NSPCs) in the adult brain. There are multiple pathways through which adult neurogenesis is regulated, and here we review the role of the N-methyl-D-aspartate receptor (NMDAR) in regulating the proliferation of NSPCs in the adult hippocampus. Hippocampal-dependent learning tasks, enriched environments, running, and activity-dependent synaptic plasticity, all potently up-regulate hippocampal NSPC proliferation. We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity, and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons. We address how specific NMDAR agonists and antagonists modulate proliferation, both in vivo and in vitro, and then review the evidence supporting the hypothesis that NMDARs are present on NSPCs. We believe it is important to understand the mechanisms underlying the activation of adult neurogenesis, given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons. In conditions such as age-related memory decline, neurodegeneration and psychiatric disease, mature neurons are lost or become defective; as such, stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions.

  15. A specific and rapid neural signature for parental instinct.

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    Morten L Kringelbach

    2008-02-01

    Full Text Available Darwin originally pointed out that there is something about infants which prompts adults to respond to and care for them, in order to increase individual fitness, i.e. reproductive success, via increased survivorship of one's own offspring. Lorenz proposed that it is the specific structure of the infant face that serves to elicit these parental responses, but the biological basis for this remains elusive. Here, we investigated whether adults show specific brain responses to unfamiliar infant faces compared to adult faces, where the infant and adult faces had been carefully matched across the two groups for emotional valence and arousal, as well as size and luminosity. The faces also matched closely in terms of attractiveness. Using magnetoencephalography (MEG in adults, we found that highly specific brain activity occurred within a seventh of a second in response to unfamiliar infant faces but not to adult faces. This activity occurred in the medial orbitofrontal cortex (mOFC, an area implicated in reward behaviour, suggesting for the first time a neural basis for this vital evolutionary process. We found a peak in activity first in mOFC and then in the right fusiform face area (FFA. In mOFC the first significant peak (p<0.001 in differences in power between infant and adult faces was found at around 130 ms in the 10-15 Hz band. These early differences were not found in the FFA. In contrast, differences in power were found later, at around 165 ms, in a different band (20-25 Hz in the right FFA, suggesting a feedback effect from mOFC. These findings provide evidence in humans of a potential brain basis for the "innate releasing mechanisms" described by Lorenz for affection and nurturing of young infants. This has potentially important clinical applications in relation to postnatal depression, and could provide opportunities for early identification of families at risk.

  16. Modality-specific axonal regeneration: toward selective regenerative neural interfaces.

    Science.gov (United States)

    Lotfi, Parisa; Garde, Kshitija; Chouhan, Amit K; Bengali, Ebrahim; Romero-Ortega, Mario I

    2011-01-01

    Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed sub-modality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF) and neurotrophin-3 (NT-3), to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5-fold compared to that in saline or NT-3, whereas the number of branches increased threefold in the NT-3 channels. These results were confirmed using a 3D "Y"-shaped in vitro assay showing that the arm containing NGF was able to entice a fivefold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a "Y"-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted toward the sural nerve, while N-52+ large-diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  17. Signaling and transcriptional regulation in neural crest specification and migration: lessons from xenopus embryos.

    Science.gov (United States)

    Pegoraro, Caterina; Monsoro-Burq, Anne H

    2013-01-01

    The neural crest is a population of highly migratory and multipotent cells, which arises from the border of the neural plate in vertebrate embryos. In the last few years, the molecular actors of neural crest early development have been intensively studied, notably by using the frog embryo, as a prime model for the analysis of the earliest embryonic inductions. In addition, tremendous progress has been made in understanding the molecular and cellular basis of Xenopus cranial neural crest migration, by combining in vitro and in vivo analysis. In this review, we examine how the action of previously known neural crest-inducing signals [bone morphogenetic protein (BMP), wingless-int (Wnt), fibroblast growth factor (FGF)] is controlled by newly discovered modulators during early neural plate border patterning and neural crest specification. This regulation controls the induction of key transcription factors that cooperate to pattern the premigratory neural crest progenitors. These data are discussed in the perspective of the gene regulatory network that controls neural and neural crest patterning. We then address recent findings on noncanonical Wnt signaling regulation, cell polarization, and collective cell migration which highlight how cranial neural crest cells populate their target tissue, the branchial arches, in vivo. More than ever, the neural crest stands as a powerful and attractive model to decipher complex vertebrate regulatory circuits in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  18. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension.

    Science.gov (United States)

    Anderson, Matthew J; Schimmang, Thomas; Lewandoski, Mark

    2016-05-01

    During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is

  19. OTX2 exhibits cell-context-dependent effects on cellular and molecular properties of human embryonic neural precursors and medulloblastoma cells

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    Ravinder Kaur

    2015-10-01

    Full Text Available Medulloblastoma (MB is the most common malignant primary pediatric brain tumor and is currently divided into four subtypes based on different genomic alterations, gene expression profiles and response to treatment: WNT, Sonic Hedgehog (SHH, Group 3 and Group 4. This extensive heterogeneity has made it difficult to assess the functional relevance of genes to malignant progression. For example, expression of the transcription factor Orthodenticle homeobox2 (OTX2 is frequently dysregulated in multiple MB variants; however, its role may be subtype specific. We recently demonstrated that neural precursors derived from transformed human embryonic stem cells (trans-hENs, but not their normal counterparts (hENs, resemble Groups 3 and 4 MB in vitro and in vivo. Here, we tested the utility of this model system as a means of dissecting the role of OTX2 in MB using gain- and loss-of-function studies in hENs and trans-hENs, respectively. Parallel experiments with MB cells revealed that OTX2 exerts inhibitory effects on hEN and SHH MB cells by regulating growth, self-renewal and migration in vitro and tumor growth in vivo. This was accompanied by decreased expression of pluripotent genes, such as SOX2, and was supported by overexpression of SOX2 in OTX2+ SHH MB and hENs that resulted in significant rescue of self-renewal and cell migration. By contrast, OTX2 is oncogenic and promotes self-renewal of trans-hENs and Groups 3 and 4 MB independent of pluripotent gene expression. Our results demonstrate a novel role for OTX2 in self-renewal and migration of hENs and MB cells and reveal a cell-context-dependent link between OTX2 and pluripotent genes. Our study underscores the value of human embryonic stem cell derivatives as alternatives to cell lines and heterogeneous patient samples for investigating the contribution of key developmental regulators to MB progression.

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

    Science.gov (United States)

    Gouti, Mina; Briscoe, James; Gavalas, Anthony

    2011-01-01

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

  1. The phytohormone precursor OPDA is isomerized in the insect gut by a single, specific glutathione transferase

    OpenAIRE

    Dąbrowska, Paulina; Freitak, Dalial; Vogel, Heiko; Heckel, David G.; Boland, Wilhelm

    2009-01-01

    Oxylipins play important roles in stress signaling in plants. The compound 12-oxophytodienoic acid (cis-OPDA) is an early biosynthetic precursor of jasmonic acid (JA), the key phytohormone orchestrating the plant anti-herbivore defense. When consumed by feeding Lepidopteran larvae, plant-derived cis-OPDA suffers rapid isomerization to iso-OPDA in the midgut and is excreted in the frass. Unlike OPDA epimerization (yielding trans-OPDA), the formation of iso-OPDA is enzyme-dependent, and is cata...

  2. CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons

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    Katerina Aravantinou-Fatorou

    2015-09-01

    Full Text Available Recent studies demonstrate that astroglia from non-neurogenic brain regions can be reprogrammed into functional neurons through forced expression of neurogenic factors. Here we explored the effect of CEND1 and NEUROG2 on reprogramming of mouse cortical astrocytes and embryonic fibroblasts. Forced expression of CEND1, NEUROG2, or both resulted in acquisition of induced neuronal cells expressing subtype-specific markers, while long-term live-cell imaging highlighted the existence of two different modes of neuronal trans-differentiation. Of note, a subpopulation of CEND1 and NEUROG2 double-transduced astrocytes formed spheres exhibiting neural stem cell properties. mRNA and protein expression studies revealed a reciprocal feedback loop existing between the two molecules, while knockdown of endogenous CEND1 demonstrated that it is a key mediator of NEUROG2-driven neuronal reprogramming. Our data suggest that common reprogramming mechanisms exist driving the conversion of lineage-distant somatic cell types to neurons and reveal a critical role for CEND1 in NEUROG2-driven astrocytic reprogramming.

  3. Enteric neurospheres are not specific to neural crest cultures : Implications for neural stem cell therapies

    NARCIS (Netherlands)

    Binder, E. (Ellen); D. Natarajan (Dipa); J.E. Cooper (Julie E.); Kronfli, R. (Rania); Cananzi, M. (Mara); J.-M. Delalande (Jean-Marie); C. Mccann; A.J. Burns (Alan); N. Thapar (Nikhil)

    2015-01-01

    textabstractObjectives Enteric neural stem cells provide hope of curative treatment for enteric neuropathies. Current protocols for their harvesting from humans focus on the generation of 'neurospheres' from cultures of dissociated gut tissue. The study aims to better understand the derivation,

  4. Identification of genes required for neural-specific glycosylation using functional genomics.

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    Miki Yamamoto-Hino

    2010-12-01

    Full Text Available Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, α1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific α1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating α1,3-fucosylation. Further analyses revealed that an RNA-binding protein, second mitotic wave missing (Swm, upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells.

  5. Transcriptional profiling of endogenous germ layer precursor cells identifies dusp4 as an essential gene in zebrafish endoderm specification

    Science.gov (United States)

    Brown, Jamie L.; Snir, Mirit; Noushmehr, Houtan; Kirby, Martha; Hong, Sung-Kook; Elkahloun, Abdel G.; Feldman, Benjamin

    2008-01-01

    A major goal for developmental biologists is to define the behaviors and molecular contents of differentiating cells. We have devised a strategy for isolating cells from diverse embryonic regions and stages in the zebrafish, using computer-guided laser photoconversion of injected Kaede protein and flow cytometry. This strategy enabled us to perform a genome-wide transcriptome comparison of germ layer precursor cells. Mesendoderm and ectoderm precursors cells isolated by this method differentiated appropriately in transplantation assays. Microarray analysis of these cells reidentified known genes at least as efficiently as previously reported strategies that relied on artificial mesendoderm activation or inhibition. We also identified a large set of uncharacterized mesendoderm-enriched genes as well as ectoderm-enriched genes. Loss-of-function studies revealed that one of these genes, the MAP kinase inhibitor dusp4, is essential for early development. Embryos injected with antisense morpholino oligonucleotides that targeted Dusp4 displayed necrosis of head tissues. Marker analysis during late gastrulation revealed a specific loss of sox17, but not of other endoderm markers, and analysis at later stages revealed a loss of foregut and pancreatic endoderm. This specific loss of sox17 establishes a new class of endoderm specification defect. PMID:18719100

  6. The phytohormone precursor OPDA is isomerized in the insect gut by a single, specific glutathione transferase.

    Science.gov (United States)

    Dabrowska, Paulina; Freitak, Dalial; Vogel, Heiko; Heckel, David G; Boland, Wilhelm

    2009-09-22

    Oxylipins play important roles in stress signaling in plants. The compound 12-oxophytodienoic acid (cis-OPDA) is an early biosynthetic precursor of jasmonic acid (JA), the key phytohormone orchestrating the plant anti-herbivore defense. When consumed by feeding Lepidopteran larvae, plant-derived cis-OPDA suffers rapid isomerization to iso-OPDA in the midgut and is excreted in the frass. Unlike OPDA epimerization (yielding trans-OPDA), the formation of iso-OPDA is enzyme-dependent, and is catalyzed by an inducible glutathione transferase (GSTs) from the larval gut. Purified GST fractions from the gut of Egyptian cotton leafworm (Spodoptera littoralis) and cotton bollworm (Helicoverpa armigera) both exhibited strong OPDA isomerization activity, most likely via transient formation of a glutathione-OPDA conjugate. Out of 16 cytosolic GST proteins cloned from the gut of cotton bollworm larvae and expressed in E. coli, only one catalyzed the OPDA isomerization. The biological function of the double bond shift might be seen in an inactivation of cis-OPDA, similar to the inactivation of prostaglandin A1 to prostaglandin B1 in mammalian tissue. The enzymatic isomerization is particularly widespread among generalist herbivores that have to cope with various amounts of cis-OPDA in their spectrum of host plants.

  7. Region-specific differences in amyloid precursor protein expression in the mouse hippocampus

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    Domenico Del Turco

    2016-11-01

    Full Text Available The physiological role of amyloid precursor protein (APP has been extensively investigated in the rodent hippocampus. Evidence suggests that APP plays a role in synaptic plasticity, dendritic and spine morphogenesis, neuroprotection and - at the behavioral level - hippocampus-dependent forms of learning and memory. Intriguingly, however, studies focusing on the role of APP in synaptic plasticity have reported diverging results and considerable differences in effect size between the dentate gyrus and area CA1 of the mouse hippocampus. We speculated that regional differences in APP expression could underlie these discrepancies and studied the expression of APP in both regions using immunostaining, in situ hybridization, and laser microdissection in combination with quantitative reverse transcription PCR and western blotting. In sum, our results show that APP is approximately 1.7-fold higher expressed in pyramidal cells of Ammon´s horn than in granule cells of the dentate gyrus. This regional difference in APP expression may explain why loss-of-function approaches using APP-deficient mice revealed a role for APP in Hebbian plasticity in area CA1, whereas this could not be shown in the dentate gyrus of the same APP mutants.

  8. Depot specific differences in the adipogenic potential of precursors are mediated by collagenous extracellular matrix and Flotillin 2 dependent signaling

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    Gerald Grandl

    2016-10-01

    Conclusions: We show that adipose tissue SVF secretes collagenous ECM, which directly modulates terminal differentiation of adipocyte precursors in a depot specific manner. These data demonstrate the importance of the tissue microenvironment in preadipocyte differentiation.

  9. Rbfox proteins regulate microRNA biogenesis by sequence-specific binding to their precursors and target downstream Dicer.

    Science.gov (United States)

    Chen, Yu; Zubovic, Lorena; Yang, Fan; Godin, Katherine; Pavelitz, Tom; Castellanos, Javier; Macchi, Paolo; Varani, Gabriele

    2016-05-19

    Rbfox proteins regulate tissue-specific splicing by targeting a conserved GCAUG sequence within pre-mRNAs. We report here that sequence-specific binding of the conserved Rbfox RRM to miRNA precursors containing the same sequence motif in their terminal loops, including miR-20b and miR-107, suppresses their nuclear processing. The structure of the complex between precursor miR-20b and Rbfox RRM shows the molecular basis for recognition, and reveals changes in the stem-loop upon protein binding. In mammalian cells, Rbfox2 downregulates mature miR-20b and miR-107 levels and increases the expression of their downstream targets PTEN and Dicer, respectively, suggesting that Rbfox2 indirectly regulates many more cellular miRNAs. Thus, some of the widespread cellular functions of Rbfox2 protein are attributable to regulation of miRNA biogenesis, and might include the mis-regulation of miR-20b and miR-107 in cancer and neurodegeneration. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos.

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    Mary Y Wu

    2011-02-01

    Full Text Available Bone morphogenetic protein (BMP gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate

  11. Activación de la neurogénesis por el CSF-E en precursores neurales de ratón adulto

    OpenAIRE

    Madrigal Fernández, Miguel Ángel

    2012-01-01

    La activación de la neurogénesis a partir de células progenitoras del cerebro de mamíferos adultos abre una expectativa terapéutica en el campo de la neuroregeneración que requiere un control del proceso de neurogénesis y maduración funcional a partir de los Precursores Neurales. La evolución ontogénica de la composición y propiedades del “Nicho Neurogénico” conduce a una neurogénesis muy limitada en el adulto, que puede ser debida a una carencia de estímulos neurogénicos. El CSF es un factor...

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

    Science.gov (United States)

    Kobayashi, Kenta; Kato, Shigeki; Kobayashi, Kazuto

    2017-01-05

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

  13. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

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    Zeynab Nayernia

    2017-10-01

    Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

  14. Identification and target prediction of miRNAs specifically expressed in rat neural tissue

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    Tu Kang

    2009-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

  15. Color selection and location selection in ERPs : differences, similarities and 'neural specificity'

    NARCIS (Netherlands)

    Lange, J.J.; Wijers, A.A.; Mulder, L.J.M.; Mulder, G.

    It was hypothesized that color selection consists of two stages. The first stage represents a feature specific selection in neural populations specialized in processing color. The second stage constitutes feature non-specific selections, related to executive attentional processes and/or motor

  16. Cognitive and linguistic precursors to early literacy achievement in children With Specific Language Impairment

    NARCIS (Netherlands)

    Weerdenburg, M.W.C. van; Verhoeven, L.T.W.; Balkom, L.J.M. van; Bosman, A.M.T.

    2009-01-01

    This study investigated the role of cognitive and language skills as predictors of early literacy skills in children with Specific Language Impairment. A range of cognitive and linguistic skills were assessed in a sample of 137 eight-year-old children with SLI at the beginning of the school year,

  17. 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.

  18. Polarity-specific high-level information propagation in neural networks.

    Science.gov (United States)

    Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

    2014-01-01

    Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals.

  19. Category-Specific Neural Oscillations Predict Recall Organization During Memory Search

    Science.gov (United States)

    Morton, Neal W.; Kahana, Michael J.; Rosenberg, Emily A.; Baltuch, Gordon H.; Litt, Brian; Sharan, Ashwini D.; Sperling, Michael R.; Polyn, Sean M.

    2013-01-01

    Retrieved-context models of human memory propose that as material is studied, retrieval cues are constructed that allow one to target particular aspects of past experience. We examined the neural predictions of these models by using electrocorticographic/depth recordings and scalp electroencephalography (EEG) to characterize category-specific oscillatory activity, while participants studied and recalled items from distinct, neurally discriminable categories. During study, these category-specific patterns predict whether a studied item will be recalled. In the scalp EEG experiment, category-specific activity during study also predicts whether a given item will be recalled adjacent to other same-category items, consistent with the proposal that a category-specific retrieval cue is used to guide memory search. Retrieved-context models suggest that integrative neural circuitry is involved in the construction and maintenance of the retrieval cue. Consistent with this hypothesis, we observe category-specific patterns that rise in strength as multiple same-category items are studied sequentially, and find that individual differences in this category-specific neural integration during study predict the degree to which a participant will use category information to organize memory search. Finally, we track the deployment of this retrieval cue during memory search: Category-specific patterns are stronger when participants organize their responses according to the category of the studied material. PMID:22875859

  20. Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

    Science.gov (United States)

    Engstrom, Anna; Wang, Hao; Xia, Zhengui

    2015-01-01

    Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. PMID:25967738

  1. Evolutionarily conserved role for SoxC genes in neural crest specification and neuronal differentiation.

    Science.gov (United States)

    Uy, Benjamin R; Simoes-Costa, Marcos; Koo, Daniel E S; Sauka-Spengler, Tatjana; Bronner, Marianne E

    2015-01-15

    Members of the Sox family of transcription factors play a variety of critical developmental roles in both vertebrates and invertebrates. Whereas SoxBs and SoxEs are involved in neural and neural crest development, respectively, far less is known about members of the SoxC subfamily. To address this from an evolutionary perspective, we compare expression and function of SoxC genes in neural crest cells and their derivatives in lamprey (Petromyzon marinus), a basal vertebrate, to frog (Xenopus laevis). Analysis of transcript distribution reveals conservation of lamprey and X. laevis SoxC expression in premigratory neural crest, branchial arches, and cranial ganglia. Moreover, morpholino-mediated loss-of-function of selected SoxC family members demonstrates essential roles in aspects of neural crest development in both organisms. The results suggest important and conserved functions of SoxC genes during vertebrate evolution and a particularly critical, previously unrecognized role in early neural crest specification. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Schwartze, Michael; Kotz, Sonja A

    2013-12-01

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

  3. High-molecular-mass substances in resinites as possible precursors of specific hydrocarbons in fossil fuels

    Energy Technology Data Exchange (ETDEWEB)

    Aarssen, B.G.K. van.; de Leeuw, J.W. (Delft University of Technology, Delft (Netherlands). Organic Geochemistry Unit)

    1992-12-01

    A critical review of the literature concerning the composition of high-molecular-mass (HMM) substances in fossil resins, or resinites, indicated that rigorous assignments of chemical structures of resins of gymnosperm origin have not been performed. Detailed knowledge of the structures of such macromolecules is needed to fully understand their diagenetic and catagenetic behaviour. Therefore a representative set of fossil gymnosperm resins (Victoria, Australia) was investigated. HMM substances were separated from the low-molecular-mass (LMM) substances and studied for their structures and thermal breakdown products. The LMM compounds consist mainly of tricyclic carboxylic acids. The presence of C[sub 40]-compounds which were tentatively identified as dimeric communic acids is shown. Specific compounds that are formed upon flash pyrolysis of the HMM substances were tentatively identified by gas chromatography-mass spectrometry. Their proposed structures indicate that the basic structural unit of the macromolecule consists of a diterpenoid carboxylic acid with a labdatriene carbon skeleton. This is in agreement with literature in which the gymnosperm resinous macromolecules are described as polycommunic acids. Prolonged heating of the resinite and the separated HMM substances yields predominantly bi- and tricyclic aromatic hydrocarbons which are often encountered in fossil fuels. 47 refs., 11 figs.

  4. Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs

    Directory of Open Access Journals (Sweden)

    Yvonne Mica

    2013-04-01

    Full Text Available Melanocytes are pigment-producing cells of neural crest (NC origin that are responsible for protecting the skin against UV irradiation. Pluripotent stem cell (PSC technology offers a promising approach for studying human melanocyte development and disease. Here, we report that timed exposure to activators of WNT, BMP, and EDN3 signaling triggers the sequential induction of NC and melanocyte precursor fates under dual-SMAD-inhibition conditions. Using a SOX10::GFP human embryonic stem cell (hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human NC induction. Subsequent maturation of hESC-derived melanocytes yields pure populations that match the molecular and functional properties of adult melanocytes. Melanocytes from Hermansky-Pudlak syndrome and Chediak-Higashi syndrome patient-specific induced PSCs (iPSCs faithfully reproduce the ultrastructural features of disease-associated pigmentation defects. Our data define a highly specific requirement for WNT signaling during NC induction and enable the generation of pure populations of human iPSC-derived melanocytes for faithful modeling of pigmentation disorders.

  5. Equation-oriented specification of neural models for simulations

    Directory of Open Access Journals (Sweden)

    Marcel eStimberg

    2014-02-01

    Full Text Available Simulating biological neuronal networks is a core method of research in computational neuroscience. A full specification of such a network model includes a description of the dynamics and state changes of neurons and synapses, as well as the synaptic connectivity patterns and the initial values of all parameters. A standard approach in neuronal modelling software is to build models based on a library of pre-defined models and mechanisms; if a model component does not yet exist, it has to be defined in a special-purpose or general low-level language and potentially be compiled and linked with the simulator. Here we propose an alternative approach that allows flexible definition of models by writing textual descriptions based on mathematical notation. We demonstrate that this approach allows the definition of a wide range of models with minimal syntax. Furthermore, such explicit model descriptions allow the generation of executable code for various target languages and devices, since the description is not tied to an implementation. Finally, this approach also has advantages for readability and reproducibility, because the model description is fully explicit, and because it can be automatically parsed and transformed into formatted descriptions.The presented approach has been implemented in the Brian2 simulator.

  6. The neurobiology of sound-specific auditory plasticity: a core neural circuit.

    Science.gov (United States)

    Xiong, Ying; Zhang, Yonghai; Yan, Jun

    2009-09-01

    Auditory learning or experience induces large-scale neural plasticity in not only the auditory cortex but also in the auditory thalamus and midbrain. Such plasticity is guided by acquired sound (sound-specific auditory plasticity). The mechanisms involved in this process have been studied from various approaches and support the presence of a core neural circuit consisting of a subcortico-cortico-subcortical tonotopic loop supplemented by neuromodulatory (e.g., cholinergic) inputs. This circuit has three key functions essential for establishing large-scale and sound-specific plasticity in the auditory cortex, auditory thalamus and auditory midbrain. They include the presence of sound information for guiding the plasticity, the communication between the cortex, thalamus and midbrain for coordinating the plastic changes and the adjustment of the circuit status for augmenting the plasticity. This review begins with an overview of sound-specific auditory plasticity in the central auditory system. It then introduces the core neural circuit which plays an essential role in inducing sound-specific auditory plasticity. Finally, the core neural circuit and its relationship to auditory learning and experience are discussed.

  7. Specific and Nonspecific Neural Activity during Selective Processing of Visual Representations in Working Memory

    Science.gov (United States)

    Oh, Hwamee; Leung, Hoi-Chung

    2010-01-01

    In this fMRI study, we investigated prefrontal cortex (PFC) and visual association regions during selective information processing. We recorded behavioral responses and neural activity during a delayed recognition task with a cue presented during the delay period. A specific cue ("Face" or "Scene") was used to indicate which one of the two…

  8. Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8.

    Science.gov (United States)

    Udobi, K C; Kokenge, A N; Hautman, E R; Ullio, G; Coene, J; Williams, M T; Vorhees, C V; Mabondzo, A; Skelton, M R

    2018-01-31

    Creatine transporter (CrT; SLC6A8) deficiency (CTD) is an X-linked disorder characterized by severe cognitive deficits, impairments in language and an absence of brain creatine (Cr). In a previous study, we generated floxed Slc6a8 (Slc6a8 flox ) mice to create ubiquitous Slc6a8 knockout (Slc6a8 -/y ) mice. Slc6a8 -/y mice lacked whole body Cr and exhibited cognitive deficits. While Slc6a8 -/y mice have a similar biochemical phenotype to CTD patients, they also showed a reduction in size and reductions in swim speed that may have contributed to the observed deficits. To address this, we created brain-specific Slc6a8 knockout (bKO) mice by crossing Slc6a8 flox mice with Nestin-cre mice. bKO mice had reduced cerebral Cr levels while maintaining normal Cr levels in peripheral tissue. Interestingly, brain concentrations of the Cr synthesis precursor guanidinoacetic acid were increased in bKO mice. bKO mice had longer latencies and path lengths in the Morris water maze, without reductions in swim speed. In accordance with data from Slc6a8 -/y mice, bKO mice showed deficits in novel object recognition as well as contextual and cued fear conditioning. bKO mice were also hyperactive, in contrast with data from the Slc6a8 -/y mice. The results show that the loss of cerebral Cr is responsible for the learning and memory deficits seen in ubiquitous Slc6a8 -/y mice. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  9. Physical exercise counteracts MPTP-induced changes in neural precursor cell proliferation in the hippocampus and restores spatial learning but not memory performance in the water maze.

    Science.gov (United States)

    Klein, C; Rasińska, J; Empl, L; Sparenberg, M; Poshtiban, A; Hain, E G; Iggena, D; Rivalan, M; Winter, Y; Steiner, B

    2016-07-01

    Parkinson's disease (PD) is characterized by a continuous loss of dopaminergic neurons in the substantia nigra, which not only leads to characteristic motor symptoms but also to cognitive impairments. Physical exercise has been shown to improve hippocampus-dependent cognitive functions in PD patients. Animal studies have demonstrated the involvement of adult hippocampal neurogenesis in exercise-induced improvements of visuo-spatial learning and memory. Here, we investigated the direct impact of voluntary wheel running on hippocampal neurogenesis and spatial learning and memory in the Morris water maze (MWM) using the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We also analyzed striatal and hippocampal dopamine transmission and mRNA expression levels of dopamine receptors. We show that MPTP-induced spatial learning deficits were alleviated by short-term physical exercise but not MPTP-induced spatial memory impairments in either exercise intervention group. Neural precursor proliferation was transiently altered in MPTP-treated mice, while the cell survival was increased by exercise. Dopamine was progressively depleted by MPTP and its turnover altered by exercise. In addition, gene expression of dopamine receptor D1/D5 was transiently upregulated following MPTP treatment but not affected by physical exercise. Our findings suggest that physical exercise benefits spatial learning but not memory performance in the MWM after MPTP-induced dopamine depletion by restoring precursor cell proliferation in the hippocampus and influencing dopamine transmission. This adds to the understanding of cognitive decline and mechanisms for potential improvements by physical exercise in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Neural correlates of side-specific odour memory in mushroom body output neurons.

    Science.gov (United States)

    Strube-Bloss, Martin F; Nawrot, Martin P; Menzel, Randolf

    2016-12-14

    Humans and other mammals as well as honeybees learn a unilateral association between an olfactory stimulus presented to one side and a reward. In all of them, the learned association can be behaviourally retrieved via contralateral stimulation, suggesting inter-hemispheric communication. However, the underlying neuronal circuits are largely unknown and neural correlates of across-brain-side plasticity have yet not been demonstrated. We report neural plasticity that reflects lateral integration after side-specific odour reward conditioning. Mushroom body output neurons that did not respond initially to contralateral olfactory stimulation developed a unique and stable representation of the rewarded compound stimulus (side and odour) predicting its value during memory retention. The encoding of the reward-associated compound stimulus is delayed by about 40 ms compared with unrewarded neural activity, indicating an increased computation time for the read-out after lateral integration. © 2016 The Author(s).

  11. The role of microRNAs in human neural stem cells, neuronal differentiation and subtype specification.

    Science.gov (United States)

    Stappert, Laura; Roese-Koerner, Beate; Brüstle, Oliver

    2015-01-01

    The impressive neuronal diversity found within the nervous system emerges from a limited pool of neural progenitor cells that proceed through different gene expression programs to acquire distinct cell fates. Here, we review recent evidence indicating that microRNAs (miRNAs) are critically involved in conferring neural cell identities during neural induction, neuronal differentiation and subtype specification. Several studies have shown that miRNAs act in concert with other gene regulatory factors and genetic switches to regulate the spatial and temporal expression profiles of important cell fate determinants. So far, most studies addressing the role of miRNAs during neurogenesis were conducted using animal models. With the advent of human pluripotent stem cells and the possibility to differentiate these into neural stem cells, we now have the opportunity to study miRNAs in a human context. More insight into the impact of miRNA-based regulation during neural fate choice could in the end be exploited to develop new strategies for the generation of distinct human neuronal cell types.

  12. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

    Science.gov (United States)

    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  13. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice

    Science.gov (United States)

    McGuire, Andrew T.; Gray, Matthew D.; Dosenovic, Pia; Gitlin, Alexander D.; Freund, Natalia T.; Petersen, John; Correnti, Colin; Johnsen, William; Kegel, Robert; Stuart, Andrew B.; Glenn, Jolene; Seaman, Michael S.; Schief, William R.; Strong, Roland K.; Nussenzweig, Michel C.; Stamatatos, Leonidas

    2016-01-01

    VRC01-class broadly neutralizing HIV-1 antibodies protect animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. Here we show that an optimized Env immunogen can engage multiple glVRC01-class antibodies. Furthermore, this immunogen activates naive B cells expressing the human germline heavy chain of 3BNC60, paired with endogenous mouse light chains in vivo. To address whether it activates B cells expressing the fully humanized gl3BNC60 B-cell receptor (BCR), we immunized mice carrying both the heavy and light chains of gl3BNC60. B cells expressing this BCR display an autoreactive phenotype and fail to respond efficiently to soluble forms of the optimized immunogen, unless it is highly multimerized. Thus, specifically designed Env immunogens can activate naive B cells expressing human BCRs corresponding to precursors of broadly neutralizing HIV-1 antibodies even when the B cells display an autoreactive phenotype. PMID:26907590

  14. An Application Specific Instruction Set Processor (ASIP) for Adaptive Filters in Neural Prosthetics.

    Science.gov (United States)

    Xin, Yao; Li, Will X Y; Zhang, Zhaorui; Cheung, Ray C C; Song, Dong; Berger, Theodore W

    2015-01-01

    Neural coding is an essential process for neuroprosthetic design, in which adaptive filters have been widely utilized. In a practical application, it is needed to switch between different filters, which could be based on continuous observations or point process, when the neuron models, conditions, or system requirements have changed. As candidates of coding chip for neural prostheses, low-power general purpose processors are not computationally efficient especially for large scale neural population coding. Application specific integrated circuits (ASICs) do not have flexibility to switch between different adaptive filters while the cost for design and fabrication is formidable. In this research work, we explore an application specific instruction set processor (ASIP) for adaptive filters in neural decoding activity. The proposed architecture focuses on efficient computation for the most time-consuming matrix/vector operations among commonly used adaptive filters, being able to provide both flexibility and throughput. Evaluation and implementation results are provided to demonstrate that the proposed ASIP design is area-efficient while being competitive to commercial CPUs in computational performance.

  15. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  16. Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease.

    Science.gov (United States)

    Spencer, Brian; Potkar, Rewati; Metcalf, Jeff; Thrin, Ivy; Adame, Anthony; Rockenstein, Edward; Masliah, Eliezer

    2016-01-22

    Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD. The recombinant NPY-apoB effectively reversed neurodegenerative pathology and behavioral deficits although it had no effect on accumulation of Aβ. The subgranular zone of the hippocampus showed a significant increase in proliferation of neural precursor cells without further differentiation into neurons. The neuroprotective and neurogenic effects of NPY-apoB appeared to involve signaling via ERK and Akt through the NPY R1 and NPY R2 receptors. Thus, widespread CNS-targeted delivery of NPY appears to be effective at reversing the neuronal and glial pathology associated with Aβ accumulation while also increasing NPC proliferation. Overall, increased delivery of NPY to the CNS for AD might be an effective therapy especially if combined with an anti-Aβ therapeutic. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Neural precursors exhibit distinctly different patterns of cell migration upon transplantation during either the acute or chronic phase of EAE: a serial MR imaging study.

    Science.gov (United States)

    Muja, Naser; Cohen, Mikhal E; Zhang, Jiangyang; Kim, Heechul; Gilad, Assaf A; Walczak, Piotr; Ben-Hur, Tamir; Bulte, Jeff W M

    2011-06-01

    As the complex pathogenesis of multiple sclerosis contributes to spatiotemporal variations in the trophic micromilieu of the central nervous system, the optimal intervention period for cell-replacement therapy must be systematically defined. We applied serial, 3D high-resolution magnetic resonance imaging to transplanted neural precursor cells (NPCs) labeled with superparamagnetic iron oxide nanoparticles and 5-bromo-2-deoxyuridine, and compared the migration pattern of NPCs in acute inflamed (n = 10) versus chronic demyelinated (n = 9) brains of mice induced with experimental allergic encephalomyelitis (EAE). Serial in vivo and ex-vivo 3D magnetic resonance imaging revealed that NPCs migrated 2.5 ± 1.3 mm along the corpus callosum in acute EAE. In chronic EAE, cell migration was slightly reduced (2.3 ± 1.3 mm) and only occurred in the lateral side of transplantation. Surprisingly, in 6/10 acute EAE brains, NPCs were found to migrate in a radial pattern along RECA-1(+) cortical blood vessels, in a pattern hitherto only reported for migrating glioblastoma cells. This striking radial biodistribution pattern was not detected in either chronic EAE or disease-free control brains. In both acute and chronic EAE brain, Iba1(+) microglia/macrophage number was significantly higher in central nervous system regions containing migrating NPCs. The existence of differential NPC migration patterns is an important consideration for implementing future translational studies in multiple sclerosis patients with variable disease. Copyright © 2011 Wiley-Liss, Inc.

  18. Training-specific functional, neural, and hypertrophic adaptations to explosive- vs. sustained-contraction strength training.

    Science.gov (United States)

    Balshaw, Thomas G; Massey, Garry J; Maden-Wilkinson, Thomas M; Tillin, Neale A; Folland, Jonathan P

    2016-06-01

    Training specificity is considered important for strength training, although the functional and underpinning physiological adaptations to different types of training, including brief explosive contractions, are poorly understood. This study compared the effects of 12 wk of explosive-contraction (ECT, n = 13) vs. sustained-contraction (SCT, n = 16) strength training vs. control (n = 14) on the functional, neural, hypertrophic, and intrinsic contractile characteristics of healthy young men. Training involved 40 isometric knee extension repetitions (3 times/wk): contracting as fast and hard as possible for ∼1 s (ECT) or gradually increasing to 75% of maximum voluntary torque (MVT) before holding for 3 s (SCT). Torque and electromyography during maximum and explosive contractions, torque during evoked octet contractions, and total quadriceps muscle volume (QUADSVOL) were quantified pre and post training. MVT increased more after SCT than ECT [23 vs. 17%; effect size (ES) = 0.69], with similar increases in neural drive, but greater QUADSVOL changes after SCT (8.1 vs. 2.6%; ES = 0.74). ECT improved explosive torque at all time points (17-34%; 0.54 ≤ ES ≤ 0.76) because of increased neural drive (17-28%), whereas only late-phase explosive torque (150 ms, 12%; ES = 1.48) and corresponding neural drive (18%) increased after SCT. Changes in evoked torque indicated slowing of the contractile properties of the muscle-tendon unit after both training interventions. These results showed training-specific functional changes that appeared to be due to distinct neural and hypertrophic adaptations. ECT produced a wider range of functional adaptations than SCT, and given the lesser demands of ECT, this type of training provides a highly efficient means of increasing function. Copyright © 2016 the American Physiological Society.

  19. Selective in vitro expansion of HLA class I-restricted HIV-1 gag-specific CD8+ T cells: cytotoxic T-lymphocyte epitopes and precursor frequencies.

    NARCIS (Netherlands)

    C.A. van Baalen (Carel); M.R. Klein (Michèl); A.M. Geretti (Anna Maria); R.I.P.M. Keet; F. Miedema (Frank); C.A.C.M. van Els (Cécile); A.D.M.E. Osterhaus (Albert)

    1993-01-01

    textabstractOBJECTIVE: To identify HIV-1 Gag cytotoxic T-lymphocyte (CTL) epitopes and HLA restriction of their recognition, and to define precursor frequencies of HIV-1 Gag-specific CTL in the blood of seropositive individuals. METHODS: B-lymphoblastoid cell lines (B-LCL) infected with recombinant

  20. The precursor form of the rat liver non-specific lipid-transfer protein, expressed in Escherichia coli, has lipid transfer activity

    NARCIS (Netherlands)

    Ossendorp, B. C.; Geijtenbeek, T. B.; Wirtz, K. W.

    1992-01-01

    The cDNA encoding the precursor form of non-specific lipid-transfer protein (pre-nsL-TP) from rat liver was cloned into the expression vector pET3d. The resulting plasmid was transformed to the Escherichia coli strain BL21(DE3). After induction of the bacteria with

  1. Blueprints for behavior: genetic specification of neural circuitry for innate behaviors.

    Science.gov (United States)

    Manoli, Devanand S; Meissner, Geoffrey W; Baker, Bruce S

    2006-08-01

    Innate behaviors offer a unique opportunity to use genetic analysis to dissect and characterize the neural substrates of complex behavioral programs. Courtship in Drosophila involves a complex series of stereotyped behaviors that include numerous exchanges of multimodal sensory information over time. As we will discuss in this review, recent work has demonstrated that male-specific expression of Fruitless transcription factors (Fru(M) proteins) is necessary and sufficient to confer the potential for male courtship behaviors. Fru(M) factors program neurons of the male central and peripheral nervous systems whose function is dedicated to sexual behaviors. This circuitry seems to integrate sensory information to define behavioral states and regulate conserved neural elements for sex-specific behavioral output. The principles that govern the circuitry specified by Fru(M) expression might also operate in subcortical networks that govern innate behaviors in mammals.

  2. Lim homeobox genes in the Ctenophore Mnemiopsis leidyi: the evolution of neural cell type specification

    Directory of Open Access Journals (Sweden)

    Simmons David K

    2012-01-01

    Full Text Available Abstract Background Nervous systems are thought to be important to the evolutionary success and diversification of metazoans, yet little is known about the origin of simple nervous systems at the base of the animal tree. Recent data suggest that ctenophores, a group of macroscopic pelagic marine invertebrates, are the most ancient group of animals that possess a definitive nervous system consisting of a distributed nerve net and an apical statocyst. This study reports on details of the evolution of the neural cell type specifying transcription factor family of LIM homeobox containing genes (Lhx, which have highly conserved functions in neural specification in bilaterian animals. Results Using next generation sequencing, the first draft of the genome of the ctenophore Mnemiopsis leidyi has been generated. The Lhx genes in all animals are represented by seven subfamilies (Lhx1/5, Lhx3/4, Lmx, Islet, Lhx2/9, Lhx6/8, and LMO of which four were found to be represented in the ctenophore lineage (Lhx1/5, Lhx3/4, Lmx, and Islet. Interestingly, the ctenophore Lhx gene complement is more similar to the sponge complement (sponges do not possess neurons than to either the cnidarian-bilaterian or placozoan Lhx complements. Using whole mount in situ hybridization, the Lhx gene expression patterns were examined and found to be expressed around the blastopore and in cells that give rise to the apical organ and putative neural sensory cells. Conclusion This research gives us a first look at neural cell type specification in the ctenophore M. leidyi. Within M. leidyi, Lhx genes are expressed in overlapping domains within proposed neural cellular and sensory cell territories. These data suggest that Lhx genes likely played a conserved role in the patterning of sensory cells in the ancestor of sponges and ctenophores, and may provide a link to the expression of Lhx orthologs in sponge larval photoreceptive cells. Lhx genes were later co-opted into patterning more

  3. A new training algorithm using artificial neural networks to classify gender-specific dynamic gait patterns.

    Science.gov (United States)

    Andrade, Andre; Costa, Marcelo; Paolucci, Leopoldo; Braga, Antônio; Pires, Flavio; Ugrinowitsch, Herbert; Menzel, Hans-Joachim

    2015-01-01

    The aim of this study was to present a new training algorithm using artificial neural networks called multi-objective least absolute shrinkage and selection operator (MOBJ-LASSO) applied to the classification of dynamic gait patterns. The movement pattern is identified by 20 characteristics from the three components of the ground reaction force which are used as input information for the neural networks in gender-specific gait classification. The classification performance between MOBJ-LASSO (97.4%) and multi-objective algorithm (MOBJ) (97.1%) is similar, but the MOBJ-LASSO algorithm achieved more improved results than the MOBJ because it is able to eliminate the inputs and automatically select the parameters of the neural network. Thus, it is an effective tool for data mining using neural networks. From 20 inputs used for training, MOBJ-LASSO selected the first and second peaks of the vertical force and the force peak in the antero-posterior direction as the variables that classify the gait patterns of the different genders.

  4. A gene network that coordinates preplacodal competence and neural crest specification in zebrafish.

    Science.gov (United States)

    Bhat, Neha; Kwon, Hye-Joo; Riley, Bruce B

    2013-01-01

    Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and nonneural ectoderm and together contribute to the peripheral nervous system in all vertebrates. Bmp activates early steps for both fates during late blastula stage. Low Bmp activates expression of transcription factors Tfap2a and Tfap2c in the lateral neural plate, thereby specifying neural crest fate. Elevated Bmp establishes preplacodal competence throughout the ventral ectoderm by coinducing Tfap2a, Tfap2c, Foxi1 and Gata3. PPE specification occurs later at the end of gastrulation and requires complete attenuation of Bmp, yet expression of PPE competence factors continues well past gastrulation. Here we show that competence factors positively regulate each other's expression during gastrulation, forming a self-sustaining network that operates independently of Bmp. Misexpression of Tfap2a in embryos blocked for Bmp from late blastula stage can restore development of both PPE and NC. However, Tfap2a alone is not sufficient to activate any other competence factors nor does it rescue individual placodes. On the other hand, misexpression of any two competence factors in Bmp-blocked embryos can activate the entire transcription factor network and support the development of NC, PPE and some individual placodes. We also show that while these factors are partially redundant with respect to PPE specification, they later provide non-redundant functions needed for development of specific placodes. Thus, we have identified a gene regulatory network that coordinates development of NC, PPE and individual placodes in zebrafish. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice

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    Lin, Y; Zhang, J-C; Yao, C-Y; Wu, Y; Abdelgawad, A F; Yao, S-L; Yuan, S-Y

    2016-01-01

    The brain and the immune system interact in complex ways after ischemic stroke, and the long-term effects of immune response associated with stroke remain controversial. As a linkage between innate and adaptive immunity, interleukin-17 A (IL-17 A) secreted from gamma delta (γδ) T cells has detrimental roles in the pathogenesis of acute ischemic stroke. However, to date, the long-term actions of IL-17 A after stroke have not been investigated. Here, we found that IL-17 A showed two distinct peaks of expression in the ischemic hemisphere: the first occurring within 3 days and the second on day 28 after stroke. Our data also showed that astrocyte was the major cellular source of IL-17 A that maintained and augmented subventricular zone (SVZ) neural precursor cells (NPCs) survival, neuronal differentiation, and subsequent synaptogenesis and functional recovery after stroke. IL-17 A also promoted neuronal differentiation in cultured NPCs from the ischemic SVZ. Furthermore, our in vitro data revealed that in primary astrocyte cultures activated astrocytes released IL-17 A via p38 mitogen-activated protein kinase (MAPK). Culture media from reactive astrocytes increased neuronal differentiation of NSCs in vitro. Blockade of IL-17 A with neutralizing antibody prevented this effect. In addition, after screening for multiple signaling pathways, we revealed that the p38 MAPK/calpain 1 signaling pathway was involved in IL-17 A-mediated neurogenesis in vivo and in vitro. Thus, our results reveal a previously uncharacterized property of astrocytic IL-17 A in the maintenance and augment of survival and neuronal differentiation of NPCs, and subsequent synaptogenesis and spontaneous recovery after ischemic stroke. PMID:27336717

  6. Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis.

