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Sample records for neural crest-derived tissues

  1. Regeneration of neural crest derivatives in the Xenopus tadpole tail

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    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.

  2. Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice.

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    Kajohnkiart Janebodin

    Full Text Available Dental pulp stem cells (DPSCs are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues.

  3. Isolation and Characterization of Neural Crest-Derived Stem Cells from Dental Pulp of Neonatal Mice

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    Janebodin, Kajohnkiart; Horst, Orapin V.; Ieronimakis, Nicholas; Balasundaram, Gayathri; Reesukumal, Kanit; Pratumvinit, Busadee; Reyes, Morayma

    2011-01-01

    Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues. PMID:22087335

  4. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body

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    Valentina Annese

    2017-04-01

    Full Text Available Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy.

  5. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

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    Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

    2017-04-18

    Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells].

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    Dupin, Elisabeth

    2011-01-01

    -like progenitors. Altogether, these studies have shown that Schwann cells and pigment cells display an unstable status of differentiation, which can be disclosed if these differentiated cells are displaced out of their native tissue. When challenged with new environmental conditions in vitro, differentiated Schwann cells and pigment cells can reacquire stem cell properties of their neural crest ancestors. Notably, such reprogramming was achieved through the effect of a single exogenous factor and without the need of any induced genetic modification. Deciphering the cellular and molecular mechanisms that regulate the plasticity and maintenance of neural crest-derived differentiated cells is likely to be an important step towards the understanding of the neurocristopathies and cancers that target neural crest derivatives in humans. © Société de Biologie, 2011.

  7. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  8. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

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    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model. ©AlphaMed Press.

  9. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

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    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  10. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

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    Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com; Wu, Yong, E-mail: wyonger@gmail.com; Wang, Bo, E-mail: wb228@126.com; Jiang, Ning, E-mail: 179639060@qq.com; Nie, Ping, E-mail: nieping1011@sina.com; Cao, Haifeng, E-mail: 0412chf@163.com; Yang, Zhi, E-mail: wcums1981@163.com; Fang, Bing, E-mail: fangbing@sjtu.edu.cn

    2016-07-08

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

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

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    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.

  12. Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations.

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    Gopinathan, Gokul; Kolokythas, Antonia; Luan, Xianghong; Diekwisch, Thomas G H

    2013-06-15

    Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.

  13. Enrichment and Schwann Cell Differentiation of Neural Crest-derived Dental Pulp Stem Cells.

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    Al-Zer, Heba; Apel, Christian; Heiland, Max; Friedrich, Reinhard E; Jung, Ole; Kroeger, Nadja; Eichhorn, Wolfgang; Smeets, Ralf

    2015-01-01

    As already described in previous studies, neural crest stem cells (NCSCs) can be found in adult human dental pulp. The present study investigated the methodology for enrichment and differentiation-induction of the above mentioned cells. Dental pulp was extracted from human wisdom teeth of four patients and subsequently cultured as explants on fibronectin-coated plates in neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin, l-glutamine and neuregulin-β1. The cells were then characterized by immunofluorescence, while their differentiation-potential was tested by the attempt to induce cells into different lineages, i.e. osteogenic, melanocytic and glial. The enriched cell population expressed nestin, CD271 and SOX10, which are well-known markers for NCSCs. Consequently, the cells were successfully induced to differentiate into osteoblasts, melanocytes and Schwann cells, expressing the corresponding differentiation markers. Human adult dental pulp contains a population of stem cells with neural crest ontogeny, which can thus be recruited for multiple regenerative therapies. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Neural crest-derived dental stem cells--where we are and where we are going.

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    Mayo, Vera; Sawatari, Yoh; Huang, C-Y Charles; Garcia-Godoy, Franklin

    2014-09-01

    There are five types of post-natal human dental stem cells that have been identified, isolated and characterized. Here, we review the information available on dental stem cells as well as their potential applications in dentistry, regenerative medicine and the development of other therapeutic approaches. Data pertinent to dental stem cells and their applications, published in peer-reviewed journals from 1982 to 2013 in English were reviewed. Sources were retrieved from PubMed databases as well as related references that the electronic search yielded. Manuscripts describing the origin, retrieval, characterization and application of dental stem cells were obtained and reviewed. Dental stem cell populations present properties similar to those of mesenchymal stem cells, such as the ability to self-renew and the potential for multilineage differentiation. While they have greater capacity to give rise to odontogenic cells and regenerate dental pulp and periodontal tissue, they have the capacity to differentiate into all three germ line cells, proving that a population of pluripotent stem cells exists in the dental tissues. Dental stem cells have the capacity to differentiate into endoderm, mesoderm and ectoderm tissues. Consequently they do not only have applications in dentistry, but also neurodegenerative and ischemic diseases, diabetes research, bone repair, and other applications in the field of tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Combination of exogenous cell transplantation and 5-HT{sub 4} receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

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

    2017-02-01

    Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT{sub 4} receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT{sub 4} receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75{sup NTR} and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT{sub 4} receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.

  16. In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75{sup +} stem cells with dental follicle cell conditioned medium

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    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Liu, Rui; Zhang, Li; Nie, Xin, E-mail: dr.xinnie@gmail.com

    2015-09-10

    Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75{sup +}) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75{sup +} CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75{sup +} cells, suggesting their differentiation along cementoblast-like lineage. p75{sup +} stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75{sup +}) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75{sup +} CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75{sup +} cells express cementoblast specific mineralization

  17. Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin

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    C.E. Wong (Christine); S. Paratore (Sabrina); M.T. Dours-Zimmermann (María); T. Rochat (Thierry); T. Pietri (Thomas); U. Suter (Ueli); D. Zimmermann (Dieter); S. Dufour (Sylvie); J.P. Thiery (Joachim); D.N. Meijer (Dies); C. Beermann (Christopher); Y. Barrandon (Yann); L. Sommer (Lukas)

    2006-01-01

    textabstractGiven their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell-like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and

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

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

    2016-05-01

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

  19. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

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    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  20. Depletion of Neural Crest-Derived Cells Leads to Reduction in Plasma Noradrenaline and Alters B Lymphopoiesis.

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    Tsunokuma, Naoki; Yamane, Toshiyuki; Matsumoto, Chiaki; Tsuneto, Motokazu; Isono, Kana; Imanaka-Yoshida, Kyoko; Yamazaki, Hidetoshi

    2017-01-01

    Hematopoietic stem cells and their lymphoid progenitors are supported by the bone marrow (BM) microenvironmental niches composed of various stromal cells and Schwann cells and sympathetic nerve fibers. Although neural crest (NC) cells contribute to the development of all the three, their function in BM is not well understood. In this study, NC-derived cells were ablated with diphtheria toxin in double-transgenic mice expressing NC-specific Cre and Cre-driven diphtheria toxin receptor with yellow fluorescent protein reporter. We found that yellow fluorescent protein-expressing, NC-derived nonhematopoietic cells in BM expressed hematopoietic factors Cxcl12 and stem cell factor The ablation of NC-derived cells led to a significant decrease in B cell progenitors but not in hematopoietic stem cells or myeloid lineage cells in BM. Interestingly, plasma noradrenaline was markedly decreased in these mice. The i.p. administration of 6-hydroxydopamine, a known neurotoxin for noradrenergic neurons, led to a similar phenotype, whereas the administration of a noradrenaline precursor in NC-ablated mice partially rescued this phenotype. Additionally, the continuous administration of adrenergic receptor β antagonists partially decreased the number of B cell progenitors while preserving B lymphopoiesis in vitro. Taken together, our results indicate that NC-derived cell depletion leads to abnormal B lymphopoiesis partially through decreased plasma noradrenaline, suggesting this as a novel mechanism regulated by molecules released by the sympathetic neurons. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Cranial neural crest-derived mesenchymal proliferation is regulated by Msx1-mediated p19(INK4d) expression during odontogenesis.

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    Han, Jun; Ito, Yoshihiro; Yeo, Jae Yong; Sucov, Henry M; Maas, Richard; Chai, Yang

    2003-09-01

    Neural crest cells are multipotential progenitors that contribute to various cell and tissue types during embryogenesis. Here, we have investigated the molecular and cellular mechanism by which the fate of neural crest cell is regulated during tooth development. Using a two- component genetic system for indelibly marking the progeny of neural crest cells, we provide in vivo evidence of a deficiency of CNC-derived dental mesenchyme in Msx1 null mutant mouse embryos. The deficiency of the CNC results from an elevated CDK inhibitor p19(INK4d) activity and the disruption of cell proliferation. Interestingly, in the absence of Msx1, the CNC-derived dental mesenchyme misdifferentiates and possesses properties consistent with a neuronal fate, possibly through a default mechanism. Attenuation of p19(INK4d) in Msx1 null mutant mandibular explants restores mitotic activity in the dental mesenchyme, demonstrating the functional significance of Msx1-mediated p19(INK4d) expression in regulating CNC cell proliferation during odontogenesis. Collectively, our results demonstrate that homeobox gene Msx1 regulates the fate of CNC cells by controlling the progression of the cell cycle. Genetic mutation of Msx1 may alternatively instruct the fate of these progenitor cells during craniofacial development.