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    Warren C Plaisted

    Full Text Available We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs derived from human embryonic stem cells (hESCs in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs. Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.

  7. Intrathecal Transplantation of Embryonic Stem Cell-Derived Spinal GABAergic Neural Precursor Cells Attenuates Neuropathic Pain in a Spinal Cord Injury Rat Model.

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    Hwang, Insik; Hahm, Suk-Chan; Choi, Kyung-Ah; Park, Sung-Ho; Jeong, Hyesun; Yea, Ji-Hye; Kim, Junesun; Hong, Sunghoi

    2016-01-01

    Neuropathic pain following spinal cord injury (SCI) is a devastating disease characterized by spontaneous pain such as hyperalgesia and allodynia. In this study, we investigated the therapeutic potential of ESC-derived spinal GABAergic neurons to treat neuropathic pain in a SCI rat model. Mouse embryonic stem cell-derived neural precursor cells (mESC-NPCs) were cultured in media supplemented with sonic hedgehog (SHH) and retinoic acid (RA) and efficiently differentiated into GABAergic neurons. Interestingly, low doses of SHH and RA induced MGE-like progenitors, which expressed low levels of DARPP32 and Nkx2.1 and high levels of Irx3 and Pax6. These cells subsequently generated the majority of the DARPP32(-) GABAergic neurons after in vitro differentiation. The spinal mESC-NPCs were intrathecally transplanted into the lesion area of the spinal cord around T10-T11 at 21 days after SCI. The engrafted spinal GABAergic neurons remarkably increased both the paw withdrawal threshold (PWT) below the level of the lesion and the vocalization threshold (VT) to the level of the lesion (T12, T11, and T10 vertebrae), which indicates attenuation of chronic neuropathic pain by the spinal GABAergic neurons. The transplanted cells were positive for GABA antibody staining in the injured region, and cells migrated to the injured spinal site and survived for more than 7 weeks in L4-L5. The mESC-NPC-derived spinal GABAergic neurons dramatically attenuated the chronic neuropathic pain following SCI, suggesting that the spinal GABAergic mESC-NPCs cultured with low doses of SHH and RA could be alternative cell sources for treatment of SCI neuropathic pain by stem cell-based therapies.

  8. Automated cell-specific laser detection and ablation of neural circuits in neonatal brain tissue

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    Wang, Xueying; Hayes, John A; Picardo, Maria Cristina D; Del Negro, Christopher A

    2013-01-01

    A key feature of neurodegenerative disease is the pathological loss of neurons that participate in generating behaviour. To investigate network properties of neural circuits and provide a complementary tool to study neurodegeneration in vitro or in situ, we developed an automated cell-specific laser detection and ablation system. The instrument consists of a two-photon and visible-wavelength confocal imaging setup, controlled by executive software, that identifies neurons in preparations based on genetically encoded fluorescent proteins or Ca2+ imaging, and then sequentially ablates cell targets while monitoring network function concurrently. Pathological changes in network function can be directly attributed to ablated cells, which are logged in real time. Here, we investigated brainstem respiratory circuits to demonstrate single-cell precision in ablation during physiological network activity, but the technique could be applied to interrogate network properties in neural systems that retain network functionality in reduced preparations in vitro or in situ. PMID:23440965

  9. Cross-Cultural Differences in the Neural Correlates of Specific and General Recognition

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    Paige, Laura E.; Ksander, John C.; Johndro, Hunter A.; Gutchess, Angela H.

    2017-01-01

    Research suggests that culture influences how people perceive the world, which extends to memory specificity, or how much perceptual detail is remembered. The present study investigated cross-cultural differences (Americans vs. East Asians) at the time of encoding in the neural correlates of specific vs. general memory formation. Participants encoded photos of everyday items in the scanner and 48 hours later completed a surprise recognition test. The recognition test consisted of same (i.e., previously seen in scanner), similar (i.e., same name, different features), or new photos (i.e., items not previously seen in scanner). For Americans compared to East Asians, we predicted greater activation in the hippocampus and right fusiform for specific memory at recognition, as these regions were implicated previously in encoding perceptual details. Results revealed that East Asians activated the left fusiform and left hippocampus more than Americans for specific vs. general memory. Follow-up analyses ruled out alternative explanations of retrieval difficulty and familiarity for this pattern of cross-cultural differences at encoding. Results overall suggest that culture should be considered as another individual difference that affects memory specificity and modulates neural regions underlying these processes. PMID:28256199

  10. Unique Preservation of Neural Cells in Hutchinson- Gilford Progeria Syndrome Is Due to the Expression of the Neural-Specific miR-9 MicroRNA

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    Xavier Nissan

    2012-07-01

    Full Text Available One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS, who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.

  11. Social cognitive conflict resolution: Contributions of domain general and domain specific neural systems

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    Zaki, Jamil; Hennigan, Kelly; Weber, Jochen; Ochsner, Kevin N.

    2010-01-01

    Cognitive control mechanisms allow individuals to behave adaptively in the face of complex and sometimes conflicting information. While the neural bases of these control mechanisms have been examined in many contexts, almost no attention has been paid to their role in resolving conflicts between competing social cues, which is surprising, given that cognitive conflicts are part of many social interactions. Evidence about the neural processing of social information suggests that two systems—the mirror neuron system (MNS) and mental state attribution system (MSAS)—are specialized for processing nonverbal and contextual social cues, respectively. This could support a model of social cognitive conflict resolution in which competition between social cues would recruit domain-general cognitive control mechanisms, which in turn would bias processing towards the MNS or MSAS. Such biasing could also alter social behaviors, such as inferences made about the internal states of others. We tested this model by scanning participants using fMRI while they drew inferences about social targets' emotional states based on congruent or incongruent nonverbal and contextual social cues. Conflicts between social cues recruited the anterior cingulate and lateral prefrontal cortex, brain areas associated with domain-general control processes. This activation was accompanied by biasing of neural activity towards areas in the MNS or MSAS, which tracked, respectively, with perceivers' behavioral reliance on nonverbal or contextual cues when drawing inferences about targets' emotions. Together, these data provide evidence about both domain general and domain specific mechanisms involved in resolving social cognitive conflicts. PMID:20573895

  12. Neural substrates of defensive reactivity in two subtypes of specific phobia.

    Science.gov (United States)

    Lueken, Ulrike; Hilbert, Kevin; Stolyar, Veronika; Maslowski, Nina I; Beesdo-Baum, Katja; Wittchen, Hans-Ulrich

    2014-11-01

    Depending on threat proximity, different defensive behaviours are mediated by a descending neural network involving forebrain (distal threat) vs midbrain areas (proximal threat). Compared to healthy subjects, it can be assumed that phobics are characterized by shortened defensive distances on a behavioural and neural level. This study aimed at characterizing defensive reactivity in two subtypes of specific phobia [snake (SP) and dental phobics (DP)]. Using functional magnetic resonance imaging (fMRI), n = 39 subjects (13 healthy controls, HC; 13 SP; 13 DP) underwent an event-related fMRI task employing an anticipation (5-10 s) and immediate perception phase (phobic pictures and matched neutral stimuli; 1250 ms) to modulate defensive distance. Although no differential brain activity in any comparisons was observed in DP, areas associated with defensive behaviours (e.g. amygdala, hippocampus, midbrain) were activated in SP. Decreasing defensive distance in SP was characterized by a shift to midbrain activity. Present findings substantiate differences between phobia types in their physiological and neural organization that can be expanded to early stages of defensive behaviours. Findings may contribute to a better understanding of the dynamic organization of defensive reactivity in different types of phobic fear. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder

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    Walshe Muriel

    2011-01-01

    Full Text Available Abstract Background Impairments in executive function and language processing are characteristic of both schizophrenia and bipolar disorder. Their functional neuroanatomy demonstrate features that are shared as well as specific to each disorder. Determining the distinct pattern of neural responses in schizophrenia and bipolar disorder may provide biomarkers for their diagnoses. Methods 104 participants underwent functional magnetic resonance imaging (fMRI scans while performing a phonological verbal fluency task. Subjects were 32 patients with schizophrenia in remission, 32 patients with bipolar disorder in an euthymic state, and 40 healthy volunteers. Neural responses to verbal fluency were examined in each group, and the diagnostic potential of the pattern of the neural responses was assessed with machine learning analysis. Results During the verbal fluency task, both patient groups showed increased activation in the anterior cingulate, left dorsolateral prefrontal cortex and right putamen as compared to healthy controls, as well as reduced deactivation of precuneus and posterior cingulate. The magnitude of activation was greatest in patients with schizophrenia, followed by patients with bipolar disorder and then healthy individuals. Additional recruitment in the right inferior frontal and right dorsolateral prefrontal cortices was observed in schizophrenia relative to both bipolar disorder and healthy subjects. The pattern of neural responses correctly identified individual patients with schizophrenia with an accuracy of 92%, and those with bipolar disorder with an accuracy of 79% in which mis-classification was typically of bipolar subjects as healthy controls. Conclusions In summary, both schizophrenia and bipolar disorder are associated with altered function in prefrontal, striatal and default mode networks, but the magnitude of this dysfunction is particularly marked in schizophrenia. The pattern of response to verbal fluency is highly

  14. Differential neural activity during search of specific and general autobiographical memories elicited by musical cues.

    Science.gov (United States)

    Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S

    2011-07-01

    Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime period, general event, and event-specific). Sixteen young adults participated in a neuroimaging study in which they retrieved autobiographical memories associated with musical cues. These musical cues led to the retrieval of highly emotional memories that had low levels of prior retrieval. Retrieval of all autobiographical memory levels was associated with activity in regions in the autobiographical memory network, specifically the ventromedial prefrontal cortex, posterior cingulate, and right medial temporal lobe. Owing to the use of music, memories from varying levels of specificity were retrieved, allowing for comparison of event memory and abstract personal knowledge, as well as comparison of specific and general event memory. Dorsolateral and dorsomedial prefrontal regions were engaged during event retrieval relative to personal knowledge retrieval, and retrieval of specific event memories was associated with increased activity in the bilateral medial temporal lobe and dorsomedial prefrontal cortex relative to retrieval of general event memories. These results suggest that the initial search processes for memories of different specificity levels preferentially engage different components of the autobiographical memory network. The potential underlying causes of these neural differences are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Neural precursor cell proliferation is disrupted through activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    Science.gov (United States)

    Latchney, Sarah E; Lioy, Daniel T; Henry, Ellen C; Gasiewicz, Thomas A; Strathmann, Frederick G; Mayer-Pröschel, Margot; Opanashuk, Lisa A

    2011-02-01

    Neurogenesis involves the proliferation of multipotent neuroepithelial stem cells followed by differentiation into lineage-restricted neural precursor cells (NPCs) during the embryonic period. Interestingly, these progenitor cells express robust levels of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates expression of genes important for growth regulation, and xenobiotic metabolism. Upon binding 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a pervasive environmental contaminant and potent AhR ligand, AhR, is activated and disrupts gene expression patterns to produce cellular toxicity. Because of its widespread distribution in the brain during critical proliferative phases of neurogenesis, it is conceivable that AhR participates in NPC expansion. Therefore, this study tested the hypothesis that AhR activation by TCDD disrupts signaling events that regulate NPC proliferation. The C17.2 NPC line served as a model system to (1) assess whether NPCs are targets for TCDD-induced neurotoxicity and (2) characterize the effects of TCDD on NPC proliferation. We demonstrated that C17.2 NPCs express an intact AhR signaling pathway that becomes transcriptionally active after TCDD exposure. (3)H-thymidine and alamar blue reduction assays indicated that TCDD suppresses NPC proliferation in a concentration-dependent manner without the loss of cell viability. Cell cycle distribution analysis by flow cytometry revealed that TCDD-induced growth arrest results from an impaired G1 to S cell cycle transition. Moreover, TCDD exposure altered p27( kip1) and cyclin D1 cell cycle regulatory protein expression levels consistent with a G1 phase arrest. Initial studies in primary NPCs isolated from the ventral forebrain of embryonic mice demonstrated that TCDD reduced cell proliferation through a G1 phase arrest, corroborating our findings in the C17.2 cell line. Together, these observations suggest that the inappropriate or sustained activation of Ah

  16. Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification.

    Science.gov (United States)

    Angibaud, Julie; Baudouin, Stéphane J; Louveau, Antoine; Nerrière-Daguin, Véronique; Bonnamain, Virginie; Csaba, Zsolt; Dournaud, Pascal; Naveilhan, Philippe; Noraz, Nelly; Pellier-Monnin, Véronique; Boudin, Hélène

    2012-02-01

    Immune signaling and neuroinflammatory mediators have recently emerged as influential variables that regulate neural precursor/stem cell (NPC) behavior and function. In this study, we investigated whether the signaling adaptor protein CD3ζ, a transmembrane protein involved in T cell differentiation and function and recently shown to regulate neuronal development in the central nervous system (CNS), may have a role in NPC differentiation. We analyzed the expression profile of CD3ζ in embryonic rat brain during neurogenic periods and in neurosphere-derived neural cells, and we investigated the action of CD3ζ on cell differentiation. We found that CD3ζ expression coincided with neuronal commitment, but its forced expression in NPCs prevented the production of neurons and oligodendrocytes, but not astroglial cells. This blockade of neuronal differentiation was operated through an ITAM-independent mechanism, but required the Asp36 of the CD3ζ transmembrane domain involved in membrane receptor interaction. Together, our findings show that ectopic CD3ζ expression in NPCs impaired their normal cell-fate specification and suggest that variations of CD3ζ expression in the developing CNS might result in neurodevelopmental anomalies.

  17. Nonlinear relationships between atmospheric aerosol and its gaseous precursors: Analysis of long-term air quality monitoring data by means of neural networks

    Directory of Open Access Journals (Sweden)

    I. B. Konovalov

    2003-01-01

    Full Text Available The nonlinear features of the relationships between concentrations of aerosol and volatile organic compounds (VOC and nitrogen oxides (NOx in urban environments are revealed directly from data of long-term routine measurements of NOx, VOC, and total suspended particulate matter (PM. The main idea of the method is development of special empirical models based on artificial neural networks. These models, that are basically, the nonlinear extension of the commonly used linear statistical models provide the best fit for the real (nonlinear PM-NOx-VOC relationships under different atmospheric conditions. Such models may be useful in the context of various scientific and practical problems related to atmospheric aerosols. The method is demonstrated on an example of two empirical models based on independent data-sets collected at two air quality monitoring stations at South Coast Air Basin, California. It is shown that in spite of a rather large distance between the monitoring stations (more than 50 km and thus substantially different environmental conditions, the empirical models demonstrate several common qualitative features. Specifically, under definite conditions, a decrease in the level of NOx or VOC may lead to an increase in mass concentration of aerosol. It is argued that these features are due to the nonlinear dependence of hydroxyl radical on VOC and NOx.

  18. Sequence-specific bias correction for RNA-seq data using recurrent neural networks.

    Science.gov (United States)

    Zhang, Yao-Zhong; Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru

    2017-01-25

    The recent success of deep learning techniques in machine learning and artificial intelligence has stimulated a great deal of interest among bioinformaticians, who now wish to bring the power of deep learning to bare on a host of bioinformatical problems. Deep learning is ideally suited for biological problems that require automatic or hierarchical feature representation for biological data when prior knowledge is limited. In this work, we address the sequence-specific bias correction problem for RNA-seq data redusing Recurrent Neural Networks (RNNs) to model nucleotide sequences without pre-determining sequence structures. The sequence-specific bias of a read is then calculated based on the sequence probabilities estimated by RNNs, and used in the estimation of gene abundance. We explore the application of two popular RNN recurrent units for this task and demonstrate that RNN-based approaches provide a flexible way to model nucleotide sequences without knowledge of predetermined sequence structures. Our experiments show that training a RNN-based nucleotide sequence model is efficient and RNN-based bias correction methods compare well with the-state-of-the-art sequence-specific bias correction method on the commonly used MAQC-III data set. RNNs provides an alternative and flexible way to calculate sequence-specific bias without explicitly pre-determining sequence structures.

  19. QRI, a retina-specific gene, encodes an extracellular matrix protein exclusively expressed during neural retina differentiation.

    Science.gov (United States)

    Casado, F J; Pouponnot, C; Jeanny, J C; Lecoq, O; Calothy, G; Pierani, A

    1996-02-01

    Neural retina development results from growth arrest of neuroectodermal precursors and differentiation of postmitotic cells. The QRI gene is specifically expressed in Müller retinal glial cells. Its expression coincides with the stage of withdrawal from the cell cycle and establishment of differentiation and is repressed upon induction of retinal cell proliferation by the v-src gene product. In this report, we show that the QR1 gene encodes several glycosylated proteins that are secreted and can either associate with the extracellular matrix or remain diffusible in the medium. By using pulse-chase experiments, the 100-103 kDa forms seem to appear first and are specifically incorporated into the extracellular matrix, whereas the 108 and 60 kDa polypeptides appear later and are detected as soluble forms in the culture medium. We also report that expression of the QR1 gene is developmentally regulated in the chicken. Its mRNA is first detectable at embryonic day 10, reaches a maximal level at embryonic day 15 and is no longer detected at embryonic day 18. Immunolocalization of the QR1 protein in chicken retina sections during development shows that expression of the protein parallels the differentiation pattern of post-miotic cells (in particular Müller cells and rods), corresponding to the two differentiation gradients in the retina: from the ganglion cell layer to the inner nuclear layer and outer nuclear layer, and from the optic nerve to the iris. At embryonic day 10, expression of the QR1 protein(s) is restricted to the optic nerve region and the inner nuclear layer, colocalizing with Müller cell bodies. As development proceeds, QR1 protein localization spreads towards the iris and towards the outer nuclear layer, following Müller cell elongations towards the photoreceptors. Between embryonic days 16 and 18, the QR1 protein is no longer detectable in the optic nerve region and is concentrated around the basal segment of the photoreceptors in the peripheral

  20. Is Neural Activity Detected by ERP-Based Brain-Computer Interfaces Task Specific?

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    Markus A Wenzel

    Full Text Available Brain-computer interfaces (BCIs that are based on event-related potentials (ERPs can estimate to which stimulus a user pays particular attention. In typical BCIs, the user silently counts the selected stimulus (which is repeatedly presented among other stimuli in order to focus the attention. The stimulus of interest is then inferred from the electroencephalogram (EEG. Detecting attention allocation implicitly could be also beneficial for human-computer interaction (HCI, because it would allow software to adapt to the user's interest. However, a counting task would be inappropriate for the envisaged implicit application in HCI. Therefore, the question was addressed if the detectable neural activity is specific for silent counting, or if it can be evoked also by other tasks that direct the attention to certain stimuli.Thirteen people performed a silent counting, an arithmetic and a memory task. The tasks required the subjects to pay particular attention to target stimuli of a random color. The stimulus presentation was the same in all three tasks, which allowed a direct comparison of the experimental conditions.Classifiers that were trained to detect the targets in one task, according to patterns present in the EEG signal, could detect targets in all other tasks (irrespective of some task-related differences in the EEG.The neural activity detected by the classifiers is not strictly task specific but can be generalized over tasks and is presumably a result of the attention allocation or of the augmented workload. The results may hold promise for the transfer of classification algorithms from BCI research to implicit relevance detection in HCI.

  1. Bottle-neck type of neural network as a mapping device towards food specifications.

    Science.gov (United States)

    Novic, Marjana; Groselj, Neva

    2009-09-01

    A novel methodology is proposed for food specifications associated with the origin of food. The methodology was tested on honey samples collected within the TRACE EU project. The data were sampled in various regions in Europe and analysed for the trace elements content. The sampling sites were characterized by different geological origins, such as limestone, shale, or magmatic. We have chosen 14 elements, B, Na, Mg, A, K, Ca, Mn, Co, Ni, Cu, Zn, Rb, Sr, and Ba, due to their influence on the separation of samples regarding the geology of the sampling sites. A special architecture of an error back-propagation neural network, so called bottle-neck type of neural network was used to project the data into a 2D plane. The data were fed into the 14-nodes input layer and then transferred through the 2-nodes hidden layer (compared to a bottle-neck) to the 14-nodes output layer. The two hidden nodes representing the two coordinates of the projection plane enable us to map the samples used for training of the bottle-neck network. With the knowledge about the classes of individual samples we determine the clusters in the projection plane and consequently obtain the coordinates of the centroid (gravity point) of a particular cluster. The clusters are characterized with an ellipse shape borders spanning the length of up to 3sigma in each dimension. Since the data were classified as regard to the geology, three main clusters were sought: (i) limestone, (ii) shale/mudstone/clay/loess, and (iii) acid-magmatic origin of honey samples. The novel methodology proposed for food specifications was demonstrated on a reduced set of samples, which shows good clustering of all three classes in the projection plane, and on the third class of the original data set.

  2. Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

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    Chen Jiun-Ching

    2007-05-01

    Full Text Available Abstract Background Genome-wide identification of specific oligonucleotides (oligos is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos. Results We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes. Conclusion The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through

  3. Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis.

    Science.gov (United States)

    Liu, Chun-Chi; Lin, Chin-Chung; Li, Ker-Chau; Chen, Wen-Shyen E; Chen, Jiun-Ching; Yang, Ming-Te; Yang, Pan-Chyr; Chang, Pei-Chun; Chen, Jeremy J W

    2007-05-22

    Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos. We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes. The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. Specific

  4. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|.

    Science.gov (United States)

    Ho, Nguyen Thi Thanh; Kutzner, Arne; Heese, Klaus

    2017-12-20

    Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2-FAM72-| may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions.

  5. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Directory of Open Access Journals (Sweden)

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  6. Geminin loss causes neural tube defects through disrupted progenitor specification and neuronal differentiation

    Science.gov (United States)

    ES, Patterson; LE, Waller; KL, Kroll

    2014-01-01

    Geminin is a nucleoprotein that can directly bind chromatin regulatory complexes to modulate gene expression during development. Geminin knockout mouse embryos are preimplantation lethal by the 32-cell stage, precluding in vivo study of Geminin's role in neural development. Therefore, here we used a conditional Geminin allele in combination with several Cre-driver lines to define an essential role for Geminin during mammalian neural tube (NT) formation and patterning. Geminin was required in the NT within a critical developmental time window (embryonic day 8.5–10.5), when NT patterning and closure occurs. Geminin excision at these stages resulted in strongly diminished expression of genes that mark and promote dorsal NT identities and decreased differentiation of ventral motor neurons, resulting in completely penetrant NT defects, while excision after embryonic day 10.5 did not result in NT defects. When Geminin was deleted specifically in the spinal NT, both NT defects and axial skeleton defects were observed, but neither defect occurred when Geminin was excised in paraxial mesenchyme, indicating a tissue autonomous requirement for Geminin in developing neuroectoderm. Despite a potential role for Geminin in cell cycle control, we found no evidence of proliferation defects or altered apoptosis. Comparisons of gene expression in the NT of Geminin mutant versus wild-type siblings at embryonic day 10.5 revealed decreased expression of key regulators of neurogenesis, including neurogenic bHLH transcription factors and dorsal interneuron progenitor markers. Together, these data demonstrate a requirement for Geminin for NT patterning and neuronal differentiation during mammalian neurulation in vivo. PMID:24995796

  7. Imaging a cognitive model of apraxia: the neural substrate of gesture-specific cognitive processes.

    Science.gov (United States)

    Peigneux, Philippe; Van der Linden, Martial; Garraux, Gaetan; Laureys, Steven; Degueldre, Christian; Aerts, Joel; Del Fiore, Guy; Moonen, Gustave; Luxen, Andre; Salmon, Eric

    2004-03-01

    The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology Press]. Regional cerebral blood flow was measured in healthy volunteers using H2 15O PET during performance of four tasks commonly used for testing upper limb apraxia, i.e., pantomime of familiar gestures on verbal command, imitation of familiar gestures, imitation of novel gestures, and an action-semantic task that consisted in matching objects for functional use. We also re-analysed data from a previous PET study in which we investigated the neural basis of the visual analysis of gestures. First, we found that two sets of discrete brain areas are predominantly engaged in the imitation of familiar and novel gestures, respectively. Segregated brain activation for novel gesture imitation concur with neuropsychological reports to support the hypothesis that knowledge about the organization of the human body mediates the transition from visual perception to motor execution when imitating novel gestures [Goldenberg Neuropsychologia 1995;33:63-72]. Second, conjunction analyses revealed distinctive neural bases for most of the gesture-specific cognitive processes proposed in this cognitive model of upper limb apraxia. However, a functional analysis of brain imaging data suggested that one single memory store may be used for "to-be-perceived" and "to-be-produced" gestural representations, departing from Rothi et al.'s proposal. Based on the above considerations, we suggest and discuss a revised model for upper limb apraxia that might best account for both brain imaging findings and neuropsychological dissociations reported in the apraxia literature. Copyright 2004 Wiley-Liss, Inc.

  8. Task-specific codes for face recognition: how they shape the neural representation of features for detection and individuation.

    Science.gov (United States)

    Nestor, Adrian; Vettel, Jean M; Tarr, Michael J

    2008-01-01

    The variety of ways in which faces are categorized makes face recognition challenging for both synthetic and biological vision systems. Here we focus on two face processing tasks, detection and individuation, and explore whether differences in task demands lead to differences both in the features most effective for automatic recognition and in the featural codes recruited by neural processing. Our study appeals to a computational framework characterizing the features representing object categories as sets of overlapping image fragments. Within this framework, we assess the extent to which task-relevant information differs across image fragments. Based on objective differences we find among task-specific representations, we test the sensitivity of the human visual system to these different face descriptions independently of one another. Both behavior and functional magnetic resonance imaging reveal effects elicited by objective task-specific levels of information. Behaviorally, recognition performance with image fragments improves with increasing task-specific information carried by different face fragments. Neurally, this sensitivity to the two tasks manifests as differential localization of neural responses across the ventral visual pathway. Fragments diagnostic for detection evoke larger neural responses than non-diagnostic ones in the right posterior fusiform gyrus and bilaterally in the inferior occipital gyrus. In contrast, fragments diagnostic for individuation evoke larger responses than non-diagnostic ones in the anterior inferior temporal gyrus. Finally, for individuation only, pattern analysis reveals sensitivity to task-specific information within the right "fusiform face area". OUR RESULTS DEMONSTRATE: 1) information diagnostic for face detection and individuation is roughly separable; 2) the human visual system is independently sensitive to both types of information; 3) neural responses differ according to the type of task-relevant information

  9. Using domain-specific basic functions for the analysis of supervised artificial neural networks

    NARCIS (Netherlands)

    van der Zwaag, B.J.

    2003-01-01

    Since the early development of artificial neural networks, researchers have tried to analyze trained neural networks in order to gain insight into their behavior. For certain applications and in certain problem domains this has been successful, for example by the development of so-called rule

  10. Preschool externalizing behavior predicts gender-specific variation in adolescent neural structure.

    Directory of Open Access Journals (Sweden)

    Jessica Z K Caldwell

    Full Text Available Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023. No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction.

  11. Specific aspects of cognitive and language proficiency account for variability in neural indices of semantic and syntactic processing in children.

    Science.gov (United States)

    Hampton Wray, Amanda; Weber-Fox, Christine

    2013-07-01

    The neural activity mediating language processing in young children is characterized by large individual variability that is likely related in part to individual strengths and weakness across various cognitive abilities. The current study addresses the following question: How does proficiency in specific cognitive and language functions impact neural indices mediating language processing in children? Thirty typically developing seven- and eight-year-olds were divided into high-normal and low-normal proficiency groups based on performance on nonverbal IQ, auditory word recall, and grammatical morphology tests. Event-related brain potentials (ERPs) were elicited by semantic anomalies and phrase structure violations in naturally spoken sentences. The proficiency for each of the specific cognitive and language tasks uniquely contributed to specific aspects (e.g., timing and/or resource allocation) of neural indices underlying semantic (N400) and syntactic (P600) processing. These results suggest that distinct aptitudes within broader domains of cognition and language, even within the normal range, influence the neural signatures of semantic and syntactic processing. Furthermore, the current findings have important implications for the design and interpretation of developmental studies of ERPs indexing language processing, and they highlight the need to take into account cognitive abilities both within and outside the classic language domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. eLoom and Flatland: specification, simulation and visualization engines for the study of arbitrary hierarchical neural architectures.

    Science.gov (United States)

    Caudell, Thomas P; Xiao, Yunhai; Healy, Michael J

    2003-01-01

    eLoom is an open source graph simulation software tool, developed at the University of New Mexico (UNM), that enables users to specify and simulate neural network models. Its specification language and libraries enables users to construct and simulate arbitrary, potentially hierarchical network structures on serial and parallel processing systems. In addition, eLoom is integrated with UNM's Flatland, an open source virtual environments development tool to provide real-time visualizations of the network structure and activity. Visualization is a useful method for understanding both learning and computation in artificial neural networks. Through 3D animated pictorially representations of the state and flow of information in the network, a better understanding of network functionality is achieved. ART-1, LAPART-II, MLP, and SOM neural networks are presented to illustrate eLoom and Flatland's capabilities.

  13. School performance as a precursor of adult health: exploring associations to disease-specific hospital care and their possible explanations.

    Science.gov (United States)

    Almquist, Ylva B

    2013-02-01

    While past research has shown that school performance is associated with some specific health outcomes in adulthood, few studies have taken a general approach to the link between school performance and adult disease. The aim of the present study was therefore to investigate sixth grade school performance in relation to disease-specific hospital care in adulthood and, moreover, to examine whether other conditions in childhood could account for any such associations. The data used was the Stockholm Birth Cohort, consisting of 14,294 individuals born in 1953. Associations between school performance and disease-specific hospital care were analysed by means of Cox regression. Poor school performance was shown to be linked to a variety of diseases in adulthood, e.g. drug dependence, stomach ulcer, cerebrovascular diseases, and accidents. Some differences according to gender were found. Most associations, but not all, were explained by the simultaneous inclusion of various family-related and individual factors (e.g. social class, cognitive ability, and behavioural problems). In sum, the results of this study suggest that poor school performance may be an essential part of risk clustering in childhood with important implications for the individual's health career.

  14. Focal adhesion kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate

    Science.gov (United States)

    Fonar, Yuri; Gutkovich, Yoni E.; Root, Heather; Malyarova, Anastasia; Aamar, Emil; Golubovskaya, Vita M.; Elias, Sarah; Elkouby, Yaniv M.; Frank, Dale

    2011-01-01

    Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linked to aggressive metastatic and invasive tumors. However, little is known about its normal embryonic function. FAK protein knockdown during early Xenopus laevis development anteriorizes the embryo. Morphant embryos express increased levels of anterior neural markers, with reciprocally reduced posterior neural marker expression. Posterior neural plate folding and convergence-extension is also inhibited. This anteriorized phenotype resembles that of embryos knocked down zygotically for canonical Wnt signaling. FAK and Wnt3a genes are both expressed in the neural plate, and Wnt3a expression is FAK dependent. Ectopic Wnt expression rescues this FAK morphant anteriorized phenotype. Wnt3a thus acts downstream of FAK to balance anterior–posterior cell fate specification in the developing neural plate. Wnt3a gene expression is also FAK dependent in human breast cancer cells, suggesting that this FAK–Wnt linkage is highly conserved. This unique observation connects the FAK- and Wnt-signaling pathways, both of which act to promote cancer when aberrantly activated in mammalian cells. PMID:21551070

  15. Neural stem cells as a novel platform for tumor-specific delivery of therapeutic antibodies.

    Directory of Open Access Journals (Sweden)

    Richard T Frank

    Full Text Available BACKGROUND: Recombinant monoclonal antibodies have emerged as important tools for cancer therapy. Despite the promise shown by antibody-based therapies, the large molecular size of antibodies limits their ability to efficiently penetrate solid tumors and precludes efficient crossing of the blood-brain-barrier into the central nervous system (CNS. Consequently, poorly vascularized solid tumors and CNS metastases cannot be effectively treated by intravenously-injected antibodies. The inherent tumor-tropic properties of human neural stem cells (NSCs can potentially be harnessed to overcome these obstacles and significantly improve cancer immunotherapy. Intravenously-delivered NSCs preferentially migrate to primary and metastatic tumor sites within and outside the CNS. Therefore, we hypothesized that NSCs could serve as an ideal cellular delivery platform for targeting antibodies to malignant tumors. METHODS AND FINDINGS: As proof-of-concept, we selected Herceptin (trastuzumab, a monoclonal antibody widely used to treat HER2-overexpressing breast cancer. HER2 overexpression in breast cancer is highly correlated with CNS metastases, which are inaccessible to trastuzumab therapy. Therefore, NSC-mediated delivery of trastuzumab may improve its therapeutic efficacy. Here we report, for the first time, that human NSCs can be genetically modified to secrete anti-HER2 immunoglobulin molecules. These NSC-secreted antibodies assemble properly, possess tumor cell-binding affinity and specificity, and can effectively inhibit the proliferation of HER2-overexpressing breast cancer cells in vitro. We also demonstrate that immunoglobulin-secreting NSCs exhibit preferential tropism to tumor cells in vivo, and can deliver antibodies to human breast cancer xenografts in mice. CONCLUSIONS: Taken together, these results suggest that NSCs modified to secrete HER2-targeting antibodies constitute a promising novel platform for targeted cancer immunotherapy. Specifically

  16. Sex Differences in the Neural Correlates of Specific and General Autobiographical Memory

    Science.gov (United States)

    Compère, Laurie; Sperduti, Marco; Gallarda, Thierry; Anssens, Adèle; Lion, Stéphanie; Delhommeau, Marion; Martinelli, Pénélope; Devauchelle, Anne-Dominique; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Autobiographical memory (AM) underlies the formation and temporal continuity over time of personal identity. The few studies on sex-related differences in AM suggest that men and women adopt different cognitive or emotional strategies when retrieving AMs. However, none of the previous works has taken into account the distinction between episodic autobiographical memory (EAM), consisting in the retrieval of specific events by means of mental time travel, and semantic autobiographical memory (SAM), which stores general personal events. Thus, it remains unclear whether differences in these strategies depend on the nature of the memory content to be retrieved. In the present study we employed functional MRI to examine brain activity underlying potential sex differences in EAM and SAM retrieval focusing on the differences in strategies related to the emotional aspects of memories while controlling for basic cognitive strategies. On the behavioral level, there was no significant sex difference in memory performances or subjective feature ratings of either type of AM. Activations common to men and women during AM retrieval were observed in a typical bilateral network comprising medial and lateral temporal regions, precuneus, occipital cortex as well as prefrontal cortex. Contrast analyses revealed that there was no difference between men and women in the EAM condition. In the SAM condition, women showed an increased activity, compared to men, in the dorsal anterior cingulate cortex, inferior parietal and precentral gyrus. Overall, these findings suggest that differential neural activations reflect sex-specific strategies related to emotional aspects of AMs, particularly regarding SAM. We propose that this pattern of activation during SAM retrieval reflects the cognitive cost linked to emotion regulation strategies recruited by women compared to men. These sex-related differences have interesting implications for understanding psychiatric disorders with differential sex

  17. VGF: an inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers.

    Science.gov (United States)

    Ferri, Gian-Luca; Noli, Barbara; Brancia, Carla; D'Amato, Filomena; Cocco, Cristina

    2011-12-01

    The vgf gene (non-acronymic) is induced in vivo by neurotrophins including Nerve Growth Factor (NGF), Brain Derived Growth Factor (BDNF) and Glial Derived Growth Factor (GDNF), by synaptic activity and by homeostatic and other stimuli. Post-translational processing of a single VGF precursor gives raise to a varied multiplicity of neuro-endocrine peptides, some of which are secreted upon stimulation both in vitro and in vivo. Several VGF peptides, accounting for ∼20% of the VGF precursor sequence, have shown biological roles including regulation of food intake, energy balance, reproductive and homeostatic mechanisms, synaptic strengthening, long-term potentiation (LTP) and anti-depressant activity. From a further ∼50% of VGF derive multiple "fragments", largely identified in the human cerebro-spinal fluid by proteomic studies searching for disease biomarkers. These represent an important starting point for discovery of further VGF products relevant to neuronal brain functions, as well as to neurodegenerative and psychiatric disease conditions. A distinct feature of VGF peptides is their cell type specific diversity in all neuroendocrine organs studied so far. Selective differential profiles are found across the cell populations of pituitary, adrenal medulla and pancreatic islets, and in gastric neuroendocrine as well as some further mucosal cells, and are yet to be investigated in neuronal systems. At the same time, specific VGF peptide/s undergo selective modulation in response to organ or cell population relevant stimuli. Such pattern argues for a multiplicity of roles for VGF peptides, including endocrine functions, local intercellular communication, as well as the possible mediation of intracellular mechanisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Deep convolutional neural networks for pan-specific peptide-MHC class I binding prediction.

    Science.gov (United States)

    Han, Youngmahn; Kim, Dongsup

    2017-12-28

    Computational scanning of peptide candidates that bind to a specific major histocompatibility complex (MHC) can speed up the peptide-based vaccine development process and therefore various methods are being actively developed. Recently, machine-learning-based methods have generated successful results by training large amounts of experimental data. However, many machine learning-based methods are generally less sensitive in recognizing locally-clustered interactions, which can synergistically stabilize peptide binding. Deep convolutional neural network (DCNN) is a deep learning method inspired by visual recognition process of animal brain and it is known to be able to capture meaningful local patterns from 2D images. Once the peptide-MHC interactions can be encoded into image-like array(ILA) data, DCNN can be employed to build a predictive model for peptide-MHC binding prediction. In this study, we demonstrated that DCNN is able to not only reliably predict peptide-MHC binding, but also sensitively detect locally-clustered interactions. Nonapeptide-HLA-A and -B binding data were encoded into ILA data. A DCNN, as a pan-specific prediction model, was trained on the ILA data. The DCNN showed higher performance than other prediction tools for the latest benchmark datasets, which consist of 43 datasets for 15 HLA-A alleles and 25 datasets for 10 HLA-B alleles. In particular, the DCNN outperformed other tools for alleles belonging to the HLA-A3 supertype. The F1 scores of the DCNN were 0.86, 0.94, and 0.67 for HLA-A*31:01, HLA-A*03:01, and HLA-A*68:01 alleles, respectively, which were significantly higher than those of other tools. We found that the DCNN was able to recognize locally-clustered interactions that could synergistically stabilize peptide binding. We developed ConvMHC, a web server to provide user-friendly web interfaces for peptide-MHC class I binding predictions using the DCNN. ConvMHC web server can be accessible via http://jumong.kaist.ac.kr:8080/convmhc

  19. El FGF2 como regulador de la actividad mitogénica de precursores neurales en el nicho celular del cerebro embrionario de ratón

    OpenAIRE

    Lamus Molina, José Francisco

    2016-01-01

    A lo largo de la vida del individuo, las células precursoras neurales se encuentran alojadas en microentornos especializados conocidos como nichos germinales neurogénicos, que garantizan su mantenimiento y posibilitan la generación de nuevas neuronas, experimentando su momento de máxima actividad neurogénica durante el desarrollo. El fluido cerebroespinal embrionario (eCSF) ha sido identificado como uno de los elementos esenciales del nicho neurogénico del cerebro embrionario, contactando de ...

  20. Laser microdissection of sensory organ precursor cells of Drosophila microchaetes.

    Directory of Open Access Journals (Sweden)

    Eulalie Buffin

    Full Text Available BACKGROUND: In Drosophila, each external sensory organ originates from the division of a unique precursor cell (the sensory organ precursor cell or SOP. Each SOP is specified from a cluster of equivalent cells, called a proneural cluster, all of them competent to become SOP. Although, it is well known how SOP cells are selected from proneural clusters, little is known about the downstream genes that are regulated during SOP fate specification. METHODOLOGY/PRINCIPAL FINDINGS: In order to better understand the mechanism involved in the specification of these precursor cells, we combined laser microdissection, toisolate SOP cells, with transcriptome analysis, to study their RNA profile. Using this procedure, we found that genes that exhibit a 2-fold or greater expression in SOPs versus epithelial cells were mainly associated with Gene Ontology (GO terms related with cell fate determination and sensory organ specification. Furthermore, we found that several genes such as pebbled/hindsight, scabrous, miranda, senseless, or cut, known to be expressed in SOP cells by independent procedures, are particularly detected in laser microdissected SOP cells rather than in epithelial cells. CONCLUSIONS/SIGNIFICANCE: These results confirm the feasibility and the specificity of our laser microdissection based procedure. We anticipate that this analysis will give new insight into the selection and specification of neural precursor cells.

  1. Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations

    Directory of Open Access Journals (Sweden)

    Tianqi Wang

    2017-01-01

    Full Text Available Major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD, autism (AUT, bipolar disorder (BD, major depressive disorder (MDD, and schizophrenia (SZ, are highly heritable and polygenic. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural connectivity abnormalities. To measure aggregate genetic risks, the polygenic risk score (PGRS was computed. Two independent general populations (N = 360 and N = 323 were separately examined to investigate whether the cross-disorder PGRS and PGRS for a specific disorder were associated with individual variability in functional connectivity. Consistent altered functional connectivity was found with the bilateral insula: for the left supplementary motor area and the left superior temporal gyrus with the cross-disorder PGRS, for the left insula and right middle and superior temporal lobe associated with the PGRS for autism, for the bilateral midbrain, posterior cingulate, cuneus, and precuneus associated with the PGRS for BD, and for the left angular gyrus and the left dorsolateral prefrontal cortex associated with the PGRS for schizophrenia. No significant functional connectivity was found associated with the PGRS for ADHD and MDD. Our findings indicated that genetic effects on the cross-disorder and disorder-specific neural connectivity of common genetic risk loci are detectable in the general population. Our findings also indicated that polygenic risk contributes to the main neurobiological phenotypes of psychiatric disorders and that identifying cross-disorder and specific functional connectivity related to polygenic risks may elucidate the neural pathways for these disorders.

  2. The contribution of the C5 protein subunit of Escherichia coli ribonuclease P to specificity for precursor tRNA is modulated by proximal 5' leader sequences.

    Science.gov (United States)

    Niland, Courtney N; Anderson, David R; Jankowsky, Eckhard; Harris, Michael E

    2017-10-01

    Recognition of RNA by RNA processing enzymes and RNA binding proteins often involves cooperation between multiple subunits. However, the interdependent contributions of RNA and protein subunits to molecular recognition by ribonucleoproteins are relatively unexplored. RNase P is an endonuclease that removes 5' leaders from precursor tRNAs and functions in bacteria as a dimer formed by a catalytic RNA subunit (P RNA) and a protein subunit (C5 in E. coli). The P RNA subunit contacts the tRNA body and proximal 5' leader sequences [N(-1) and N(-2)] while C5 binds distal 5' leader sequences [N(-3) to N(-6)]. To determine whether the contacts formed by P RNA and C5 contribute independently to specificity or exhibit cooperativity or anti-cooperativity, we compared the relative kcat/Km values for all possible combinations of the six proximal 5' leader nucleotides (n = 4096) for processing by the E. coli P RNA subunit alone and by the RNase P holoenzyme. We observed that while the P RNA subunit shows specificity for 5' leader nucleotides N(-2) and N(-1), the presence of the C5 protein reduces the contribution of P RNA to specificity, but changes specificity at N(-2) and N(-3). The results reveal that the contribution of C5 protein to RNase P processing is controlled by the identity of N(-2) in the pre-tRNA 5' leader. The data also clearly show that pairing of the 5' leader with the 3' ACCA of tRNA acts as an anti-determinant for RNase P cleavage. Comparative analysis of genomically encoded E. coli tRNAs reveals that both anti-determinants are subject to negative selection in vivo. © 2017 Niland et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  3. Material-Specific Neural Correlates of Recollection: Objects, Words, and Faces

    Science.gov (United States)

    Galli, Giulia; Otten, Leun J.