  2. Neural Crest Stem Cells from Dental Tissues: A New Hope for Dental and Neural Regeneration

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    Gaskon Ibarretxe

    2012-01-01

    Full Text Available Several stem cell sources persist in the adult human body, which opens the doors to both allogeneic and autologous cell therapies. Tooth tissues have proven to be a surprisingly rich and accessible source of neural crest-derived ectomesenchymal stem cells (EMSCs, which may be employed to repair disease-affected oral tissues in advanced regenerative dentistry. Additionally, one area of medicine that demands intensive research on new sources of stem cells is nervous system regeneration, since this constitutes a therapeutic hope for patients affected by highly invalidating conditions such as spinal cord injury, stroke, or neurodegenerative diseases. However, endogenous adult sources of neural stem cells present major drawbacks, such as their scarcity and complicated obtention. In this context, EMSCs from dental tissues emerge as good alternative candidates, since they are preserved in adult human individuals, and retain both high proliferation ability and a neural-like phenotype in vitro. In this paper, we discuss some important aspects of tissue regeneration by cell therapy and point out some advantages that EMSCs provide for dental and neural regeneration. We will finally review some of the latest research featuring experimental approaches and benefits of dental stem cell therapy.

  3. 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...

  4. 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.

  5. Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

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    Yoshihiro Sowa

    Full Text Available Recent studies have shown that adipose-derived stromal/stem cells (ASCs contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs. This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2 and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta. NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

  6. Electrospun Nanofibrous Materials for Neural Tissue Engineering

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    Yee-Shuan Lee

    2011-02-01

    Full Text Available The use of biomaterials processed by the electrospinning technique has gained considerable interest for neural tissue engineering applications. The tissue engineering strategy is to facilitate the regrowth of nerves by combining an appropriate cell type with the electrospun scaffold. Electrospinning can generate fibrous meshes having fiber diameter dimensions at the nanoscale and these fibers can be nonwoven or oriented to facilitate neurite extension via contact guidance. This article reviews studies evaluating the effect of the scaffold’s architectural features such as fiber diameter and orientation on neural cell function and neurite extension. Electrospun meshes made of natural polymers, proteins and compositions having electrical activity in order to enhance neural cell function are also discussed.

  7. CHARGEd with neural crest defects.

    Science.gov (United States)

    Pauli, Silke; Bajpai, Ruchi; Borchers, Annette

    2017-10-30

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

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

    Science.gov (United States)

    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.

  9. Pax7 lineage contributions to the mammalian neural crest.

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    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.

  10. Adhesion molecule-modified biomaterials for neural tissue engineering

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    Shreyas S Rao

    2009-06-01

    Full Text Available Adhesion molecules (AMs represent one class of biomolecules that promote central nervous system regeneration. These tethered molecules provide cues to regenerating neurons that recapitulate the native brain environment. Improving cell adhesive potential of non-adhesive biomaterials is therefore a common goal in neural tissue engineering. This review discusses common AMs used in neural biomaterials and the mechanism of cell attachment to these AMs. Methods to modify materials with AMs are discussed and compared. Additionally, patterning of AMs for achieving specific neuronal responses is explored.

  11. Structural Analysis of Three-dimensional Human Neural Tissue derived from Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Terrence Brooks, Patrick; Rasmussen, Mikkel Aabech; Hyttel, Poul

    2016-01-01

    Objective: The present study aimed at establishing a method for production of a three-dimensional (3D) human neural tissue derived from induced pluripotent stem cells (iPSCs) and analyzing the outcome by a combination of tissue ultrastructure and expression of neural markers. Methods: A two......-step cell culture procedure was implemented by subjecting human iPSCs to a 3D scaffoldbased neural differentiation protocol. First, neural fate-inducing small molecules were used to create a neuroepithelial monolayer. Second, the monolayer was trypsinized into single cells and seeded into a porous...... polystyrene scaffold and further cultured to produce a 3D neural tissue. The neural tissue was characterized by a combination of immunohistochemistry and transmission electron microscopy (TEM). Results: iPSCs developed into a 3D neural tissue expressing markers for neural progenitor cells, early neural...

  12. Classifications of multispectral colorectal cancer tissues using convolution neural network

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    Hawraa Haj-Hassan

    2017-01-01

    Full Text Available Background: Colorectal cancer (CRC is the third most common cancer among men and women. Its diagnosis in early stages, typically done through the analysis of colon biopsy images, can greatly improve the chances of a successful treatment. This paper proposes to use convolution neural networks (CNNs to predict three tissue types related to the progression of CRC: benign hyperplasia (BH, intraepithelial neoplasia (IN, and carcinoma (Ca. Methods: Multispectral biopsy images of thirty CRC patients were retrospectively analyzed. Images of tissue samples were divided into three groups, based on their type (10 BH, 10 IN, and 10 Ca. An active contour model was used to segment image regions containing pathological tissues. Tissue samples were classified using a CNN containing convolution, max-pooling, and fully-connected layers. Available tissue samples were split into a training set, for learning the CNN parameters, and test set, for evaluating its performance. Results: An accuracy of 99.17% was obtained from segmented image regions, outperforming existing approaches based on traditional feature extraction, and classification techniques. Conclusions: Experimental results demonstrate the effectiveness of CNN for the classification of CRC tissue types, in particular when using presegmented regions of interest.

  13. Multifunctional nanowire scaffolds for neural tissue engineering applications

    Science.gov (United States)

    Bechara, Samuel Leo

    Unlike other regions of the body, the nervous system is extremely vulnerable to damage and injury because it has a limited ability to self-repair. Over 250,000 people in the United States have spinal cord injuries and due to the complicated pathophysiology of such injuries, there are few options available for functional regeneration of the spinal column. Furthermore, peripheral nerve damage is troublingly common in the United States, with an estimated 200,000 patients treated surgically each year. The current gold standard in treatment for peripheral nerve damage is a nerve autograft. This technique was pioneered over 45 years ago, but suffers from a major drawback. By transecting a nerve from another part of the body, function is regained at the expense of destroying a nerve connection elsewhere. Because of these issues, the investigation of different materials for regenerating nervous tissue is necessary. This work examines multi-functional nanowire scaffolds to provide physical and chemical guidance cues to neural stem cells to enhance cellular activity from a biomedical engineering perspective. These multi-functional scaffolds include a unique nanowire nano-topography to provide physical cues to guide cellular adhesion. The nanowires were then coated with an electrically conductive polymer to further enhance cellular activity. Finally, nerve growth factor was conjugated to the surface of the scaffolds to provide chemical cues for the neural stem cells. The results in this work suggest that these multifunctional nanowire scaffolds could be used in vivo to repair nervous system tissue.

  14. Expression of Intermediate Filament Nestin in Blood Vessels of Neural and Non-neural Tissues

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    Jaroslav Mokrý

    2008-01-01

    Full Text Available Our previous findings performed in rat tissues demonstrated that intermediate filament nestin is expressed in endothelial cells of newly formed blood vessels of developing organs and neural transplants. The aim of the present study was to identify other cellular markers expressed in nestin-positive (nestin+ blood vessels. To reach this goal we performed double immunofluorescent study to co-localize nestin with endothelium-specific markers (CD31, CD34 II, vimentin or markers of perivascular cells (GFAP, SMA in paraffin-embedded sections of normal human brain tissue, low- and high-grade gliomas, postinfarcted heart and samples of non-neural tumours. Our findings documented that all the samples examined contained blood vessels with different ratio of nestin+ endothelial cells. Double immunostaining provided unambiguous evidence that endothelial cells expressed nestin and allowed them to distinguish from other nestin+ elements (perivascular astrocytic endfeet, undifferentiated tumour cells, smooth muscle cells and pericytes. Nestin+ endothelium was not confined only to newly formed capillaries but was also observed in blood vessels of larger calibres, frequently in arterioles and venules. We conclude that nestin represents a reliable vascular marker that is expressed in endothelial cells. Elevation of nestin expression likely corresponds to reorganization of intermediate filament network in the cytoskeleton of endothelial cells in the course of their maturation or adaptation to changes in growing tissues.