    2011-01-01

    It is unclear how neural correlates of episodic memory retrieval differ depending on the type of material that is retrieved. Here, we used a source memory task to compare electrical brain activity for the recollection of three types of stimulus material. At study, healthy adults judged how well visually presented objects, words, and faces fitted…

  4. Discovery of a Prefusion Respiratory Syncytial Virus F-Specific Monoclonal Antibody That Provides Greater In Vivo Protection than the Murine Precursor of Palivizumab.

    Science.gov (United States)

    Zhao, Min; Zheng, Zi-Zheng; Chen, Man; Modjarrad, Kayvon; Zhang, Wei; Zhan, Lu-Ting; Cao, Jian-Li; Sun, Yong-Peng; McLellan, Jason S; Graham, Barney S; Xia, Ning-Shao

    2017-08-01

    Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the respiratory syncytial virus (RSV) F glycoprotein, is the only prophylactic agent approved for use for the treatment of RSV infection. However, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high-potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F protein trimer. We compared in vitro and in vivo the potency and protective efficacy of 5C4 and the murine precursor of palivizumab, antibody 1129. Both antibodies were synthesized on identical murine backbones as either an IgG1 or IgG2a subclass and evaluated for binding to multiple F protein conformations, in vitro inhibition of RSV infection and propagation, and protective efficacy in mice. Although 1129 and 5C4 had similar pre-F protein binding affinities, the 5C4 neutralizing activity was nearly 50-fold greater than that of 1129 in vitro In BALB/c mice, 5C4 reduced the peak titers of RSV 1,000-fold more than 1129 did in both the upper and lower respiratory tracts. These data indicate that antibodies specific for antigenic site Ø are more efficacious at preventing RSV infection than antibodies specific for antigenic site II. Our data also suggest that site Ø-specific antibodies may be useful for the prevention or treatment of RSV infection and support the use of the pre-F protein as a vaccine antigen.IMPORTANCE There is no vaccine yet available to prevent RSV infection. The use of the licensed antibody palivizumab, which recognizes site II on both the pre-F and post-F proteins, is restricted to prophylaxis in neonates at high risk of severe RSV disease. Recommendations for using passive immunization in the general population or for therapy in immunocompromised persons with

  5. Methylmercury exposure during early Xenopus laevis development affects cell proliferation and death but not neural progenitor specification.

    Science.gov (United States)

    Huyck, Ryan W; Nagarkar, Maitreyi; Olsen, Nina; Clamons, Samuel E; Saha, Margaret S

    2015-01-01

    Methylmercury (MeHg) is a widespread environmental toxin that preferentially and adversely affects developing organisms. To investigate the impact of MeHg toxicity on the formation of the vertebrate nervous system at physiologically relevant concentrations, we designed a graded phenotype scale for evaluating Xenopus laevis embryos exposed to MeHg in solution. Embryos displayed a range of abnormalities in response to MeHg, particularly in brain development, which is influenced by both MeHg concentration and the number of embryos per ml of exposure solution. A TC50 of ~50μg/l and LC50 of ~100μg/l were found when maintaining embryos at a density of one per ml, and both increased with increasing embryo density. In situ hybridization and microarray analysis showed no significant change in expression of early neural patterning genes including sox2, en2, or delta; however a noticeable decrease was observed in the terminal neural differentiation genes GAD and xGAT, but not xVGlut. PCNA, a marker for proliferating cells, was negatively correlated with MeHg dose, with a significant reduction in cell number in the forebrain and spinal cord of exposed embryos by tadpole stages. Conversely, the number of apoptotic cells in neural regions detected by a TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was significantly increased. These results provide evidence that disruption of embryonic neural development by MeHg may not be directly due to a loss of neural progenitor specification and gene transcription, but to a more general decrease in cell proliferation and increase in cell death throughout the developing nervous system. Copyright © 2014. Published by Elsevier Inc.

  6. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Brault

    2016-08-01

    Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  7. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nazneen N Dewji

    Full Text Available β-Amyloid (Aβ accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD. Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP and Presenilin (PS, as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  8. Specific glucosinolate analysis reveals variable levels of epimeric glucobarbarins, dietary precursors of 5-phenyloxazolidine-2-thiones, in watercress types with contrasting chromosome numbers.

    Science.gov (United States)

    Agerbirk, Niels; Olsen, Carl Erik; Cipollini, Don; Ørgaard, Marian; Linde-Laursen, Ib; Chew, Frances S

    2014-10-01

    Watercress obtained in food stores in the United States contained significant levels of epiglucobarbarin [(R)-2-hydroxy-2-phenylethylglucosinolate] and low levels of the 2S-epimer glucobarbarin identified by an HPLC+NMR+MS/MS approach. Typical combined levels were 4-7 μmol/g dry wt. The hydrolysis product, 5-phenyloxazolidine-2-thione (barbarin), was detected at similar levels as the precursor glucosinolates after autolysis of fresh watercress in water. Fragmentation patterns in MS(2) of reference desulfoglucosinolates were side chain specific and suitable for routine identification. Watercress was of two main glucosinolate chemotypes: Material from U.S. food stores had a complex profile including glucobarbarins, gluconasturtiin, indole glucosinolates and high levels (6-28 μmol/g dry wt.) of long-chain methylsulfinylalkyl and methylthioalkyl glucosinolates. Material from European food stores had a simple profile dominated by gluconasturtiin, with low levels of epiglucobarbarin and moderate levels of indole glucosinolates. Some wild U.S. material was similar to the U.S. food store type. Both types were found to be Nasturtium officinale by floral parts morphology. Cytological analysis of one U.S. food store accession indicated that it represented a chromosome-doubled variant within N. officinale. The nutritional consequences and invasive potential of the U.S. food store chemotype are discussed.

  9. Body-specific motor imagery of hand actions: neural evidence from right- and left-handers

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    Roel M Willems

    2009-11-01

    Full Text Available If motor imagery uses neural structures involved in action execution, then the neural correlates of imagining an action should differ between individuals who tend to execute the action differently. Here we report fMRI data showing that motor imagery is influenced by the way people habitually perform motor actions with their particular bodies; that is, motor imagery is ‘body-specific’ (Casasanto, 2009. During mental imagery for complex hand actions, activation of cortical areas involved in motor planning and execution was left-lateralized in right-handers but right-lateralized in left-handers. We conclude that motor imagery involves the generation of an action plan that is grounded in the participant’s motor habits, not just an abstract representation at the level of the action’s goal. People with different patterns of motor experience form correspondingly different neurocognitive representations of imagined actions.

  10. Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra in a dopamine-dependent manner

    Directory of Open Access Journals (Sweden)

    Klaissle Philipp

    2012-10-01

    Full Text Available Abstract Background Parkinson’s disease is characterized by a continuous loss of neurons within the substantia nigra (SN leading to a depletion of dopamine. Within the adult SN as a non-neurogenic region, cells with mainly oligodendrocytic precursor characteristics, expressing the neuro-glial antigen-2 (NG2 are continuously generated. Proliferation of these cells is altered in animal models of Parkinson’s disease (PD. Exercise and environmental enrichment re-increase proliferation of NG2+ cells in PD models, however, a possible mechanistic role of dopamine for this increase is not completely understood. NG2+ cells can differentiate into oligodendrocytes but also into microglia and neurons as observed in vitro suggesting a possible hint for endogenous regenerative capacity of the SN. We investigated the role of dopamine in NG2-generation and differentiation in the adult SN stimulated by physical activity and environmental enrichment. Results We used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-model for dopamine depletion and analysed newborn cells in the SN at different maturation stages and time points depending on voluntary physical activity, enriched environment and levodopa-treatment. We describe an activity- induced increase of new NG2-positive cells and also mature oligodendrocytes in the SN of healthy mice. Running and enriched environment refused to stimulate NG2-generation and oligodendrogenesis in MPTP-mice, an effect which could be reversed by pharmacological levodopa-induced rescue. Conclusion We suggest dopamine being a key regulator for activity-induced generation of NG2-cells and oliogodendrocytes in the SN as a potentially relevant mechanism in endogenous nigral cellular plasticity.

  11. Frequency analysis of simian virus 40-specific cytotoxic T lymphocyte precursors in the high responder C57BL/6 mouse strain.

    Science.gov (United States)

    Jennings, S R; Fresa, K L; Lippe, P A; Milici, J E; Tevethia, S S

    1988-10-01

    Studies in this laboratory have shown that long term simian virus 40 (SV40)-specific cytolytic T lymphocyte (CTL) cultures established from the spleens of high responder C57BL/6 (B6; H-2b) mice exhibit a preference for the selection of H-2Db-restricted CTL clones. In this study, we have investigated the basis for this selection. Limiting dilution cultures were established using responder cells from the popliteal lymph nodes and the spleens of B6 mice immunized subcutaneously in the hind footpads or via the intraperitoneal route, respectively, with syngeneic SV40-transformed cells expressing a full length (1 to 708 amino acid residues) SV40 large T antigen. The relative frequency of CTL precursors (CTLp) able to expand in vitro in the presence of SV40-transformed stimulator cells and interleukin 2 and exhibit lytic activity against H-2b cells expressing full length T antigen ranged from 1/1900 to 1/15,000 in the popliteal lymph node and from 1/8000 to 1/55,000 in the spleen. In these two experimental systems, CTLp restricted to H-2Kb were apparently present at higher frequency than H-2Db-restricted CTLp. Furthermore, CTLp recognizing determinants within the amino-terminal or carboxy-terminal halves of T antigen were generated in approximately equal numbers. The relative affinity of SV40-specific CTL, assessed by inhibition with anti-Lyt 2 monoclonal antibody, indicated that CTL restricted to H-2Db interacted with their target with greater affinity than CTL restricted to H-2Kb. These data suggest that the predominance of isolation of H-2Db-restricted CTL clones from long term in vitro cultures may be a function of the relative affinity of this population as a whole, rather than due to the immunodominance of this subpopulation during the in vivo response to SV40 T antigen.

  12. Low-level neural auditory discrimination dysfunctions in specific language impairment-A review on mismatch negativity findings.

    Science.gov (United States)

    Kujala, Teija; Leminen, Miika

    2017-12-01

    In specific language impairment (SLI), there is a delay in the child's oral language skills when compared with nonverbal cognitive abilities. The problems typically relate to phonological and morphological processing and word learning. This article reviews studies which have used mismatch negativity (MMN) in investigating low-level neural auditory dysfunctions in this disorder. With MMN, it is possible to tap the accuracy of neural sound discrimination and sensory memory functions. These studies have found smaller response amplitudes and longer latencies for speech and non-speech sound changes in children with SLI than in typically developing children, suggesting impaired and slow auditory discrimination in SLI. Furthermore, they suggest shortened sensory memory duration and vulnerability of the sensory memory to masking effects. Importantly, some studies reported associations between MMN parameters and language test measures. In addition, it was found that language intervention can influence the abnormal MMN in children with SLI, enhancing its amplitude. These results suggest that the MMN can shed light on the neural basis of various auditory and memory impairments in SLI, which are likely to influence speech perception. Copyright © 2017. Published by Elsevier Ltd.

  13. Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome.

    Science.gov (United States)

    Harrison, Susan J; Nishinakamura, Ryuichi; Jones, Kevin R; Monaghan, A Paula

    2012-05-01

    Progenitor cells in the cerebral cortex undergo dynamic cellular and molecular changes during development. Sall1 is a putative transcription factor that is highly expressed in progenitor cells during development. In humans, the autosomal dominant developmental disorder Townes-Brocks syndrome (TBS) is associated with mutations of the SALL1 gene. TBS is characterized by renal, anal, limb and auditory abnormalities. Although neural deficits have not been recognized as a diagnostic characteristic of the disease, ~10% of patients exhibit neural or behavioral abnormalities. We demonstrate that, in addition to being expressed in peripheral organs, Sall1 is robustly expressed in progenitor cells of the central nervous system in mice. Both classical- and conditional-knockout mouse studies indicate that the cerebral cortex is particularly sensitive to loss of Sall1. In the absence of Sall1, both the surface area and depth of the cerebral cortex were decreased at embryonic day 18.5 (E18.5). These deficiencies are associated with changes in progenitor cell properties during development. In early cortical progenitor cells, Sall1 promotes proliferative over neurogenic division, whereas, at later developmental stages, Sall1 regulates the production and differentiation of intermediate progenitor cells. Furthermore, Sall1 influences the temporal specification of cortical laminae. These findings present novel insights into the function of Sall1 in the developing mouse cortex and provide avenues for future research into potential neural deficits in individuals with TBS.

  14. Identity of zinc finger nucleases with specificity to herpes simplex virus type II genomic DNA: novel HSV-2 vaccine/therapy precursors

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2011-06-01

    5' and 3' ends of the HSV-2 genome (genomic context coordinates 0.02 and 0.98, respectively were specificity sites of ZFNs suited for the complete excision of over 60% of HSV-2 genomic material from within infected human cells, through the process of non-homologous end joining (NHEJ. Furthermore, a model concerning a recombinant (ICP10-PK mutant replication competent HSV-2 viral vector for delivering and transducing a diploid copy (or pair of the HSV-2-genome-specific ZFN genotype within neuronal tissue, is presented. Conclusion ZFNs with specificity to HSV-2 genomic DNA that are precursors of novel host-genome expressed HSV-2 gene-therapeutics or vaccines were identified.

  15. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

    The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially re...

  16. Decreased N-TAF1 expression in X-linked dystonia-parkinsonism patient-specific neural stem cells

    Directory of Open Access Journals (Sweden)

    Naoto Ito

    2016-04-01

    Full Text Available X-linked dystonia-parkinsonism (XDP is a hereditary neurodegenerative disorder involving a progressive loss of striatal medium spiny neurons. The mechanisms underlying neurodegeneration are not known, in part because there have been few cellular models available for studying the disease. The XDP haplotype consists of multiple sequence variations in a region of the X chromosome containing TAF1, a large gene with at least 38 exons, and a multiple transcript system (MTS composed of five unconventional exons. A previous study identified an XDP-specific insertion of a SINE-VNTR-Alu (SVA-type retrotransposon in intron 32 of TAF1, as well as a neural-specific TAF1 isoform, N-TAF1, which showed decreased expression in post-mortem XDP brain compared with control tissue. Here, we generated XDP patient and control fibroblasts and induced pluripotent stem cells (iPSCs in order to further probe cellular defects associated with this disease. As initial validation of the model, we compared expression of TAF1 and MTS transcripts in XDP versus control fibroblasts and iPSC-derived neural stem cells (NSCs. Compared with control cells, XDP fibroblasts exhibited decreased expression of TAF1 transcript fragments derived from exons 32-36, a region spanning the SVA insertion site. N-TAF1, which incorporates an alternative exon (exon 34′, was not expressed in fibroblasts, but was detectable in iPSC-differentiated NSCs at levels that were ∼threefold lower in XDP cells than in controls. These results support the previous findings that N-TAF1 expression is impaired in XDP, but additionally indicate that this aberrant transcription might occur in neural cells at relatively early stages of development that precede neurodegeneration.

  17. Commonalities and differences in the neural substrates of threat predictability in panic disorder and specific phobia

    Directory of Open Access Journals (Sweden)

    Anna Luisa Klahn

    2017-01-01

    Group independent neural activity in the right dlPFC increased with decreasing threat predictability. PD patients showed a sustained hyperactivation of the vmPFC under threat and safety conditions. The magnitude of hyperactivation was inversely correlated with PDs subjective arousal and anxiety sensitivity. Both PD and SP patients revealed decreased parietal processing of affective stimuli. Findings indicate overgeneralization between threat and safety conditions and increased need for emotion regulation via the vmPFC in PD, but not SP patients. Both anxiety disorders showed decreased activation in parietal networks possibly indicating attentional avoidance of affective stimuli. Present results complement findings from fear conditioning studies and underline overgeneralization of fear, particularly in PD.

  18. Gender-specific strategy use and neural correlates in a spatial perspective taking task.

    Science.gov (United States)

    Kaiser, Stefan; Walther, Stephan; Nennig, Ernst; Kronmüller, Klaus; Mundt, Christoph; Weisbrod, Matthias; Stippich, Christoph; Vogeley, Kai

    2008-08-01

    In the context of the present study spatial perspective taking refers to the ability to translocate one's own egocentric viewpoint to somebody else's viewpoint in space. We adopted a spatial perspective taking paradigm and performed a functional magnetic resonance imaging study to assess gender differences of neural activity during perspective taking. 24 healthy subjects (12 male/12 female) were asked to systematically either take their own (first-person-perspective, 1PP) or another person's perspective (third-person-perspective, 3PP). Presented stimuli consisted of a virtual scenery with an avatar and red balls around him that had to be counted, if visible, from 1PP or 3PP. Reaction time was increased and correctness scores were decreased during the cognitively more effortful 3PP condition. Correctness scores showed a trend towards a more pronounced decline of performance during 3PP as compared to 1PP in female subjects. Female subjects correctness scores declined by 6.7% from 1PP to 3PP, while in male subjects this performance decline was only 2.7%. Debriefings after the experiment, reaction times depending on angle of rotation and error rates suggest that males are more likely to employ an object-based strategy in contrast to a consistently employed egocentric perspective transformation in females. In the whole group, neural activity was increased in the parieto-occipital, right inferior frontal and supplementary motor areas, confirming previous studies. With respect to gender, male subjects showed stronger activation in the precuneus and the right inferior frontal gyrus than female subjects in a region-of-interest approach. In a subgroup of male subjects whose strategy reports suggest object-based strategies these differences seem to be more pronounced. In conclusion, the differential recruitment of brain regions most likely reflects different strategies in solving this spatial perspective taking task.

  19. Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility

    Science.gov (United States)

    Meredith, David M.; Borromeo, Mark D.; Deering, Tye G.; Casey, Bradford H.; Savage, Trisha K.; Mayer, Paul R.; Hoang, Chinh; Tung, Kuang-Chi; Kumar, Manonmani; Shen, Chengcheng; Swift, Galvin H.

    2013-01-01

    The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 colocalize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA binding of Ptf1a, and they identify Fox and Sox gene families as part of this process. PMID:23754747

  20. A category-specific top-down attentional set can affect the neural responses outside the current focus of attention.

    Science.gov (United States)

    Jiang, Yunpeng; Wu, Xia; Gao, Xiaorong

    2017-10-17

    A top-down set can guide attention to enhance the processing of task-relevant objects. Many studies have found that the top-down set can be tuned to a category level. However, it is unclear whether the category-specific top-down set involving a central search task can exist outside the current area of attentional focus. To directly probe the neural responses inside and outside the current focus of attention, we recorded continuous EEG to measure the contralateral ERP components for central targets and the steady-state visual evoked potential (SSVEP) oscillations associated with a flickering checkerboard placed on the visual periphery. The relationship of color categories between targets and non-targets was manipulated to investigate the effect of category-specific top-down set. Results showed that when the color categories of targets and non-targets in the central search arrays were the same, larger SSVEP oscillations were evoked by target color peripheral checkerboards relative to the non-target color ones outside the current attentional focus. However, when the color categories of targets and non-targets were different, the peripheral checkerboards in two different colors of the same category evoked similar SSVEP oscillations, indicating the effects of category-specific top-down set. These results firstly demonstrate that the category-specific top-down set can affect the neural responses of peripheral distractors. The results could support the idea of a global selection account and challenge the attentional window account in selective attention. Copyright © 2017. Published by Elsevier B.V.

  1. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    Energy Technology Data Exchange (ETDEWEB)

    Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  2. Adolescent-specific patterns of behavior and neural activity during social reinforcement learning

    Science.gov (United States)

    Jones, Rebecca M.; Somerville, Leah H.; Li, Jian; Ruberry, Erika J.; Powers, Alisa; Mehta, Natasha; Dyke, Jonathan; Casey, BJ

    2014-01-01

    Humans are sophisticated social beings. Social cues from others are exceptionally salient, particularly during adolescence. Understanding how adolescents interpret and learn from variable social signals can provide insight into the observed shift in social sensitivity during this period. The current study tested 120 participants between the ages of 8 and 25 years on a social reinforcement learning task where the probability of receiving positive social feedback was parametrically manipulated. Seventy-eight of these participants completed the task during fMRI scanning. Modeling trial-by-trial learning, children and adults showed higher positive learning rates than adolescents, suggesting that adolescents demonstrated less differentiation in their reaction times for peers who provided more positive feedback. Forming expectations about receiving positive social reinforcement correlated with neural activity within the medial prefrontal cortex and ventral striatum across age. Adolescents, unlike children and adults, showed greater insular activity during positive prediction error learning and increased activity in the supplementary motor cortex and the putamen when receiving positive social feedback regardless of the expected outcome, suggesting that peer approval may motivate adolescents towards action. While different amounts of positive social reinforcement enhanced learning in children and adults, all positive social reinforcement equally motivated adolescents. Together, these findings indicate that sensitivity to peer approval during adolescence goes beyond simple reinforcement theory accounts and suggests possible explanations for how peers may motivate adolescent behavior. PMID:24550063

  3. Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease.

    Science.gov (United States)

    Taylor, Alexander N W; Kambeitz-Ilankovic, Lana; Gesierich, Benno; Simon-Vermot, Lee; Franzmeier, Nicolai; Araque Caballero, Miguel Á; Müller, Sophia; Hesheng, Liu; Ertl-Wagner, Birgit; Bürger, Katharina; Weiner, Michael W; Dichgans, Martin; Duering, Marco; Ewers, Michael

    2017-03-01

    White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Generation of Integration-free and Region-Specific Neural Progenitors from Primate Fibroblasts

    Directory of Open Access Journals (Sweden)

    Jianfeng Lu

    2013-05-01

    Full Text Available Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF, transforming growth factor (TGF-β inhibitor SB431542, and glycogen synthase kinase (GSK-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same defined condition, no induced pluripotent stem cell (iPSC colonies formed at either 37°C or 39°C. The iNPs predominantly express hindbrain genes and differentiate into hindbrain neurons, and when caudalized, they produced an enriched population of spinal motor neurons. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. The ability to generate defined, integration-free iNPs from adult primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and therapeutic development.

  5. Neural correlates of conflict between gestures and words: A domain-specific role for a temporal-parietal complex

    National Research Council Canada - National Science Library

    J Adam Noah; Swethasri Dravida; Xian Zhang; Shaul Yahil; Joy Hirsch

    2017-01-01

    .... To gain insight into these underlying neural processes, we compared neural responses in a traditional color/word conflict task and to a gesture/word conflict task to test hypotheses of domain-general...

  6. Differential Neural Activity during Search of Specific and General Autobiographical Memories Elicited by Musical Cues

    Science.gov (United States)

    Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S.

    2011-01-01

    Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime…

  7. The specificity of neural responses to music and their relation to voice processing: an fMRI-adaptation study.

    Science.gov (United States)

    Armony, Jorge L; Aubé, William; Angulo-Perkins, Arafat; Peretz, Isabelle; Concha, Luis

    2015-04-23

    Several studies have identified, using functional magnetic resonance imaging (fMRI), a region within the superior temporal gyrus that preferentially responds to musical stimuli. However, in most cases, significant responses to other complex stimuli, particularly human voice, were also observed. Thus, it remains unknown if the same neurons respond to both stimulus types, albeit with different strengths, or whether the responses observed with fMRI are generated by distinct, overlapping neural populations. To address this question, we conducted an fMRI experiment in which short music excerpts and human vocalizations were presented in a pseudo-random order. Critically, we performed an adaptation-based analysis in which responses to the stimuli were analyzed taking into account the category of the preceding stimulus. Our results confirm the presence of a region in the anterior STG that responds more strongly to music than voice. Moreover, we found a music-specific adaptation effect in this area, consistent with the existence of music-preferred neurons. Lack of differences between musicians and non-musicians argues against an expertise effect. These findings provide further support for neural separability between music and speech within the temporal lobe. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders

    Science.gov (United States)

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

    2015-01-01

    Background Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders and those distinct to a particular diagnosis. Aims To delineate common and distinct abnormalities within generalised anxiety (GAD), panic and social anxiety disorder (SAD) during affective processing. Method Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic resonance imaging while completing a facial emotion matching task with fearful, angry and happy faces. Results Greater differential right amygdala activation to matching fearful v. happy facial expressions related to greater negative affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder groups compared with controls. Collapsing across emotional face types, participants with panic disorder uniquely displayed greater posterior insula activation. Conclusions These preliminary results highlight a common neural basis for clinical anxiety in these diagnoses and also suggest the presence of disorder-specific dysfunction. PMID:25573399

  9. Prokaryotic expression, purification, and production of glutathione S-transferase-tagged neural stem cell specific peptides from phage display screening.

    Science.gov (United States)

    Jin, Lei; Zhao, Wenxiu; Ma, Lan

    2013-02-01

    Combining stem cell with phage display to discover novel biomarkers is a new field in stem cell studies. Novel peptides obtained through phage display panning have been functionally identified and involved into initial applications as cell culture support or cell label. In the present study, we designed a glutathione S-transferase (GST)-tagged peptide complex to construct an easy and efficient prokaryotic expression and purification platform for peptides obtained from phage display panning. The purified GST-peptide protein could specifically bind to neural stem (NS) cells and could be flexibly used for GST pull down assay or NS cell labeling in future studies. The results of the present study would be useful for cell labeling and future investigations of special receptors on stem cell surface.

  10. Neural-specific deletion of Htra2 causes cerebellar neurodegeneration and defective processing of mitochondrial OPA1.

    Science.gov (United States)

    Patterson, Victoria L; Zullo, Alfred J; Koenig, Claire; Stoessel, Sean; Jo, Hakryul; Liu, Xinran; Han, Jinah; Choi, Murim; DeWan, Andrew T; Thomas, Jean-Leon; Kuan, Chia-Yi; Hoh, Josephine

    2014-01-01

    HTRA2, a serine protease in the intermembrane space, has important functions in mitochondrial stress signaling while its abnormal activity may contribute to the development of Parkinson's disease. Mice with a missense or null mutation of Htra2 fail to thrive, suffer striatal neuronal loss, and a parkinsonian phenotype that leads to death at 30-40 days of age. While informative, these mouse models cannot separate neural contributions from systemic effects due to the complex phenotypes of HTRA2 deficiency. Hence, we developed mice carrying a Htra2-floxed allele to query the consequences of tissue-specific HTRA2 deficiency. We found that mice with neural-specific deletion of Htra2 exhibited atrophy of the thymus and spleen, cessation to gain weight past postnatal (P) day 18, neurological symptoms including ataxia and complete penetrance of premature death by P40. Histologically, increased apoptosis was detected in the cerebellum, and to a lesser degree in the striatum and the entorhinal cortex, from P25. Even earlier at P20, mitochondria in the cerebella already exhibited abnormal morphology, including swelling, vesiculation, and fragmentation of the cristae. Furthermore, the onset of these structural anomalies was accompanied by defective processing of OPA1, a key molecule for mitochondrial fusion and cristae remodeling, leading to depletion of the L-isoform. Together, these findings suggest that HTRA2 is essential for maintenance of the mitochondrial integrity in neurons. Without functional HTRA2, a lifespan as short as 40 days accumulates a large quantity of dysfunctional mitochondria that contributes to the demise of mutant mice.

  11. Neural-specific deletion of Htra2 causes cerebellar neurodegeneration and defective processing of mitochondrial OPA1.

    Directory of Open Access Journals (Sweden)

    Victoria L Patterson

    Full Text Available HTRA2, a serine protease in the intermembrane space, has important functions in mitochondrial stress signaling while its abnormal activity may contribute to the development of Parkinson's disease. Mice with a missense or null mutation of Htra2 fail to thrive, suffer striatal neuronal loss, and a parkinsonian phenotype that leads to death at 30-40 days of age. While informative, these mouse models cannot separate neural contributions from systemic effects due to the complex phenotypes of HTRA2 deficiency. Hence, we developed mice carrying a Htra2-floxed allele to query the consequences of tissue-specific HTRA2 deficiency. We found that mice with neural-specific deletion of Htra2 exhibited atrophy of the thymus and spleen, cessation to gain weight past postnatal (P day 18, neurological symptoms including ataxia and complete penetrance of premature death by P40. Histologically, increased apoptosis was detected in the cerebellum, and to a lesser degree in the striatum and the entorhinal cortex, from P25. Even earlier at P20, mitochondria in the cerebella already exhibited abnormal morphology, including swelling, vesiculation, and fragmentation of the cristae. Furthermore, the onset of these structural anomalies was accompanied by defective processing of OPA1, a key molecule for mitochondrial fusion and cristae remodeling, leading to depletion of the L-isoform. Together, these findings suggest that HTRA2 is essential for maintenance of the mitochondrial integrity in neurons. Without functional HTRA2, a lifespan as short as 40 days accumulates a large quantity of dysfunctional mitochondria that contributes to the demise of mutant mice.

  12. Sensitive and specific peak detection for SELDI-TOF mass spectrometry using a wavelet/neural-network based approach.

    Directory of Open Access Journals (Sweden)

    Vincent A Emanuele

    Full Text Available SELDI-TOF mass spectrometer's compact size and automated, high throughput design have been attractive to clinical researchers, and the platform has seen steady-use in biomarker studies. Despite new algorithms and preprocessing pipelines that have been developed to address reproducibility issues, visual inspection of the results of SELDI spectra preprocessing by the best algorithms still shows miscalled peaks and systematic sources of error. This suggests that there continues to be problems with SELDI preprocessing. In this work, we study the preprocessing of SELDI in detail and introduce improvements. While many algorithms, including the vendor supplied software, can identify peak clusters of specific mass (or m/z in groups of spectra with high specificity and low false discover rate (FDR, the algorithms tend to underperform estimating the exact prevalence and intensity of peaks in those clusters. Thus group differences that at first appear very strong are shown, after careful and laborious hand inspection of the spectra, to be less than significant. Here we introduce a wavelet/neural network based algorithm which mimics what a team of expert, human users would call for peaks in each of several hundred spectra in a typical SELDI clinical study. The wavelet denoising part of the algorithm optimally smoothes the signal in each spectrum according to an improved suite of signal processing algorithms previously reported (the LibSELDI toolbox under development. The neural network part of the algorithm combines those results with the raw signal and a training dataset of expertly called peaks, to call peaks in a test set of spectra with approximately 95% accuracy. The new method was applied to data collected from a study of cervical mucus for the early detection of cervical cancer in HPV infected women. The method shows promise in addressing the ongoing SELDI reproducibility issues.

  13. Effects of category-specific costs on neural systems for perceptual decision-making

    DEFF Research Database (Denmark)

    Fleming, Stephen M; Whiteley, Louise Emma; Hulme, Oliver James

    2010-01-01

    Perceptual judgments are often biased by prospective losses, leading to changes in decision criteria. Little is known about how and where sensory evidence and cost information interact in the brain to influence perceptual categorization. Here we show that prospective losses systematically bias...... the perception of noisy face-house images. Asymmetries in category-specific cost were associated with enhanced blood-oxygen-level-dependent signal in a frontoparietal network. We observed selective activation of parahippocampal gyrus for changes in category-specific cost in keeping with the hypothesis that loss...... functions enact a particular task set that is communicated to visual regions. Across subjects, greater shifts in decision criteria were associated with greater activation of the anterior cingulate cortex (ACC). Our results support a hypothesis that costs bias an intermediate representation between...

  14. Neural correlates of conflict between gestures and words: A domain-specific role for a temporal-parietal complex.

    Directory of Open Access Journals (Sweden)

    J Adam Noah

    Full Text Available The interpretation of social cues is a fundamental function of human social behavior, and resolution of inconsistencies between spoken and gestural cues plays an important role in successful interactions. To gain insight into these underlying neural processes, we compared neural responses in a traditional color/word conflict task and to a gesture/word conflict task to test hypotheses of domain-general and domain-specific conflict resolution. In the gesture task, recorded spoken words ("yes" and "no" were presented simultaneously with video recordings of actors performing one of the following affirmative or negative gestures: thumbs up, thumbs down, head nodding (up and down, or head shaking (side-to-side, thereby generating congruent and incongruent communication stimuli between gesture and words. Participants identified the communicative intent of the gestures as either positive or negative. In the color task, participants were presented the words "red" and "green" in either red or green font and were asked to identify the color of the letters. We observed a classic "Stroop" behavioral interference effect, with participants showing increased response time for incongruent trials relative to congruent ones for both the gesture and color tasks. Hemodynamic signals acquired using functional near-infrared spectroscopy (fNIRS were increased in the right dorsolateral prefrontal cortex (DLPFC for incongruent trials relative to congruent trials for both tasks consistent with a common, domain-general mechanism for detecting conflict. However, activity in the left DLPFC and frontal eye fields and the right temporal-parietal junction (TPJ, superior temporal gyrus (STG, supramarginal gyrus (SMG, and primary and auditory association cortices was greater for the gesture task than the color task. Thus, in addition to domain-general conflict processing mechanisms, as suggested by common engagement of right DLPFC, socially specialized neural modules localized to

  15. Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

    2017-12-29

    Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. A realistic neural mass model of the cortex with laminar-specific connections and synaptic plasticity - evaluation with auditory habituation.

    Directory of Open Access Journals (Sweden)

    Peng Wang

    Full Text Available In this work we propose a biologically realistic local cortical circuit model (LCCM, based on neural masses, that incorporates important aspects of the functional organization of the brain that have not been covered by previous models: (1 activity dependent plasticity of excitatory synaptic couplings via depleting and recycling of neurotransmitters and (2 realistic inter-laminar dynamics via laminar-specific distribution of and connections between neural populations. The potential of the LCCM was demonstrated by accounting for the process of auditory habituation. The model parameters were specified using Bayesian inference. It was found that: (1 besides the major serial excitatory information pathway (layer 4 to layer 2/3 to layer 5/6, there exists a parallel "short-cut" pathway (layer 4 to layer 5/6, (2 the excitatory signal flow from the pyramidal cells to the inhibitory interneurons seems to be more intra-laminar while, in contrast, the inhibitory signal flow from inhibitory interneurons to the pyramidal cells seems to be both intra- and inter-laminar, and (3 the habituation rates of the connections are unsymmetrical: forward connections (from layer 4 to layer 2/3 are more strongly habituated than backward connections (from Layer 5/6 to layer 4. Our evaluation demonstrates that the novel features of the LCCM are of crucial importance for mechanistic explanations of brain function. The incorporation of these features into a mass model makes them applicable to modeling based on macroscopic data (like EEG or MEG, which are usually available in human experiments. Our LCCM is therefore a valuable building block for future realistic models of human cognitive function.

  17. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kristen J. Brennand

    2015-12-01

    Full Text Available As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  18. Gender-specific differences between the concentrations of nonvolatile (R)/(S)-3-methyl-3-sulfanylhexan-1-Ol and (R)/(S)-3-hydroxy-3-methyl-hexanoic acid odor precursors in axillary secretions.

    Science.gov (United States)

    Troccaz, Myriam; Borchard, Gerrit; Vuilleumier, Christine; Raviot-Derrien, Sophie; Niclass, Yvan; Beccucci, Sabine; Starkenmann, Christian

    2009-03-01

    The volatile fatty acid, (R)/(S)-3-hydroxy-3-methylhexanoic acid ((R)/(S)-HMHA), and the human specific volatile thiol, (R)/(S)-3-methyl-3-sulfanylhexan-1-ol ((R)/(S)-MSH), were recently identified as major components of human sweat malodor. Their 2 corresponding precursors were subsequently isolated from sterile and odorless axillary secretions. The purpose of this work was to analyze these 2 odor precursors in 49 male and female volunteers over a period of 3 years to elucidate to which extent they are implicated in the gender-specific character of body odor. Surprisingly, the ratio between the acid precursor 1, a glutamine conjugate, and the "sulfur" precursor 2, a cysteinylglycine-S-conjugate, was 3 times higher in men than in women with no correlation with either the sweat volume or the protein concentration. Indeed, women have the potential to liberate significantly more (R)/(S)-MSH, which has a tropical fruit- and onion-like odor than (R)/(S)-HMHA (possibly transformed into (E)/(Z)-3-methyl-2-hexenoic acid) that has a cheesy, rancid odor. Parallel to this work, sensory analysis on sweat incubated with isolated skin bacteria (Staphylococcus epidermidis Ax3, Corynebacterium jeikeium American Type Culture Collection 43217, or Staphylococcus haemolyticus Ax4) confirmed that intrinsic composition of sweat is important for the development of body odors and may be modulated by gender differences in bacterial compositions. Sweat samples having the highest sulfur intensity were also found to be the most intense and the most unpleasant.

  19. Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders

    National Research Council Canada - National Science Library

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

    2015-01-01

    Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders...

  20. Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth

    Science.gov (United States)

    Jennemann, Richard; Sandhoff, Roger; Wang, Shijun; Kiss, Eva; Gretz, Norbert; Zuliani, Cecilia; Martin-Villalba, Ana; Jäger, Richard; Schorle, Hubert; Kenzelmann, Marc; Bonrouhi, Mahnaz; Wiegandt, Herbert; Gröne, Hermann-Josef

    2005-01-01

    Sialic acid-containing glycosphingolipids, i.e., gangliosides, constitute a major component of neuronal cells and are thought to be essential for brain function. UDP-glucose:ceramide glucosyltransferase (Ugcg) catalyzes the initial step of glycosphingolipid (GSL) biosynthesis. To gain insight into the role of GSLs in brain development and function, a cell-specific disruption of Ugcg was performed as indicated by the absence of virtually all glucosylceramide-based GSLs. Shortly after birth, mice showed dysfunction of cerebellum and peripheral nerves, associated with structural defects. Axon branching of Purkinje cells was significantly reduced. In primary cultures of neurons, dendritic complexity was clearly diminished, and pruning occurred early. Myelin sheaths of peripheral nerves were broadened and focally severely disorganized. GSL deficiency also led to a down-regulation of gene expression sets involved in brain development and homeostasis. Mice died ≈3 weeks after birth. These results imply that GSLs are essential for brain maturation. PMID:16109770

  1. Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

    Science.gov (United States)

    Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

    2017-09-05

    In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Facilitation of Memory Encoding in Primate Hippocampus by a Neuroprosthesis that Promotes Task Specific Neural Firing

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Opris, Ioan; Santos, Lucas M.; Shin, Dae C.; Gerhardt, Greg A.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2014-01-01

    Objective Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s’, aging and dementia resulting from impaired hippocampal function in medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach NHPs trained to perform a short-term delayed match to sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main Results The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for successful encoding of Sample phase information on more difficult DMS trials. This was validated by delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the Sample phase which facilitated task performance in the subsequent delayed Match phase on difficult trials that required more precise encoding of Sample information. Significance These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain. PMID:24216292

  4. Electrophysiological evidence for a specific neural correlate of musical violation expectation in primary-school children.

    Science.gov (United States)

    James, Clara E; Cereghetti, Donato M; Roullet Tribes, Elodie; Oechslin, Mathias S

    2015-01-01

    The majority of studies on music processing in children used simple musical stimuli. Here, primary schoolchildren judged the appropriateness of musical closure in expressive polyphone music, while high-density electroencephalography was recorded. Stimuli ended either regularly or contained refined in-key harmonic transgressions at closure. The children discriminated the transgressions well above chance. Regular and transgressed endings evoked opposite scalp voltage configurations peaking around 400ms after stimulus onset with bilateral frontal negativity for regular and centro-posterior negativity (CPN) for transgressed endings. A positive correlation could be established between strength of the CPN response and rater sensitivity (d-prime). We also investigated whether the capacity to discriminate the transgressions was supported by auditory domain specific or general cognitive mechanisms, and found that working memory capacity predicted transgression discrimination. Latency and distribution of the CPN are reminiscent of the N400, typically observed in response to semantic incongruities in language. Therefore our observation is intriguing, as the CPN occurred here within an intra-musical context, without any symbols referring to the external world. Moreover, the harmonic in-key transgressions that we implemented may be considered syntactical as they transgress structural rules. Such structural incongruities in music are typically followed by an early right anterior negativity (ERAN) and an N5, but not so here. Putative contributive sources of the CPN were localized in left pre-motor, mid-posterior cingulate and superior parietal regions of the brain that can be linked to integration processing. These results suggest that, at least in children, processing of syntax and meaning may coincide in complex intra-musical contexts. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A Smaug2-Based Translational Repression Complex Determines the Balance between Precursor Maintenance versus Differentiation during Mammalian Neurogenesis.

    Science.gov (United States)

    Amadei, Gianluca; Zander, Mark A; Yang, Guang; Dumelie, Jason G; Vessey, John P; Lipshitz, Howard D; Smibert, Craig A; Kaplan, David R; Miller, Freda D

    2015-11-25

    Here, we have asked about post-transcriptional mechanisms regulating murine developmental neurogenesis, focusing upon the RNA-binding proteins Smaug2 and Nanos1. We identify, in embryonic neural precursors of the murine cortex, a Smaug2 protein/nanos1 mRNA complex that is present in cytoplasmic granules with the translational repression proteins Dcp1 and 4E-T. We show that Smaug2 inhibits and Nanos1 promotes neurogenesis, with Smaug2 knockdown enhancing neurogenesis and depleting precursors, and Nanos1 knockdown inhibiting neurogenesis and maintaining precursors. Moreover, we show that Smaug2 likely regulates neurogenesis by silencing nanos1 mRNA. Specifically, Smaug2 knockdown inappropriately increases Nanos1 protein, and the Smaug2 knockdown-mediated neurogenesis is rescued by preventing this increase. Thus, Smaug2 and Nanos1 function as a bimodal translational repression switch to control neurogenesis, with Smaug2 acting in transcriptionally primed precursors to silence mRNAs important for neurogenesis, including nanos1 mRNA, and Nanos1 acting during the transition to neurons to repress the precursor state. The mechanisms instructing neural stem cells to generate the appropriate progeny are still poorly understood. Here, we show that the RNA-binding proteins Smaug2 and Nanos1 are critical regulators of this balance and provide evidence supporting the idea that neural precursors are transcriptionally primed to generate neurons but translational regulation maintains these precursors in a stem cell state until the appropriate developmental time. Copyright © 2015 the authors 0270-6474/15/3515666-16$15.00/0.

  6. Wireless hippocampal neural recording via a multiple input RF receiver to construct place-specific firing fields.

    Science.gov (United States)

    Lee, Seung Bae; Manns, Joseph R; Ghovanloo, Maysam

    2012-01-01

    This paper reports scientifically meaningful in vivo experiments using a 32-channel wireless neural recording system (WINeR). The WINeR system is divided into transmitter (Tx) and receiver (Rx) parts. On the Tx side, we had WINeR-6, a system-on-a-chip (SoC) that operated based on time division multiplexing (TDM) of pulse width modulated (PWM) samples. The chip was fabricated in a 0.5-µm CMOS process, occupying 4.9 × 3.3 mm(2) and consuming 15 mW from ±1.5V supplies. The Rx used two antennas with separate pathways to down-convert the RF signal from a large area. A time-to-digital converter (TDC) in an FPGA converted the PWM pulses into digitized samples. In order to further increase the wireless coverage area and eliminate blind spots within a large experimental arena, two receivers were synchronized. The WINeR system was used to record epileptic activities from a rat that was injected with tetanus toxin (TT) in the dorsal hippocampus. In a different in vivo experiment, place-specific firing fields of place cells, which are parts of the hippocampal-dependent memory, were mapped from a series of behavioral experiments from a rat running in a circular track. Results from the same animal were compared against a commercial hard-wired recording system to evaluate the quality of the wireless recordings.

  7. Structural Basis for Partial Redundancy in a Class of Transcription Factors, the LIM Homeodomain Proteins, in Neural Cell Type Specification*

    Science.gov (United States)

    Gadd, Morgan S.; Bhati, Mugdha; Jeffries, Cy M.; Langley, David B.; Trewhella, Jill; Guss, J. Mitchell; Matthews, Jacqueline M.

    2011-01-01

    Combinations of LIM homeodomain proteins form a transcriptional “LIM code” to direct the specification of neural cell types. Two paralogous pairs of LIM homeodomain proteins, LIM homeobox protein 3/4 (Lhx3/Lhx4) and Islet-1/2 (Isl1/Isl2), are expressed in developing ventral motor neurons. Lhx3 and Isl1 interact within a well characterized transcriptional complex that triggers motor neuron development, but it was not known whether Lhx4 and Isl2 could participate in equivalent complexes. We have identified an Lhx3-binding domain (LBD) in Isl2 based on sequence homology with the Isl1LBD and show that both Isl2LBD and Isl1LBD can bind each of Lhx3 and Lhx4. X-ray crystal- and small-angle x-ray scattering-derived solution structures of an Lhx4·Isl2 complex exhibit many similarities with that of Lhx3·Isl1; however, structural differences supported by mutagenic studies reveal differences in the mechanisms of binding. Differences in binding have implications for the mode of exchange of protein partners in transcriptional complexes and indicate a divergence in functions of Lhx3/4 and Isl1/2. The formation of weaker Lhx·Isl complexes would likely be masked by the availability of the other Lhx·Isl complexes in postmitotic motor neurons. PMID:22025611

  8. Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation.

    Science.gov (United States)

    Droms, K; Sueoka, N

    1987-01-01

    This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of three derivative cell types, RT4-B, RT4-D, or RT4-E, with a frequency of about 10(-5). The RT4-AC cells express some properties characteristic of both neuronal and glial cells. Of these neural properties expressed by RT4-AC cells, only the neuronal properties are expressed by the RT4-B and RT4-E cells, and only the glial properties are expressed by the RT4-D cells. This in vitro cell-type conversion of RT4-AC to three derivative cell types is a branch point for the coordinate regulation of several properties and seems to resemble determination in vivo. In our standard culture conditions, several other neuronal and glial properties are not expressed by these cell types. However, addition of dibutyryl-cAMP induces expression of additional properties, in a cell-type-specific manner: formation of long cellular processes in the RT4-B8 and RT4-E5 cell lines and expression of high-affinity uptake of gamma-aminobutyric acid, by a glial-cell-specific mechanism, in the RT4-D6-2 cell line. These new properties are maximally expressed 2-3 days after addition of dibutyryl-cAMP. This indicates that conversion of RT4-AC to the derivative cell types is also a branch point for the regulation of cell-type-specific properties whose expression is responsive to cAMP. Thus, the potential for maturation in response to increased cAMP is a property that segregates in a cell-type-specific manner and is activated at the determinational level in this system. Images PMID:3029777

  9. Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

    Science.gov (United States)

    Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

    2018-03-01

    Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

  10. Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

    NARCIS (Netherlands)

    Fernandez, G.S.E.; Weis, S.; Stoffel-Wagner, B.; Tendolkar, I.; Reuber, M.; Beyenburg, S.; Klaver, P.; Fell, J.; Greiff, A. de; Ruhlmann, J.; Reul, J.; Elger, C.E.

    2003-01-01

    In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle

  11. Increased secreted amyloid precursor protein-α (sAPPα in severe autism: proposal of a specific, anabolic pathway and putative biomarker.

    Directory of Open Access Journals (Sweden)

    Balmiki Ray

    Full Text Available Autism is a neurodevelopmental disorder characterized by deficits in verbal communication, social interactions, and the presence of repetitive, stereotyped and compulsive behaviors. Excessive early brain growth is found commonly in some patients and may contribute to disease phenotype. Reports of increased levels of brain-derived neurotrophic factor (BDNF and other neurotrophic-like factors in autistic neonates suggest that enhanced anabolic activity in CNS mediates this overgrowth effect. We have shown previously that in a subset of patients with severe autism and aggression, plasma levels of the secreted amyloid-β (Aβ precursor protein-alpha form (sAPPα were significantly elevated relative to controls and patients with mild-to-moderate autism. Here we further tested the hypothesis that levels of sAPPα and sAPPβ (proteolytic cleavage products of APP by α- and β-secretase, respectively are deranged in autism and may contribute to an anabolic environment leading to brain overgrowth. We measured plasma levels of sAPPα, sAPPβ, Aβ peptides and BDNF by corresponding ELISA in a well characterized set of subjects. We included for analysis 18 control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We have observed that sAPPα levels are increased and BDNF levels decreased in the plasma of patients with severe autism as compared to controls. Further, we show that Aβ1-40, Aβ1-42, and sAPPβ levels are significantly decreased in the plasma of patients with severe autism. These findings do not extend to patients with mild-to-moderate autism, providing a biochemical correlate of phenotypic severity. Taken together, this study provides evidence that sAPPα levels are generally elevated in severe autism and suggests that these patients may have aberrant non-amyloidogenic processing of APP.

  12. Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

    Science.gov (United States)

    Touyarot, K.; Sandi, C.

    2002-01-01

    Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

  13. Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene.

    Science.gov (United States)

    Sawamoto, K; Nakao, N; Kakishita, K; Ogawa, Y; Toyama, Y; Yamamoto, A; Yamaguchi, M; Mori, K; Goldman, S A; Itakura, T; Okano, H

    2001-06-01

    Mesencephalic precursor cells may one day provide dopaminergic neurons for the treatment of Parkinson's disease. However, the generation of dopaminergic neurons from mesencephalic precursors has been difficult to follow, partly because an appropriate means for recognizing mesencephalic ventricular zone precursors has not been available. To visualize and isolate mesencephalic precursor cells from a mixed population, we used transgenic mice and rats carrying green fluorescent protein (GFP) cDNA under the control of the nestin enhancer. nestin-driven GFP was detected in the mesencephalic ventricular zone, and it colocalized with specific markers for neural precursor cells. In addition, data from flow-cytometry indicated that Prominin/CD133, a cell-surface marker for ventricular zone cells, was expressed specifically in these GFP-positive (GFP(+)) cells. After sorting by fluorescence-activated cell sorting, the GFP(+) cells proliferated in vitro and expressed precursor cell markers but not neuronal markers. Using clonogenic sphere formation assays, we showed that this sorted population was enriched in multipotent precursor cells that could differentiate into both neurons and glia. Importantly, many neurons generated from nestin-GFP-sorted mesencephalic precursors developed a dopaminergic phenotype in vitro. Finally, nestin-GFP(+) cells were transplanted into the striatum of a rat model of Parkinson's disease. Bromodeoxyuridine-tyrosine hydroxylase double-labeling revealed that the transplanted cells generated new dopaminergic neurons within the host striatum. The implanted cells were able to restore dopaminergic function in the host striatum, as assessed by a behavioral measure: recovery from amphetamine-induced rotation. Together, these findings indicate that precursor cells harvested from the embryonic ventral mesencephalon can generate dopaminergic neurons able to restore function to the chemically denervated adult striatum.

  14. Annotation of novel neuropeptide precursors in the migratory locust based on transcript screening of a public EST database and mass spectrometry

    Directory of Open Access Journals (Sweden)

    De Loof Arnold

    2006-08-01

    Full Text Available Abstract Background For holometabolous insects there has been an explosion of proteomic and peptidomic information thanks to large genome sequencing projects. Heterometabolous insects, although comprising many important species, have been far less studied. The migratory locust Locusta migratoria, a heterometabolous insect, is one of the most infamous agricultural pests. They undergo a well-known and profound phase transition from the relatively harmless solitary form to a ferocious gregarious form. The underlying regulatory mechanisms of this phase transition are not fully understood, but it is undoubtedly that neuropeptides are involved. However, neuropeptide research in locusts is hampered by the absence of genomic information. Results Recently, EST (Expressed Sequence Tag databases from Locusta migratoria were constructed. Using bioinformatical tools, we searched these EST databases specifically for neuropeptide precursors. Based on known locust neuropeptide sequences, we confirmed the sequence of several previously identified neuropeptide precursors (i.e. pacifastin-related peptides, which consolidated our method. In addition, we found two novel neuroparsin precursors and annotated the hitherto unknown tachykinin precursor. Besides one of the known tachykinin peptides, this EST contained an additional tachykinin-like sequence. Using neuropeptide precursors from Drosophila melanogaster as a query, we succeeded in annotating the Locusta neuropeptide F, allatostatin-C and ecdysis-triggering hormone precursor, which until now had not been identified in locusts or in any other heterometabolous insect. For the tachykinin precursor, the ecdysis-triggering hormone precursor and the allatostatin-C precursor, translation of the predicted neuropeptides in neural tissues was confirmed with mass spectrometric techniques. Conclusion In this study we describe the annotation of 6 novel neuropeptide precursors and the neuropeptides they encode from the

  15. Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation.

    Directory of Open Access Journals (Sweden)

    David Zada

    2014-09-01

    Full Text Available The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2 gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8-/- zebrafish using zinc-finger nuclease (ZFN-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8-/- larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8-/- larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8-/- larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8-/- larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit

  16. Precursors and BRST symmetry

    Science.gov (United States)

    de Boer, Jan; Freivogel, Ben; Kabir, Laurens; Lokhande, Sagar F.

    2017-07-01

    In the AdS/CFT correspondence, bulk information appears to be encoded in the CFT in a redundant way. A local bulk field corresponds to many different non-local CFT operators (precursors). We recast this ambiguity in the language of BRST symmetry, and propose that in the large N limit, the difference between two precursors is a BRST exact and ghost-free term. This definition of precursor ambiguities has the advantage that it generalizes to any gauge theory. Using the BRST formalism and working in a simple model with global symmetries, we re-derive a precursor ambiguity appearing in earlier work. Finally, we show within this model that the obtained ambiguity has the right number of parameters to explain the freedom to localize precursors within different spatial regions of the boundary order by order in the large N expansion.

  17. Neural Activation During Cognitive Emotion Regulation in Previously Depressed Compared to Healthy Children: Evidence of Specific Alterations.

    Science.gov (United States)

    Belden, Andy C; Pagliaccio, David; Murphy, Eric R; Luby, Joan L; Barch, Deanna M

    2015-09-01

    Impairments in cognitive emotion regulation (CER) have been linked to functional neural abnormalities and the pathogenesis of major depressive disorder (MDD). Few functional magnetic resonance imaging (fMRI) studies have investigated the neural underpinnings of CER in samples with depression. As CER develops in childhood, understanding dysfunctional CER-related alterations in brain function during this period could advance knowledge of the developmental psychopathology of MDD. This study tested whether neural activity in brain regions known to support cognitive reappraisal differed between healthy 7- to 15-year-old children and same-age peers with a history of MDD (MDD-ever). A total of 64 children participated in this event-related fMRI study, which used a developmentally appropriate and validated fMRI reappraisal task. Children were instructed to passively view sad or neutral images and to decrease negative emotions using cognitive reappraisal. MDD-ever and healthy children showed similar patterns of cortical activation during reappraisal, but with a significant difference found in 1 key CER region, the left inferior frontal gyrus (IFG). In addition, individual differences in CER were associated with left IFG activity during reappraisal. Alterations in the neurocircuitry of reappraisal are evident in children with a depression history compared to healthy controls. The finding that MDD-ever children showed reappraisal-related neural responses in many regions similar to healthy controls has clinical implications. Findings suggest that identification of alterations in reappraisal in children with remitted depression, for whom much, although not all, of the neural circuitry remains intact, may be an important window of opportunity for intervention. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Low-level neural auditory discrimination dysfunctions in specific language impairment—A review on mismatch negativity findings

    Directory of Open Access Journals (Sweden)

    Teija Kujala

    2017-12-01

    Full Text Available In specific language impairment (SLI, there is a delay in the child’s oral language skills when compared with nonverbal cognitive abilities. The problems typically relate to phonological and morphological processing and word learning. This article reviews studies which have used mismatch negativity (MMN in investigating low-level neural auditory dysfunctions in this disorder. With MMN, it is possible to tap the accuracy of neural sound discrimination and sensory memory functions. These studies have found smaller response amplitudes and longer latencies for speech and non-speech sound changes in children with SLI than in typically developing children, suggesting impaired and slow auditory discrimination in SLI. Furthermore, they suggest shortened sensory memory duration and vulnerability of the sensory memory to masking effects. Importantly, some studies reported associations between MMN parameters and language test measures. In addition, it was found that language intervention can influence the abnormal MMN in children with SLI, enhancing its amplitude. These results suggest that the MMN can shed light on the neural basis of various auditory and memory impairments in SLI, which are likely to influence speech perception. Keywords: Specific language impairment, Auditory processing, Mismatch negativity (MMN

  19. Cleavage of intron from the standard or non-standard position of the precursor tRNA by the splicing endonuclease of Aeropyrum pernix, a hyper-thermophilic Crenarchaeon, involves a novel RNA recognition site in the Crenarchaea specific loop.

    Science.gov (United States)

    Hirata, Akira; Kitajima, Tsubasa; Hori, Hiroyuki

    2011-11-01

    In Crenarchaea, several tRNA genes are predicted to express precursor-tRNAs (pre-tRNAs) with canonical or non-canonical introns at various positions. We initially focused on the tRNA(Thr) species of hyperthermophilic crenarchaeon, Aeropyrum pernix (APE) and found that in the living APE cells three tRNA(Thr) species were transcribed and subsequently matured to functional tRNAs. During maturation, introns in two of them were cleaved from standard and non-standard positions. Biochemical studies revealed that the APE splicing endonuclease (APE-EndA) removed both types of introns, including the non-canonical introns, without any nucleotide modification. To clarify the underlying reasons for broad substrate specificity of APE-EndA, we determined the crystal structure of wild-type APE-EndA and subsequently compared its structure with that of Archaeaoglobus fulgidus (AFU)-EndA, which has narrow substrate specificity. Remarkably, structural comparison revealed that APE-EndA possesses a Crenarchaea specific loop (CSL). Introduction of CSL into AFU-EndA enhanced its intron-cleaving activity irrespective of the position or motif of the intron. Thus, our biochemical and crystallographic analyses of the chimera-EndA demonstrated that the CSL is responsible for the broad substrate specificity of APE-EndA. Furthermore, mutagenesis studies revealed that Lys44 in CSL functions as the RNA recognition site.

  20. Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts.

    Science.gov (United States)

    Bayer, Ronny; Franke, Heike; Ficker, Christoph; Richter, Monique; Lessig, Rüdiger; Büttner, Andreas; Weber, Marco

    2015-11-01

    Adult neurogenesis has been shown to occur throughout life and different brain pathologies were demonstrated to be associated with altered neurogenesis. Here, an impact of heroin addiction on neurogenesis in humans is hypothesised. Post mortem hippocampal specimens of drug addicts with known heroin abuse and a group of non-addictive control subjects were analysed, using antibodies indicating different stages of neurogenesis. The subgranular zone of the dentate gyrus was examined qualitatively and quantitatively. The data indicate (i) a decreased number of neural precursor cells, (ii) accompanied by low rates of proliferation and (iii) a marked loss of dendritic trees in targeting cells in heroin fatalities. (iv) The age-dependent increase of differentiating cells in the healthy controls was not observed in the addicts. Additionally, double immunofluorescence labelling indicated the precursor nature of Musashi-1 positive cells in the human subgranular zone of the dentate gyrus. Present data firstly demonstrate the influence of drug addiction with known heroin abuse on different developmental stages of progenitors in the dentate gyrus. The patterns of antibody staining suggest a distinct inhibition of neurogenesis at the stage of neural precursor cells and revealed morphological changes in targeting cells in cases of heroin addicts as compared to healthy controls. These alterations could be considerable for memory and cognitive deficits as well as addictive behaviour in chronic drug abusers and may give rise to specific pro-neurogenic therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Parental phonological memory contributes to prediction of outcome of late talkers from 20 months to 4 years: a longitudinal study of precursors of specific language impairment

    Directory of Open Access Journals (Sweden)

    Bishop Dorothy VM

    2012-02-01

    Full Text Available Abstract Background Many children who are late talkers go on to develop normal language, but others go on to have longer-term language difficulties. In this study, we considered which factors were predictive of persistent problems in late talkers. Methods Parental report of expressive vocabulary at 18 months of age was used to select 26 late talkers and 70 average talkers, who were assessed for language and cognitive ability at 20 months of age. Follow-up at 4 years of age was carried out for 24 late and 58 average talkers. A psychometric test battery was used to categorize children in terms of language status (unimpaired or impaired and nonverbal ability (normal range or more than 1 SD below average. The vocabulary and non-word repetition skills of the accompanying parent were also assessed. Results Among the late talkers, seven (29% met our criteria for specific language impairment (SLI at 4 years of age, and a further two (8% had low nonverbal ability. In the group of average talkers, eight (14% met the criteria for SLI at 4 years, and five other children (8% had low nonverbal ability. Family history of language problems was slightly better than late-talker status as a predictor of SLI.. The best predictors of SLI at 20 months of age were score on the receptive language scale of the Mullen Scales of Early Learning and the parent's performance on a non-word repetition task. Maternal education was not a significant predictor of outcome. Conclusions In this study, around three-quarters of late talkers did not have any language difficulties at 4 years of age, provided there was no family history of language impairment. A family history of language-literacy problems was found to be a significant predictor for persisting problems. Nevertheless, there are children with SLI for whom prediction is difficult because they did not have early language delay.

  2. Earthquakes: hydrogeochemical precursors

    Science.gov (United States)

    Ingebritsen, Steven E.; Manga, Michael

    2014-01-01

    Earthquake prediction is a long-sought goal. Changes in groundwater chemistry before earthquakes in Iceland highlight a potential hydrogeochemical precursor, but such signals must be evaluated in the context of long-term, multiparametric data sets.

  3. Identification of specific markers for amphetamine synthesised from the pre-precursor APAAN following the Leuckart route and retrospective search for APAAN markers in profiling databases from Germany and the Netherlands.

    Science.gov (United States)

    Hauser, Frank M; Rößler, Thorsten; Hulshof, Janneke W; Weigel, Diana; Zimmermann, Ralf; Pütz, Michael

    2017-08-30

    α-Phenylacetoacetonitrile (APAAN) is one of the most important pre-precursors for amphetamine production in recent years. This assumption is based on seizure data but there is little analytical data available showing how much amphetamine really originated from APAAN. In this study, several syntheses of amphetamine following the Leuckart route were performed starting from different organic compounds including APAAN. The organic phases were analysed using gas chromatography-mass spectrometry (GC-MS) to search for signals caused by possible APAAN markers. Three compounds were discovered, isolated, and based on the performed syntheses it was found that they are highly specific for the use of APAAN. Using mass spectra, high resolution MS and nuclear magnetic resonance (NMR) data the compounds were characterised and identified as 2-phenyl-2-butenenitrile, 3-amino-2-phenyl-2-butenenitrile, and 4-amino-6-methyl-5-phenylpyrimidine. To investigate their significance, they were searched in data from seized amphetamine samples to determine to what extent they were present in illicitly produced amphetamine. Data of more than 580 cases from amphetamine profiling databases in Germany and the Netherlands were used for this purpose. These databases allowed analysis of the yearly occurrence of the markers going back to 2009. The markers revealed a trend that was in agreement with seizure reports and reflected an increasing use of APAAN from 2010 on. This paper presents experimental proof that APAAN is indeed the most important pre-precursor of amphetamine in recent years. It also illustrates how important it is to look for new ways to identify current trends in drug production since such trends can change within a few years. Copyright © 2017 John Wiley & Sons, Ltd.

  4. High-sensitivity and specificity of laser-induced autofluorescence spectra for detection of colorectal cancer with an artificial neural network

    Science.gov (United States)

    Kwek, L. C.; Fu, Sheng; Chia, T. C.; Diong, C. H.; Tang, C. L.; Krishnan, S. M.

    2005-07-01

    An artificial neural network (ANN) has been used in various clinical research for the prediction and classification of data in cancer disease. Previous research in this direction focused on the correlation between various input parameters such as age, antigen, and size of tumor growth. Recently, laser-induced autofluorescence (LIAF) techniques have been shown to be a useful noninvasive early diagnostic tool for various cancer diseases. We report on a successful application of ANN to in vitro LIAF spectra. We show that classification of tumor samples with ANN can be done with high sensitivity, specificity, and accuracy. Thus a combination of LIAF techniques and ANN can provide a robust method for clinical diagnosis.

  5. Use of plankton-derived vitamin B1 precursors, especially thiazole-related precursor, by key marine picoeukaryotic phytoplankton.

    Science.gov (United States)

    Paerl, Ryan W; Bouget, Francois-Yves; Lozano, Jean-Claude; Vergé, Valérie; Schatt, Philippe; Allen, Eric E; Palenik, Brian; Azam, Farooq

    2017-03-01

    Several cosmopolitan marine picoeukaryotic phytoplankton are B1 auxotrophs requiring exogenous vitamin B1 or precursor to survive. From genomic evidence, representatives of picoeukaryotic phytoplankton (Ostreococcus and Micromonas spp.) were predicted to use known thiazole and pyrimidine B1 precursors to meet their B1 demands, however, recent culture-based experiments could not confirm this assumption. We hypothesized these phytoplankton strains could grow on precursors alone, but required a thiazole-related precursor other the well-known and extensively tested 4-methyl-5-thiazoleethanol. This hypothesis was tested using bioassays and co-cultures of picoeukaryotic phytoplankton and bacteria. We found that specific B1-synthesizing proteobacteria and phytoplankton are sources of a yet-to-be chemically identified thiazole-related precursor(s) that, along with pyrimidine B1 precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine, can support growth of Ostreococcus spp. (also Micromonas spp.) without B1. We additionally found that the B1-synthesizing plankton do not require contact with picoeukaryotic phytoplankton cells to produce thiazole-related precursor(s). Experiments with wild-type and genetically engineered Ostreococcus lines revealed that the thiazole kinase, ThiM, is required for growth on precursors, and that thiazole-related precursor(s) accumulate to appreciable levels in the euphotic ocean. Overall, our results point to thiazole-related B1 precursors as important micronutrients promoting the survival of abundant phytoplankton influencing surface ocean production and biogeochemical cycling.

  6. Neural network-based crop growth model to predict processing tomato yield on a site-specific basis using remotely sensed data

    Science.gov (United States)

    Koller, Michal

    Remote sensing is one of the major data acquisition tools available to rapidly acquire soil and plant related information over a wide area for use in precision agriculture. Green canopy has very specific reflectance characteristics distinguishing it from other materials such as soil and dry vegetative matter. Reflectance values in red (R) and near infra-red (NIR) spectral bands have been widely used for calculating normalized difference vegetation index (NDVI). Many researchers have related NDVI values to plant vigor, water stress, leaf area index (LAI) and/or yield. However, vegetative indices such as NDVI are usually sensitive to background reflectance characteristics. Often soil adjusted vegetation indices (SAVI) are used to minimize the background effect. In this study we have developed a relationship between the processing tomato yield and SAVI based on the R and NIR reflectance. Eight three band (R, NIR and green) aerial images were obtained at approximately two-week intervals during the 2000 processing tomato growing season. These images were analyzed to obtain SAVI values which were in turn related to LAI using regression techniques. A tuned neural network was developed to predict daily LAI values based on the biweekly experimental LAI values derived from aerial images. The coefficients of multiple determination between the actual LAI and neural network predicted LAI values were greater than 0.96 for all 56 grid points. The LAI values were numerically integrated over the whole growing season to obtain cumulative leaf area index days (CLAID). The CLAID values predicted from the neural network correlated very well with experimentally derived CLAID values (coefficient of determination, r2 = 0.83) indicating that the neural network model simulated processing tomato growth well. A crop growth model that was capable of predicting crop yield based on neural network predicted LAI values and CIMIS weather data was developed. Although predicted yield tended to be low

  7. Silencer-delimited transgenesis: NRSE/RE1 sequences promote neural-specific transgene expression in a NRSF/REST-dependent manner

    Directory of Open Access Journals (Sweden)

    Xie Xiayang

    2012-11-01

    Full Text Available Abstract Background We have investigated a simple strategy for enhancing transgene expression specificity by leveraging genetic silencer elements. The approach serves to restrict transgene expression to a tissue of interest - the nervous system in the example provided here - thereby promoting specific/exclusive targeting of discrete cellular subtypes. Recent innovations are bringing us closer to understanding how the brain is organized, how neural circuits function, and how neurons can be regenerated. Fluorescent proteins enable mapping of the 'connectome', optogenetic tools allow excitable cells to be short-circuited or hyperactivated, and targeted ablation of neuronal subtypes facilitates investigations of circuit function and neuronal regeneration. Optimally, such toolsets need to be expressed solely within the cell types of interest as off-site expression makes establishing causal relationships difficult. To address this, we have exploited a gene 'silencing' system that promotes neuronal specificity by repressing expression in non-neural tissues. This methodology solves non-specific background issues that plague large-scale enhancer trap efforts and may provide a means of leveraging promoters/enhancers that otherwise express too broadly to be of value for in vivo manipulations. Results We show that a conserved neuron-restrictive silencer element (NRSE can function to restrict transgene expression to the nervous system. The neuron-restrictive silencing factor/repressor element 1 silencing transcription factor (NRSF/REST transcriptional repressor binds NRSE/repressor element 1 (RE1 sites and silences gene expression in non-neuronal cells. Inserting NRSE sites into transgenes strongly biased expression to neural tissues. NRSE sequences were effective in restricting expression of bipartite Gal4-based 'driver' transgenes within the context of an enhancer trap and when associated with a defined promoter and enhancer. However, NRSE sequences did

  8. Biochemical Removal of HAP Precursors From Coal

    Energy Technology Data Exchange (ETDEWEB)

    Olson, G.; Tucker, L.; Richards, J.

    1997-07-01

    This project addresses DOE`s interest in advanced concepts for controlling emissions of air toxics from coal-fired utility boilers. We are determining the feasibility of developing a biochemical process for the precombustion removal of substantial percentages of 13 inorganic hazardous air pollutant (HAP) precursors from coal. These HAP precursors are Sb, As, Be, Cd, Cr, Cl, Co, F, Pb, Hg, Mn, Ni, and Se. Although rapid physical coal cleaning is done routinely in preparation plants, biochemical processes for removal of HAP precursors from coal potentially offer advantages of deeper cleaning, more specificity, and less coal loss. Compared to chemical processes for coal cleaning, biochemical processes potentially offer lower costs and milder process conditions. Pyrite oxidizing bacteria, most notably Thiobacillusferrooxidans, are being evaluated in this project for their ability to remove HAP precursors from U.S. coals.

  9. A study on precursors leading to geomagnetic storms using artificial ...

    Indian Academy of Sciences (India)

    Space weather prediction involves advance forecasting of the magnitude and onset time of major geomag- netic storms on Earth. In this paper, we discuss the development of an artificial neural network-based model to study the precursor leading to intense and moderate geomagnetic storms, following halo coronal.

  10. A study on precursors leading to geomagnetic storms using artificial ...

    Indian Academy of Sciences (India)

    Space weather prediction involves advance forecasting of the magnitude and onset time of major geomagneticstorms on Earth. In this paper, we discuss the development of an artificial neural network-basedmodel to study the precursor leading to intense and moderate geomagnetic storms, following halo coronalmass ...

  11. CD44-positive cells are candidates for astrocyte precursor cells in developing mouse cerebellum.

    Science.gov (United States)

    Cai, Na; Kurachi, Masashi; Shibasaki, Koji; Okano-Uchida, Takayuki; Ishizaki, Yasuki

    2012-03-01

    Neural stem cells are generally considered to be committed to becoming precursor cells before terminally differentiating into either neurons or glial cells during neural development. Neuronal and oligodendrocyte precursor cells have been identified in several areas in the murine central nervous system. The presence of astrocyte precursor cells (APCs) is not so well understood. The present study provides several lines of evidence that CD44-positive cells are APCs in the early postnatal mouse cerebellum. In developing mouse cerebellum, CD44-positive cells, mostly located in the white matter, were positive for the markers of the astrocyte lineage, but negative for the markers of mature astrocytes. CD44-positive cells were purified from postnatal cerebellum by fluorescence-activated cell sorting and characterized in vitro. In the absence of any signaling molecule, many cells died by apoptosis. The surviving cells gradually expressed glial fibrillary acidic protein, a marker for mature astrocytes, indicating that differentiation into mature astrocytes is the default program for these cells. The cells produced no neurospheres nor neurons nor oligodendrocytes under any condition examined, indicating these cells are not neural stem cells. Leukemia inhibitory factor greatly promoted astrocytic differentiation of CD44-positive cells, whereas bone morphogenetic protein 4 (BMP4) did not. Fibroblast growth factor-2 was a potent mitogen for these cells, but was insufficient for survival. BMP4 inhibited activation of caspase-3 and greatly promoted survival, suggesting a novel role for BMP4 in the control of development of astrocytes in cerebellum. We isolated and characterized only CD44 strongly positive large cells and discarded small and/or CD44 weakly positive cells in this study. Further studies are necessary to characterize these cells to help determine whether CD44 is a selective and specific marker for APCs in the developing mouse cerebellum. In conclusion, we succeeded in

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

    Science.gov (United States)

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

    2018-02-01

    Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O2-) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by O2- dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sex-specific neural activity when resolving cognitive interference in individuals with or without prior internalizing disorders.

    Science.gov (United States)

    Wang, Zhishun; Jacobs, Rachel H; Marsh, Rachel; Horga, Guillermo; Qiao, Jianping; Warner, Virginia; Weissman, Myrna M; Peterson, Bradley S

    2016-03-30

    The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n=63) and females (n=80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task-positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference. Copyright © 2016. Published by Elsevier Ireland Ltd.

  14. Mapping the brain's orchestration during speech comprehension: task-specific facilitation of regional synchrony in neural networks

    Directory of Open Access Journals (Sweden)

    Keil Andreas

    2004-10-01

    Full Text Available Abstract Background How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension. Results Amplitude-modulated (sinusoidal 41.5 Hz auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a an incomprehensible string of words, (b the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c nonverbal stimulations that included a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates, increased within left- temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right hemisphere for the sentence (condition (b relative to all other conditions, and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c, tone and melody relative to the other conditions, leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material. Conclusions We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.

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

    Directory of Open Access Journals (Sweden)

    Hideo eOtsuna

    2014-02-01

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

  16. Neural simulation of actions: effector- versus action-specific motor maps within the human premotor and posterior parietal area?

    Science.gov (United States)

    Lorey, Britta; Naumann, Tim; Pilgramm, Sebastian; Petermann, Carmen; Bischoff, Matthias; Zentgraf, Karen; Stark, Rudolf; Vaitl, Dieter; Munzert, Jörn

    2014-04-01

    This study addresses the controversy over how motor maps are organized during action simulation by examining whether action simulation states, that is, motor imagery and action observation, run on either effector-specific and/or action-specific motor maps. Subjects had to observe or imagine three types of movements effected by the right hand or the right foot with different action goals. The functional magnetic resonance imaging results showed an action-specific organization within premotor and posterior parietal areas of both hemispheres during action simulation, especially during action observation. There were also less pronounced effector-specific activation sites during both simulation processes. It is concluded that the premotor and parietal areas contain multiple motor maps rather than a single, continuous map of the body. The forms of simulation (observation, imagery), the task contexts (movements related to an object, with usual/unusual effector), and the underlying reason for performing the simulation (rate your subjective success afterwards) lead to the specific use of different representational motor maps within both regions. In our experimental setting, action-specific maps are dominant especially, during action observation, whereas effector-specific maps are recruited to only a lesser degree. Copyright © 2013 Wiley Periodicals, Inc.

  17. Remote sensing of harmful algal events in optically complex waters using regionally specific neural network-based algorithms for MERIS data

    Science.gov (United States)

    Gonzalez Vilas, L.; Castro Fernandez, M.; Spyrakos, E.; Torres Palenzuela, J.

    2013-08-01

    In typical case 2 waters an accurate remote sensing retrieval of chlorophyll a (chla) is still challenging. There is a widespread understanding that universally applicable water constituent retrieval algorithms are currently not feasible, shifting the research focus to regionally specific implementations of powerful inversion methods. This study takes advantage of regionally specific chlorophyll a (chla) algorithms, which were developed by the authors of this abstract in previous works, and the characteristics of Medium Resolution Imaging Spectrometer (MERIS) in order to study harmful algal events in the optically complex waters of the Galician Rias (NW). Harmful algal events are a frequent phenomenon in this area with direct and indirect impacts to the mussel production that constitute a very important economic activity for the local community. More than 240 106 kg of mussel per year are produced in these highly primary productive upwelling systems. A MERIS archive from nine years (2003-2012) was analysed using regionally specific chla algorithms. The latter were developed based on Multilayer perceptron (MLP) artificial neural networks and fuzzy c-mean clustering techniques (FCM). FCM specifies zones (based on water leaving reflectances) where the retrieval algorithms normally provide more reliable results. Monthly chla anomalies and other statistics were calculated for the nine years MERIS archive. These results were then related to upwelling indices and other associated measurements to determine the driver forces for specific phytoplankton blooms. The distribution and changes of chla are also discussed.

  18. Wilson loops as precursors

    Energy Technology Data Exchange (ETDEWEB)

    Susskind, Leonard [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States); Toumbas, Nicolaos [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States)

    2000-02-15

    There is substantial evidence that string theory on AdS{sub 5}xS{sub 5} is a holographic theory in which the number of degrees of freedom scales as the area of the boundary in Planck units. Precisely how the theory can describe bulk physics using only surface degrees of freedom is not well understood. A particularly paradoxical situation involves an event deep in the interior of the bulk space. The event must be recorded in the (Schroedinger picture) state vector of the boundary theory long before a signal, such as a gravitational wave, can propagate from the event to the boundary. In a previous paper with Polchinski, we argued that the ''precursor'' operators which carry information stored in the wave during the time when it vanishes in a neighborhood of the boundary are necessarily non-local. In this paper we argue that the precursors cannot be products of local gauge invariant operators such as the energy momentum tensor. In fact gauge theories have a class of intrinsically non-local operators which cannot be built from local gauge invariant objects. These are the Wilson loops. We show that the precursors can be identified with Wilson loops whose spatial size is dictated by the UV-IR connection. (c) 2000 The American Physical Society.

  19. Sequentially acting Sox transcription factors in neural lineage development.

    Science.gov (United States)

    Bergsland, Maria; Ramsköld, Daniel; Zaouter, Cécile; Klum, Susanne; Sandberg, Rickard; Muhr, Jonas

    2011-12-01

    Pluripotent embryonic stem (ES) cells can generate all cell types, but how cell lineages are initially specified and maintained during development remains largely unknown. Different classes of Sox transcription factors are expressed during neurogenesis and have been assigned important roles from early lineage specification to neuronal differentiation. Here we characterize the genome-wide binding for Sox2, Sox3, and Sox11, which have vital functions in ES cells, neural precursor cells (NPCs), and maturing neurons, respectively. The data demonstrate that Sox factor binding depends on developmental stage-specific constraints and reveal a remarkable sequential binding of Sox proteins to a common set of neural genes. Interestingly, in ES cells, Sox2 preselects for neural lineage-specific genes destined to be bound and activated by Sox3 in NPCs. In NPCs, Sox3 binds genes that are later bound and activated by Sox11 in differentiating neurons. Genes prebound by Sox proteins are associated with a bivalent chromatin signature, which is resolved into a permissive monovalent state upon binding of activating Sox factors. These data indicate that a single key transcription factor family acts sequentially to coordinate neural gene expression from the early lineage specification in pluripotent cells to later stages of neuronal development.

  20. PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer’s amyloid-β precursor protein via a tissue-specific proximal regulatory element (PRE

    Directory of Open Access Journals (Sweden)

    Lahiri Debomoy K

    2013-01-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is intimately tied to amyloid-β (Aβ peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or “proximal regulatory element” (PRE, at −76/−47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2, nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF, and specificity protein 1 (SP1. These sites crossed a known single nucleotide polymorphism (SNP. EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also

  1. Neural Computations in Binaural Hearing

    Science.gov (United States)

    Wagner, Hermann

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

  2. Layer-specific entrainment of gamma-band neural activity by the alpha rhythm in monkey visual cortex

    NARCIS (Netherlands)

    Spaak, E.; Bonnefond, M.; Maier, A.; Leopold, D.A.; Jensen, O.

    2012-01-01

    Although the mammalian neocortex has a clear laminar organization, layer-specific neuronal computations remain to be uncovered. Several studies suggest that gamma band activity in primary visual cortex (V1) is produced in granular and superficial layers and is associated with the processing of

  3. Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects.

    Science.gov (United States)

    Wang, L; Chang, S; Guan, J; Shangguan, S; Lu, X; Wang, Z; Wu, L; Zou, J; Zhao, H; Bao, Y; Qiu, Z; Niu, B; Zhang, T

    2015-01-01

    Epigenetic regulation of long interspersed nucleotide element-1 (LINE-1) retrotransposition events plays crucial roles during early development. Previously we showed that LINE-1 hypomethylation in neuronal tissues is associated with pathogenesis of neural tube defect (NTD). Herein, we further evaluated LINE-1 Homo sapiens (L1Hs) methylation in tissues derived from three germ layers of stillborn NTD fetuses, to define patterns of tissue specific methylation and site-specific hypomethylation at CpG sites within an L1Hs promoter region. Stable, tissue-specific L1Hs methylation patterns throughout three germ layer lineages of the fetus, placenta, and maternal peripheral blood were observed. Samples from maternal peripheral blood exhibited the highest level of L1Hs methylation (64.95%) and that from placenta showed the lowest (26.82%). Between samples from NTDs and controls, decrease in L1Hs methylation was only significant in NTD-affected brain tissue at 7.35%, especially in females (8.98%). L1Hs hypomethylation in NTDs was also associated with a significant increase in expression level of an L1Hs-encoded transcript in females (r = -0.846, p = 0.004). This could be due to genomic DNA instability and alternation in chromatins accessibility resulted from abnormal L1Hs hypomethylation, as showed in this study with HCT-15 cells treated with methylation inhibitor 5-Aza.

  4. Electrosensory processing in Apteronotus albifrons: implications for general and specific neural coding strategies across wave-type weakly electric fish species.

    Science.gov (United States)

    Martinez, Diana; Metzen, Michael G; Chacron, Maurice J

    2016-12-01

    Understanding how the brain processes sensory input to generate behavior remains an important problem in neuroscience. Towards this end, it is useful to compare results obtained across multiple species to gain understanding as to the general principles of neural coding. Here we investigated hindbrain pyramidal cell activity in the weakly electric fish Apteronotus albifrons We found strong heterogeneities when looking at baseline activity. Additionally, ON- and OFF-type cells responded to increases and decreases of sinusoidal and noise stimuli, respectively. While both cell types displayed band-pass tuning, OFF-type cells were more broadly tuned than their ON-type counterparts. The observed heterogeneities in baseline activity as well as the greater broadband tuning of OFF-type cells were both similar to those previously reported in other weakly electric fish species, suggesting that they constitute general features of sensory processing. However, we found that peak tuning occurred at frequencies ∼15 Hz in A. albifrons, which is much lower than values reported in the closely related species Apteronotus leptorhynchus and the more distantly related species Eigenmannia virescens In response to stimuli with time-varying amplitude (i.e., envelope), ON- and OFF-type cells displayed similar high-pass tuning curves characteristic of fractional differentiation and possibly indicate optimized coding. These tuning curves were qualitatively similar to those of pyramidal cells in the closely related species A. leptorhynchus In conclusion, comparison between our and previous results reveals general and species-specific neural coding strategies. We hypothesize that differences in coding strategies, when observed, result from different stimulus distributions in the natural/social environment. Copyright © 2016 the American Physiological Society.

  5. In a non-human primate model, aging disrupts the neural control of intestinal smooth muscle contractility in a region-specific manner.

    Science.gov (United States)

    Tran, L; Greenwood-Van Meerveld, B

    2014-03-01

    Incidences of gastrointestinal (GI) motility disorders increase with age. However, there is a paucity of knowledge about the aging mechanisms leading to GI dysmotility. Motility in the GI tract is a function of smooth muscle contractility, which is modulated in part by the enteric nervous system (ENS). Evidence suggests that aging impairs the ENS, thus we tested the hypothesis that senescence in the GI tract precipitates abnormalities in smooth muscle and neurally mediated contractility in a region-specific manner. Jejunal and colonic circular muscle strips were isolated from young (4-10 years) and old (18+ years) baboons. Myogenic responses were investigated using potassium chloride (KCl) and carbachol (CCh). Neurally mediated contractile responses were evoked by electrical field stimulation (EFS) and were recorded in the absence and presence of atropine (1 μM) or NG-Nitro-l-arginine methyl ester (l-NAME; 100 μM). The myogenic responses to KCl in the jejunum and colon were unaffected by age. In the colon, but not the jejunum, CCh-induced contractile responses were reduced in aged animals. Compared to young baboons, there was enhanced EFS-induced contractility of old baboon jejunal smooth muscle in contrast to the reduced contractility in the colon. The effect of atropine on the EFS response was lower in aged colonic tissue, suggesting reduced participation of acetylcholine. In aged jejunal tissue, higher contractile responses to EFS were found to be due to reduced nitregic inhibition. These findings provide key evidence for the importance of intestinal smooth muscle and ENS senescence in age-associated GI motility disorders. © 2014 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

  6. Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation.

    OpenAIRE

    Droms, K; Sueoka, N

    1987-01-01

    This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of...

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

    Directory of Open Access Journals (Sweden)

    Athanasios eStergiopoulos

    2015-01-01

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

  8. Novel insights into the role of NF-κB p50 in astrocyte-mediated fate specification of adult neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Valeria Bortolotto

    2017-01-01

    Full Text Available Within the CNS nuclear factor-kappa B (NF-κB transcription factors are involved in a wide range of functions both in homeostasis and in pathology. Over the years, our and other groups produced a vast array of information on the complex involvement of NF-κB proteins in different aspects of postnatal neurogenesis. In particular, several extracellular signals and membrane receptors have been identified as being able to affect neural progenitor cells (NPC and their progeny via NF-κB activation. A crucial role in the regulation of neuronal fate specification in adult hippocampal NPC is played by the NF-κB p50 subunit. NF-κB p50KO mice display a remarkable reduction in adult hippocampal neurogenesis which correlates with a selective defect in hippocampal-dependent short-term memory. Moreover absence of NF-κB p50 can profoundly affect the in vitro proneurogenic response of adult hippocampal NPC (ahNPC to several endogenous signals and drugs. Herein we briefly review the current knowledge on the pivotal role of NF-κB p50 in the regulation of adult hippocampal neurogenesis. In addition we discuss more recent data that further extend the relevance of NF-κB p50 to novel astroglia-derived signals which can influence neuronal specification of ahNPC and to astrocyte-NPC cross-talk.

  9. Evaluation of specific neural marker GAP-43 and TH combined with Masson-trichrome staining for forensic autopsy cases with old myocardial infarction.

    Science.gov (United States)

    Yu, Tian-Shui; Wang, Xu; Zhang, Hai-Dong; Bai, Ru-Feng; Zhao, Rui; Guan, Da-Wei

    2018-01-01

    It has been a puzzling forensic task to determine the cause of death as a result of old myocardial infarction (OMI) in the absence of recognizable acute myocardial infarction. Recent studies indicated that the heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation at border zones of the infarcted site played important roles in sudden cardiac death (SCD). So, the present study explored the value of growth associated protein-43 (GAP-43) and tyrosine hydroxylase (TH) as objective and specific neural biomarkers combined with Masson-trichrome staining for forensic autopsy cases. Myocardium of left ventricle of 58 medicolegal autopsy cases, 12 OMI cases, 12 acute/OMI cases, and 34 control cases, were immunostained with anti-GAP-43 and anti-TH antibodies. Immunoreactivity of GAP-43 and TH identified nerve fibers and vascular wall in OMI cases and acute/OMI cases. Specifically, TH-positive nerve fibers were abundant at border zones of the infarcted site. There were a few GAP-43 and TH expressions in the control cases. With Masson-trichrome staining, collagen fibers were blue and cardiac muscle fibers were pink in marked contrast with the surrounding tissue, which improved the location of nerve fibers. Thus, these findings suggest that immunohistochemical detection of GAP-43 and TH combined with Masson-trichrome staining can provide the evidence for the medicolegal expertise of SCD due to OMI, and further demonstrate a close relationship between sympathetic hyperinnervation and SCD.

  10. Comparison studies of ozone precursors in Phoenix, Arizona

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, C.; Guyton, J.; Lee, C.P. [Arizona Dept. of Environmental Quality, Phoenix, AZ (United States); Parmar, S. [Atmospheric Analysis and Consulting Co., Ventura, CA (United States)

    1994-12-31

    This paper will present the comparison of the ozone precursors monitoring program for Phoenix, Arizona during 1992 and 1993. Specific details and methodologies will be presented involving collection of air samples and analysis of speciated measurements for reactive VOC and carbonyl precursors responsible for ozone formation. Quality control and quality assurance techniques will also be discussed.

  11. Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Opris, Ioan; Santos, Lucas M.; Shin, Dae C.; Gerhardt, Greg A.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2013-12-01

    Objective. Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s, ageing and dementia resulting from impaired hippocampal function in the medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach. NHPs trained to perform a short-term delayed match-to-sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main results. The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for the successful encoding of sample phase information on more difficult DMS trials. This was validated by the delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the sample phase which facilitated task performance in the subsequent, delayed match phase, on difficult trials that required more precise encoding of sample information. Significance. These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain.