  15. Deep convolutional neural network approach for forehead tissue thickness estimation

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    Manit Jirapong

    2017-09-01

    Full Text Available In this paper, we presented a deep convolutional neural network (CNN approach for forehead tissue thickness estimation. We use down sampled NIR laser backscattering images acquired from a novel marker-less near-infrared laser-based head tracking system, combined with the beam’s incident angle parameter. These two-channel augmented images were constructed for the CNN input, while a single node output layer represents the estimated value of the forehead tissue thickness. The models were – separately for each subject – trained and tested on datasets acquired from 30 subjects (high resolution MRI data is used as ground truth. To speed up training, we used a pre-trained network from the first subject to bootstrap training for each of the other subjects. We could show a clear improvement for the tissue thickness estimation (mean RMSE of 0.096 mm. This proposed CNN model outperformed previous support vector regression (mean RMSE of 0.155 mm or Gaussian processes learning approaches (mean RMSE of 0.114 mm and eliminated their restrictions for future research.

  16. How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

    Science.gov (United States)

    Chevalier, N. R.; Gazguez, E.; Bidault, L.; Guilbert, T.; Vias, C.; Vian, E.; Watanabe, Y.; Muller, L.; Germain, S.; Bondurand, N.; Dufour, S.; Fleury, V.

    2016-02-01

    Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

  17. Analytic Modeling of Neural Tissue: I. A Spherical Bidomain.

    Science.gov (United States)

    Schwartz, Benjamin L; Chauhan, Munish; Sadleir, Rosalind J

    2016-12-01

    Presented here is a model of neural tissue in a conductive medium stimulated by externally injected currents. The tissue is described as a conductively isotropic bidomain, i.e. comprised of intra and extracellular regions that occupy the same space, as well as the membrane that divides them, and the injection currents are described as a pair of source and sink points. The problem is solved in three spatial dimensions and defined in spherical coordinates [Formula: see text]. The system of coupled partial differential equations is solved by recasting the problem to be in terms of the membrane and a monodomain, interpreted as a weighted average of the intra and extracellular domains. The membrane and monodomain are defined by the scalar Helmholtz and Laplace equations, respectively, which are both separable in spherical coordinates. Product solutions are thus assumed and given through certain transcendental functions. From these electrical potentials, analytic expressions for current density are derived and from those fields the magnetic flux density is calculated. Numerical examples are considered wherein the interstitial conductivity is varied, as well as the limiting case of the problem simplifying to two dimensions due to azimuthal independence. Finally, future modeling work is discussed.

  18. Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications.

    Science.gov (United States)

    Lee, Jae Y; Bashur, Chris A; Goldstein, Aaron S; Schmidt, Christine E

    2009-09-01

    Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40-50% longer neurites and 40-90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications.

  19. Polypyrrole-Coated Electrospun PLGA Nanofibers for Neural Tissue Applications

    Science.gov (United States)

    Lee, Jae Young; Bashur, Chris A.; Goldstein, Aaron S.; Schmidt, Christine E.

    2009-01-01

    Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40–50% longer neurites and 40–90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications. PMID:19501901

  20. ChainMail based neural dynamics modeling of soft tissue deformation for surgical simulation.

    Science.gov (United States)

    Zhang, Jinao; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-07-20

    Realistic and real-time modeling and simulation of soft tissue deformation is a fundamental research issue in the field of surgical simulation. In this paper, a novel cellular neural network approach is presented for modeling and simulation of soft tissue deformation by combining neural dynamics of cellular neural network with ChainMail mechanism. The proposed method formulates the problem of elastic deformation into cellular neural network activities to avoid the complex computation of elasticity. The local position adjustments of ChainMail are incorporated into the cellular neural network as the local connectivity of cells, through which the dynamic behaviors of soft tissue deformation are transformed into the neural dynamics of cellular neural network. Experiments demonstrate that the proposed neural network approach is capable of modeling the soft tissues' nonlinear deformation and typical mechanical behaviors. The proposed method not only improves ChainMail's linear deformation with the nonlinear characteristics of neural dynamics but also enables the cellular neural network to follow the principle of continuum mechanics to simulate soft tissue deformation.

  1. Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue.