  12. Facilitation and restoration of cognitive function in primate prefrontal cortex by a neuroprosthesis that utilizes minicolumn-specific neural firing

    Science.gov (United States)

    Hampson, Robert E.; Gerhardt, Greg A.; Marmarelis, Vasilis; Song, Dong; Opris, Ioan; Santos, Lucas; Berger, Theodore W.; Deadwyler, Sam A.

    2012-10-01

    Objective. Maintenance of cognitive control is a major concern for many human disease conditions; therefore, a major goal of human neuroprosthetics is to facilitate and/or recover the cognitive function when such circumstances impair appropriate decision making. Approach. Minicolumnar activity from the prefrontal cortex (PFC) was recorded from nonhuman primates trained to perform a delayed match to sample (DMS), via custom-designed conformal multielectrode arrays that provided inter-laminar recordings from neurons in the PFC layer 2/3 and layer 5. Such recordings were analyzed via a previously demonstrated nonlinear multi-input-multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized multicolumnar firing patterns during DMS performance. Main results. The MIMO model verified that the conformal recorded individual PFC minicolumns responded to entrained target selections in patterns critical for successful DMS performance. This allowed the substitution of task-related layer 5 neuron firing patterns with electrical stimulation in the same recording regions during columnar transmission from layer 2/3 at the time of target selection. Such stimulation improved normal task performance, but more importantly, recovered performance when applied as a neuroprosthesis following the pharmacological disruption of decision making in the same task. Significance. These findings provide the first successful application of neuroprosthesis in the primate brain designed specifically to restore or repair the disrupted cognitive function.

  13. Rapid transgene expression in multiple precursor cell types of adult rat subventricular zone mediated by adeno-associated type 1 vectors.

    Science.gov (United States)

    Bockstael, Olivier; Melas, Catherine; Pythoud, Catherine; Levivier, Marc; McCarty, Douglas; Samulski, R Jude; De Witte, Olivier; Tenenbaum, Liliane

    2012-07-01

    The adult rat brain subventricular zone (SVZ) contains proliferative precursors that migrate to the olfactory bulb (OB) and differentiate into mature neurons. Recruitment of precursors constitutes a potential avenue for brain repair. We have investigated the kinetics and cellular specificity of transgene expression mediated by AAV2/1 vectors (i.e., adeno-associated virus type 2 pseudotyped with AAV1 capsid) in the SVZ. Self-complementary (sc) and single-stranded (ss) AAV2/1 vectors mediated efficient GFP expression, respectively, at 17 and 24 hr postinjection. Transgene expression was efficient in all the rapidly proliferating cells types, that is, Mash1(+) precursors (30% of the GFP(+) cells), Dlx2(+) neuronal progenitors (55%), Olig2(+) oligodendrocyte progenitors (35%), and doublecortin-positive (Dcx(+)) migrating cells (40%), but not in the slowly proliferating glial fibrillary acidic protein-positive (GFAP(+)) neural stem cell pool (5%). Because cell cycle arrest by wild-type and recombinant AAV has been described in primary cultures, we examined SVZ proliferative activity after vector injection. Indeed, cell proliferation was reduced immediately after vector injection but was normal after 1 month. In contrast, migration and differentiation of GFP(+) precursors were unaltered. Indeed, the proportion of Dcx(+) cells was similar in the injected and contralateral hemispheres. Furthermore, 1 month after vector injection into the SVZ, GFP(+) cells, found, as expected, in the OB granular cell layer, were mature GABAergic neurons. In conclusion, the rapid and efficient transgene expression in SVZ neural precursors mediated by scAAV2/1 vectors underlines their potential usefulness for brain repair via recruitment of immature cells. The observed transient precursor proliferation inhibition, not affecting their migration and differentiation, will likely not compromise this strategy.

  14. A subpopulation of smooth muscle cells, derived from melanocyte-competent precursors, prevents patent ductus arteriosus.

    Directory of Open Access Journals (Sweden)

    Ichiro Yajima

    Full Text Available BACKGROUND: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA, a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2 and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes.

  15. A Subpopulation of Smooth Muscle Cells, Derived from Melanocyte-Competent Precursors, Prevents Patent Ductus Arteriosus

    Science.gov (United States)

    Puig, Isabel; Champeval, Delphine; Kumasaka, Mayuko; Belloir, Elodie; Bonaventure, Jacky; Mark, Manuel; Yamamoto, Hiroaki; Taketo, Mark M.; Choquet, Philippe; Etchevers, Heather C.; Beermann, Friedrich; Delmas, Véronique; Monassier, Laurent; Larue, Lionel

    2013-01-01

    Background Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes. PMID:23382837

  16. Peeling without precursors

    Science.gov (United States)

    Lister, John; Skinner, Dominic; Large, Tim

    2017-11-01

    The peeling by fluid injection of an elastic sheet away from a substrate is often regularised by invoking a thin prewetting film or a low-viscosity phase in the tip. Here we analyse fluid-driven peeling without such precursors, and consider an elastic sheet either bonded to, or simply laid on, an elastic substrate. To resolve the `elastic contact-line problem' that arises from viscous flow and beam theory, we determine the near-tip behaviour from lubrication theory coupled to the full equations of elasticity and fracture. The result is a law for the tip propagation speed in terms of the remote loading and the toughness of the sheet-substrate bonding (which might be zero). There are distinct modes of failure, according to whether there is slip ahead of the fluid front. The propagation-speed law gives rise to new similarity solutions for the spread of a fluid-filled blister in different regimes.

  17. Identified EM Earthquake Precursors

    Science.gov (United States)

    Jones, Kenneth, II; Saxton, Patrick

    2014-05-01

    Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After a number of custom rock experiments, two hypotheses were formed which could answer the EM wave model. The first hypothesis concerned a sufficient and continuous electron movement either by surface or penetrative flow, and the second regarded a novel approach to radio transmission. Electron flow along fracture surfaces was determined to be inadequate in creating strong EM fields, because rock has a very high electrical resistance making it a high quality insulator. Penetrative flow could not be corroborated as well, because it was discovered that rock was absorbing and confining electrons to a very thin skin depth. Radio wave transmission and detection worked with every single test administered. This hypothesis was reviewed for propagating, long-wave generation with sufficient amplitude, and the capability of penetrating solid rock. Additionally, fracture spaces, either air or ion-filled, can facilitate this concept from great depths and allow for surficial detection. A few propagating precursor signals have been detected in the field occurring with associated phases using custom-built loop antennae. Field testing was conducted in Southern California from 2006-2011, and outside the NE Texas town of Timpson in February, 2013. The antennae have mobility and observations were noted for

  18. Visual motion imagery neurofeedback based on the hMT+/V5 complex: evidence for a feedback-specific neural circuit involving neocortical and cerebellar regions

    Science.gov (United States)

    Banca, Paula; Sousa, Teresa; Catarina Duarte, Isabel; Castelo-Branco, Miguel

    2015-12-01

    Objective. Current approaches in neurofeedback/brain-computer interface research often focus on identifying, on a subject-by-subject basis, the neural regions that are best suited for self-driven modulation. It is known that the hMT+/V5 complex, an early visual cortical region, is recruited during explicit and implicit motion imagery, in addition to real motion perception. This study tests the feasibility of training healthy volunteers to regulate the level of activation in their hMT+/V5 complex using real-time fMRI neurofeedback and visual motion imagery strategies. Approach. We functionally localized the hMT+/V5 complex to further use as a target region for neurofeedback. An uniform strategy based on motion imagery was used to guide subjects to neuromodulate hMT+/V5. Main results. We found that 15/20 participants achieved successful neurofeedback. This modulation led to the recruitment of a specific network as further assessed by psychophysiological interaction analysis. This specific circuit, including hMT+/V5, putative V6 and medial cerebellum was activated for successful neurofeedback runs. The putamen and anterior insula were recruited for both successful and non-successful runs. Significance. Our findings indicate that hMT+/V5 is a region that can be modulated by focused imagery and that a specific cortico-cerebellar circuit is recruited during visual motion imagery leading to successful neurofeedback. These findings contribute to the debate on the relative potential of extrinsic (sensory) versus intrinsic (default-mode) brain regions in the clinical application of neurofeedback paradigms. This novel circuit might be a good target for future neurofeedback approaches that aim, for example, the training of focused attention in disorders such as ADHD.

  19. CtBP2 downregulation during neural crest specification induces expression of Mitf and REST, resulting in melanocyte differentiation and sympathoadrenal lineage suppression.

    Science.gov (United States)

    Liang, Hongzi; Fekete, Donna M; Andrisani, Ourania M

    2011-03-01

    Trunk neural crest (NC) cells differentiate to neurons, melanocytes, and glia. In NC cultures, cyclic AMP (cAMP) induces melanocyte differentiation while suppressing the neuronal sympathoadrenal lineage, depending on the signal intensity. Melanocyte differentiation requires activation of CREB and cAMP-dependent protein kinase A (PKA), but the role of PKA is not understood. We have demonstrated, in NC cultures, cAMP-induced transcription of the microphthalmia-associated transcription factor gene (Mitf) and the RE-1 silencing transcription factor gene (REST), both Wnt-regulated genes. In NC cultures and zebrafish, knockdown of the corepressor of Wnt-mediated transcription C-terminal binding protein 2 (CtBP2) but not CtBP1 derepressed Mitf and REST expression and enhanced melanocyte differentiation. cAMP in NC and B16 melanoma cells decreased CtBP2 protein levels, while inhibition of PKA or proteasome rescued CtBP2 degradation. Interestingly, knockdown of homeodomain-interacting protein kinase 2 (HIPK2), a CtBP stability modulator, increased CtBP2 levels, suppressed expression of Mitf, REST, and melanocyte differentiation, and increased neuronal gene expression and sympathoadrenal lineage differentiation. We conclude that cAMP/PKA via HIPK2 promotes CtBP2 degradation, leading to Mitf and REST expression. Mitf induces melanocyte specification, and REST suppresses neuron-specific gene expression and the sympathoadrenal lineage. Our studies identify a novel role for REST in NC cell differentiation and suggest cross talk between cAMP and Wnt signaling in NC lineage specification.

  20. CtBP2 Downregulation during Neural Crest Specification Induces Expression of Mitf and REST, Resulting in Melanocyte Differentiation and Sympathoadrenal Lineage Suppression ▿

    Science.gov (United States)

    Liang, Hongzi; Fekete, Donna M.; Andrisani, Ourania M.

    2011-01-01

    Trunk neural crest (NC) cells differentiate to neurons, melanocytes, and glia. In NC cultures, cyclic AMP (cAMP) induces melanocyte differentiation while suppressing the neuronal sympathoadrenal lineage, depending on the signal intensity. Melanocyte differentiation requires activation of CREB and cAMP-dependent protein kinase A (PKA), but the role of PKA is not understood. We have demonstrated, in NC cultures, cAMP-induced transcription of the microphthalmia-associated transcription factor gene (Mitf) and the RE-1 silencing transcription factor gene (REST), both Wnt-regulated genes. In NC cultures and zebrafish, knockdown of the corepressor of Wnt-mediated transcription C-terminal binding protein 2 (CtBP2) but not CtBP1 derepressed Mitf and REST expression and enhanced melanocyte differentiation. cAMP in NC and B16 melanoma cells decreased CtBP2 protein levels, while inhibition of PKA or proteasome rescued CtBP2 degradation. Interestingly, knockdown of homeodomain-interacting protein kinase 2 (HIPK2), a CtBP stability modulator, increased CtBP2 levels, suppressed expression of Mitf, REST, and melanocyte differentiation, and increased neuronal gene expression and sympathoadrenal lineage differentiation. We conclude that cAMP/PKA via HIPK2 promotes CtBP2 degradation, leading to Mitf and REST expression. Mitf induces melanocyte specification, and REST suppresses neuron-specific gene expression and the sympathoadrenal lineage. Our studies identify a novel role for REST in NC cell differentiation and suggest cross talk between cAMP and Wnt signaling in NC lineage specification. PMID:21199918

  1. Conducting Polymers for Neural Prosthetic and Neural Interface Applications

    Science.gov (United States)

    2015-01-01

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

  2. PRECURSOR FLARES IN OJ 287

    Energy Technology Data Exchange (ETDEWEB)

    Pihajoki, P.; Berdyugin, A.; Lindfors, E.; Reinthal, R.; Sillanpaeae, A.; Takalo, L. [Tuorla Observatory, Department of Physics and Astronomy, University of Turku, FI-21500 Piikkioe (Finland); Valtonen, M.; Nilsson, K. [Finnish Centre for Astronomy with ESO, University of Turku, FI-21500 Piikkioe (Finland); Zola, S.; Koziel-Wierzbowska, D. [Astronomical Observatory, Jagiellonian University, ul. Orla 171, PL-30-244 Krakow (Poland); Liakos, A. [Department of Astrophysics, Astronomy and Mechanics, University of Athens, GR 157 84 Zografos, Athens, Hellas (Greece); Drozdz, M.; Winiarski, M.; Ogloza, W. [Mount Suhora Observatory, Pedagogical University, ul. Podchorazych 2, PL-30-084 Krakow (Poland); Provencal, J. [Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States); Santangelo, M. M. M. [O.A.C. Osservatorio Astronomico di Capannori, Via di Valle, I-55060 Vorno, Capannori (Italy); Salo, H. [Department of Physical Sciences, University of Oulu, P.O. Box 3000, FI-90014 University of Oulu (Finland); Chandra, S.; Ganesh, S.; Baliyan, K. S., E-mail: popiha@utu.fi [Astronomy and Astrophysics Division, Physical Research Laboratory, Ahmedabad 380009 (India); and others

    2013-02-10

    We have studied three most recent precursor flares in the light curve of the blazar OJ 287 while invoking the presence of a precessing binary black hole in the system to explain the nature of these flares. Precursor flare timings from the historical light curves are compared with theoretical predictions from our model that incorporate effects of an accretion disk and post-Newtonian description for the binary black hole orbit. We find that the precursor flares coincide with the secondary black hole descending toward the accretion disk of the primary black hole from the observed side, with a mean z-component of approximately z{sub c} = 4000 AU. We use this model of precursor flares to predict that precursor flare of similar nature should happen around 2020.96 before the next major outburst in 2022.

  3. [Neural repair].

    Science.gov (United States)

    Kitada, Masaaki; Dezawa, Mari

    2008-05-01

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

  4. Rapid generation of sub-type, region-specific neurons and neural networks from human pluripotent stem cell-derived neurospheres

    Directory of Open Access Journals (Sweden)

    Aynun N. Begum

    2015-11-01

    Full Text Available Stem cell-based neuronal differentiation has provided a unique opportunity for disease modeling and regenerative medicine. Neurospheres are the most commonly used neuroprogenitors for neuronal differentiation, but they often clump in culture, which has always represented a challenge for neurodifferentiation. In this study, we report a novel method and defined culture conditions for generating sub-type or region-specific neurons from human embryonic and induced pluripotent stem cells derived neurosphere without any genetic manipulation. Round and bright-edged neurospheres were generated in a supplemented knockout serum replacement medium (SKSRM with 10% CO2, which doubled the expression of the NESTIN, PAX6 and FOXG1 genes compared with those cultured with 5% CO2. Furthermore, an additional step (AdSTEP was introduced to fragment the neurospheres and facilitate the formation of a neuroepithelial-type monolayer that we termed the “neurosphederm”. The large neural tube-type rosette (NTTR structure formed from the neurosphederm, and the NTTR expressed higher levels of the PAX6, SOX2 and NESTIN genes compared with the neuroectoderm-derived neuroprogenitors. Different layers of cortical, pyramidal, GABAergic, glutamatergic, cholinergic neurons appeared within 27 days using the neurosphederm, which is a shorter period than in traditional neurodifferentiation-protocols (42–60 days. With additional supplements and timeline dopaminergic and Purkinje neurons were also generated in culture too. Furthermore, our in vivo results indicated that the fragmented neurospheres facilitated significantly better neurogenesis in severe combined immunodeficiency (SCID mouse brains compared with the non-fragmented neurospheres. Therefore, this neurosphere-based neurodifferentiation protocol is a valuable tool for studies of neurodifferentiation, neuronal transplantation and high throughput screening assays.

  5. Neural Manifolds for the Control of Movement.

    Science.gov (United States)

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

    2017-06-07

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

  6. Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy.

    Directory of Open Access Journals (Sweden)

    Daniel Rodríguez-Martínez

    Full Text Available Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE, a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80% and yield (>70%. Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies.

  7. Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy

    Science.gov (United States)

    2017-01-01

    Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE), a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80%) and yield (>70%). Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies. PMID:28122047

  8. Bioprinting for Neural Tissue Engineering.

    Science.gov (United States)

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

    2018-01-01

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

  9. Signalling through the Type 1 Insulin-Like Growth Factor Receptor (IGF1R Interacts with Canonical Wnt Signalling to Promote Neural Proliferation in Developing Brain

    Directory of Open Access Journals (Sweden)

    Qichen Hu

    2012-05-01

    Full Text Available Signalling through the IGF1R [type 1 IGF (insulin-like growth factor receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin–KO mice the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i the activity of a LacZ (β-galactosidase reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene and (ii the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin–KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i retarded brain growth, (ii reduced precursor proliferation and (iii decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

  10. Hidden neural networks

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose; Riis, Søren Kamaric

    1999-01-01

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

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

    Science.gov (United States)

    Kondiles, Bethany R; Horner, Philip J

    2018-02-01

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

  12. Biphasic influence of Miz1 on neural crest development by regulating cell survival and apical adhesion complex formation in the developing neural tube

    Science.gov (United States)

    Kerosuo, Laura; Bronner, Marianne E.

    2014-01-01

    Myc interacting zinc finger protein-1 (Miz1) is a transcription factor known to regulate cell cycle– and cell adhesion–related genes in cancer. Here we show that Miz1 also plays a critical role in neural crest development. In the chick, Miz1 is expressed throughout the neural plate and closing neural tube. Its morpholino-mediated knockdown affects neural crest precursor survival, leading to reduction of neural plate border and neural crest specifier genes Msx-1, Pax7, FoxD3, and Sox10. Of interest, Miz1 loss also causes marked reduction of adhesion molecules (N-cadherin, cadherin6B, and α1-catenin) with a concomitant increase of E-cadherin in the neural folds, likely leading to delayed and decreased neural crest emigration. Conversely, Miz1 overexpression results in up-regulation of cadherin6B and FoxD3 expression in the neural folds/neural tube, leading to premature neural crest emigration and increased number of migratory crest cells. Although Miz1 loss effects cell survival and proliferation throughout the neural plate, the neural progenitor marker Sox2 was unaffected, suggesting a neural crest–selective effect. The results suggest that Miz1 is important not only for survival of neural crest precursors, but also for maintenance of integrity of the neural folds and tube, via correct formation of the apical adhesion complex therein. PMID:24307680

  13. Ras signal triggers β-Amyloid Precursor Protein (APP) expression

    OpenAIRE

    Mora, Natalia; Santa Bárbara Ruiz, Paula; Ferreira, Nuno; Serras, Florenci

    2013-01-01

    It has recently been discovered that the Drosophila β-amyloid protein precursor like (Appl) gene, the ortholog of the human β-Amyloid Precursor Protein (APP) gene, is transcriptionally activated by receptor tyrosine kinase activity that involves Ras/MAPK signaling in vivo. This regulation is specifically controlled in photoreceptor neurons of the Drosophila retina. This suggests that some cases of Alzheimer disease, those which have been associated with high expression of the APP gene, may in...

  14. Msx genes define a population of mural cell precursors required for head blood vessel maturation.

    Science.gov (United States)

    Lopes, Miguel; Goupille, Olivier; Saint Cloment, Cécile; Lallemand, Yvan; Cumano, Ana; Robert, Benoît

    2011-07-01

    Vessels are primarily formed from an inner endothelial layer that is secondarily covered by mural cells, namely vascular smooth muscle cells (VSMCs) in arteries and veins and pericytes in capillaries and veinules. We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells. To unravel the role of Msx genes in vascular development, we have inactivated the two Msx genes specifically in mural cells by combining the Msx1(lacZ), Msx2(lox) and Sm22α-Cre alleles. Optical projection tomography demonstrated abnormal branching of the cephalic vessels in E11.5 mutant embryos. The carotid and vertebral arteries showed an increase in caliber that was related to reduced vascular smooth muscle coverage. Taking advantage of a newly constructed Msx1(CreERT2) allele, we demonstrated by lineage tracing that the primary defect lies in a population of VSMC precursors. The abnormal phenotype that ensues is a consequence of impaired BMP signaling in the VSMC precursors that leads to downregulation of the metalloprotease 2 (Mmp2) and Mmp9 genes, which are essential for cell migration and integration into the mural layer. Improper coverage by VSMCs secondarily leads to incomplete maturation of the endothelial layer. Our results demonstrate that both Msx1 and Msx2 are required for the recruitment of a population of neural crest-derived VSMCs.

  15. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  16. [Artificial neural networks in Neurosciences].

    Science.gov (United States)

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

    2011-11-01

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

  17. Identification of Phox2b-regulated genes by expression profiling of cranial motoneuron precursors

    Directory of Open Access Journals (Sweden)

    Reiprich Simone

    2008-06-01

    Full Text Available Abstract Background Branchiomotor neurons comprise an important class of cranial motor neurons that innervate the branchial-arch-derived muscles of the face, jaw and neck. They arise in the ventralmost progenitor domain of the rhombencephalon characterized by expression of the homeodomain transcription factors Nkx2.2 and Phox2b. Phox2b in particular plays a key role in the specification of branchiomotor neurons. In its absence, generic neuronal differentiation is defective in the progenitor domain and no branchiomotor neurons are produced. Conversely, ectopic expression of Phox2b in spinal regions of the neural tube promotes cell cycle exit and neuronal differentiation and, at the same time, induces genes and an axonal phenotype characteristic for branchiomotor neurons. How Phox2b exerts its pleiotropic functions, both as a proneural gene and a neuronal subtype determinant, has remained unknown. Results To gain further insights into the genetic program downstream of Phox2b, we searched for novel Phox2b-regulated genes by cDNA microarray analysis of facial branchiomotor neuron precursors from heterozygous and homozygous Phox2b mutant embryos. We selected for functional studies the genes encoding the axonal growth promoter Gap43, the Wnt antagonist Sfrp1 and the transcriptional regulator Sox13, which were not previously suspected to play roles downstream of Phox2b and whose expression was affected by Phox2b misexpression in the spinal cord. While Gap43 did not produce an obvious phenotype when overexpressed in the neural tube, Sfrp1 induced the interneuron marker Lhx1,5 and Sox13 inhibited neuronal differentiation. We then tested whether Sfrp1 and Sox13, which are down-regulated by Phox2b in the facial neuron precursors, would antagonize some aspects of Phox2b activity. Co-expression of Sfrp1 prevented Phox2b from repressing Lhx1,5 and alleviated the commissural axonal phenotype. When expressed together with Sox13, Phox2b was still able to promote

  18. Transcriptional stimulation of the retina-specific QR1 gene upon growth arrest involves a Maf-related protein.

    OpenAIRE

    Pouponnot, C; Nishizawa, M; Calothy, G; Pierani, A

    1995-01-01

    The avian neural retina (NR) is derived from proliferating neuroectodermal precursors which differentiate after terminal mitosis and become organized in cell strata. Proliferation of postmitotic NR cells can be induced by infection with Rous sarcoma virus (RSV) and requires the expression of a functional v-Src protein. QR1 is a retina-specific gene expressed exclusively at the stage of growth arrest and differentiation during retinal development. In NR cells infected with tsPA101, an RSV muta...

  19. Precursors to glycogen in ovine fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Levitsky, L.L.; Paton, J.B.; Fisher, D.E. (Univ. of Chicago, IL (USA))

    1988-11-01

    Postprandial hepatic glycogenesis in the adult animal is now felt to proceed largely through gluconeogenic pathways rather than directly from glucose. The ovine fetus, like the mature sheep, lacks specific hepatic glucokinase. Therefore, the authors examined the role of lactate as a fetal glycogenic precursor in seven chronically catheterized 125-day sheep fetuses. Fetuses were infused with L-(U-{sup 14}C)lactate and D-(3-{sup 3}H)glucose, while maternal glucose was maintained at 50 mg/dl. Mean fetal hepatic glycogen specific activity ({mu}Ci/mg {times} 10{sup 3}) was 0.82 {plus minus} 0.08 for {sup 14}C and 2.6 {plus minus} 0.4 for {sup 3}H, whereas fetal renal glycogen specific activity was 0.46 {plus minus} 0.22 for {sup 14}C and 0.78 {plus minus} 0.16 for {sup 3}H. In contrast, ({sup 14}C)glucose specific activity was undetectable in blood and mean ({sup 3}H)glucose specific activity was 8.9 {plus minus} 1.3 {mu}Ci/mg {times} 10{sup 3}. The least detectable specific activity of ({sup 14}C)glucose did not differ significantly from the ({sup 14}C)glycogen enrichment in liver, whereas ({sup 3}H)glucose specific activity was significantly greater than ({sup 3}H)glycogen enrichment. The authors conclude that glycogenesis from glucose is partly through the indirect gluconeogenic route and that lactate may be a glycogenic precursor in the ovine fetus.

  20. Characterization of Porcine Ventral Mesencephalic Precursor Cells following Long-Term Propagation in 3D Culture

    Directory of Open Access Journals (Sweden)

    Pia S. Jensen

    2012-01-01

    Full Text Available The potential use of predifferentiated neural precursor cells for treatment of a neurological disorder like Parkinson’s disease combines stem cell research with previous experimental and clinical transplantation of developing dopaminergic neurons. One current obstacle is, however, the lack of ability to generate dopaminergic neurons after long-term in vitro propagation of the cells. The domestic pig is considered a useful nonprimate large animal model in neuroscience, because of a better resemblance of the larger gyrencephalic pig brain to the human brain than the commonly used brains of smaller rodents. In the present study, porcine embryonic (28–30 days, ventral mesencephalic precursor cells were isolated and propagated as free-floating neural tissue spheres in medium containing epidermal growth factor and fibroblast growth factor 2. For passaging, the tissue spheres were cut into quarters, avoiding mechanical or enzymatic dissociation in order to minimize cellular trauma and preserve intercellular contacts. Spheres were propagated for up to 237 days with analysis of cellular content and differentiation at various time points. Our study provides the first demonstration that porcine ventral mesencephalic precursor cells can be long-term propagated as neural tissue spheres, thereby providing an experimental 3D in vitro model for studies of neural precursor cells, their niche, and differentiation capacity.

  1. Characterization of Porcine Ventral Mesencephalic Precursor Cells following Long-Term Propagation in 3D Culture

    Science.gov (United States)

    Jensen, Pia S.; Lyck, Lise; Jensen, Pia; Zimmer, Jens; Meyer, Morten

    2012-01-01

    The potential use of predifferentiated neural precursor cells for treatment of a neurological disorder like Parkinson's disease combines stem cell research with previous experimental and clinical transplantation of developing dopaminergic neurons. One current obstacle is, however, the lack of ability to generate dopaminergic neurons after long-term in vitro propagation of the cells. The domestic pig is considered a useful nonprimate large animal model in neuroscience, because of a better resemblance of the larger gyrencephalic pig brain to the human brain than the commonly used brains of smaller rodents. In the present study, porcine embryonic (28–30 days), ventral mesencephalic precursor cells were isolated and propagated as free-floating neural tissue spheres in medium containing epidermal growth factor and fibroblast growth factor 2. For passaging, the tissue spheres were cut into quarters, avoiding mechanical or enzymatic dissociation in order to minimize cellular trauma and preserve intercellular contacts. Spheres were propagated for up to 237 days with analysis of cellular content and differentiation at various time points. Our study provides the first demonstration that porcine ventral mesencephalic precursor cells can be long-term propagated as neural tissue spheres, thereby providing an experimental 3D in vitro model for studies of neural precursor cells, their niche, and differentiation capacity. PMID:23258982

  2. PAGOSA Sample Problem. Elastic Precursor

    Energy Technology Data Exchange (ETDEWEB)

    Weseloh, Wayne N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Clancy, Sean Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-03

    A PAGOSA simulation of a flyer plate impact which produces an elastic precursor wave is examined. The simulation is compared to an analytic theory for the Mie-Grüneisen equation of state and an elastic-perfectly-plastic strength model.

  3. Preparation of superconductor precursor powders

    Science.gov (United States)

    Bhattacharya, Raghunath; Blaugher, Richard D.

    1995-01-01

    A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals, such as nitrate salts of thallium, barium, calcium, and copper, which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of thallium in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

  4. c-Myc Enhances Sonic Hedgehog-Induced Medulloblastoma Formation from Nestin-Expressing Neural Progenitors in Mice

    Directory of Open Access Journals (Sweden)

    Ganesh Rao

    2003-05-01

    Full Text Available Medulloblastomas are malignant brain tumors that arise in the cerebella of children. The presumed cellsof-origin are undifferentiated precursors of granule neurons that occupy the external granule layer (EGL of the developing cerebellum. The overexpression of proteins that normally stimulate proliferation of neural progenitor cells may initiate medulloblastoma formation. Two known mitogens for neural progenitors are the c-Myc oncoprotein and Sonic hedgehog (Shh, a crucial determinant of embryonic pattern formation in the central nervous system. We modeled the ability of c-Myc and Shh to induce medulloblastoma in mice using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell type-specific manner. We targeted the expression of Shh and c-Myc to nestin-expressing neural progenitor cells by injecting replication-competent ALV splice acceptor (RCAS vectors into the cerebella of newborn mice. Following injection with RCAS-Shh alone, 3/32 (9% mice developed medulloblastomas and 5/32 showed multifocal hyperproliferation of the EGL, possibly a precursor stage of medulloblastoma. Following injection with RCAS-Shh plus RCAS-Myc, 9/39 (23% mice developed medulloblastomas. We conclude that nestin-expressing neural progenitors, present in the cerebellum at birth, can act as the cells-of-origin for medulloblastoma, and that c-Myc cooperates with Shh to enhance tumorigenicity.

  5. Early specification of dopaminergic phenotype during ES cell differentiation

    Directory of Open Access Journals (Sweden)

    Li Meng

    2007-07-01

    Full Text Available Abstract Background Understanding how lineage choices are made during embryonic stem (ES cell differentiation is critical for harnessing strategies for controlled production of therapeutic somatic cell types for cell transplantation and pharmaceutical drug screens. The in vitro generation of dopaminergic neurons, the type of cells lost in Parkinson's disease patients' brains, requires the inductive molecules sonic hedgehog and FGF8, or an unknown stromal cell derived inducing activity (SDIA. However, the exact identity of the responding cells and the timing of inductive activity that specify a dopaminergic fate in neural stem/progenitors still remain elusive. Results Using ES cells carrying a neuroepithelial cell specific vital reporter (Sox1-GFP and FACS purification of Sox1-GFP neural progenitors, we have investigated the temporal aspect of SDIA mediated dopaminergic neuron specification during ES cell differentiation. Our results establish that SDIA induces a dopaminergic neuron fate in nascent neural stem or progenitor cells at, or prior to, Sox1 expression and does not appear to have further instructive role or neurotrophic activity during late neuronal differentiation of neural precursors. Furthermore, we show that dopaminergic neurons could be produced efficiently in a monolayer differentiation paradigm independent of SDIA activity or exogenous signalling molecules. In this case, the competence for dopaminergic neuron differentiation is also established at the level of Sox1 expression. Conclusion Dopaminergic neurons are specified early during mouse ES cell differentiation. The subtype specification seems to be tightly linked with the acquisition of a pan neuroectoderm fate.

  6. Cultural effects on the neural basis of theory of mind.

    Science.gov (United States)

    Kobayashi Frank, Chiyoko; Temple, Elise

    2009-01-01

    "Theory of mind" has been described as the ability to attribute and understand other people's desires and intentions as distinct from one's own. It has been found to develop as early as between 3 and 4 years old, with precursor abilities possibly developing much earlier. There has been debate about the extent to which the developmental trajectory of theory of mind may differ across cultures or language systems. Although very few neuroimaging studies have directly compared different groups from different culture and language systems, across studies of a number of cultural/language groups have been used to explore the neural correlates of theory of mind. A summary of these findings suggests that there may be both universal and culture or language-specific neural correlates related to theory of mind. These studies, while still preliminary in many ways, illustrate the importance of taking into account the cultural background of participants. Furthermore these results suggest that there may be important cultural influence on theory of mind and the neural correlates associated with this ability.

  7. RBFOX1 and RBFOX2 are dispensable in iPSCs and iPSC-derived neurons and do not contribute to neural-specific paternal UBE3A silencing

    Science.gov (United States)

    Chen, Pin-Fang; Hsiao, Jack S.; Sirois, Carissa L.; Chamberlain, Stormy J.

    2016-01-01

    Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function of the maternally inherited copy of UBE3A, an imprinted gene expressed biallelically in most tissues, but expressed exclusively from the maternal allele in neurons. Active transcription of the neuron-specific long non-coding RNA (lncRNA), UBE3A-ATS, has been shown to silence paternal UBE3A. We hypothesized that alternative splicing factors RBFOX2 and RBFOX1 might mediate splicing changes and result in the transcription of UBE3A-ATS in neurons. We found that RBFOX2 and RBFOX1 both bind to UBE3A-ATS transcript in neurons, but are not required for gene expression and/or neuron-specific processing in the SNURF/SNRPN-UBE3A region. However, we found that depletion of RBFOX2 causes a proliferation phenotype in immature neural cultures, suggesting that RBFOX2 is involved in division versus differentiation decisions in iPSC-derived neural progenitors. Absence of RBFOX2 also altered the expression of some genes that are important for glutamatergic neocortical development and Wnt-Frizzled signalling in mature neuronal cultures. Our data show that while RBFOX1 and RBFOX2 do not mediate neuron-specific processing of UBE3A-ATS, these proteins play important roles in developing neurons and are not completely functionally redundant. PMID:27146458

  8. The absence of high-risk HPV combined with specific p53 and p16INK4a expression patterns points to the HPV-independent pathway as the causative agent for vulvar squamous cell carcinoma and its precursor simplex VIN in a young patient.

    Science.gov (United States)

    Kruse, Arnold-Jan; Bottenberg, Marcel J H; Tosserams, Janna; Slangen, Brigitte; van Marion, Ariënne M W; van Trappen, Philippe O

    2008-10-01

    Simplex vulvar intraepithelial neoplasia (VIN) is an important precursor of vulvar invasive squamous cell carcinoma and characteristically occurs in postmenopausal women. In this report, the absence of high-risk human papillomavirus (HPV) combined with specific p53 and p16INK4a expression patterns points to the HPV-independent pathway as the causative agent for vulvar squamous cell carcinoma in a 28-year-old woman. Its precursor simplex VIN was initially interpreted as eczema. Although simplex VIN has a predilection for postmenopausal women, it can occur in young patients. The development of invasive vulvar squamous cell carcinoma underlines the importance of including simplex VIN in the differential diagnosis of vulvar lesions, even at a young age. Furthermore, knowledge about the HPV status in the tumor and thus the underlying causative pathway can alert the gynecologist for the presence or absence of multicentric lower genital tract disease, as this is frequent in the HPV-dependent and not in the HPV-independent pathway.

  9. Data mining methods in the prediction of Dementia: A real-data comparison of the accuracy, sensitivity and specificity of linear discriminant analysis, logistic regression, neural networks, support vector machines, classification trees and random forests.

    Science.gov (United States)

    Maroco, João; Silva, Dina; Rodrigues, Ana; Guerreiro, Manuela; Santana, Isabel; de Mendonça, Alexandre

    2011-08-17

    Dementia and cognitive impairment associated with aging are a major medical and social concern. Neuropsychological testing is a key element in the diagnostic procedures of Mild Cognitive Impairment (MCI), but has presently a limited value in the prediction of progression to dementia. We advance the hypothesis that newer statistical classification methods derived from data mining and machine learning methods like Neural Networks, Support Vector Machines and Random Forests can improve accuracy, sensitivity and specificity of predictions obtained from neuropsychological testing. Seven non parametric classifiers derived from data mining methods (Multilayer Perceptrons Neural Networks, Radial Basis Function Neural Networks, Support Vector Machines, CART, CHAID and QUEST Classification Trees and Random Forests) were compared to three traditional classifiers (Linear Discriminant Analysis, Quadratic Discriminant Analysis and Logistic Regression) in terms of overall classification accuracy, specificity, sensitivity, Area under the ROC curve and Press'Q. Model predictors were 10 neuropsychological tests currently used in the diagnosis of dementia. Statistical distributions of classification parameters obtained from a 5-fold cross-validation were compared using the Friedman's nonparametric test. Press' Q test showed that all classifiers performed better than chance alone (p classification accuracy (Median (Me) = 0.76) an area under the ROC (Me = 0.90). However this method showed high specificity (Me = 1.0) but low sensitivity (Me = 0.3). Random Forest ranked second in overall accuracy (Me = 0.73) with high area under the ROC (Me = 0.73) specificity (Me = 0.73) and sensitivity (Me = 0.64). Linear Discriminant Analysis also showed acceptable overall accuracy (Me = 0.66), with acceptable area under the ROC (Me = 0.72) specificity (Me = 0.66) and sensitivity (Me = 0.64). The remaining classifiers showed overall classification accuracy above a median value of 0.63, but for most

  10. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

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

  11. Leukemia inhibitory factor favours neurogenic differentiation of long-term propagated human midbrain precursor cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Widmer, Hans R; Zimmer, Jens

    2009-01-01

    There is a lot of excitement about the potential use of multipotent neural stem cells for the treatment of neurodegenerative diseases. However, the strategy is compromised by the general loss of multipotency and ability to generate neurons after long-term in vitro propagation. In the present study...... EGF+FGF2, EGF+FGF2+heparin or leukemia inhibitory factor (LIF; 10 ng/ml)+FGF2+heparin. Cultures were subsequently propagated for more than 180 days with NTS analyzed at various time-points. Our data show for the first time that human VM neural precursor cells can be long-term propagated as NTS......, human embryonic (5 weeks post-conception) ventral mesencephalic (VM) precursor cells were propagated as neural tissue-spheres (NTS) in epidermal growth factor (EGF; 20 ng/ml) and fibroblast growth factor 2 (FGF2; 20 ng/ml). After more than 325 days, the NTS were transferred to media containing either...

  12. The Innate Lymphoid Cell Precursor.

    Science.gov (United States)

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  13. Precursor polymer compositions comprising polybenzimidazole

    Energy Technology Data Exchange (ETDEWEB)

    Klaehn, John R.; Peterson, Eric S.; Orme, Christopher J.

    2015-07-14

    Stable, high performance polymer compositions including polybenzimidazole (PBI) and a melamine-formaldehyde polymer, such as methylated, poly(melamine-co-formaldehyde), for forming structures such as films, fibers and bulky structures. The polymer compositions may be formed by combining polybenzimidazole with the melamine-formaldehyde polymer to form a precursor. The polybenzimidazole may be reacted and/or intertwined with the melamine-formaldehyde polymer to form the polymer composition. For example, a stable, free-standing film having a thickness of, for example, between about 5 .mu.m and about 30 .mu.m may be formed from the polymer composition. Such films may be used as gas separation membranes and may be submerged into water for extended periods without crazing and cracking. The polymer composition may also be used as a coating on substrates, such as metal and ceramics, or may be used for spinning fibers. Precursors for forming such polymer compositions are also disclosed.

  14. Artificial Neural Networks as a powerful numerical tool to classify specific features of a tooth based on 3D scan data.

    Science.gov (United States)

    Raith, Stefan; Vogel, Eric Per; Anees, Naeema; Keul, Christine; Güth, Jan-Frederik; Edelhoff, Daniel; Fischer, Horst

    2017-01-01

    Chairside manufacturing based on digital image acquisition is gainingincreasing importance in dentistry. For the standardized application of these methods, it is paramount to have highly automated digital workflows that can process acquired 3D image data of dental surfaces. Artificial Neural Networks (ANNs) arenumerical methods primarily used to mimic the complex networks of neural connections in the natural brain. Our hypothesis is that an ANNcan be developed that is capable of classifying dental cusps with sufficient accuracy. This bears enormous potential for an application in chairside manufacturing workflows in the dental field, as it closes the gap between digital acquisition of dental geometries and modern computer-aided manufacturing techniques.Three-dimensional surface scans of dental casts representing natural full dental arches were transformed to range image data. These data were processed using an automated algorithm to detect candidates for tooth cusps according to salient geometrical features. These candidates were classified following common dental terminology and used as training data for a tailored ANN.For the actual cusp feature description, two different approaches were developed and applied to the available data: The first uses the relative location of the detected cusps as input data and the second method directly takes the image information given in the range images. In addition, a combination of both was implemented and investigated.Both approaches showed high performance with correct classifications of 93.3% and 93.5%, respectively, with improvements by the combination shown to be minor.This article presents for the first time a fully automated method for the classification of teeththat could be confirmed to work with sufficient precision to exhibit the potential for its use in clinical practice,which is a prerequisite for automated computer-aided planning of prosthetic treatments with subsequent automated chairside manufacturing. Copyright

  15. Anise oil as para-methoxyamphetamine (PMA) precursor.

    Science.gov (United States)

    Waumans, Dieter; Bruneel, Noël; Tytgat, Jan

    2003-04-23

    These days, MDMA is one of the most popular drugs of abuse. Due to its illegality, MDMA and its chemical precursors are watched by governmental organizations in many countries. To avoid conflicts with legal instances, underground chemists have tried to market several new unregulated amphetamine analogues, such as 4-MTA. Para-methoxyamphetamine (PMA), on the other hand, is regulated by law but its precursors are easily obtained since they are cheap and unwatched. This article presents such a case, namely the large scale synthesis of PMA using anethole, a main constituent of anise oil, as precursor. Anethole has been converted to its phenyl acetone analogue via peracid oxidation, while PMA itself has been synthesized using this ketone as precursor in the Leuckart synthesis. The synthesis of PMA using anethole as starting product has been investigated applying GC/MS and GC-HSPME/MS techniques, hereby discovering new specific (4-methoxyphenol) and already identified synthesis impurities (4-methyl-5-(4-methoxyphenyl)pyrimidine, N-(beta-4-methoxyphenylisopropyl)-4-methoxybenzyl methyl ketimine, 1-(4-methoxyphenyl)-N-(2-(4-methoxyphenyl)-1-methylethyl-2-propanamine, 1-(4-methoxyphenyl)-N-methyl-N-(2-(4-methoxyphenyl)-1-methylethyl-2-propanamine, N-(beta-4-methoxyphenylisopropyl)-4-methoxybenzaldimine). The new impurity 4-methoxyphenol is specific for the application of a peracid oxidation method where anethole is used as precursor.

  16. Subcellular Distribution of Glutathione Precursors in Arabidopsis thaliana

    Science.gov (United States)

    Koffler, Barbara Eva; Maier, Romana; Zechmann, Bernd

    2011-01-01

    Abstract Glutathione is an important antioxidant and has many important functions in plant development, growth and defense. Glutathione synthesis and degradation is highly compartment-specific and relies on the subcellular availability of its precursors, cysteine, glutamate, glycine and γ-glutamylcysteine especially in plastids and the cytosol which are considered as the main centers for glutathione synthesis. The availability of glutathione precursors within these cell compartments is therefore of great importance for successful plant development and defense. The aim of this study was to investigate the compartment-specific importance of glutathione precursors in Arabidopsis thaliana. The subcellular distribution was compared between wild type plants (Col-0), plants with impaired glutathione synthesis (glutathione deficient pad2-1 mutant, wild type plants treated with buthionine sulfoximine), and one complemented line (OE3) with restored glutathione synthesis. Immunocytohistochemistry revealed that the inhibition of glutathione synthesis induced the accumulation of the glutathione precursors cysteine, glutamate and glycine in most cell compartments including plastids and the cytosol. A strong decrease could be observed in γ-glutamylcysteine (γ-EC) contents in these cell compartments. These experiments demonstrated that the inhibition of γ-glutamylcysteine synthetase (GSH1) – the first enzyme of glutathione synthesis – causes a reduction of γ-EC levels and an accumulation of all other glutathione precursors within the cells. PMID:22050910

  17. The Neural Correlates of Race

    Science.gov (United States)

    Ito, Tiffany A.; Bartholow, Bruce D.

    2009-01-01

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

  18. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  19. Critical role of PI3K/Akt/GSK3β in motoneuron specification from human neural stem cells in response to FGF2 and EGF.

    Directory of Open Access Journals (Sweden)

    Luis Ojeda

    Full Text Available Fibroblast growth factor (FGF and epidermal growth factor (EGF are critical for the development of the nervous system. We previously discovered that FGF2 and EGF had opposite effects on motor neuron differentiation from human fetal neural stem cells (hNSCs, but the underlying mechanisms remain unclear. Here, we show that FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen synthase kinase 3 beta (GSK3β activation. High levels of phosphatidylinositol 3-kinase (PI3K/Akt activation accompanied with GSK3β inactivation result in reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by chemical inhibitors or RNA interference or overexpression of a constitutively active form of GSK3β enhances HB9 expression. Consequently, PI3K inhibition increases hNSCs differentiation into HB9(+/microtubule-associated protein 2 (MAP2(+ motor neurons in vitro. More importantly, blocking PI3K not only enhances motor neuron differentiation from hNSCs grafted into the ventral horn of adult rat spinal cords, but also permits ectopic generation of motor neurons in the dorsal horn by overriding environmental influences. Our data suggest that FGF2 and EGF affect the motor neuron fate decision in hNSCs differently through a fine tuning of the PI3K/AKT/GSK3β pathway, and that manipulation of this pathway can enhance motor neuron generation.

  20. Norepinephrine directly activates adult hippocampal precursors via β3 adrenergic receptors

    Science.gov (United States)

    Jhaveri, Dhanisha J.; Mackay, Eirinn W.; Hamlin, Adam S.; Marathe, Swananda V.; Nandam, L. Sanjay; Vaidya, Vidita A.; Bartlett, Perry F.

    2010-01-01

    Adult hippocampal neurogenesis is a critical form of cellular plasticity that is greatly influenced by neural activity. Among the neurotransmitters that are widely implicated in regulating this process are serotonin and norepinephrine, levels of which are modulated by stress, depression and clinical antidepressants. However, studies to date have failed to address a direct role for either neurotransmitter in regulating hippocampal precursor activity. Here we show that norepinephrine but not serotonin directly activates self-renewing and multipotent neural precursors, including stem cells, from the hippocampus of adult mice. Mechanistically, we provide evidence that β3 adrenergic receptors, which are preferentially expressed on a Hes5-expressing precursor population in the subgranular zone (SGZ), mediate this norepinephrine-dependent activation. Moreover, intrahippocampal injection of a selective β3 adrenergic receptor agonist in vivo increases the number of proliferating cells in the SGZ. Similarly, systemic injection of the β adrenergic receptor agonist isoproterenol not only results in enhancement of proliferation in the SGZ but also leads to an increase in the percentage of nestin/glial fibrillary acidic protein double-positive neural precursors in vivo. Finally, using a novel ex vivo ‘slice-sphere’ assay that maintains an intact neurogenic niche, we demonstrate that antidepressants that selectively block the reuptake of norepinephrine, but not serotonin, robustly increase hippocampal precursor activity via β adrenergic receptors. These findings suggest that the activation of neurogenic precursors and stem cells via β3 adrenergic receptors could be a potent mechanism to increase neuronal production, providing a putative target for the development of novel antidepressants. PMID:20164362

  1. Precursor missions to interstellar exploration.

    Science.gov (United States)

    Wallace, R. A.

    This paper summarizes material developed over a three-month period by a JPL team of mission architects/analysts and advanced technology developers for presentation to NASA Headquarters in the summer of 1998. A preliminary mission roadmap is suggested that leads to the exploration of star systems within 40 light years of our Solar System. The precursor missions include technology demonstrations as well as missions that return significant new knowledge about the space environment reached. Three propulsion technology candidates are selected on the basis of allowing eventual travel to the nearest star taking 10 years. One of the three propulsion technologies has a near term version applicable to early missions (prior to 2010) - the solar sail. Using early sail missions other critical supporting technologies can be developed that will later enable Interstellar travel. Example precursor missions are sail demonstration missions, including a solar storm warning mission demonstrating a simple sail, a solar polar imaging mission using an intermediate sail, and a 200-AU Heliosphere Explorer mission using an advanced solar sail. Mission and technology strategy, science return, and potential mission spin-offs are described.

  2. Indices for Testing Neural Codes

    OpenAIRE

    Jonathan D. Victor; Nirenberg, Sheila

    2008-01-01

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

  3. A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

    Energy Technology Data Exchange (ETDEWEB)

    Lamprianou, Smaragda; Chatzopoulou, Elli; Thomas, Jean-Léon; Bouyain, Samuel; Harroch, Sheila (IP-Korea); (UPMC); (UMKC)

    2013-09-23

    The six members of the contactin (CNTN) family of neural cell adhesion molecules are involved in the formation and maintenance of the central nervous system (CNS) and have been linked to mental retardation and neuropsychiatric disorders such as autism. Five of the six CNTNs bind to the homologous receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ), but the biological roles of these interactions remain unclear. We report here the cocrystal structure of the carbonic anhydrase-like domain of PTPRZ bound to tandem Ig repeats of CNTN1 and combine these structural data with binding assays to show that PTPRZ binds specifically to CNTN1 expressed at the surface of oligodendrocyte precursor cells. Furthermore, analyses of glial cell populations in wild-type and PTPRZ-deficient mice show that the binding of PTPRZ to CNTN1 expressed at the surface of oligodendrocyte precursor cells inhibits their proliferation and promotes their development into mature oligodendrocytes. Overall, these results implicate the PTPRZ/CNTN1 complex as a previously unknown modulator of oligodendrogenesis.

  4. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence.

    Science.gov (United States)

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These

  5. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence

    Science.gov (United States)

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These

  6. An arthropod cis-regulatory element functioning in sensory organ precursor development dates back to the Cambrian

    Directory of Open Access Journals (Sweden)

    Simpson Pat

    2010-09-01

    Full Text Available Abstract Background An increasing number of publications demonstrate conservation of function of cis-regulatory elements without sequence similarity. In invertebrates such functional conservation has only been shown for closely related species. Here we demonstrate the existence of an ancient arthropod regulatory element that functions during the selection of neural precursors. The activity of genes of the achaete-scute (ac-sc family endows cells with neural potential. An essential, conserved characteristic of proneural genes is their ability to restrict their own activity to single or a small number of progenitor cells from their initially broad domains of expression. This is achieved through a process called lateral inhibition. A regulatory element, the sensory organ precursor enhancer (SOPE, is required for this process. First identified in Drosophila, the SOPE contains discrete binding sites for four regulatory factors. The SOPE of the Drosophila asense gene is situated in the 5' UTR. Results Through a manual comparison of consensus binding site sequences we have been able to identify a SOPE in UTR sequences of asense-like genes in species belonging to all four arthropod groups (Crustacea, Myriapoda, Chelicerata and Insecta. The SOPEs of the spider Cupiennius salei and the insect Tribolium castaneum are shown to be functional in transgenic Drosophila. This would place the origin of this regulatory sequence as far back as the last common ancestor of the Arthropoda, that is, in the Cambrian, 550 million years ago. Conclusions The SOPE is not detectable by inter-specific sequence comparison, raising the possibility that other ancient regulatory modules in invertebrates might have escaped detection.

  7. Expression patterns of neural genes in Euperipatoides kanangrensis suggest divergent evolution of onychophoran and euarthropod neurogenesis.

    Science.gov (United States)

    Eriksson, Bo Joakim; Stollewerk, Angelika

    2010-12-28

    One of the controversial debates on euarthropod relationships centers on the question as to whether insects, crustaceans, and myriapods (Mandibulata) share a common ancestor or whether myriapods group with the chelicerates (Myriochelata). The debate was stimulated recently by studies in chelicerates and myriapods that show that neural precursor groups (NPGs) segregate from the neuroectoderm generating the nervous system, whereas in insects and crustaceans the nervous tissue is produced by stem cells. Do the shared neural characters of myriapods and chelicerates represent derived characters that support the Myriochelata grouping? Or do they rather reflect the ancestral pattern? Analyses of neurogenesis in a group closely related to euarthropods, the onychophorans, show that, similar to insects and crustaceans, single neural precursors are formed in the neuroectoderm, potentially supporting the Myriochelata hypothesis. Here we show that the nature and the selection of onychophoran neural precursors are distinct from euarthropods. The onychophoran nervous system is generated by the massive irregular segregation of single neural precursors, contrasting with the limited number and stereotyped arrangement of NPGs/stem cells in euarthropods. Furthermore, neural genes do not show the spatiotemporal pattern that sets up the precise position of neural precursors as in euarthropods. We conclude that neurogenesis in onychophorans largely does not reflect the ancestral pattern of euarthropod neurogenesis, but shows a mixture of derived characters and ancestral characters that have been modified in the euarthropod lineage. Based on these data and additional evidence, we suggest an evolutionary sequence of arthropod neurogenesis that is in line with the Mandibulata hypothesis.

  8. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

    Full Text Available This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p. corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  9. Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles

    Directory of Open Access Journals (Sweden)

    Kong Lingxin

    2008-04-01

    Full Text Available Abstract Background Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1 particles that contain chimeric glycoprotein C (gC – glial cell line-derived neurotrophic factor (GDNF or brain-derived neurotrophic factor (BDNF proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression. Results Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal-specific

  10. Premarital precursors of marital infidelity.

    Science.gov (United States)

    Allen, Elizabeth S; Rhoades, Galena Kline; Stanley, Scott M; Markman, Howard J; Williams, Tamara; Melton, Jessica; Clements, Mari L

    2008-06-01

    Premarital precursors of infidelity were evaluated in a sample of 72 couples (N = 144) who were taking part in a longitudinal study of marriage. Premarital self-report and observational data were compared for couples who experienced infidelity and those who did not experience infidelity in the first years of marriage. Couples in which the male engaged in marital infidelity were characterized, premaritally, by significantly lower male sexual satisfaction, lower male positive communication, and higher female invalidation, whereas couples in which the female went on to engage in infidelity were characterized, premaritally, by significantly lower levels of female positive communication, higher levels of male and female negative communication, and higher levels of male and female invalidation. Implications of the findings for future research on the prediction and prevention of infidelity are discussed.

  11. Embryonic cerebrospinal fluid in brain development: neural progenitor control.

    Science.gov (United States)

    Gato, Angel; Alonso, M Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M F; Lamus, Francisco; Desmond, Mary E

    2014-08-28

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called "embryonic CSF." Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life.

  12. Isolation and characterization of adult neural stem cells.

    Science.gov (United States)

    Siebzehnrubl, Florian A; Vedam-Mai, Vinata; Azari, Hassan; Reynolds, Brent A; Deleyrolle, Loic P

    2011-01-01

    It has been thought for a long time that the adult brain is incapable of generating new neurons, or that neurons cannot be added to its complex circuitry. However, recent technology has resulted in an explosion of research demonstrating that neurogenesis, or the birth of new neurons from adult stem cells constitutively occurs in two specific regions of the mammalian brain; namely the subventricular zone and hippocampal dentate gyrus. Adult CNS stem cells exhibit three main characteristics: (1) they are "self-renewing," i.e., they possess a theoretically unlimited ability to produce progeny indistinguishable from themselves, (2) they are proliferative (undergoing mitosis) and (3) they are multipotent for the different neuroectodermal lineages of the CNS, including the different neuronal, and glial subtypes. CNS stem cells and all progenitor cell types are broadly termed "precursors." In this chapter, we describe methods to identify, isolate and experimentally manipulate stem cells of the adult brain. We outline how to prepare a precursor cell culture from naive brain tissue and how to test the "stemness" potential of different cell types present in that culture, which is achieved in a three-step paradigm. Following their isolation, stem/progenitor cells are expanded in neurosphere culture. Single cells obtained from these neurospheres are sorted for the expression of surface markers by flow cytometry. Finally, putative stem cells from cell sorting will be subjected to the so-called neural colony-forming cell assay, which allows discrimination between stem and progenitor cells. At the end of this chapter we will also describe how to identify neural stem cells in vivo.

  13. Differentiation of retinal ganglion cells and photoreceptor precursors from mouse induced pluripotent stem cells carrying an Atoh7/Math5 lineage reporter.

    Directory of Open Access Journals (Sweden)

    Bin-Bin Xie

    Full Text Available The neural retina is a critical component of the visual system, which provides the majority of sensory input in humans. Various retinal degenerative diseases can result in the permanent loss of retinal neurons, especially the light-sensing photoreceptors and the centrally projecting retinal ganglion cells (RGCs. The replenishment of lost RGCs and the repair of optic nerve damage are particularly challenging, as both RGC specification and their subsequent axonal growth and projection involve complex and precise regulation. To explore the developmental potential of pluripotent stem cell-derived neural progenitors, we have established mouse iPS cells that allow cell lineage tracing of progenitors that have expressed Atoh7/Math5, a bHLH transcription factor required for RGC production. These Atoh7 lineage reporter iPS cells encode Cre to replace one copy of the endogenous Atoh7 gene and a Cre-dependent YFP reporter in the ROSA locus. In addition, they express pluripotent markers and are capable of generating teratomas in vivo. Under anterior neural induction and neurogenic conditions in vitro, the Atoh7-Cre/ROSA-YFP iPS cells differentiate into neurons that co-express various RGC markers and YFP, indicating that these neurons are derived from Atoh7-expressing progenitors. Consistent with previous in vivo cell lineage studies, the Atoh7-Cre/ROSA-YFP iPS cells also give rise to a subset of Crx-positive photoreceptor precursors. Furthermore, inhibition of Notch signaling in the iPSC cultures results in a significant increase of YFP-positive RGCs and photoreceptor precursors. Together, these results show that Atoh7-Cre/ROSA-YFP iPS cells can be used to monitor the development and survival of RGCs and photoreceptors from pluripotent stem cells.

  14. Ezh2 Expression in Astrocytes Induces Their Dedifferentiation Toward Neural Stem Cells

    NARCIS (Netherlands)

    Sher, Falak; Boddeke, Erik; Copray, Sjef

    Recently, we have demonstrated the expression of the polycomb group protein Ezh2 in embryonic and adult neural stem cells. Although Ezh2 remained highly expressed when neural stem cells differentiate into oligodendrocyte precursor cells, it is downregulated during the differentiation into neurons or

  15. A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus

    NARCIS (Netherlands)

    Rodríguez, Esteban M; Guerra, María M; Vío, Karin; González, César; Ortloff, Alexander; Bátiz, Luis F; Rodríguez, Sara; Jara, María C; Muñoz, Rosa I; Ortega, Eduardo; Jaque, Jaime; Guerra, Francisco; Sival, Deborah A; den Dunnen, Wilfred F A; Jiménez, Antonio J; Domínguez-Pinos, María D; Pérez-Fígares, José M; McAllister, James P; Johanson, Conrad

    2012-01-01

    Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal

  16. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

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

  17. Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells.

    Science.gov (United States)

    Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Scionti, Domenico; Diomede, Francesca; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-06-01

    In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties. This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate toward neuronal precursor cells. Specifically, we have treated the hGMSCs with CBD (5 µM) for 24 h in order to evaluate the expression of genes involved in cannabidiol signaling, cell proliferation, self-renewal and multipotency, and neural progenitor cells differentiation. Next generation sequencing (NGS) demonstrated that CBD activates genes associated with G protein coupled receptor signaling in hGMSCs. Genes involved in DNA replication, cell cycle, proliferation, and apoptosis were regulated. Moreover, genes associated with the biological process of neuronal progenitor cells (NCPs) proliferation, neuron differentiation, neurogenesis, and nervous system development were significantly modulated. From our results, we hypothesize that human gingiva-derived MSCs conditioned with CBD could represent a valid method for improving the hGMSCs phenotype and thus might be a potential therapeutic tool in the treatment of neurodegenerative diseases. J. Cell. Biochem. 118: 1531-1546, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Neural Tube Defects

    Science.gov (United States)

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

  19. Precursor/product antiport in bacteria

    NARCIS (Netherlands)

    Poolman, B.

    1990-01-01

    Many microorganisms metabolize their substrates (precursors) only partially and excrete the products of the metabolism into the medium. Although uptake of precursor and exit of product can proceed as two independent steps, there is increasing evidence that these processes are often linked and that

  20. Transcription factor Runx1 is pro-neurogenic in adult hippocampal precursor cells.

    Directory of Open Access Journals (Sweden)

    Hirokazu Fukui

    Full Text Available Transcription factor Runx1 (Runt Related Transcription Factor 1, plays an important role in the differentiation of hematopoetic stem cells, angiogenesis and the development of nociceptive neurons. These known functions have in common that they relate to lineage decisions. We thus asked whether such role might also be found for Runx1 in adult hippocampal neurogenesis as a process, in which such decisions have to be regulated lifelong. Runx1 shows a widespread low expression in the adult mouse brain, not particularly prominent in the hippocampus and the resident neural precursor cells. Isoforms 1 and 2 of Runx1 (but not 3 to 5 driven by the proximal promoter were expressed in hippocampal precursor cells ex vivo, albeit again at very low levels, and were markedly increased after stimulation with TGF-β1. Under differentiation conditions (withdrawal of growth factors Runx1 became down-regulated. Overexpression of Runx1 in vitro reduced proliferation, increased survival of precursor cells by reducing apoptosis, and increased neuronal differentiation, while slightly reducing dendritic morphology and complexity. Transfection with dominant-negative Runx1 in hippocampal precursor cells in vitro did not result in differences in neurogenesis. Hippocampal expression of Runx1 correlated with adult neurogenesis (precursor cell proliferation across BXD recombinant strains of mice and covarying transcripts enriched in the GO categories "neural precursor cell proliferation" and "neuron differentiation". Runx1 is thus a plausible candidate gene to be involved in regulating initial differentiation-related steps of adult neurogenesis. It seems, however, that the relative contribution of Runx1 to such effect is complementary and will explain only small parts of the cell-autonomous pro-differentiation effect.

  1. Measurement of excitation energy of neutron-rich precursor fragments

    Science.gov (United States)

    Mosby, Michelle Anthea

    Projectile fragmentation forms the basis for beam production at radioactive beam facilities such as the National Superconducting Cyclotron Laboratory (NSCL), yet uncertainties remain about the specifics of the production mechanism. For example, very little is known about the excitation energy of the precursors of the observed final fragments. In the present work, isotopes of sodium, neon, and fluorine produced in the fragmentation of a 32 Mg beam at 86 MeV/nucleon in a beryllium target, ranging in mass loss from DeltaA = 3--12, were observed and the coincident neutrons were detected using the Modular Neutron Array (MoNA). Neutron hit multiplicity in MoNA was compared to output from the statistical evaporation model PACE which was passed through a GEANT4 simulation to account for detector response with a X2v analysis. The neutron hit multiplicity distributions were used to determine the mass loss and excitation energy of the precursor fragments created in the fast step of the reaction. The mass loss and excitation energy were compared to abrasion/ablation models and an internuclear cascade model, ISABEL. For sodium and neon observed fragments, a single precursor mass was found, with a wide range of high excitation energies, up to 60 MeV. Observed fluorine isotopes were also found to have high excitation energies, ranging from 40--80 MeV, but with some variation in precursor mass.

  2. Identification and characterization of secondary neural tube-derived embryonic neural stem cells in vitro.

    Science.gov (United States)

    Shaker, Mohammed R; Kim, Joo Yeon; Kim, Hyun; Sun, Woong

    2015-05-15

    Secondary neurulation is an embryonic progress that gives rise to the secondary neural tube, the precursor of the lower spinal cord region. The secondary neural tube is derived from aggregated Sox2-expressing neural cells at the dorsal region of the tail bud, which eventually forms rosette or tube-like structures to give rise to neural tissues in the tail bud. We addressed whether the embryonic tail contains neural stem cells (NSCs), namely secondary NSCs (sNSCs), with the potential for self-renewal in vitro. Using in vitro neurosphere assays, neurospheres readily formed at the rosette and neural-tube levels, but less frequently at the tail bud tip level. Furthermore, we identified that sNSC-generated neurospheres were significantly smaller in size compared with cortical neurospheres. Interestingly, various cell cycle analyses revealed that this difference was not due to a reduction in the proliferation rate of NSCs, but rather the neuronal commitment of sNSCs, as sNSC-derived neurospheres contain more committed neuronal progenitor cells, even in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). These results suggest that the higher tendency for sNSCs to spontaneously differentiate into progenitor cells may explain the limited expansion of the secondary neural tube during embryonic development.

  3. Learning from large scale neural simulations

    DEFF Research Database (Denmark)

    Serban, Maria

    2017-01-01

    -possibly explanations of neural and cognitive phenomena, or they can be used to test explanatory hypotheses and identify sufficient causal factors in specific neurobiological mechanisms, or yet again they can be deployed exploratorily to evaluate the hierarchy of multiple neural and cognitive models that are put...

  4. Acrylonitrile, an advantageous precursor to synthesize nitrogen doped carbon nanotubes

    Science.gov (United States)

    Aguilar-Elguézabal, A.; Román-Aguirre, M.; De la Torre, L.; Zaragoza, E. A.

    2017-05-01

    The nitrogen doped carbon nanotubes present specific characteristics that offer better performance than pure carbon nanotubes for application like biomedicine, hydrogen adsorption and electrocataytic devices. This work present a simple method to obtain well-aligned nitrogen doped multi wall carbon nanotubes, which present open channels with diameter around 50 nm. These carbon nanotubes are obtained using acrylonitrile as carbon and nitrogen source, which offers some advantages on the use of other precursors like ammonia, pyridine, benzylamine, acetonitrile or melamine.

  5. Electrophysiological precursors of social conformity.

    Science.gov (United States)

    Shestakova, Anna; Rieskamp, Jörg; Tugin, Sergey; Ossadtchi, Alexey; Krutitskaya, Janina; Klucharev, Vasily

    2013-10-01

    Humans often change their beliefs or behavior due to the behavior or opinions of others. This study explored, with the use of human event-related potentials (ERPs), whether social conformity is based on a general performance-monitoring mechanism. We tested the hypothesis that conflicts with a normative group opinion evoke a feedback-related negativity (FRN) often associated with performance monitoring and subsequent adjustment of behavior. The experimental results show that individual judgments of facial attractiveness were adjusted in line with a normative group opinion. A mismatch between individual and group opinions triggered a frontocentral negative deflection with the maximum at 200 ms, similar to FRN. Overall, a conflict with a normative group opinion triggered a cascade of neuronal responses: from an earlier FRN response reflecting a conflict with the normative opinion to a later ERP component (peaking at 380 ms) reflecting a conforming behavioral adjustment. These results add to the growing literature on neuronal mechanisms of social influence by disentangling the conflict-monitoring signal in response to the perceived violation of social norms and the neural signal of a conforming behavioral adjustment.

  6. Electrophysiological precursors of social conformity

    Science.gov (United States)

    Rieskamp, Jörg; Tugin, Sergey; Ossadtchi, Alexey; Krutitskaya, Janina; Klucharev, Vasily

    2013-01-01

    Humans often change their beliefs or behavior due to the behavior or opinions of others. This study explored, with the use of human event-related potentials (ERPs), whether social conformity is based on a general performance-monitoring mechanism. We tested the hypothesis that conflicts with a normative group opinion evoke a feedback-related negativity (FRN) often associated with performance monitoring and subsequent adjustment of behavior. The experimental results show that individual judgments of facial attractiveness were adjusted in line with a normative group opinion. A mismatch between individual and group opinions triggered a frontocentral negative deflection with the maximum at 200 ms, similar to FRN. Overall, a conflict with a normative group opinion triggered a cascade of neuronal responses: from an earlier FRN response reflecting a conflict with the normative opinion to a later ERP component (peaking at 380 ms) reflecting a conforming behavioral adjustment. These results add to the growing literature on neuronal mechanisms of social influence by disentangling the conflict-monitoring signal in response to the perceived violation of social norms and the neural signal of a conforming behavioral adjustment. PMID:22683703

  7. Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

    Science.gov (United States)

    Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

    2017-07-04

    Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

    Science.gov (United States)

    Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

    2010-01-15

    Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

  9. Neurally-mediated sincope.

    Science.gov (United States)

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

    2009-08-01

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

  10. Bmps and id2a act upstream of Twist1 to restrict ectomesenchyme potential of the cranial neural crest.

    Directory of Open Access Journals (Sweden)

    Ankita Das

    Full Text Available Cranial neural crest cells (CNCCs have the remarkable capacity to generate both the non-ectomesenchyme derivatives of the peripheral nervous system and the ectomesenchyme precursors of the vertebrate head skeleton, yet how these divergent lineages are specified is not well understood. Whereas studies in mouse have indicated that the Twist1 transcription factor is important for ectomesenchyme development, its role and regulation during CNCC lineage decisions have remained unclear. Here we show that two Twist1 genes play an essential role in promoting ectomesenchyme at the expense of non-ectomesenchyme gene expression in zebrafish. Twist1 does so by promoting Fgf signaling, as well as potentially directly activating fli1a expression through a conserved ectomesenchyme-specific enhancer. We also show that Id2a restricts Twist1 activity to the ectomesenchyme lineage, with Bmp activity preferentially inducing id2a expression in non-ectomesenchyme precursors. We therefore propose that the ventral migration of CNCCs away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme development by relieving Id2a-dependent repression of Twist1 function. Together our model shows how the integration of Bmp inhibition at its origin and Fgf activation along its migratory route would confer temporal and spatial specificity to the generation of ectomesenchyme from the neural crest.

  11. Enzymatic synthesis of vitamin B6 precursor

    Directory of Open Access Journals (Sweden)

    Prlainović Nevena Ž.

    2013-01-01

    Full Text Available 3-Cyano-4-ethoxymethyl-6-methyl-2-pyridone is an important precursor in the synthesis of vitamin B6, obtained in the addition reaction between 2-cyanoacetamide and 1-ethoxy-2,4-pentanedione catalyzed by lipase from Candida rugosa (triacylglycerol ester hydrolases, EC 3.1.1.3. This work shows new experimental data and mathematical modeling of lipase catalyzed synthesis of 3-cyano-4-ethoxymethyl-6-methyl-2-pyridone, starting from 1-ethoxy-2,4-pentanedione and 2-cyanoacetamide. Kinetic measurements were done at 50 oC with enzyme concentration of 1.2 % w/v. Experimental results were fitted with two kinetic models: the ordered bi-ter and ping-pong bi-ter model, and the initial rates of the reaction were found to correlate best with a ping-pong bi-ter mechanism with inhibition by 2-cyanoacetamide. Obtained specificity constants indicated that lipase from C. rugosa had higher affinity towards 1-ethoxy-2,4-pentanedione and less bulky substrates. [Projekat Ministarstva nauke Republike Srbije, br. 172013, br. III 46010 and br. 172049

  12. Cystic precursors to invasive pancreatic cancer

    Science.gov (United States)

    Matthaei, Hanno; Schulick, Richard D.; Hruban, Ralph H.; Maitra, Anirban

    2011-01-01

    Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not. PMID:21383670

  13. Synthesis and structures of metal chalcogenide precursors

    Science.gov (United States)

    Hepp, Aloysius F.; Duraj, Stan A.; Eckles, William E.; Andras, Maria T.

    1990-01-01

    The reactivity of early transition metal sandwich complexes with sulfur-rich molecules such as dithiocarboxylic acids was studied. Researchers recently initiated work on precursors to CuInSe2 and related chalcopyrite semiconductors. Th every high radiation tolerance and the high absorption coefficient of CuInSe2 makes this material extremely attractive for lightweight space solar cells. Their general approach in early transition metal chemistry, the reaction of low-valent metal complexes or metal powders with sulfur and selenium rich compounds, was extended to the synthesis of chalcopyrite precursors. Here, the researchers describe synthesis, structures, and and routes to single molecule precursors to metal chalcogenides.

  14. Mechanistic modeling study on process optimization and precursor utilization with atmospheric spatial atomic layer deposition

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Zhang; He, Wenjie; Duan, Chenlong [State Key Laboratory of Digital Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Chen, Rong, E-mail: rongchen@mail.hust.edu.cn [State Key Laboratory of Digital Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Shan, Bin [State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China)

    2016-01-15

    Spatial atomic layer deposition (SALD) is a promising technology with the aim of combining the advantages of excellent uniformity and conformity of temporal atomic layer deposition (ALD), and an industrial scalable and continuous process. In this manuscript, an experimental and numerical combined model of atmospheric SALD system is presented. To establish the connection between the process parameters and the growth efficiency, a quantitative model on reactant isolation, throughput, and precursor utilization is performed based on the separation gas flow rate, carrier gas flow rate, and precursor mass fraction. The simulation results based on this model show an inverse relation between the precursor usage and the carrier gas flow rate. With the constant carrier gas flow, the relationship of precursor usage and precursor mass fraction follows monotonic function. The precursor concentration, regardless of gas velocity, is the determinant factor of the minimal residual time. The narrow gap between precursor injecting heads and the substrate surface in general SALD system leads to a low Péclet number. In this situation, the gas diffusion act as a leading role in the precursor transport in the small gap rather than the convection. Fluid kinetics from the numerical model is independent of the specific structure, which is instructive for the SALD geometry design as well as its process optimization.

  15. Designing of an artificial neural network model to evaluate the association of three combined Y-specific microsatellite loci on the actual and predicted postthaw motility in crossbred bull semen.

    Science.gov (United States)

    Deb, Rajib; Singh, Umesh; Raja, Thirvvothur Venkatesan; Kumar, Sushil; Tyagi, Shrikant; Alyethodi, Rafeeque R; Alex, Rani; Sengar, Gyanendra; Sharma, Sheetal

    2015-06-01

    The freezing of bull semen significantly hamper the motility of sperm which reduces the conception rate in dairy cattle. The prediction of postthaw motility (PTM) before freezing will be useful to take the decision on discarding or freezing of the germplasm. The artificial neural network (ANN) methodology found to be useful in prediction and classification problems related to animal science, and hence, the present study was undertaken to compare the efficiency of ANN in prediction of PTM on the basis of the number of ejaculates, volume, and concentration of sperms. The combined effect of Y-specific microsatellite alleles on the actual and predicted PTM was also studied. The results revealed that the prediction accuracy of PTM based on the semen quality parameters was comparatively lower because of higher variability in the data set. The ANN gave better prediction accuracy (34.88%) than the multiple regression analysis models (32.04%). The root mean square error was lower for ANN (8.4353) than that in the multiple regression analysis (8.6168). The haplotype or combined effect of microsatellite alleles on actual and predicted PTM was found to be highly significant (P bulls. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Precursor Parameter Identification for IGBT Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Precursor parameters have been identified to enable development of a prognostic approach for insulated gate bipolar transistors (IGBT). The IGBT were subjected to...

  17. Progress in molecular precursors for electronic materials

    Energy Technology Data Exchange (ETDEWEB)

    Buhro, W.E. [Washington Univ., St. Louis, MO (United States)

    1996-09-01

    Molecular-precursor chemistry provides an essential underpinning to all electronic-materials technologies, including photovoltaics and related areas of direct interest to the DOE. Materials synthesis and processing is a rapidly developing field in which advances in molecular precursors are playing a major role. This article surveys selected recent research examples that define the exciting current directions in molecular-precursor science. These directions include growth of increasingly complex structures and stoichiometries, surface-selective growth, kinetic growth of metastable materials, growth of size-controlled quantum dots and quantum-dot arrays, and growth at progressively lower temperatures. Continued progress in molecular-precursor chemistry will afford precise control over the crystal structures, nanostructures, and microstructures of electronic materials.

  18. Rapid synthesis of macrocycles from diol precursors

    DEFF Research Database (Denmark)

    Wingstrand, Magnus; Madsen, Charlotte Marie; Clausen, Mads Hartvig

    2009-01-01

    A method for the formation of synthetic macrocycles with different ring sizes from diols is presented. Reacting a simple diol precursor with electrophilic reagents leads to a cyclic carbonate, sulfite or phosphate in a single step in 25-60% yield. Converting the cyclization precursor to a bis-ele......-electrophilic iodide or aldehyde enables preparation of a cyclic sulfide and amine, respectively, the latter using a double reductive amination to induce ring closure....

  19. Acoustic precursor wave propagation in viscoelastic media.

    Science.gov (United States)

    Zhu, Guangran Kevin; Mojahedi, Mohammad; Sarris, Costas D

    2014-03-01

    Precursor field theory has been developed to describe the dynamics of electromagnetic field evolution in causally attenuative and dispersive media. In Debye dielectrics, the so-called Brillouin precursor exhibits an algebraic attenuation rate that makes it an ideal pulse waveform for communication, sensing, and imaging applications. Inspired by these studies in the electromagnetic domain, the present paper explores the propagation of acoustic precursors in dispersive media, with emphasis on biological media. To this end, a recently proposed causal dispersive model is employed, based on its interpretation as the acoustic counterpart of the Cole¿Cole model for dielectrics. The model stems from the fractional stress¿strain relation, which is consistent with the empirically known frequency power-law attenuation in viscoelastic media. It is shown that viscoelastic media described by this model, including human blood, support the formation and propagation of Brillouin precursors. The amplitude of these precursors exhibits a sub-exponential attenuation rate as a function of distance, actually being proportional to z(-p), where z is the distance traveled within the medium and 0.5

    precursors identified in this work facilitate the design of optimal waveforms for propagation in complex media, creating new possibilities for acoustic-pulse-based communication and imaging systems.

  20. NeuroMEMS: Neural Probe Microtechnologies

    Directory of Open Access Journals (Sweden)

    Sam Musallam

    2008-10-01

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

  1. The Neural Crest in Cardiac Congenital Anomalies

    Science.gov (United States)

    Keyte, Anna; Hutson, Mary Redmond

    2012-01-01

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

  2. Neural crest contributions to the lamprey head

    Science.gov (United States)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

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

  3. Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts.

    Science.gov (United States)

    Thompson, Lachlan H; Björklund, Anders

    2009-01-01

    Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations using rodent models of PD, paying particular attention to the use of transgenic reporter mice as tools for neural transplantation studies. Cell type-specific expression of reporter genes, such as green fluorescent protein, affords valuable technical advantages in transplantation experiments, such as the ability to selectively isolate specific cell fractions from mixed populations prior to grafting, and the unambiguous visualization of graft-derived dopamine neuron fiber patterns after transplantation. The results from these investigations have given new insights into the transplantability of mDA precursors as well as their connectivity after grafting and have interesting implications for the development of stem cell based approaches for the treatment of PD.

  4. Human iPSC-Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0558 TITLE: Human iPSC-Derived GABA-Ergic Precursor Cell Therapy for Chronic Epilepsy PRINCIPAL INVESTIGATOR: Ashok K...AND SUBTITLE 5a. CONTRACT NUMBER Human iPSC-Derived GABA-Ergic Precursor Cell Therapy for Chronic Epilepsy 5b. GRANT NUMBER W81XWH-14-1-0558 5c...exhibiting chronic temporal lobe epilepsy (TLE) would: (1) greatly diminish the frequency and intensity of spontaneous recurrent seizures (SRS, Specific

  5. Understanding perception through neural "codes".

    Science.gov (United States)

    Freeman, Walter J

    2011-07-01

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

  6. Neural correlates of stimulus reportability.

    Science.gov (United States)

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

    2009-08-01

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

  7. Neural Approaches to Machine Consciousness

    Science.gov (United States)

    Aleksander, Igor; Eng., F. R.

    2008-10-01

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

  8. PRECOMBUSTION REMOVAL OF HAZARDOUS AIR POLLUTANT PRECURSORS

    Energy Technology Data Exchange (ETDEWEB)

    Unknown

    2000-10-09

    In response to growing environmental concerns reflected in the 1990 Clean Air Act Amendment (CAAA), the United States Department of Energy (DOE) sponsored several research and development projects in late 1995 as part of an initiative entitled Advanced Environmental Control Technologies for Coal-Based Power Systems. The program provided cost-shared support for research and development projects that could accelerate the commercialization of affordable, high-efficiency, low-emission, coal-fueled electric generating technologies. Clean coal technologies developed under this program would serve as prototypes for later generations of technologies to be implemented in the industrial sector. In order to identify technologies with the greatest potential for commercial implementation, projects funded under Phase I of this program were subject to competitive review by DOE before being considered for continuation funding under Phase II. One of the primary topical areas identified under the DOE initiative relates to the development of improved technologies for reducing the emissions of air toxics. Previous studies have suggested that many of the potentially hazardous air pollutant precursors (HAPPs) occur as trace elements in the mineral matter of run-of-mine coals. As a result, these elements have the potential to be removed prior to combustion at the mine site by physical coal cleaning processes (i.e., coal preparation). Unfortunately, existing coal preparation plants are generally limited in their ability to remove HAPPs due to incomplete liberation of the mineral matter and high organic associations of some trace elements. In addition, existing physical coal cleaning plants are not specifically designed or optimized to ensure that high trace element rejections may be achieved.

  9. Large precursor tolerance database search - a simple approach for estimation of the amount of spectra with precursor mass shifts in proteomic data.

    Science.gov (United States)

    Weng, Rueyhung Roc; Chu, Lichieh Julie; Shu, Hung-Wei; Wu, Timothy H; Chen, Mengchieh Claire; Chang, Yuwei; Tsai, Yihsuan Shannon; Wilson, Michael C; Tsay, Yeou-Guang; Goodlett, David R; Ng, Wailap Victor

    2013-10-08

    Mass measurement and precursor mass assignment are independent processes in proteomic data acquisition. Due to misassignments to C-13 peak, or for other reasons, extensive precursor mass shifts (i.e., deviations of the measured from calculated precursor neutral masses) in LC-MS/MS data obtained with the high-accuracy LTQ-Orbitrap mass spectrometers have been reported in previous studies. Although computational methods for post-acquisition reassignment to monoisotopic mass have been developed to curate the MS/MS spectra prior to database search, a simpler method for estimating the fraction of spectra with precursor mass shift so as to determine whether the data require curation remains desirable. Here, we provide the evidence that an easy approach, which applies a large precursor tolerance (2.1Da or higher) in SEQUEST search against a forward and decoy protein sequence database and then filters the data with PeptideProphet peptide identification probability (p≥0.9), could detect most of the MS/MS spectra containing inaccurate precursor masses. Furthermore, through the implementation of artificial mass shifts on 4000 randomly selected MS/MS spectra, which originally had accurate precursor mass assigned by the mass spectrometers, we demonstrated that the accuracy of the precursor mass has almost negligible influence on the efficacy and fidelity of peptide identification. Integral precursor mass shift is a known problem and thus proteomic data should be handled and analyzed properly to avoid losing important protein identification and/or quantification information. A quick and easy approach for estimating the number of MS/MS spectra with inaccurate precursor mass assignments would be helpful for evaluating the performance of the instrument, determining whether the data requires curation prior to database search or should be searched with specific search parameter(s). Here we demonstrated most of the MS/MS spectra with inaccurate mass assignments (integral or non

  10. Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors

    Directory of Open Access Journals (Sweden)

    Hayashi Katsuhiko

    2007-12-01

    Full Text Available Abstract Background The extraembryonic tissues, visceral endoderm (VE and extraembryonic ectoderm (ExE are known to be important for the induction of primordial germ cells (PGCs in mice via activation of the bone morphogenetic protein (BMP signalling pathway. We investigated whether the VE and ExE have a direct role in the specification of PGCs, or in an earlier event, namely the induction of the PGC precursors in the proximal posterior epiblast cells. Results We cultured embryonic day (E 5.75 to E7.0 mouse embryos in an explant-assay with or without extraembryonic tissues. The reconstituted pieces of embryonic and extraembryonic tissues were assessed for the formation of both PGC precursors and specified PGCs. For this, Blimp1:gfp and Stella:gfp transgenic mouse lines were used to distinguish between PGC precursors and specified PGC, respectively. We observed that the VE regulates formation of an appropriate number of PGC precursors between E6.25–E7.25, but it is not essential for the subsequent specification of PGCs from the precursor cells. Furthermore, we show that the ExE has a different role from that of the VE, which is to restrict localization of PGC precursors to the posterior part of the embryo. Conclusion We show that the VE and ExE have distinct roles in the induction of PGC precursors, namely the formation of a normal number of PGC precursors, and their appropriate localization during early development. However, these tissues do not have a direct role during the final stages of specification of the founder population of PGCs.

  11. Nanomaterial-enabled neural stimulation

    Directory of Open Access Journals (Sweden)

    Yongchen eWang

    2016-03-01

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

  12. Introduction to neural networks

    CERN Document Server

    James, Frederick E

    1994-02-02

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

  13. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

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

  14. Nozzle designs with pitch precursor ablatives

    Science.gov (United States)

    Blevins, H. R.; Bedard, R. J.

    1976-01-01

    Recent developments in carbon phenolic ablatives for solid rocket motor nozzles have yielded a pitch precursor carbon fiber offering significant raw material availability and cost saving advantages as compared to conventional rayon precursor material. This paper discusses the results of an experimental program conducted to assess the thermal performance and characterize the thermal properties of pitch precursor carbon phenolic ablatives. The end result of this program is the complete thermal characterization of pitch fabric, pitch mat, hybrid pitch/rayon fabric and pitch mat molding compound. With these properties determined an analytic capability now exists for predicting the thermal performance of these materials in rocket nozzle liner applications. Further planned efforts to verify material performance and analytical prediction procedures through actual rocket motor firings are also discussed.

  15. Ceramic fibers from Sol-Gel precursors

    Energy Technology Data Exchange (ETDEWEB)

    Glaubitt, W.; Sporn, D.; Jahn, R. [Fraunhofer Institut fuer Silicatforschung, Wuerzburg (Germany)

    1995-09-01

    Powderless methods for the preparation of continuously spirmable alumina, mullite, spinel, yttrium alumina garnet (YAG) and lead zirconium titanate (PZT) precursors are presented. The Al containing solutions are based on alcoholysis, carboxylation and hydrolysis reactions, which are described in detail. In addition, a synthesis route for the preparation of piezoelectric PZT long fibers has also been developed. This novel PZT precursor contains lead subcarboxylate and zirconium titanium oxohydroxocarboxylate. In all cases, continuously spinnable precursors which have been extruded with velocities up to 200 m/min, have been obtained. Gel fibers of several kilometer length could be drawn directly from sols. After drying, pyrolysis and sintering, each of the {alpha}-Al{sub 2}O{sub 3}, mullite. spinel, YAG and PZT, fibers have been obtained.

  16. Analysis of neural networks

    CERN Document Server

    Heiden, Uwe

    1980-01-01

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

  17. Optics in neural computation

    Science.gov (United States)

    Levene, Michael John

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

  18. Postnatal administration of memantine rescues TNF-α-induced decreased hippocampal precursor proliferation.

    Science.gov (United States)

    Wang, Zhongke; He, Xie; Fan, Xiaotang

    2018-01-01

    Pro-inflammatory cytokine exposure in early postnatal life triggers clear neurotoxic effects on the developing hippocampus. Tumor necrosis factor alpha (TNF-α) is one of the inflammatory mediators and is a potent inhibitor of neurogenesis. Memantine (MEM) is an uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that has been demonstrated to increase the proliferation of hippocampal progenitor cells. However, the effects of MEM on TNF-α-mediated impairment of hippocampal precursor proliferation remain unclear. In this study, mice were exposed to TNF-α and later treated with MEM to evaluate its protective effects on TNF-α-mediated toxicity during hippocampal development. The results indicated that brief exposure to TNF-α on postnatal days 3 and 5 resulted in a significant impairment of hippocampal precursor proliferation and a depletion of hippocampal neural precursor cells (NPCs). This effect was attenuated by MEM treatment. We further confirmed that MEM treatment reversed the TNF-α-induced microglia activation and up-regulation of hippocampal NF-κB, MCP-1 and IL-6 mRNA levels, which may be related to the proliferation and maintenance of NPCs. Overall, our results suggest that MEM treatment protects against TNF-α-induced repression of hippocampal precursor proliferation in postnatal mice by partially attenuating neuroinflammatory responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Ion Propulsion - An Enabling Technology for Interstellar Precursor Missions

    Science.gov (United States)

    Fearn, D. G.

    In this paper it is shown that an advanced form of gridded ion thruster, employing a 4-grid ion extraction and acceleration system, can provide a velocity increment and specific impulse of interest to interstellar precursor missions, extending to a few hundred astronomical units from the sun. In this it is assumed that a nuclear power source is available with a mass-to-power ratio of 15 to 35 kg/kW and an output of several tens of kW. Mission durations are of about 25 years and the velocity increment provided exceeds 37 km/s.

  20. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Diabetic retinopathy screening using deep neural network.