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    Geir Halnes

    2016-11-01

    Full Text Available Recorded potentials in the extracellular space (ECS of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1 the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2 the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii The power spectral density (PSD of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in

  2. Electric field effects in hyperexcitable neural tissue: A review

    Energy Technology Data Exchange (ETDEWEB)

    Durand, D.M

    2003-07-01

    Uniform electric fields applied to neural tissue can modulate neuronal excitability with a threshold value of about 1mV mm{sup -1} in normal physiological conditions. However, electric fields could have a lower threshold in conditions where field sensitivity is enhanced, such as those simulating epilepsy. Uniform electrical fields were applied to hippocampal brain slices exposed to picrotoxin, high potassium or low calcium solutions. The results in the low calcium medium show that neuronal activity can be completely blocked in 10% of the 30 slices tested with a field amplitude of 1mV mm{sup -1}. These results suggest that the threshold for this effect is clearly smaller than 1mV mm{sup -1}. The hypothesis that the extracellular resistance could affect the sensitivity to the electrical fields was tested by measuring the effect of the osmolarity of the extracellular solution on the efficacy of the field. A 10% decrease on osmolarity resulted in a 56% decrease (n=4) in the minimum field required for full suppression. A 14% in osmolarity produced an 81% increase in the minimum field required for full suppression. These results show that the extracellular volume can modulate the efficacy of the field and could lower the threshold field amplitudes to values lower than {approx}1mmV mm{sup -.} (author)

  3. Central neural control of thermoregulation and brown adipose tissue.

    Science.gov (United States)

    Morrison, Shaun F

    2016-04-01

    Central neural circuits orchestrate the homeostatic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response. This review summarizes the experimental underpinnings of our current model of the CNS pathways controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction controlling heat loss, and shivering and brown adipose tissue for thermogenesis. The activation of these effectors is regulated by parallel but distinct, effector-specific, core efferent pathways within the CNS that share a common peripheral thermal sensory input. Via the lateral parabrachial nucleus, skin thermal afferent input reaches the hypothalamic preoptic area to inhibit warm-sensitive, inhibitory output neurons which control heat production by inhibiting thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to thermogenesis-controlling premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation of spinal circuits necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus sympathetic premotor neurons controlling cutaneous vasoconstriction. The model proposed for central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation and elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Michael Polanco

    2016-06-01

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

  6. Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

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    Satoru Morikawa

    2016-01-01

    Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

  7. Sphere-Derived Multipotent Progenitor Cells Obtained From Human Oral Mucosa Are Enriched in Neural Crest Cells.

    Science.gov (United States)

    Abe, Shigehiro; Yamaguchi, Satoshi; Sato, Yutaka; Harada, Kiyoshi

    2016-01-01

    : Although isolation of oral mucosal stromal stem cells has been previously reported, complex isolation methods are not suitable for clinical application. The neurosphere culture technique is a convenient method for the isolation of neural stem cells and neural crest stem cells (NCSCs); neurosphere generation is a phenotype of NCSCs. However, the molecular details underlying the isolation and characterization of human oral mucosa stromal cells (OMSCs) by neurosphere culture are not understood. The purpose of the present study was to isolate NCSCs from oral mucosa using the neurosphere technique and to establish effective in vivo bone tissue regeneration methods. Human OMSCs were isolated from excised human oral mucosa; these cells formed spheres in neurosphere culture conditions. Oral mucosa sphere-forming cells (OMSFCs) were characterized by biological analyses of stem cells. Additionally, composites of OMSFCs and multiporous polylactic acid scaffolds were implanted subcutaneously into immunocompromised mice. OMSFCs had the capacity for self-renewal and expressed neural crest-related markers (e.g., nestin, CD44, slug, snail, and MSX1). Furthermore, upregulated expression of neural crest-related genes (EDNRA, Hes1, and Sox9) was observed in OMSFCs, which are thought to contain an enriched population of neural crest-derived cells. The expression pattern of α2-integrin (CD49b) in OMSFCs also differed from that in OMSCs. Finally, OMSFCs were capable of differentiating into neural crest lineages in vitro and generating ectopic bone tissues even in the subcutaneous region. The results of the present study suggest that OMSFCs are an ideal source of cells for the neural crest lineage and hard tissue regeneration. The sphere culture technique is a convenient method for isolating stem cells. However, the isolation and characterization of human oral mucosa stromal cells (OMSCs) using the sphere culture system are not fully understood. The present study describes the

  8. Cellular neural network modelling of soft tissue dynamics for surgical simulation.

    Science.gov (United States)

    Zhang, Jinao; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-07-20

    Currently, the mechanical dynamics of soft tissue deformation is achieved by numerical time integrations such as the explicit or implicit integration; however, the explicit integration is stable only under a small time step, whereas the implicit integration is computationally expensive in spite of the accommodation of a large time step. This paper presents a cellular neural network method for stable simulation of soft tissue deformation dynamics. The non-rigid motion equation is formulated as a cellular neural network with local connectivity of cells, and thus the dynamics of soft tissue deformation is transformed into the neural dynamics of the cellular neural network. Results show that the proposed method can achieve good accuracy at a small time step. It still remains stable at a large time step, while maintaining the computational efficiency of the explicit integration. The proposed method can achieve stable soft tissue deformation with efficiency of explicit integration for surgical simulation.