    Science.gov (United States)

    Ramachandran, Nishanthan; Hong, Sheng Chiong; Sime, Mary J; Wilson, Graham A

    2017-09-07

    There is a burgeoning interest in the use of deep neural network in diabetic retinal screening. To determine whether a deep neural network could satisfactorily detect diabetic retinopathy that requires referral to an ophthalmologist from a local diabetic retinal screening programme and an international database. Retrospective audit. Diabetic retinal photos from Otago database photographed during October 2016 (485 photos), and 1200 photos from Messidor international database. Receiver operating characteristic curve to illustrate the ability of a deep neural network to identify referable diabetic retinopathy (moderate or worse diabetic retinopathy or exudates within one disc diameter of the fovea). Area under the receiver operating characteristic curve, sensitivity and specificity. For detecting referable diabetic retinopathy, the deep neural network had an area under receiver operating characteristic curve of 0.901 (95% confidence interval 0.807-0.995), with 84.6% sensitivity and 79.7% specificity for Otago and 0.980 (95% confidence interval 0.973-0.986), with 96.0% sensitivity and 90.0% specificity for Messidor. This study has shown that a deep neural network can detect referable diabetic retinopathy with sensitivities and specificities close to or better than 80% from both an international and a domestic (New Zealand) database. We believe that deep neural networks can be integrated into community screening once they can successfully detect both diabetic retinopathy and diabetic macular oedema. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  2. Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals

    Science.gov (United States)

    The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularize...

  3. Astrocytes derived from glial-restricted precursors promote spinal cord repair

    Directory of Open Access Journals (Sweden)

    Mayer-Proschel Margot

    2006-04-01

    Full Text Available Abstract Background Transplantation of embryonic stem or neural progenitor cells is an attractive strategy for repair of the injured central nervous system. Transplantation of these cells alone to acute spinal cord injuries has not, however, resulted in robust axon regeneration beyond the sites of injury. This may be due to progenitors differentiating to cell types that support axon growth poorly and/or their inability to modify the inhibitory environment of adult central nervous system (CNS injuries. We reasoned therefore that pre-differentiation of embryonic neural precursors to astrocytes, which are thought to support axon growth in the injured immature CNS, would be more beneficial for CNS repair. Results Transplantation of astrocytes derived from embryonic glial-restricted precursors (GRPs promoted robust axon growth and restoration of locomotor function after acute transection injuries of the adult rat spinal cord. Transplantation of GRP-derived astrocytes (GDAs into dorsal column injuries promoted growth of over 60% of ascending dorsal column axons into the centers of the lesions, with 66% of these axons extending beyond the injury sites. Grid-walk analysis of GDA-transplanted rats with rubrospinal tract injuries revealed significant improvements in locomotor function. GDA transplantation also induced a striking realignment of injured tissue, suppressed initial scarring and rescued axotomized CNS neurons with cut axons from atrophy. In sharp contrast, undifferentiated GRPs failed to suppress scar formation or support axon growth and locomotor recovery. Conclusion Pre-differentiation of glial precursors into GDAs before transplantation into spinal cord injuries leads to significantly improved outcomes over precursor cell transplantation, providing both a novel strategy and a highly effective new cell type for repairing CNS injuries.

  4. Elicitation and precursor feeding influence phenolic acids ...

    African Journals Online (AJOL)

    Plant cell cultures have been industrially used for the synthesis of secondary metabolites. Different elicitors, [jasmonic acid (JA), salicylic acid (SA) and ethephone (E)] and precursors [shicimic acid (SH) and phenylalanine (PHE)] were independently used to enhance the synthesis of phenolics in suspension cultures of Vitis ...

  5. Biochemical Removal of HAP Precursors from Coal

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Gregory J

    1997-05-12

    Column biooxidation tests with Kentucky coal confirmed results of earlier shake flask tests showing significant removal from the coal of arsenic, selenium, cobalt, manganese, nickel and cadmium. Rates of pyrite biooxidation in Kentucky coal were only slightly more than half the rates found previously for Indiana and Pittsburgh coals. Removal of pyrite from Pittsburgh coal by ferric ion oxidation slows markedly as ferrous ions accumulate in solution, requiring maintenance of high redox potentials in processes designed for removal of pyrite and hazardous air pollutant (HAP) precursors by circulation of ferric solutions through coal. The pyrite oxidation rates obtained in these tests were used by Unifield Engineering to support the conceptual designs for alternative pyrite and HAP precursor bioleaching processes for the phase 2 pilot plant. Thermophilic microorganisms were tested to determine if mercury could be mobilized from coal under elevated growth temperatures. There was no evidence for mercury removal from coal under these conditions. However, the activity of the organisms may have liberated mercury physically. It is also possible that the organisms dissolved mercury and it readsorbed to the clay preferentially. Both of these possibilities are undergoing further testing. The Idaho National Engineering and Environmental Laboratory's (INEEL) slurry column reactor was operated and several batches of feed coal, product coal, waste solids and leach solutions were submitted to LBL for HAP precursor analysis. Results to date indicate significant removal of mercury, arsenic and other HAP precursors in the combined physical-biological process.

  6. Sol-gel precursors and products thereof

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Scott C.; DiSalvo, Jr., Francis J.; Weisner, Ulrich B.

    2017-02-14

    The present invention provides a generalizable single-source sol-gel precursor capable of introducing a wide range of functionalities to metal oxides such as silica. The sol-gel precursor facilitates a one-molecule, one-step approach to the synthesis of metal-silica hybrids with combinations of biological, catalytic, magnetic, and optical functionalities. The single-source precursor also provides a flexible route for simultaneously incorporating functional species of many different types. The ligands employed for functionalizing the metal oxides are derived from a library of amino acids, hydroxy acids, or peptides and a silicon alkoxide, allowing many biological functionalities to be built into silica hybrids. The ligands can coordinate with a wide range of metals via a carboxylic acid, thereby allowing direct incorporation of inorganic functionalities from across the periodic table. Using the single-source precursor a wide range of functionalized nanostructures such as monolith structures, mesostructures, multiple metal gradient mesostructures and Stober-type nanoparticles can be synthesized. ##STR00001##

  7. 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

    2015-10-06

    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.

  8. Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ.

    Science.gov (United States)

    Pfeiffer, Michael; Betizeau, Marion; Waltispurger, Julie; Pfister, Sabina Sara; Douglas, Rodney J; Kennedy, Henry; Dehay, Colette

    2016-02-15

    Generation of the primate cortex is characterized by the diversity of cortical precursors and the complexity of their lineage relationships. Recent studies have reported miscellaneous precursor types based on observer classification of cell biology features including morphology, stemness, and proliferative behavior. Here we use an unsupervised machine learning method for Hidden Markov Trees (HMTs), which can be applied to large datasets to classify precursors on the basis of morphology, cell-cycle length, and behavior during mitosis. The unbiased lineage analysis automatically identifies cell types by applying a lineage-based clustering and model-learning algorithm to a macaque corticogenesis dataset. The algorithmic results validate previously reported observer classification of precursor types and show numerous advantages: It predicts a higher diversity of progenitors and numerous potential transitions between precursor types. The HMT model can be initialized to learn a user-defined number of distinct classes of precursors. This makes it possible to 1) reveal as yet undetected precursor types in view of exploring the significant features of precursors with respect to specific cellular processes; and 2) explore specific lineage features. For example, most precursors in the experimental dataset exhibit bidirectional transitions. Constraining the directionality in the HMT model leads to a reduction in precursor diversity following multiple divisions, thereby suggesting that one impact of bidirectionality in corticogenesis is to maintain precursor diversity. In this way we show that unsupervised lineage analysis provides a valuable methodology for investigating fundamental features of corticogenesis. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  9. Unsupervised lineage‐based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ

    Science.gov (United States)

    Betizeau, Marion; Waltispurger, Julie; Pfister, Sabina Sara; Douglas, Rodney J.; Kennedy, Henry; Dehay, Colette

    2015-01-01

    ABSTRACT Generation of the primate cortex is characterized by the diversity of cortical precursors and the complexity of their lineage relationships. Recent studies have reported miscellaneous precursor types based on observer classification of cell biology features including morphology, stemness, and proliferative behavior. Here we use an unsupervised machine learning method for Hidden Markov Trees (HMTs), which can be applied to large datasets to classify precursors on the basis of morphology, cell‐cycle length, and behavior during mitosis. The unbiased lineage analysis automatically identifies cell types by applying a lineage‐based clustering and model‐learning algorithm to a macaque corticogenesis dataset. The algorithmic results validate previously reported observer classification of precursor types and show numerous advantages: It predicts a higher diversity of progenitors and numerous potential transitions between precursor types. The HMT model can be initialized to learn a user‐defined number of distinct classes of precursors. This makes it possible to 1) reveal as yet undetected precursor types in view of exploring the significant features of precursors with respect to specific cellular processes; and 2) explore specific lineage features. For example, most precursors in the experimental dataset exhibit bidirectional transitions. Constraining the directionality in the HMT model leads to a reduction in precursor diversity following multiple divisions, thereby suggesting that one impact of bidirectionality in corticogenesis is to maintain precursor diversity. In this way we show that unsupervised lineage analysis provides a valuable methodology for investigating fundamental features of corticogenesis. J. Comp. Neurol. 524:535–563, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26053631

  10. Neural Reranking for Named Entity Recognition

    OpenAIRE

    Yang, Jie; Zhang, Yue; Dong, Fei

    2017-01-01

    We propose a neural reranking system for named entity recognition (NER). The basic idea is to leverage recurrent neural network models to learn sentence-level patterns that involve named entity mentions. In particular, given an output sentence produced by a baseline NER model, we replace all entity mentions, such as \\textit{Barack Obama}, into their entity types, such as \\textit{PER}. The resulting sentence patterns contain direct output information, yet is less sparse without specific named ...

  11. Functional neural anatomy of talent.

    Science.gov (United States)

    Kalbfleisch, M Layne

    2004-03-01

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

  12. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells].

    Science.gov (United States)

    Dupin, Elisabeth

    2011-01-01

    Melanocytes, the pigmented cells of the skin, and the glial Schwann cells lining peripheral nerves are developmentally derived from an early and transient ectodermal structure of the vertebrate embryo, the neural crest, which is also at the origin of multiple neural and non-neural cell types. Besides melanocytes and neural cells of the peripheral nervous system, the neural crest cells give rise to mesenchymal cell types in the head, which form most of the craniofacial skeleton, dermis, fat tissue and vascular musculo-connective components. How such a wide diversity of differentiation fates is established during embryogenesis and is later maintained in adult tissues are among key questions in developmental and stem cell biology. The analysis of the developmental potentials of single neural crest cells cultured in vitro led to characterizing multipotent stem/progenitor cells as well as more restricted precursors in the early neural crest of avian and mammalian embryos. Data support a hierarchical model of the diversification of neural crest lineages through progressive restrictions of multipotent stem cell potentials driven by local environmental factors. In particular, melanocytes and glial Schwann cells were shown to arise from a common bipotent progenitor, which depends upon the peptide endothelin-3 for proliferation and self-renewal ability. In vivo, signaling by endothelin-3 and its receptor is also required for the early development of melanocytes and proper pigmentation of the vertebrate body. It is generally assumed that, after lineage specification and terminal differentiation, specialized cell types, like the melanocytes and Schwann cells, do not change their identity. However, this classic notion that somatic cell differentiation is a stable and irreversible process has been challenged by emerging evidence that dedifferentiation can occur in different biological systems through nuclear transfer, cell fusion, epigenetic modifications and ectopic gene

  13. ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate.

    Science.gov (United States)

    Morales Diaz, Heidi; Mejares, Emil; Newman-Smith, Erin; Smith, William C

    2016-01-01

    The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. The homeostatic astroglia emerges from evolutionary specialization of neural cells

    DEFF Research Database (Denmark)

    Verkhratsky, Alexei; Nedergaard, Maiken

    2016-01-01

    and defence. Astrocytes are integrated into neural networks through multipartite synapses; astroglial perisynaptic processes closely enwrap synaptic contacts and control homeostasis of the synaptic cleft, supply neurons with glutamate and GABA obligatory precursor glutamine and contribute to synaptic...... plasticity, learning and memory. In neuropathology, astrocytes may undergo reactive remodelling or degeneration; to a large extent, astroglial reactions define progression of the pathology and neurological outcome.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control...

  15. Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor proliferation and apical constriction during mouse brain development.

    Science.gov (United States)

    Badouel, Caroline; Zander, Mark A; Liscio, Nicole; Bagherie-Lachidan, Mazdak; Sopko, Richelle; Coyaud, Etienne; Raught, Brian; Miller, Freda D; McNeill, Helen

    2015-08-15

    Mammalian brain development requires coordination between neural precursor proliferation, differentiation and cellular organization to create the intricate neuronal networks of the adult brain. Here, we examined the role of the atypical cadherins Fat1 and Fat4 in this process. We show that mutation of Fat1 in mouse embryos causes defects in cranial neural tube closure, accompanied by an increase in the proliferation of cortical precursors and altered apical junctions, with perturbations in apical constriction and actin accumulation. Similarly, knockdown of Fat1 in cortical precursors by in utero electroporation leads to overproliferation of radial glial precursors. Fat1 interacts genetically with the related cadherin Fat4 to regulate these processes. Proteomic analysis reveals that Fat1 and Fat4 bind different sets of actin-regulating and junctional proteins. In vitro data suggest that Fat1 and Fat4 form cis-heterodimers, providing a mechanism for bringing together their diverse interactors. We propose a model in which Fat1 and Fat4 binding coordinates distinct pathways at apical junctions to regulate neural progenitor proliferation, neural tube closure and apical constriction. © 2015. Published by The Company of Biologists Ltd.

  16. Maintenance of neural stem cell regional identity in culture.

    Science.gov (United States)

    Delgado, Ryan N; Lu, Changqing; Lim, Daniel A

    2016-01-01

    Neural stem cells (NSCs) are distributed throughout the ventricular-subventricular zone (V-SVZ) in the adult mouse brain. NSCs located in spatially distinct regions of the V-SVZ generate different types of olfactory bulb (OB) neurons, and the regional expression of specific transcription factors correlates with these differences in NSC developmental potential. In a recent article, we show that Nkx2.1-expressing embryonic precursors give rise to NKX2.1+ NSCs located in the ventral V-SVZ of adult mice. Here we characterize a V-SVZ monolayer culture system that retains regional gene expression and neurogenic potential of NSCs from the dorsal and ventral V-SVZ. In particular, we find that Nkx2.1-lineage V-SVZ NSCs maintain Nkx2.1 expression through serial passage and can generate new neurons in vitro. Thus, V-SVZ NSCs retain key aspects of their in vivo regional identity in culture, providing new experimental opportunities for understanding how such developmental patterns are established and maintained during development.

  17. Polysialic acid bioengineering of neuronal cells by N-acyl sialic acid precursor treatment.

    Science.gov (United States)

    Pon, Robert A; Biggs, Nancy J; Jennings, Harold J

    2007-03-01

    The inherent promiscuity of the polysialic acid (PSA) biosynthetic pathway has been exploited by the use of exogenous unnatural sialic acid precursor molecules to introduce unnatural modifications into cellular PSA, and has found applications in nervous system development and tumor vaccine studies. The sialic acid precursor molecules N-propionyl- and N-butanoyl-mannosamine (ManPr, ManBu) have been variably reported to affect PSA biosynthesis ranging from complete inhibition to de novo production of modified PSA, thus illustrating the need for further investigation into their effects. In this study, we have used a monoclonal antibody (mAb) 13D9, specific to both N-propionyl-PSA and N-butanoyl-PSA (NPrPSA and NBuPSA), together with flow cytometry, to study precursor-treated tumor cells and NT2 neurons at different stages of their maturation. We report that both ManPr and ManBu sialic acid precursors are metabolized and the resultant unnatural sialic acids are incorporated into de novo surface sialylglycoconjugates in murine and human tumor cells and, for the first time, in human NT2 neurons. Furthermore, neither precursor treatment deleteriously affected endogenous PSA expression; however, with NT2 cells, PSA levels were naturally downregulated as a function of their maturation into polarized neurons independent of sialic acid precursor treatment.

  18. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

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

  19. N-Myc and GCN5 regulate significantly overlapping transcriptional programs in neural stem cells.

    Directory of Open Access Journals (Sweden)

    Verónica Martínez-Cerdeño

    Full Text Available Here we examine the functions of the Myc cofactor and histone acetyltransferase, GCN5/KAT2A, in neural stem and precursor cells (NSC using a conditional knockout approach driven by nestin-cre. Mice with GCN5-deficient NSC exhibit a 25% reduction in brain mass with a microcephaly phenotype similar to that observed in nestin-cre driven knockouts of c- or N-myc. In addition, the loss of GCN5 inhibits precursor cell proliferation and reduces their populations in vivo, as does loss of N-myc. Gene expression analysis indicates that about one-sixth of genes whose expression is affected by loss of GCN5 are also affected in the same manner by loss of N-myc. These findings strongly support the notion that GCN5 protein is a key N-Myc transcriptional cofactor in NSC, but are also consistent with recruitment of GCN5 by other transcription factors and the use by N-Myc of other histone acetyltransferases. Putative N-Myc/GCN5 coregulated transcriptional pathways include cell metabolism, cell cycle, chromatin, and neuron projection morphogenesis genes. GCN5 is also required for maintenance of histone acetylation both at its putative specific target genes and at Myc targets. Thus, we have defined an important role for GCN5 in NSC and provided evidence that GCN5 is an important Myc transcriptional cofactor in vivo.

  20. Differentiation state determines neural effects on microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Muffley, Lara A., E-mail: muffley@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: pansc@mail.ncku.edu.tw [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: gnaunderwater@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: marga16@uw.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

    2012-10-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

  1. In vitro generation of neuromesodermal progenitors reveals distinct roles for wnt signalling in the specification of spinal cord and paraxial mesoderm identity.

    Directory of Open Access Journals (Sweden)

    Mina Gouti

    2014-08-01

    Full Text Available Cells of the spinal cord and somites arise from shared, dual-fated precursors, located towards the posterior of the elongating embryo. Here we show that these neuromesodermal progenitors (NMPs can readily be generated in vitro from mouse and human pluripotent stem cells by activating Wnt and Fgf signalling, timed to emulate in vivo development. Similar to NMPs in vivo, these cells co-express the neural factor Sox2 and the mesodermal factor Brachyury and differentiate into neural and paraxial mesoderm in vitro and in vivo. The neural cells produced by NMPs have spinal cord but not anterior neural identity and can differentiate into spinal cord motor neurons. This is consistent with the shared origin of spinal cord and somites and the distinct ontogeny of the anterior and posterior nervous system. Systematic analysis of the transcriptome during differentiation identifies the molecular correlates of each of the cell identities and the routes by which they are obtained. Moreover, we take advantage of the system to provide evidence that Brachyury represses neural differentiation and that signals from mesoderm are not necessary to induce the posterior identity of spinal cord cells. This indicates that the mesoderm inducing and posteriorising functions of Wnt signalling represent two molecularly separate activities. Together the data illustrate how reverse engineering normal developmental mechanisms allows the differentiation of specific cell types in vitro and the analysis of previous difficult to access aspects of embryo development.

  2. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  3. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

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

  4. Conformal Dynamics of Precursors to Fracture

    OpenAIRE

    Barra, Felipe; Herrera, Mauricio; Procaccia, Itamar

    2002-01-01

    An exact integro-differential equation for the conformal map from the unit circle to the boundary of an evolving cavity in a stressed 2-dimensional solid is derived. This equation provides an accurate description of the dynamics of precursors to fracture when surface diffusion is important. The solution predicts the creation of sharp grooves that eventually lead to material failure via rapid fracture. Solutions of the new equation are demonstrated for the dynamics of an elliptical cavity and ...

  5. Calculations of precursor propagation in dispersive dielectrics.

    Energy Technology Data Exchange (ETDEWEB)

    Bacon, Larry Donald

    2003-08-01

    The present study is a numerical investigation of the propagation of electromagnetic transients in dispersive media. It considers propagation in water using Debye and composite Rocard-Powles-Lorentz models for the complex permittivity. The study addresses this question: For practical transmitted spectra, does precursor propagation provide any features that can be used to advantage over conventional signal propagation in models of dispersive media of interest? A companion experimental study is currently in progress that will attempt to measure the effects studied here.

  6. PRECURSORS OF EARTHQUAKES: VLF SIGNALSIONOSPHERE IONOSPHERE RELATION

    Directory of Open Access Journals (Sweden)

    Mustafa ULAS

    2013-01-01

    Full Text Available lot of people have died because of earthquakes every year. Therefore It is crucial to predict the time of the earthquakes reasonable time before it had happed. This paper presents recent information published in the literature about precursors of earthquakes. The relationships between earthquakes and ionosphere are targeted to guide new researches in order to study further to find novel prediction methods.

  7. Cellular kinetics of perivascular MSC precursors.

    Science.gov (United States)

    Chen, William C W; Park, Tea Soon; Murray, Iain R; Zimmerlin, Ludovic; Lazzari, Lorenza; Huard, Johnny; Péault, Bruno

    2013-01-01

    Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  8. Cellular Kinetics of Perivascular MSC Precursors

    Directory of Open Access Journals (Sweden)

    William C. W. Chen

    2013-01-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  9. Ionospheric precursors for crustal earthquakes in Italy

    Directory of Open Access Journals (Sweden)

    L. Perrone

    2010-04-01

    Full Text Available Crustal earthquakes with magnitude 6.0>M≥5.5 observed in Italy for the period 1979–2009 including the last one at L'Aquila on 6 April 2009 were considered to check if the earlier obtained relationships for ionospheric precursors for strong Japanese earthquakes are valid for the Italian moderate earthquakes. The ionospheric precursors are based on the observed variations of the sporadic E-layer parameters (h'Es, fbEs and foF2 at the ionospheric station Rome. Empirical dependencies for the seismo-ionospheric disturbances relating the earthquake magnitude and the epicenter distance are obtained and they have been shown to be similar to those obtained earlier for Japanese earthquakes. The dependences indicate the process of spreading the disturbance from the epicenter towards periphery during the earthquake preparation process. Large lead times for the precursor occurrence (up to 34 days for M=5.8–5.9 tells about a prolong preparation period. A possibility of using the obtained relationships for the earthquakes prediction is discussed.

  10. Radiative precursors driven by converging blast waves in noble gases

    Energy Technology Data Exchange (ETDEWEB)

    Burdiak, G. C.; Lebedev, S. V.; Harvey-Thompson, A. J.; Swadling, G. F.; Suzuki-Vidal, F.; Hall, G. N.; Khoory, E.; Pickworth, L.; Bland, S. N.; Grouchy, P. de; Skidmore, J.; Suttle, L.; Bennett, M.; Niasse, N. P. L. [Blackett Laboratory, Imperial College London SW7 2BW (United Kingdom); Williams, R. J. R. [Atomic Weapons Establishment, Aldermaston RG7 4PR (United Kingdom); Blesener, K.; Atoyan, L.; Cahill, A.; Hoyt, C.; Potter, W. [Laboratory of Plasma Studies, Cornell University, Ithaca, New York 14853 (United States); and others

    2014-03-15

    A detailed study of the radiative precursor that develops ahead of converging blast waves in gas-filled cylindrical liner z-pinch experiments is presented. The experiment is capable of magnetically driving 20 km s{sup −1} blast waves through gases of densities of the order 10{sup −5} g cm{sup −3} (see Burdiak et al. [High Energy Density Phys. 9(1), 52–62 (2013)] for a thorough description). Data were collected for Ne, Ar, and Xe gas-fills. The geometry of the setup allows a determination of the plasma parameters both in the precursor and across the shock, along a nominally uniform line of sight that is perpendicular to the propagation of the shock waves. Radiation from the shock was able to excite NeI, ArII, and XeII/XeIII precursor spectral features. It is shown that the combination of interferometry and optical spectroscopy data is inconsistent with upstream plasmas being in LTE. Specifically, electron density gradients do not correspond to any apparent temperature change in the emission spectra. Experimental data are compared to 1D radiation hydrodynamics HELIOS-CR simulations and to PrismSPECT atomic physics calculations to assist in a physical interpretation of the observations. We show that upstream plasma is likely in the process of being radiatively heated and that the emission from a small percentage of ionised atoms within a cool background plasma dominates the emission spectra. Experiments were carried out on the MAGPIE and COBRA pulsed-power facilities at Imperial College London and Cornell University, respectively.

  11. Fuzzy and neural control

    Science.gov (United States)

    Berenji, Hamid R.

    1992-01-01

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

  12. Hardware Acceleration of Adaptive Neural Algorithms.

    Energy Technology Data Exchange (ETDEWEB)

    James, Conrad D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-11-01

    As tradit ional numerical computing has faced challenges, researchers have turned towards alternative computing approaches to reduce power - per - computation metrics and improve algorithm performance. Here, we describe an approach towards non - conventional computing that strengthens the connection between machine learning and neuroscience concepts. The Hardware Acceleration of Adaptive Neural Algorithms (HAANA) project ha s develop ed neural machine learning algorithms and hardware for applications in image processing and cybersecurity. While machine learning methods are effective at extracting relevant features from many types of data, the effectiveness of these algorithms degrades when subjected to real - world conditions. Our team has generated novel neural - inspired approa ches to improve the resiliency and adaptability of machine learning algorithms. In addition, we have also designed and fabricated hardware architectures and microelectronic devices specifically tuned towards the training and inference operations of neural - inspired algorithms. Finally, our multi - scale simulation framework allows us to assess the impact of microelectronic device properties on algorithm performance.

  13. Blood glucose prediction using neural network

    Science.gov (United States)

    Soh, Chit Siang; Zhang, Xiqin; Chen, Jianhong; Raveendran, P.; Soh, Phey Hong; Yeo, Joon Hock

    2008-02-01

    We used neural network for blood glucose level determination in this study. The data set used in this study was collected using a non-invasive blood glucose monitoring system with six laser diodes, each laser diode operating at distinct near infrared wavelength between 1500nm and 1800nm. The neural network is specifically used to determine blood glucose level of one individual who participated in an oral glucose tolerance test (OGTT) session. Partial least squares regression is also used for blood glucose level determination for the purpose of comparison with the neural network model. The neural network model performs better in the prediction of blood glucose level as compared with the partial least squares model.

  14. Artificial neural networks a practical course

    CERN Document Server

    da Silva, Ivan Nunes; Andrade Flauzino, Rogerio; Liboni, Luisa Helena Bartocci; dos Reis Alves, Silas Franco

    2017-01-01

    This book provides comprehensive coverage of neural networks, their evolution, their structure, the problems they can solve, and their applications. The first half of the book looks at theoretical investigations on artificial neural networks and addresses the key architectures that are capable of implementation in various application scenarios. The second half is designed specifically for the production of solutions using artificial neural networks to solve practical problems arising from different areas of knowledge. It also describes the various implementation details that were taken into account to achieve the reported results. These aspects contribute to the maturation and improvement of experimental techniques to specify the neural network architecture that is most appropriate for a particular application scope. The book is appropriate for students in graduate and upper undergraduate courses in addition to researchers and professionals.

  15. What Is Neural Plasticity?

    Science.gov (United States)

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

    2017-01-01

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

  16. Neural Systems Laboratory

    Data.gov (United States)

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

  17. A neural flow estimator

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  18. Spacecraft Neural Network Control System Design using FPGA

    OpenAIRE

    Hanaa T. El-Madany; Faten H. Fahmy; Ninet M. A. El-Rahman; Hassen T. Dorrah

    2011-01-01

    Designing and implementing intelligent systems has become a crucial factor for the innovation and development of better products of space technologies. A neural network is a parallel system, capable of resolving paradigms that linear computing cannot. Field programmable gate array (FPGA) is a digital device that owns reprogrammable properties and robust flexibility. For the neural network based instrument prototype in real time application, conventional specific VLSI neural chip design suffer...

  19. Dysfunction of Rapid Neural Adaptation in Dyslexia.

    Science.gov (United States)

    Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

    2016-12-21

    Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Neural plasticity across the lifespan.

    Science.gov (United States)

    Power, Jonathan D; Schlaggar, Bradley L

    2017-01-01

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

  1. Neural Mobilization: A Systematic Review of Randomized Controlled Trials with an Analysis of Therapeutic Efficacy

    Science.gov (United States)

    Ellis, Richard F.; Hing, Wayne A.

    2008-01-01

    Neural mobilization is a treatment modality used in relation to pathologies of the nervous system. It has been suggested that neural mobilization is an effective treatment modality, although support of this suggestion is primarily anecdotal. The purpose of this paper was to provide a systematic review of the literature pertaining to the therapeutic efficacy of neural mobilization. A search to identify randomized controlled trials investigating neural mobilization was conducted using the key words neural mobilisation/mobilization, nerve mobilisation/mobilization, neural manipulative physical therapy, physical therapy, neural/nerve glide, nerve glide exercises, nerve/neural treatment, nerve/neural stretching, neurodynamics, and nerve/neural physiotherapy. The titles and abstracts of the papers identified were reviewed to select papers specifically detailing neural mobilization as a treatment modality. The PEDro scale, a systematic tool used to critique RCTs and grade methodological quality, was used to assess these trials. Methodological assessment allowed an analysis of research investigating therapeutic efficacy of neural mobilization. Ten randomized clinical trials (discussed in 11 retrieved articles) were identified that discussed the therapeutic effect of neural mobilization. This review highlights the lack in quantity and quality of the available research. Qualitative analysis of these studies revealed that there is only limited evidence to support the use of neural mobilization. Future research needs to re-examine the application of neural mobilization with use of more homogeneous study designs and pathologies; in addition, it should standardize the neural mobilization interventions used in the study. PMID:19119380

  2. Inducible expression of noggin selectively expands neural progenitors in the adult SVZ

    Directory of Open Access Journals (Sweden)

    M. Morell

    2015-01-01

    Full Text Available Multipotent, self-renewing stem cells are present throughout the developing nervous system remaining in discrete regions of the adult brain. In the subventricular zone (SVZ signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, noggin appear to play a critical role in controlling neural stem cell (NSC behavior. To examine the function of this signaling pathway in the intact nervous system, we developed a transgenic mouse model in which noggin expression can be induced specifically in NSC via a nestin-driven reverse tetracycline-controlled transactivator (rtTA. In adult animals, the induction of noggin expression promotes the proliferation of neural progenitors in the SVZ, and shifts the differentiation of B cells (NSC from mature astrocytes to transit amplifying C cells and oligodendrocyte precursor cells without depleting the NSC population. Noggin expression significantly increases neuronal and oligodendrocyte differentiation both in vivo and in vitro when NSCs are grown as neurospheres. These results demonstrate that noggin/BMP interactions tightly control cell fate in the SVZ.

  3. Ionospheric parameters as the precursors of disturbed geomagnetic conditions

    Science.gov (United States)

    Blagoveshchensky, D. V.; Sergeeva, M. A.; Kozlovsky, A.

    2017-12-01

    Geomagnetic storms and substorms are the principal elements of the disturbed Space Weather conditions. The aim of the study was to reveal the ionospheric precursors that can be used to forecast geomagnetic disturbance beginning. To study the ionospheric processes before, during and after magnetic storms and substorms data from Sodankylä Geophysical Observatory was used (geomagnetic coordinates: 64.1oN, 119.2oE). In earlier works the Main Effect (ME) was revealed for substorms. It consists of the following steps: (a) the increase of critical frequency foF2 from its quiet median before and during the substorm growth phase, four-five hours before To moment that is the moment of the expansion phase onset, (b) the foF2 decrease to the level lower than its median just after To and until Te that is the moment of the end of the expansion phase, (c) the issue ;a; repeated during the recovery phase (d) two bell-shape spikes in the cutoff frequency values foEs: first spike occurs three hours before To, second spike - during the expansion phase within the interval between To and Te. In the present work it is shown that ME manifestations can be used as precursors of magnetic substorms at high-latitudes (geomagnetic latitudes 50oN-65oN). In particular, the foF2 growth some hours before To can be used as a precursor of substorm development. The first foEs bell-shaped spike also can be used for short-term forecasting, two-three hours in advance of a substorm. Furthermore, the storms between 2008 and 2012 were studied. It was revealed that the similar ME also takes place in the case of magnetic storms but within the different time scale. More specifically, the first ME maximum in foF2 values occurs one-two days before the storm beginning and can be used as its precursor. In addition, the foEs spike takes place approximately ten hours before a storm and also can be used for the prediction of the storm beginning.

  4. Neural Networks: Implementations and Applications

    NARCIS (Netherlands)

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

    1996-01-01

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

  5. An Accident Precursor Analysis Process Tailored for NASA Space Systems

    Science.gov (United States)

    Groen, Frank; Stamatelatos, Michael; Dezfuli, Homayoon; Maggio, Gaspare

    2010-01-01

    Accident Precursor Analysis (APA) serves as the bridge between existing risk modeling activities, which are often based on historical or generic failure statistics, and system anomalies, which provide crucial information about the failure mechanisms that are actually operative in the system and which may differ in frequency or type from those in the various models. These discrepancies between the models (perceived risk) and the system (actual risk) provide the leading indication of an underappreciated risk. This paper presents an APA process developed specifically for NASA Earth-to-Orbit space systems. The purpose of the process is to identify and characterize potential sources of system risk as evidenced by anomalous events which, although not necessarily presenting an immediate safety impact, may indicate that an unknown or insufficiently understood risk-significant condition exists in the system. Such anomalous events are considered accident precursors because they signal the potential for severe consequences that may occur in the future, due to causes that are discernible from their occurrence today. Their early identification allows them to be integrated into the overall system risk model used to intbrm decisions relating to safety.

  6. AMYPdb: A database dedicated to amyloid precursor proteins

    Directory of Open Access Journals (Sweden)

    Delamarche Christian

    2008-06-01

    Full Text Available Abstract Background Misfolding and aggregation of proteins into ordered fibrillar structures is associated with a number of severe pathologies, including Alzheimer's disease, prion diseases, and type II diabetes. The rapid accumulation of knowledge about the sequences and structures of these proteins allows using of in silico methods to investigate the molecular mechanisms of their abnormal conformational changes and assembly. However, such an approach requires the collection of accurate data, which are inconveniently dispersed among several generalist databases. Results We therefore created a free online knowledge database (AMYPdb dedicated to amyloid precursor proteins and we have performed large scale sequence analysis of the included data. Currently, AMYPdb integrates data on 31 families, including 1,705 proteins from nearly 600 organisms. It displays links to more than 2,300 bibliographic references and 1,200 3D-structures. A Wiki system is available to insert data into the database, providing a sharing and collaboration environment. We generated and analyzed 3,621 amino acid sequence patterns, reporting highly specific patterns for each amyloid family, along with patterns likely to be involved in protein misfolding and aggregation. Conclusion AMYPdb is a comprehensive online database aiming at the centralization of bioinformatic data regarding all amyloid proteins and their precursors. Our sequence pattern discovery and analysis approach unveiled protein regions of significant interest. AMYPdb is freely accessible 1.

  7. Temperature Sensitivity of Neural Tube Defects in Zoep Mutants.

    Science.gov (United States)

    Ma, Phyo; Swartz, Morgan R; Kindt, Lexy M; Kangas, Ashley M; Liang, Jennifer Ostrom

    2015-12-01

    Neural tube defects (NTD) occur when the flat neural plate epithelium fails to fold into the neural tube, the precursor to the brain and spinal cord. Squint (Sqt/Ndr1), a Nodal ligand, and One-eyed pinhead (Oep), a component of the Nodal receptor, are required for anterior neural tube closure in zebrafish. The NTD in sqt and Zoep mutants are incompletely penetrant. The penetrance of several defects in sqt mutants increases upon heat or cold shock. In this project, undergraduate students tested whether temperature influences the Zoep open neural tube phenotype. Single pairs of adults were spawned at 28.5°C, the normal temperature for zebrafish, and one half of the resulting embryos were moved to 34°C at different developmental time points. Analysis of variance indicated temperature and clutch/genetic background significantly contributed to the penetrance of the open neural tube phenotype. Heat shock affected the embryos only at or before the midblastula stage. Many factors, including temperature changes in the mother, nutrition, and genetic background, contribute to NTD in humans. Thus, sqt and Zoep mutants may serve as valuable models for studying the interactions between genetics and the environment during neurulation.

  8. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-01-01

    The ‘neural plate border’ of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure. DOI: http://dx.doi.org/10.7554/eLife.21620.001 PMID:28355135

  9. 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…

  10. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette

    1994-01-01

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

  11. Bioluminescence Imaging of Olig2-Neural Stem Cells Reveals Improved Engraftment in a Demyelination Mouse Model

    NARCIS (Netherlands)

    Sher, Falak; van Dam, Go; Boddeke, Erik; Copray, Sjef

    2009-01-01

    A major issue in the potential application of neural stem cell (NSC)-based cell replacement therapy for demyelinating diseases is the question of the survival, functional behavior, and stability of implanted NSC-derived oligodendrocyte precursor cells (OPCs) over an extended period. To address this

  12. Meat flavor precursors and factors influencing flavor precursors--A systematic review.

    Science.gov (United States)

    Khan, Muhammad Issa; Jo, Cheorun; Tariq, Muhammad Rizwan

    2015-12-01

    Flavor is the sensory impression sensed by taste and smell buds and is a leading factor determining the meat quality and purchasing decision of the consumer. Meat flavor is characteristic of volatiles produced as a result of reactions of non-volatile components that are induced thermally. The water soluble compounds having low molecular weight and meat lipids are important precursors of cooked meat flavor. The Maillard reaction, lipid oxidation, and vitamin degradation are leading reactions during cooking which develop meat flavor from uncooked meat with little aroma and bloody taste. The pre-slaughter and postmortem factors like animal breed, sex, age, feed, aging and cooking conditions contribute to flavor development of cooked meat. The objective of this review is to highlight the flavor chemistry, meat flavor precursors and factors affecting meat flavor precursors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Amorphous Alloy: Promising Precursor to Form Nanoflowerpot

    Directory of Open Access Journals (Sweden)

    Guo Lan

    2014-01-01

    Full Text Available Nanoporous copper is fabricated by dealloying the amorphous Ti2Cu alloy in 0.03 M HF electrolyte. The pore and ligament sizes of the nanoporous copper can be readily tailored by controlling the dealloying time. The as-prepared nanoporous copper provides fine and uniform nanoflowerpots to grow highly dispersed Au nanoflowers. The blooming Au nanoflowers in the nanoporous copper flowerpots exhibit both high catalytic activity and stability towards the oxidation of glucose, indicating that the amorphous alloys are ideal precursors to form nanoflowerpot which can grow functional nanoflowers.

  14. The Laplacian spectrum of neural networks

    Science.gov (United States)

    de Lange, Siemon C.; de Reus, Marcel A.; van den Heuvel, Martijn P.

    2014-01-01

    The brain is a complex network of neural interactions, both at the microscopic and macroscopic level. Graph theory is well suited to examine the global network architecture of these neural networks. Many popular graph metrics, however, encode average properties of individual network elements. Complementing these “conventional” graph metrics, the eigenvalue spectrum of the normalized Laplacian describes a network's structure directly at a systems level, without referring to individual nodes or connections. In this paper, the Laplacian spectra of the macroscopic anatomical neuronal networks of the macaque and cat, and the microscopic network of the Caenorhabditis elegans were examined. Consistent with conventional graph metrics, analysis of the Laplacian spectra revealed an integrative community structure in neural brain networks. Extending previous findings of overlap of network attributes across species, similarity of the Laplacian spectra across the cat, macaque and C. elegans neural networks suggests a certain level of consistency in the overall architecture of the anatomical neural networks of these species. Our results further suggest a specific network class for neural networks, distinct from conceptual small-world and scale-free models as well as several empirical networks. PMID:24454286

  15. Neural correlates of paediatric dysgraphia.

    Science.gov (United States)

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

    2013-11-01

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

  16. Neural mechanisms of social dominance

    Directory of Open Access Journals (Sweden)

    Noriya eWatanabe

    2015-06-01

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

  17. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

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

  18. Single Source Precursors for Thin Film Solar Cells

    Science.gov (United States)

    Banger, Kulbinder K.; Hollingsworth, Jennifer A.; Harris, Jerry D.; Cowen, Jonathan; Buhro, William E.; Hepp, Aloysius F.

    2002-01-01

    The development of thin film solar cells on flexible, lightweight, space-qualified substrates provides an attractive cost solution to fabricating solar arrays with high specific power, (W/kg). The use of a polycrystalline chalcopyrite absorber layer for thin film solar cells is considered as the next generation photovoltaic devices. At NASA GRC we have focused on the development of new single source precursors (SSP) and their utility to deposit the chalcopyrite semi-conducting layer (CIS) onto flexible substrates for solar cell fabrication. The syntheses and thermal modulation of SSPs via molecular engineering is described. Thin-film fabrication studies demonstrate the SSPs can be used in a spray CVD (chemical vapor deposition) process, for depositing CIS at reduced temperatures, which display good electrical properties, suitable for PV (photovoltaic) devices.

  19. alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1986-01-01

    The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1......-39). Fractionation by reverse-phase h.p.l.c. revealed ACTH(1-17) and their acetylated analogues. The intermediate lobe contained NO-diacetyl-ACTH-(1-13)-NH2, N-acetyl-ACTH-(1-13)-NH2 and ACTH-(1-13)-NH2. In addition, the corresponding ACTH-(1-14) peptides (the glycine-extended precursor of the amidated peptides...

  20. Calibrations for studies of neutron-rich precursor fragments

    Science.gov (United States)

    Mazza, Maria; Parkhurst, Rachel; Wilensky, Samuel; Mosby, Michelle; Stephenson, Sharon; Rogers, Warren; MoNA Collaboration Collaboration

    2015-10-01

    Heavy ion collisions at relativistic energies produce the radioactive beams used at nuclear structure facilities worldwide. However, there are still unanswered questions about the reaction mechanism of projectile fragmentation and the specific roles that ablation, evaporation, and abrasion play. Using the projectile fragmentation of a 32Mg beam at 86 MeV/u on a natural Beryllium target at the National Superconducting Cyclotron Laboratory (NSCL), our experimental goal is to better understand the excitation energy and the momentum distribution of the precursors of the observed final fragments (neon, sodium, and fluorine). A suite of charged particle detectors in conjunction with the Modular Neutron Array (MoNA) allows us to analyze both the charged final fragments as well as the coincident neutrons. Detector calibration results and preliminary results will be presented. This material is based upon work supported by the National Science Foundation under Grants PHY-1205537.

  1. Pax7 lineage contributions to the mammalian neural crest.

    Directory of Open Access Journals (Sweden)

    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  2. Convection and Mixing in Classical Novae Precursors

    Science.gov (United States)

    Dursi, L. J.; Calder, A. C.; Alexakis, A.; Truran, J. W.; Zingale, M.; Times, F. X.; Ricker, P. M.; Fryxell, B.; Olson, K.; Rosner, R.; MacNeice, P.

    2002-06-01

    To explain observed abundances from classical nova outbursts, and to help explain their energetics, nova models must incorporate a mechanism that will dredge up the heavier white dwarf material into the lighter accreted atmosphere. One proposed mechanism relies on the fluid motions from an early convective phase to do the mixing. We present recent work investigating two aspects of this mechanism. We examine results from two-dimensional simulations of classical nova precursor models that demonstrate the beginning of a convective phase during the `simmering' of a nova precursor. We use a new hydrostatic equilibrium hydrodynamics module recently developed for the adaptive-mesh code FLASH. The two-dimensional models are based on the one-dimensional models of Ami Glasner (Glasner et al. 1997), and were evolved with FLASH from a pre-convective state to the onset of convection. The onset of convection induces a velocity field near the C,O/H,He interface, which can then cause mixing through interactions with gravity waves. We show results from simulations of these wind-wave interactions, and estimate whether the `wind' caused by the convection could induce sufficient dredge-up to power a classical novae. This research has been supported by the US. Department of Energy under grant no. B341495 to the ASCI Flash Center at the University of Chicago

  3. Characterization of the precursors of trihalomethanes and haloacetic acids in the Yuqiao Reservoir in China.

    Science.gov (United States)

    Niu, Zhi-Guang; Wei, Xiao-Ting; Zhang, Ying

    2015-11-01

    To identify the primary precursors of trihalomethanes and haloacetic acids in the Yuqiao Reservoir in China, dissolved organic matters in the source water were isolated and fractionated into five different fractions (with XAD resin), and both trihalomethane and haloacetic acid formation potentials in each fraction were analysed by liquid-liquid extraction and GC-ECD. The primary precursors of trihalomethanes and haloacetic acids were identified using the index of disinfection by-product formation potential and specific disinfection by-product formation potential. In addition, the relationship between the specific ultraviolet absorbance and the specific disinfection by-product formation potential was studied using correlation analysis. The results indicated that during the sampling period, the hydrophobic acids and hydrophilic matter are the primary organic fractions in the Yuqiao Reservoir, accounting for 27.6-40.9% and 21.2-32.5%, respectively. Among the five fractions, the hydrophobic acids had the highest disinfection by-product formation potential and specific disinfection by-product formation potential, indicating that the hydrophobic acids were the primary precursors of the disinfection by-products in the Yuqiao Reservoir. A correlation analysis indicates that the specific ultraviolet absorbance had a moderately positive correlation with the specific disinfection by-product formation potential; therefore, the specific ultraviolet absorbance can be a reference index to analyse the ability of organic matter to generate disinfection by-products.

  4. Dynamics of neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-01

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

  5. Precursor Mediated Synthesis of Nanostructured Silicas: From Precursor-Surfactant Ion Pairs to Structured Materials

    Directory of Open Access Journals (Sweden)

    Peter Hesemann

    2014-04-01

    Full Text Available The synthesis of nanostructured anionic-surfactant-templated mesoporous silica (AMS recently appeared as a new strategy for the formation of nanostructured silica based materials. This method is based on the use of anionic surfactants together with a co-structure-directing agent (CSDA, mostly a silylated ammonium precursor. The presence of this CSDA is necessary in order to create ionic interactions between template and silica forming phases and to ensure sufficient affinity between the two phases. This synthetic strategy was for the first time applied in view of the synthesis of surface functionalized silica bearing ammonium groups and was then extended on the formation of materials functionalized with anionic carboxylate and bifunctional amine-carboxylate groups. In the field of silica hybrid materials, the “anionic templating” strategy has recently been applied for the synthesis of silica hybrid materials from cationic precursors. Starting from di- or oligosilylated imidazolium and ammonium precursors, only template directed hydrolysis-polycondensation reactions involving complementary anionic surfactants allowed accessing structured ionosilica hybrid materials. The mechanistic particularity of this approach resides in the formation of precursor-surfactant ion pairs in the hydrolysis-polycondensation mixture. This review gives a systematic overview over the various types of materials accessed from this cooperative ionic templating approach and highlights the high potential of this original strategy for the formation of nanostructured silica based materials which appears as a complementary strategy to conventional soft templating approaches.

  6. Precursor Mediated Synthesis of Nanostructured Silicas: From Precursor-Surfactant Ion Pairs to Structured Materials

    Science.gov (United States)

    Hesemann, Peter; Nguyen, Thy Phung; Hankari, Samir El

    2014-01-01

    The synthesis of nanostructured anionic-surfactant-templated mesoporous silica (AMS) recently appeared as a new strategy for the formation of nanostructured silica based materials. This method is based on the use of anionic surfactants together with a co-structure-directing agent (CSDA), mostly a silylated ammonium precursor. The presence of this CSDA is necessary in order to create ionic interactions between template and silica forming phases and to ensure sufficient affinity between the two phases. This synthetic strategy was for the first time applied in view of the synthesis of surface functionalized silica bearing ammonium groups and was then extended on the formation of materials functionalized with anionic carboxylate and bifunctional amine-carboxylate groups. In the field of silica hybrid materials, the “anionic templating” strategy has recently been applied for the synthesis of silica hybrid materials from cationic precursors. Starting from di- or oligosilylated imidazolium and ammonium precursors, only template directed hydrolysis-polycondensation reactions involving complementary anionic surfactants allowed accessing structured ionosilica hybrid materials. The mechanistic particularity of this approach resides in the formation of precursor-surfactant ion pairs in the hydrolysis-polycondensation mixture. This review gives a systematic overview over the various types of materials accessed from this cooperative ionic templating approach and highlights the high potential of this original strategy for the formation of nanostructured silica based materials which appears as a complementary strategy to conventional soft templating approaches. PMID:28788602

  7. Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

    Science.gov (United States)

    2013-09-01

    in multiple sclerosis. PLoS One 7:e48078. Turan RG, Brehm M, Koestering M, Tobias Z, Bartsch T, Steiner S, Picard F, Ebner P, Schannwell CM... Ebner P, Schannwell CM, Strauer BE (2007) Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial

  8. A novel three-dimensional system to study interactions between endothelial cells and neural cells of the developing central nervous system

    Directory of Open Access Journals (Sweden)

    Milner Richard

    2007-01-01

    Full Text Available Abstract Background During angiogenesis in the developing central nervous system (CNS, endothelial cells (EC detach from blood vessels growing on the brain surface, and migrate into the expanding brain parenchyma. Brain angiogenesis is regulated by growth factors and extracellular matrix (ECM proteins secreted by cells of the developing CNS. In addition, recent evidence suggests that EC play an important role in establishing the neural stem cell (NSC niche. Therefore, two-way communication between EC and neural cells is of fundamental importance in the developing CNS. To study the interactions between brain EC and neural cells of the developing CNS, a novel three-dimensional (3-D murine co-culture system was developed. Fluorescent-labelled brain EC were seeded onto neurospheres; floating cellular aggregates that contain NSC/neural precursor cells (NPC and smaller numbers of differentiated cells. Using this system, brain EC attachment, survival and migration into neurospheres was evaluated and the role of integrins in mediating the early adhesive events addressed. Results Brain EC attached, survived and migrated deep into neurospheres over a 5-day period. Neurospheres express the ECM proteins fibronectin and laminin, and brain EC adhesion to neurospheres was inhibited by RGD peptides and antibodies specific for the β1, but not the α6 integrin subunit. Conclusion A novel 3-D co-culture system for analysing the interactions between EC and neural cells of the developing CNS is presented. This system could be used to investigate the reciprocal influence of EC and NSC/NPC; to examine how NSC/NPC influence cerebral angiogenesis, and conversely, to examine how EC regulate the maintenance and differentiation of NSC/NPC. Using this system it is demonstrated that EC attachment to neurospheres is mediated by the fibronectin receptor, α5β1 integrin.

  9. Neural network modeling of emotion

    Science.gov (United States)

    Levine, Daniel S.

    2007-03-01

    This article reviews the history and development of computational neural network modeling of cognitive and behavioral processes that involve emotion. The exposition starts with models of classical conditioning dating from the early 1970s. Then it proceeds toward models of interactions between emotion and attention. Then models of emotional influences on decision making are reviewed, including some speculative (not and not yet simulated) models of the evolution of decision rules. Through the late 1980s, the neural networks developed to model emotional processes were mainly embodiments of significant functional principles motivated by psychological data. In the last two decades, network models of these processes have become much more detailed in their incorporation of known physiological properties of specific brain regions, while preserving many of the psychological principles from the earlier models. Most network models of emotional processes so far have dealt with positive and negative emotion in general, rather than specific emotions such as fear, joy, sadness, and anger. But a later section of this article reviews a few models relevant to specific emotions: one family of models of auditory fear conditioning in rats, and one model of induced pleasure enhancing creativity in humans. Then models of emotional disorders are reviewed. The article concludes with philosophical statements about the essential contributions of emotion to intelligent behavior and the importance of quantitative theories and models to the interdisciplinary enterprise of understanding the interactions of emotion, cognition, and behavior.

  10. ANT Advanced Neural Tool

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-07-01

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

  11. SPECTRUM OF NEURAL-TUBE DEFECTS IN 34 INFANTS PRENATALLY EXPOSED TO ANTIEPILEPTIC DRUGS

    NARCIS (Netherlands)

    LINDHOUT, D; OMTZIGT, JGC; CORNEL, MC

    We analyzed the spectrum of neural-tube defects associated with maternal exposure to antiepileptic drugs (AEDs) and the possible contribution of familial and genetic factors to epilepsy or neural-tube defects. No specific association with maternal family history of neural-tube defects or epilepsy

  12. Automated identification and quantification of glycerophospholipid molecular species by multiple precursor ion scanning

    DEFF Research Database (Denmark)

    Ejsing, Christer S.; Duchoslav, Eva; Sampaio, Julio

    2006-01-01

    We report a method for the identification and quantification of glycerophospholipid molecular species that is based on the simultaneous automated acquisition and processing of 41 precursor ion spectra, specific for acyl anions of common fatty acids moieties and several lipid class-specific fragme...... of glycerophospholipids. The automated analysis of total lipid extracts was powered by a robotic nanoflow ion source and produced currently the most detailed description of the glycerophospholipidome....

  13. miR-381 Regulates Neural Stem Cell Proliferation and Differentiation via Regulating Hes1 Expression.

    Directory of Open Access Journals (Sweden)

    Xiaodong Shi

    Full Text Available Neural stem cells are self-renewing, multipotent and undifferentiated precursors that retain the capacity for differentiation into both glial (astrocytes and oligodendrocytes and neuronal lineages. Neural stem cells offer cell-based therapies for neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and spinal cord injuries. However, their cellular behavior is poorly understood. MicroRNAs (miRNAs are a class of small noncoding RNAs involved in cell development, proliferation and differentiation through regulating gene expression at post-transcriptional level. The role of miR-381 in the development of neural stem cells remains unknown. In this study, we showed that overexpression of miR-381 promoted neural stem cells proliferation. It induced the neural stem cells differentiation to neurons and inhibited their differentiation to astrocytes. Furthermore, we identified HES1 as a direct target of miR-381 in neural stem cells. Moreover, re-expression of HES1 impaired miR-381-induced promotion of neural stem cells proliferation and induce neural stem cells differentiation to neurons. In conclusion, miR-381 played important role in neural stem cells proliferation and differentiation.

  14. Empirical generalization assessment of neural network models

    DEFF Research Database (Denmark)

    Larsen, Jan; Hansen, Lars Kai

    1995-01-01

    This paper addresses the assessment of generalization performance of neural network models by use of empirical techniques. We suggest to use the cross-validation scheme combined with a resampling technique to obtain an estimate of the generalization performance distribution of a specific model...

  15. A Neural Region of Abstract Working Memory

    Science.gov (United States)

    Cowan, Nelson; Li, Dawei; Moffitt, Amanda; Becker, Theresa M.; Martin, Elizabeth A.; Saults, J. Scott; Christ, Shawn E.

    2011-01-01

    Over 350 years ago, Descartes proposed that the neural basis of consciousness must be a brain region in which sensory inputs are combined. Using fMRI, we identified at least one such area for working memory, the limited information held in mind, described by William James as the trailing edge of consciousness. Specifically, a region in the left…

  16. Identifying Emotions on the Basis of Neural Activation.

    Directory of Open Access Journals (Sweden)

    Karim S Kassam

    Full Text Available We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1 neural activation of the same individual in other trials, 2 neural activation of other individuals who experienced similar trials, and 3 neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

  17. [Neural codes for perception].

    Science.gov (United States)

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

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

  18. Neural Oscillators Programming Simplified

    Directory of Open Access Journals (Sweden)

    Patrick McDowell

    2012-01-01

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

  19. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    Energy Technology Data Exchange (ETDEWEB)

    Genethliou, Nicholas; Panayiotou, Elena [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Gasperi, Rita De; Elder, Gregory [James J. Peters VA Medical Center, Research and Development (3F22), 130 West Kingsbridge Road, Bronx, NY 10468 (United States); Kessaris, Nicoletta; Richardson, William D. [Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT (United Kingdom); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  20. Functional Nanoporous Polymers from Block Copolymer Precursors

    DEFF Research Database (Denmark)

    Guo, Fengxiao

    applications as, e.g., membranes for separation and purification, templates for nanostructured materials, sensors, substrates for catalysis, low dielectric constant materials, photonic materials, and depots for controlled drug delivery. The development of nanoporous polymers with well controlled pore wall......Abstract Self-assembly of block copolymers provides well-defined morphologies with characteristic length scales in the nanometer range. Nanoporous polymers prepared by selective removal of one block from self-assembled block copolymers offer great technological promise due to their many potential...... functionalities remains a great challenge due to the limitation of available polymer synthesis and the nanoscale confinement of the porous cavities. The main topic of this thesis is to develop methods for fabrication of functional nanoporous polymers from block copolymer precursors. A method has been developed...

  1. Ancient engineers' inventions precursors of the present

    CERN Document Server

    Rossi, Cesare

    2017-01-01

    This book describes the inventions and designs of ancient engineers who are the precursors of the present. The period ranges mainly from 300 B.C. to 1600 A.D. with several exceptions. Many of the oldest inventions are documented by archaeological finds, often very little known, mainly from Pompeii, Herculaneum and Stabiae and reveal a surprising modernity in their conception. Most of the inventions presented in the first four parts of the book were conceived up to the late Roman Empire and may be considered as milestones, each in their respective field. The fifth part concentrates on more recent centuries. The sixth part deals with some building construction techniques. Generally, for each of the presented inventions, three elements of research and reference are provided: written documents (the classics), iconic references (coins, bas-reliefs, etc.) and archaeological findings. The authors did not write this book for engineers only; hence they describe all the devices without assuming wide technical knowledge...

  2. Budget of ozone and precursors over Europe

    Energy Technology Data Exchange (ETDEWEB)

    Roemer, M.G.M.; Bosman, R.; Thijsse, T.; Builtjes, P.J.H.; Esser, P. [IMW-TNO, Delft (Netherlands); Beck, J.P. [RIVM-LLO, Bilthoven (Netherlands); Vosbeek, M. [KEMA, Arnhem (Netherlands)

    1997-12-31

    A three dimensional model for the European boundary layer (the LOTOS model) was used to calculate the budget of ozone and precursors over Europe. For two summer months (July and August) in 1990 the net chemical production of ozone is about 21 Tg/m. By dry deposition 17 Tg/m is lost and transport accounts for a net export of 4 Tg/m into the free troposphere. Large differences in chemical ozone production occur for different regions in Europe. Though the ozone efficiency in terms of ozone produced per NO{sub x} molecule oxidised is much lower in western Europe than elsewhere in Europe the ozone chemically produced per unit area is the highest in western Europe due to the high NO{sub x} emission in this region. (orig.)

  3. The intramolecular click reaction using 'carbocontiguous' precursors.

    Science.gov (United States)

    Patil, Pravin C; Luzzio, Frederick A

    2017-07-20

    The synthesis and utilization of all carbon-chain 'carbocontiguous' azidoalkynyl precursors for an intramolecular click reaction is described. The substrates contain both azidoalkyl and ethynylmethyl groups which are conjoined by a 2-(phenylsulfonylmethyl)-4,5-diphenyloxazole lynchpin and are suitably disposed for ring closure. On promotion by copper salts, a number of cyclic click products having the 1,4-disubstituted endo-fused triazole component and the 4,5-diphenyloxazole component are obtained. In one case, removal of the phenylsulfonylmethyl group from the substrate prior to cyclization gave the 1,5-disubstituted exo-fused triazole. The utilization of CuSO4/sodium ascorbate system appears to be the optimal conditions for closure/cyclization and afforded the cyclized products in yields of 84-95%.

  4. Neural network approaches for noisy language modeling.

    Science.gov (United States)

    Li, Jun; Ouazzane, Karim; Kazemian, Hassan B; Afzal, Muhammad Sajid

    2013-11-01

    Text entry from people is not only grammatical and distinct, but also noisy. For example, a user's typing stream contains all the information about the user's interaction with computer using a QWERTY keyboard, which may include the user's typing mistakes as well as specific vocabulary, typing habit, and typing performance. In particular, these features are obvious in disabled users' typing streams. This paper proposes a new concept called noisy language modeling by further developing information theory and applies neural networks to one of its specific application-typing stream. This paper experimentally uses a neural network approach to analyze the disabled users' typing streams both in general and specific ways to identify their typing behaviors and subsequently, to make typing predictions and typing corrections. In this paper, a focused time-delay neural network (FTDNN) language model, a time gap model, a prediction model based on time gap, and a probabilistic neural network model (PNN) are developed. A 38% first hitting rate (HR) and a 53% first three HR in symbol prediction are obtained based on the analysis of a user's typing history through the FTDNN language modeling, while the modeling results using the time gap prediction model and the PNN model demonstrate that the correction rates lie predominantly in between 65% and 90% with the current testing samples, and 70% of all test scores above basic correction rates, respectively. The modeling process demonstrates that a neural network is a suitable and robust language modeling tool to analyze the noisy language stream. The research also paves the way for practical application development in areas such as informational analysis, text prediction, and error correction by providing a theoretical basis of neural network approaches for noisy language modeling.

  5. Precursor conditions related to Zimbabwe's summer droughts

    Science.gov (United States)

    Nangombe, Shingirai; Madyiwa, Simon; Wang, Jianhong

    2018-01-01

    Despite the increasing severity of droughts and their effects on Zimbabwe's agriculture, there are few tools available for predicting these droughts in advance. Consequently, communities and farmers are more exposed, and policy makers are always ill prepared for such. This study sought to investigate possible cycles and precursor meteorological conditions prior to drought seasons that could be used to predict impending droughts in Zimbabwe. The Single Z-Index was used to identify and grade drought years between 1951 and 2010 according to rainfall severity. Spectral analysis was used to reveal the cycles of droughts for possible use of these cycles for drought prediction. Composite analysis was used to investigate circulation and temperature anomalies associated with severe and extreme drought years. Results indicate that severe droughts are more highly correlated with circulation patterns and embedded weather systems in the Indian Ocean and equatorial Pacific Ocean than any other area. This study identified sea surface temperatures in the average period June to August, geopotential height and wind vector in July to September period, and air temperature in September to November period as precursors that can be used to predict a drought occurrence several months in advance. Therefore, in addition to sea surface temperature, which was identified through previous research for predicting Zimbabwean droughts, the other parameters identified in this study can aid in drought prediction. Drought cycles were established at 20-, 12.5-, 3.2-, and 2.7-year cycles. The spectral peaks, 12.5, 3.2, and 2.7, had a similar timescale with the luni-solar tide, El Niño Southern Oscillation and Quasi Biennial Oscillation, respectively, and hence, occurrence of these phenomena have a possibility of indicating when the next drought might be.

  6. Neural cryptography with feedback.

    Science.gov (United States)

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

    2004-04-01

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

  7. Neural cryptography with feedback

    Science.gov (United States)

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

    2004-04-01

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

  8. Neural network applications

    Science.gov (United States)

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

    1993-01-01

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

  9. Building Neural Net Software

    OpenAIRE

    Neto, João Pedro; Costa, José Félix

    1999-01-01

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

  10. NEMEFO: NEural MEteorological FOrecast

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-07-01

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

  11. Preparation of boron nitride fiber by organic precursor method

    Directory of Open Access Journals (Sweden)

    Yingying Zhou

    Full Text Available In this paper, boron nitride polymer precursor was made by boric acid, melamine, twelve sodium alkyl sulfate as raw materials and pure water as medium which is heated to 70 °C. Boron nitride precursor polymer was soluble in formic acid solution. The boron nitride precursor can be electrostatically spun at the voltage in 23 kV and the distance between the positive and negative poles is 15 cm. The formed fiber is very uniform. The properties of the precursors were analyzed through electron microscope, infrared spectrum, X-ray and ultraviolet spectrum. The aim of the job is to got the precursor of BN and spun it. Keywords: Melamine, Boric acid, Boron nitride precursor, Electrostatic spinning

  12. New bioactive motifs and their use in functionalized self-assembling peptides for NSC differentiation and neural tissue engineering

    Science.gov (United States)

    Gelain, F.; Cigognini, D.; Caprini, A.; Silva, D.; Colleoni, B.; Donegá, M.; Antonini, S.; Cohen, B. E.; Vescovi, A.

    2012-04-01

    Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the discovery of novel functional motifs fostering transplanted stem cell engraftment and nervous fiber regeneration. Using phage display technology we have discovered new peptide sequences that bind to murine neural stem cell (NSC)-derived neural precursor cells (NPCs), and promote their viability and differentiation in vitro when linked to LDLK12 self-assembling peptide (SAPeptide). We characterized the newly functionalized LDLK12 SAPeptides via atomic force microscopy, circular dichroism and rheology, obtaining nanostructured hydrogels that support human and murine NSC proliferation and differentiation in vitro. One functionalized SAPeptide (Ac-FAQ), showing the highest stem cell viability and neural differentiation in vitro, was finally tested in acute contusive spinal cord injury in rats, where it fostered nervous tissue regrowth and improved locomotor recovery. Interestingly, animals treated with the non-functionalized LDLK12 had an axon sprouting/regeneration intermediate between Ac-FAQ-treated animals and controls. These results suggest that hydrogels functionalized with phage-derived peptides may constitute promising biomimetic scaffolds for in vitro NSC differentiation, as well as regenerative therapy of the injured nervous system. Moreover, this multi-disciplinary approach can be used to customize SAPeptides for other specific tissue engineering applications.Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the

  13. Maturation of HIV envelope glycoprotein precursors by cellular endoproteases.

    Science.gov (United States)

    Moulard, M; Decroly, E

    2000-11-10

    The entry of enveloped viruses into its host cells is a crucial step for the propagation of viral infection. The envelope glycoprotein complex controls viral tropism and promotes the membrane fusion process. The surface glycoproteins of enveloped viruses are synthesized as inactive precursors and sorted through the constitutive secretory pathway of the infected cells. To be infectious, most of the viruses require viral envelope glycoprotein maturation by host cell endoproteases. In spite of the strong variability of primary sequences observed within different viral envelope glycoproteins, the endoproteolytical cleavage occurs mainly in a highly conserved domain at the carboxy terminus of the basic consensus sequence (Arg-X-Lys/Arg-Arg downward arrow). The same consensus sequence is recognized by the kexin/subtilisin-like serine proteinases (so called convertases) in many cellular substrates such as prohormones, proprotein of receptors, plasma proteins, growth factors and bacterial toxins. Therefore, several groups of investigators have evaluated the implication of convertases in viral envelope glycoprotein cleavage. Using the vaccinia virus overexpression system, furin was first shown to mediate the proteolytic maturation of both human immunodeficiency virus (HIV-1) and influenza virus envelope glycoproteins. In vitro studies demonstrated that purified convertases directly and specifically cleave viral envelope glycoproteins. Although these studies suggested the participation of several enzymes belonging to the convertases family, recent data suggest that other protease families may also participate in the HIV envelope glycoprotein processing. Their role in the physiological maturation process is still hypothetical and the molecular mechanism of the cleavage is not well documented. Crystallization of the hemagglutinin precursor (HA0) of influenza virus allowed further understanding of the molecular interaction between viral precursors and the cellular endoproteases

  14. Geochemical characterization of oceanic basalts using artificial neural network

    Digital Repository Service at National Institute of Oceanography (India)

    Das, P.; Iyer, S.D.

    method is specifically needed to identify the OFB as normal (N-MORB), enriched (E-MORB) and ocean island basalts (OIB). Artificial Neural Network (ANN) technique as a supervised Learning Vector Quantisation (LVQ) is applied to identify the inherent...

  15. Analysis of Amyloid Precursor Protein function in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Doris Kretzschmar

    2016-07-01

    Full Text Available The Amyloid precursor protein (APP has mainly been investigated in connection with its role in Alzheimer’s disease due to its cleavage resulting in the production of the Aβ peptides that accumulate in the plaques characteristic for this disease. However, APP is an evolutionary conserved protein that is not only found in humans but also in many other species, including Drosophila, suggesting an important physiological function. Besides Aβ, several other fragments are produced by the cleavage of APP; large secreted fragments derived from the N-terminus and a small intracellular C-terminal fragment. Although these fragments have received much less attention than Aβ, a picture about their function is finally emerging. In contrast to mammals, which express three APP family members, Drosophila expresses only one APP protein called Amyloid Precursor Protein-like or APPL. Therefore APPL functions can be studied in flies without the complication that other APP family members may have redundant functions. Flies lacking APPL are viable but show defects in neuronal outgrowth in the central and peripheral nervous system in addition to synaptic changes. Furthermore, APPL has been connected with axonal transport functions. In the adult nervous system, APPL, and more specifically its secreted fragments, can protect neurons from degeneration. APPL cleavage also prevents glial death. Lastly, APPL was found to be involved in behavioural deficits and in regulating sleep/activity patterns. This review, will describe the role of APPL in neuronal development and maintenance and briefly touch on its emerging function in circadian rhythms while an accompanying review will focus on its role in learning and memory formation.

  16. Effect of different nickel precursors on capacitive behavior of electrodeposited NiO thin films

    Energy Technology Data Exchange (ETDEWEB)

    Kore, R. M.; Ghadge, T. S.; Ambare, R. C.; Lokhande, B. J., E-mail: bjlokhande@yahoo.com [School of Physical Sciences, Solapur University, Solapur-413 255, M.S. (India)

    2016-04-13

    In the present study, the effect of nickel precursors containing different anions like nitrate, chloride and sulphate on the morphology and pseudocapacitance behavior of NiO is investigated. The NiO samples were prepared by using a potentiondynamic electrodeposition technique in the three electrode cell. Cyclic voltammetry technique was exploited for potentiodynamic deposition of the films. The obtained samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), etc. The XRD reveals the cubic crystal structure for all samples. The SEM micrograph shows nanoflakelike, up grown nanoflakes and honeycomb like nanostructured morphologies for nitrate, chloride and sulphate precursors respectively. The capacitive behavior of these samples was recorded using cyclic voltammetry (CV), charge-discharge and electrochemical impedance spectroscopy (EIS) in 1 M KOH electrolyte. The specific capacitance values of NiO samples obtained using CV for nitrate, chloride and sulphate precursors were 136, 214 and 893 Fg{sup −1} respectively, at the scan rate of 5 mVs{sup −1}. The charge discharge study shows high specific energy for the sample obtained from sulphate (23.98 Whkg{sup −1}) as compared to chloride (9.67 Whkg{sup −1}) and nitrate (4.9 Whkg{sup −1}), whereas samples of cholride (13.9 kWkg{sup −1} and nitrate (10.5 kWkg{sup −1}) shows comparatively more specific power than samples obtained from sulphate (7.6 kWkg{sup −1}). The equivalent series resistance of NiO samples observed from EIS study are 1.34, 1.29 and 1.27 Ω respectively for nitrate, chloride and sulphate precursors. These results emphasizes that the samples obtained from sulphate precursors provides very low impedance through honeycomb like nanostructured morphology which supports good capacitive behavior of NiO.

  17. Regeneration of neural crest derivatives in the Xenopus tadpole tail

    Directory of Open Access Journals (Sweden)

    Slack Jonathan MW

    2007-05-01

    Full Text Available Abstract Background After amputation of the Xenopus tadpole tail, a functionally competent new tail is regenerated. It contains spinal cord, notochord and muscle, each of which has previously been shown to derive from the corresponding tissue in the stump. The regeneration of the neural crest derivatives has not previously been examined and is described in this paper. Results Labelling of the spinal cord by electroporation, or by orthotopic grafting of transgenic tissue expressing GFP, shows that no cells emigrate from the spinal cord in the course of regeneration. There is very limited regeneration of the spinal ganglia, but new neurons as well as fibre tracts do appear in the regenerated spinal cord and the regenerated tail also contains abundant peripheral innervation. The regenerated tail contains a normal density of melanophores. Cell labelling experiments show that melanophores do not arise from the spinal cord during regeneration, nor from the mesenchymal tissues of the skin, but they do arise by activation and proliferation of pre-existing melanophore precursors. If tails are prepared lacking melanophores, then the regenerates also lack them. Conclusion On regeneration there is no induction of a new neural crest similar to that seen in embryonic development. However there is some regeneration of neural crest derivatives. Abundant melanophores are regenerated from unpigmented precursors, and, although spinal ganglia are not regenerated, sufficient sensory systems are produced to enable essential functions to continue.

  18. Photochemical CVD of Ru on functionalized self-assembled monolayers from organometallic precursors

    Science.gov (United States)

    Johnson, Kelsea R.; Arevalo Rodriguez, Paul; Brewer, Christopher R.; Brannaka, Joseph A.; Shi, Zhiwei; Yang, Jing; Salazar, Bryan; McElwee-White, Lisa; Walker, Amy V.

    2017-02-01

    Chemical vapor deposition (CVD) is an attractive technique for the metallization of organic thin films because it is selective and the thickness of the deposited film can easily be controlled. However, thermal CVD processes often require high temperatures which are generally incompatible with organic films. In this paper, we perform proof-of-concept studies of photochemical CVD to metallize organic thin films. In this method, a precursor undergoes photolytic decomposition to generate thermally labile intermediates prior to adsorption on the sample. Three readily available Ru precursors, CpRu(CO)2Me, (η3-allyl)Ru(CO)3Br, and (COT)Ru(CO)3, were employed to investigate the role of precursor quantum yield, ligand chemistry, and the Ru oxidation state on the deposition. To investigate the role of the substrate chemistry on deposition, carboxylic acid-, hydroxyl-, and methyl-terminated self-assembled monolayers were used. The data indicate that moderate quantum yields for ligand loss (φ ≥ 0.4) are required for ruthenium deposition, and the deposition is wavelength dependent. Second, anionic polyhapto ligands such as cyclopentadienyl and allyl are more difficult to remove than carbonyls, halides, and alkyls. Third, in contrast to the atomic layer deposition, acid-base reactions between the precursor and the substrate are more effective for deposition than nucleophilic reactions. Finally, the data suggest that selective deposition can be achieved on organic thin films by judicious choice of precursor and functional groups present on the substrate. These studies thus provide guidelines for the rational design of new precursors specifically for selective photochemical CVD on organic substrates.

  19. Homeodomain transcription factor Phox2a, via cyclic AMP-mediated activation, induces p27Kip1 transcription, coordinating neural progenitor cell cycle exit and differentiation.

    Science.gov (United States)

    Paris, Maryline; Wang, Wen-Horng; Shin, Min-Hwa; Franklin, David S; Andrisani, Ourania M

    2006-12-01

    Mechanisms coordinating neural progenitor cell cycle exit and differentiation are incompletely understood. The cyclin-dependent kinase inhibitor p27(Kip1) is transcriptionally induced, switching specific neural progenitors from proliferation to differentiation. However, neuronal differentiation-specific transcription factors mediating p27(Kip1) transcription have not been identified. We demonstrate the homeodomain transcription factor Phox2a, required for central nervous system (CNS)- and neural crest (NC)-derived noradrenergic neuron differentiation, coordinates cell cycle exit and differentiation by inducing p27(Kip1) transcription. Phox2a transcription and activation in the CNS-derived CAD cell line and primary NC cells is mediated by combined cyclic AMP (cAMP) and bone morphogenetic protein 2 (BMP2) signaling. In the CAD cellular model, cAMP and BMP2 signaling initially induces proliferation of the undifferentiated precursors, followed by p27(Kip1) transcription, G(1) arrest, and neuronal differentiation. Small interfering RNA silencing of either Phox2a or p27(Kip1) suppresses p27(Kip1) transcription and neuronal differentiation, suggesting a causal link between p27(Kip1) expression and differentiation. Conversely, ectopic Phox2a expression via the Tet-off expression system promotes accelerated CAD cell neuronal differentiation and p27(Kip1) transcription only in the presence of cAMP signaling. Importantly, endogenous or ectopically expressed Phox2a activated by cAMP signaling binds homeodomain cis-acting elements of the p27(Kip1) promoter in vivo and mediates p27(Kip1)-luciferase expression in CAD and NC cells. We conclude that developmental cues of cAMP signaling causally link Phox2a activation with p27(Kip1) transcription, thereby coordinating neural progenitor cell cycle exit and differentiation.

  20. Genetic control of active neural circuits

    Directory of Open Access Journals (Sweden)

    Leon Reijmers

    2009-12-01

    Full Text Available The use of molecular tools to study the neurobiology of complex behaviors has been hampered by an inability to target the desired changes to relevant groups of neurons. Specific memories and specific sensory representations are sparsely encoded by a small fraction of neurons embedded in a sea of morphologically and functionally similar cells. In this review we discuss genetics techniques that are being developed to address this difficulty. In several studies the use of promoter elements that are responsive to neural activity have been used to drive long lasting genetic alterations into neural ensembles that are activated by natural environmental stimuli. This approach has been used to examine neural activity patterns during learning and retrieval of a memory, to examine the regulation of receptor trafficking following learning and to functionally manipulate a specific memory trace. We suggest that these techniques will provide a general approach to experimentally investigate the link between patterns of environmentally activated neural firing and cognitive processes such as perception and memory.

  1. Digital Neural Networks for New Media

    Science.gov (United States)

    Spaanenburg, Lambert; Malki, Suleyman

    Neural Networks perform computationally intensive tasks offering smart solutions for many new media applications. A number of analog and mixed digital/analog implementations have been proposed to smooth the algorithmic gap. But gradually, the digital implementation has become feasible, and the dedicated neural processor is on the horizon. A notable example is the Cellular Neural Network (CNN). The analog direction has matured for low-power, smart vision sensors; the digital direction is gradually being shaped into an IP-core for algorithm acceleration, especially for use in FPGA-based high-performance systems. The chapter discusses the next step towards a flexible and scalable multi-core engine using Application-Specific Integrated Processors (ASIP). This topographic engine can serve many new media tasks, as illustrated by novel applications in Homeland Security. We conclude with a view on the CNN kaleidoscope for the year 2020.

  2. Effect of precursor solutions on ZnO film via solution precursor plasma spray and corresponding gas sensing performances

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Z.X., E-mail: zexin.yu@utbm.fr [Univ Bourgogne Franche Comte, CNRS, Lab ICB, UMR 6303, Site UTBM, F-90010 Belfort (France); Ma, Y.Z., E-mail: yangzhou.ma@outlook.com [School of Materials Science and Engineering, Anhui University of Technology, Ma’anshan 243002 (China); Zhao, Y.L. [Univ Bourgogne Franche Comte, CNRS, Lab ICB, UMR 6303, Site UTBM, F-90010 Belfort (France); Huang, J.B.; Wang, W.Z. [Key Lab of Safety Science of Pressurized System, Ministry of Education, School of Mechanical and Power Engineering, East China University of Science and Technology, Shanghai 200237 (China); Moliere, M.; Liao, H.L. [Univ Bourgogne Franche Comte, CNRS, Lab ICB, UMR 6303, Site UTBM, F-90010 Belfort (France)

    2017-08-01

    Highlights: • C-axis preferential oriented grown ZnO films were firstly deposited via SPPS with different solutions. • ZnO films were hydrophobic due to cauliflower and honeycomb-like surface morphologies with high surface specific area. • Gas detecting performance of (002) plane oriented ZnO was predicted and compared by “first principle calculation method”. - Abstract: Solution precursor plasma spraying (SPPS) as a novel thermal spray method was employed to deposit nano-structured ZnO thin film using different formulations of the precursor solution. This article focuses on the influence of the solution composition on the preferential orientation of crystal growth, on crystal size and surface morphology of the resulting ZnO films. The trend of preferential growth along (002) lattice plane of ZnO film was studied by slow scanning X-ray diffraction using a specific coefficient P{sub (002).} It appears that the thermal spray process promotes the buildup of ZnO films preferentially oriented along the c-axis. The shape of single particle tends to change from round shaped beads to hexagonal plates by increasing the volume ratio of ethanol in the solvent. Both cauliflower and honeycomb-like surface morphologies featuring high specific surface area and roughness were obtained through the SPPS process by varying solution composition. These ZnO films are hydrophobic with contact angle as high as 136°, which is seemingly associated with micro reliefs developing high surface specific area. Then the gas sensing performances of ZnO films preferentially oriented along (002) face were tentatively predicted using the “first principle calculation method” and were compared with those of conventional films that are mainly oriented along the (101) face. The (002) face displays better hydrogen adsorption capability than the (101) face with much larger resulting changes in electrical resistance. In conclusion, the c-axis oriented ZnO films obtained through SSPS have

  3. Eruption precursors: Manifestations and strategies for detection

    Science.gov (United States)

    Poland, Michael; Pritchard, Matthew

    2017-04-01

    The past several decades have seen a rapid increase in volcano monitoring and modeling capabilities. Diverse arrays of instrument networks can detect a variety of pre-, co-, and post-eruptive phenomena, and remote sensing observations are available across a range of spatial, temporal, and spectral resolutions. A growing class of models, based on the physics of magmatic systems, are making use of these expanding datastreams, providing probabilistic assessments of such parameters as magma supply, volatile content, and eruption duration. To what extent, however, do these developments heighten our ability to identify eruption precursors? The advent of better data and new models provides an opportunity to reexamine our understanding of pre-eruption unrest, as well as our ability to detect and recognize it as such. An idealized model of the buildup to a volcanic eruption might include magma ascent from a deep source region and accumulation in the mid- to upper crust in the preceding months to years. The process might be manifested by surface inflation and deep long-period earthquakes, and accompanied by an increase in CO2 emissions. As magma continues to accumulate, distal volcano-tectonic earthquakes may result as stress builds on nearby faults, H2S emissions may increase as sulfur in a shallow reservoir is hydrolyzed by groundwater, and fumarole and spring temperatures may increase and show changes in chemistry. In the days to hours before an eruption, sudden changes in the rate and style of earthquakes (including repeating earthquakes and tremor) and deformation may occur as the magma reservoir ruptures and magma moves laterally or vertically. Phreatic eruptions might result as ascending magma comes into contact with groundwater, and SO2 emissions might increase as the path between the magma and surface dries out. How often does such a sequence actually occur? Relatively few volcanoes are comprehensively monitored prior to obvious expressions of unrest, so this is not

  4. Frog Swarms: Earthquake Precursors or False Alarms?

    Directory of Open Access Journals (Sweden)

    Rachel A. Grant

    2013-10-01

    Full Text Available In short-term earthquake risk forecasting, the avoidance of false alarms is of utmost importance to preclude the possibility of unnecessary panic among populations in seismic hazard areas. Unusual animal behaviour prior to earthquakes has been reported for millennia but has rarely been scientifically documented. Recently large migrations or unusual behaviour of amphibians have been linked to large earthquakes, and media reports of large frog and toad migrations in areas of high seismic risk such as Greece and China have led to fears of a subsequent large earthquake. However, at certain times of year large migrations are part of the normal behavioural repertoire of amphibians. News reports of “frog swarms” from 1850 to the present day were examined for evidence that this behaviour is a precursor to large earthquakes. It was found that only two of 28 reported frog swarms preceded large earthquakes (Sichuan province, China in 2008 and 2010. All of the reported mass migrations of amphibians occurred in late spring, summer and autumn and appeared to relate to small juvenile anurans (frogs and toads. It was concluded that most reported “frog swarms” are actually normal behaviour, probably caused by juvenile animals migrating away from their breeding pond, after a fruitful reproductive season. As amphibian populations undergo large fluctuations in numbers from year to year, this phenomenon will not occur on a yearly basis but will depend on successful reproduction, which is related to numerous climatic and geophysical factors. Hence, most large swarms of amphibians, particularly those involving very small frogs and occurring in late spring or summer, are not unusual and should not be considered earthquake precursors. In addition, it is likely that reports of several mass migration of small toads prior to the Great Sichuan Earthquake in 2008 were not linked to the subsequent M = 7.9 event (some occurred at a great distance from the epicentre

  5. Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours.

    Science.gov (United States)

    Rodríguez-Zarco, E; Vallejo-Benítez, A; Umbría-Jiménez, S; Pereira-Gallardo, S; Pabón-Carrasco, S; Azueta, A; González-Cámpora, R; Espinal, P S; García-Escudero, A

    2017-10-01

    Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets. Copyright © 2017 AEU. All rights reserved.

  6. Silicon deposition in nanopores using a liquid precursor

    Science.gov (United States)

    Masuda, Takashi; Tatsuda, Narihito; Yano, Kazuhisa; Shimoda, Tatsuya

    2016-11-01

    Techniques for depositing silicon into nanosized spaces are vital for the further scaling down of next-generation devices in the semiconductor industry. In this study, we filled silicon into 3.5-nm-diameter nanopores with an aspect ratio of 70 by exploiting thermodynamic behaviour based on the van der Waals energy of vaporized cyclopentasilane (CPS). We originally synthesized CPS as a liquid precursor for semiconducting silicon. Here we used CPS as a gas source in thermal chemical vapour deposition under atmospheric pressure because vaporized CPS can fill nanopores spontaneously. Our estimation of the free energy of CPS based on Lifshitz van der Waals theory clarified the filling mechanism, where CPS vapour in the nanopores readily undergoes capillary condensation because of its large molar volume compared to those of other vapours such as water, toluene, silane, and disilane. Consequently, a liquid-specific feature was observed during the deposition process; specifically, condensed CPS penetrated into the nanopores spontaneously via capillary force. The CPS that filled the nanopores was then transformed into solid silicon by thermal decomposition at 400 °C. The developed method is expected to be used as a nanoscale silicon filling technology, which is critical for the fabrication of future quantum scale silicon devices.

  7. The HIV Tat protein affects processing of ribosomal RNA precursor

    Directory of Open Access Journals (Sweden)

    Bellenchi Gian

    2008-06-01

    Full Text Available Abstract Background Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown. Results To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in Drosophila melanogaster strain transgenic for HIV-tat gene. Here we show that Tat localizes in the nucleoli of Drosophila oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation. Conclusion Our data contribute to understanding the function of Tat in the nucleolus, where ribosomal RNA synthesis and cell cycle control take place. The impairment of nucleolar pre-rRNA maturation through the interaction of Tat with fibrillarin-U3snoRNA complex suggests a process by which the virus modulates host response, thus contributing to apoptosis and protein shut-off in HIV-uninfected cells.

  8. Sentinel-5 Precursor: Global Monitoring of Atmospheric Trace Gases & Aerosols

    Science.gov (United States)

    Nett, Herbert; McMullan, Kevin; Ingmann, Paul

    2013-04-01

    ESA's Sentinel 5 Precursor (S5P) Mission will form part of the Space Component under the Global Monitoring for Environment and Security (GMES) initiative. It represents a preparatory project for the GMES atmospheric missions that comprise both a geo-stationary (Sentinel-4 / part of MTG-S payload) and a polar orbiting (Sentinel-5 / MetOp Second Generation) component. In view of the planned launch date of around 2020 for the first S-4 MTG-S and MetOp-SG spacecrafts, respectively, S5P (launch: mid 2015) shall minimize gaps in the availability of global atmospheric data products as provided by its predecessor missions SCIAMACHY (Envisat) and OMI (AURA). The satellite's single payload instrument, TROPOMI (TROPOspheric Monitoring Instrument), is jointly developed by The Netherlands and ESA. Covering spectral channels located in the UV, visible, near- and short-wave infrared it will measure various key species including stratospheric ozone, as well as NO2, SO2, CO, CH4, CH2O and aerosols, specifically in the lower Troposphere. The envisaged formation flying with NASA's Suomi NPP satellite will allow use of high spatial resolution imager data for enhanced cloud clearing of the observational data specifically in the short-wave infrared range. An outline of the Sentinel-5P mission objectives will be given. The status of development activities, covering Spacecraft and the Ground Segment will be presented.

  9. Observations of Precursor Breakdown Prior to Intracloud Lightning Discharges

    Science.gov (United States)

    Rison, W.; Krehbiel, P. R.; Thomas, R. J.; Brown, M. F.

    2009-12-01

    Using the New Mexico Tech VHF Lightning Mapping Array (LMA) we have detected weak precursor discharges occurring up to a few tens of seconds before the initiation of normal polarity intracloud (IC) lightning discharges. With the very sensitive LMA installed at White Sands Missile Range (WSMR) in south central New Mexico, we observe low-power VHF precursor events in about 10% of lightning discharges. Most of the precursors occur within horizontal distances of about 200 meters of the locations of the initial LMA sources observed in the subsequent discharges, with altitudes about the same as the altitudes of the initial LMA sources. Most precursors consist of a single LMA source, indicating that the duration of the RF emission is less than the 80 μs time window of the WSMR LMA. Occasionally, a given precursor event lasts for up to 400 μs. For most discharges with precursors, only one precursor is observed, occurring anywhere from a few hundred milliseconds to 30 seconds before the discharge. For some flashes, more precursors are observed, several seconds apart. In a few cases, some of the precursor sources are several kilometers from the initial LMA source. In these cases, the leader channels of the ensuing discharge propagate from the flash initiation point to the horizontal locations of the distant precursors. The precursors apparently occur in the regions of the highest pre-discharge fields in the cell, indicating high field regions before the lightning discharge. The precursors are observed only at altitudes of about 8 to 10 km, corresponding to the region between the mid-level negative and upper positive storm charges. We have not observed precursors at altitudes in the 5 to 7 km range, corresponding to the region below the mid-level negative charge where CG discharges are initiated. The altitude dependence of the precursors may result from the fact that breakdown is easier to initiate at lower pressures. Because of RF emission restrictions at WSMR, the

  10. Comparison of neurosphere-like cell clusters derived from dental follicle precursor cells and retinal Müller cells

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Petersen, Jørgen; Felthaus, Oliver

    2011-01-01

    Unrelated cells such as dental follicle precursor cells (DFPCs) and retinal Müller cells (MCs) make spheres after cultivation in serum-replacement medium (SRM). Until today, the relation and molecular processes of sphere format