  9. Glucocorticoid control of gene transcription in neural tissue

    NARCIS (Netherlands)

    Morsink, Maarten Christian

    2007-01-01

    Glucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), are ligand-inducible transcription factors. Therefore, changes in gene

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.

    Science.gov (United States)

    Barry, Christopher; Schmitz, Matthew T; Propson, Nicholas E; Hou, Zhonggang; Zhang, Jue; Nguyen, Bao K; Bolin, Jennifer M; Jiang, Peng; McIntosh, Brian E; Probasco, Mitchell D; Swanson, Scott; Stewart, Ron; Thomson, James A; Schwartz, Michael P; Murphy, William L

    2017-11-01

    The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies. Spearman's rank correlation analysis of global gene expression profiles and a comparison of coefficient of variation for expressed genes demonstrated that replicate neural constructs were highly uniform to at least day 21 for samples from independent experiments. We also demonstrate that model neural tissues formed on PEG hydrogels using a simplified neural differentiation protocol correlated more strongly to in vivo brain development than samples cultured on tissue culture polystyrene surfaces alone. These results provide a proof-of-concept demonstration that 3D cellular models that mimic aspects of human brain development can be produced from human pluripotent stem cells with high sample uniformity between experiments by using standard culture techniques, cryopreserved cell stocks, and a synthetic extracellular matrix. Impact statement Pluripotent stem (PS) cells have been characterized by an inherent ability to self-organize into 3D "organoids" resembling stomach, intestine, liver, kidney, and brain tissues, offering a potentially powerful tool for modeling human development and disease. However, organoid formation must be quantitatively reproducible for applications such as drug and toxicity screening. Here, we report a strategy to produce uniform neural tissue constructs with reproducible global gene expression profiles for replicate samples from multiple

  12. The in vivo developmental potential of porcine skin-derived progenitors and neural stem cells.

    Science.gov (United States)

    Zhao, Ming-Tao; Yang, Xiaoyu; Lee, Kiho; Mao, Jiude; Teson, Jennifer M; Whitworth, Kristin M; Samuel, Melissa S; Spate, Lee D; Murphy, Clifton N; Prather, Randall S

    2012-09-20

    Multipotent skin-derived progenitors (SKPs) can be traced back to embryonic neural crest cells and are able to differentiate into both neural and mesodermal progeny in vitro. Neural stem cells (NSCs) are capable of self-renewing and can contribute to neuron and glia in the nervous system. Recently, we derived porcine SKPs and NSCs from the same enhanced green fluorescent protein (EGFP) transgenic fetuses and demonstrated that SKPs could contribute to neural and mesodermal lineages in vivo. However, it remains unclear whether porcine SKPs and NSCs can generate ectoderm and mesoderm lineages or other germ layers in vivo. Embryonic chimeras are a well-established tool for investigating cell lineage determination and cell potency through normal embryonic development. Thus, the purpose of this study was to investigate the in vivo developmental potential of porcine SKPs and fetal brain-derived NSCs by chimera production. Porcine SKPs, NSCs, and fibroblasts were injected into precompact in vitro fertilized embryos (IVF) and then transferred into corresponding surrogates 24 h postinjection. We found that porcine SKPs could incorporate into the early embryos and contribute to various somatic tissues of the 3 germ layers in postnatal chimera, and especially have an endodermal potency. However, this developmental potential is compromised when they differentiate into fibroblasts. In addition, porcine NSCs fail to incorporate into host embryos and contribute to chimeric piglets. Therefore, neural crest-derived SKPs may represent a more primitive state than their counterpart neural stem cells in terms of their contributions to multiple cell lineages.

  13. Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

    2017-08-31

    Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

  14. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    Directory of Open Access Journals (Sweden)

    Sethuraman Swaminathan

    2009-11-01

    Full Text Available Abstract Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.

  15. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    Science.gov (United States)

    2009-01-01

    Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves. PMID:19939265

  16. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration.

    Science.gov (United States)

    Subramanian, Anuradha; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2009-11-25

    Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.

  17. Engineering three dimensional micro nerve tissue using postnatal stem cells from human dental apical papilla.

    Science.gov (United States)

    Kim, Byung-Chul; Jun, Sung-Min; Kim, So Yeon; Kwon, Yong-Dae; Choe, Sung Chul; Kim, Eun-Chul; Lee, Jae-Hyung; Kim, Jinseok; Suh, Jun-Kyo Francis; Hwang, Yu-Shik

    2017-04-01

    The in vitro generation of cell-based three dimensional (3D) nerve tissue is an attractive subject to improve graft survival and integration into host tissue for neural tissue regeneration or to model biological events in stem cell differentiation. Although 3D organotypic culture strategies are well established for 3D nerve tissue formation of pluripotent stem cells to study underlying biology in nerve development, cell-based nerve tissues have not been developed using human postnatal stem cells with therapeutic potential. Here, we established a culture strategy for the generation of in vitro cell-based 3D nerve tissue from postnatal stem cells from apical papilla (SCAPs) of teeth, which originate from neural crest-derived ectomesenchyme cells. A stem cell population capable of differentiating into neural cell lineages was generated during the ex vivo expansion of SCAPs in the presence of EGF and bFGF, and SCAPs differentiated into neural cells, showing neural cell lineage-related molecular and gene expression profiles, morphological changes and electrophysical property under neural-inductive culture conditions. Moreover, we showed the first evidence that 3D cell-based nerve-like tissue with axons and myelin structures could be generated from SCAPs via 3D organotypic culture using an integrated bioprocess composed of polyethylene glycol (PEG) microwell-mediated cell spheroid formation and subsequent dynamic culture in a high aspect ratio vessel (HARV) bioreactor. In conclusion, the culture strategy in our study provides a novel approach to develop in vitro engineered nerve tissue using SCAPs and a foundation to study biological events in the neural differentiation of postnatal stem cells. Biotechnol. Bioeng. 2017;114: 903-914. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Multiple cranial organ defects after conditionally knocking out Fgf10 in the neural crest

    Directory of Open Access Journals (Sweden)

    Tathyane H.N. Teshima

    2016-10-01

    Full Text Available Fgf10 is necessary for the development of a number of organs that fail to develop or are reduced in size in the null mutant. Here we have knocked out Fgf10 specifically in the neural crest driven by Wnt1cre. The Wnt1creFgf10fl/fl mouse phenocopies many of the null mutant defects, including cleft palate, loss of salivary glands and ocular glands, highlighting the neural crest origin of the Fgf10 expressing mesenchyme surrounding these organs. In contrast tissues such as the limbs and lungs, where Fgf10 is expressed by the surrounding mesoderm, were unaffected, as was the pituitary gland where Fgf10 is expressed by the neuroepithelium. The circumvallate papilla of the tongue formed but was hypoplastic in the conditional and Fgf10 null embryos, suggesting that other sources of FGF can compensate in development of this structure. The tracheal cartilage rings showed normal patterning in the conditional knockout, indicating that the source of Fgf10 for this tissue is mesodermal, which was confirmed using Wnt1cre-dtTom to lineage trace the boundary of the neural crest in this region. The thyroid, thymus and parathyroid glands surrounding the trachea were present but hypoplastic in the conditional mutant, indicating that a neighbouring source of mesodermal Fgf10 might be able to partially compensate for loss of neural crest derived Fgf10.

  19. Involvement of Neptune in induction of the hatching gland and neural crest in the Xenopus embryo.

    Science.gov (United States)

    Kurauchi, Takayuki; Izutsu, Yumi; Maéno, Mitsugu

    2010-01-01

    Neptune, a Krüppel-like transcription factor, is expressed in various regions of the developing Xenopus embryo and it has multiple functions in the process of development in various organs. In situ hybridization analysis showed that Neptune is expressed in the boundary region between neural and non-neural tissues at the neurula stage, but little is known about the function of Neptune in this region. Here, we examined the expression and function of Neptune in the neural plate border (NPB) in the Xenopus embryo. Depletion of Neptune protein in developing embryos by using antisense MO caused loss of the hatching gland and otic vesicle as well as malformation of neural crest-derived cranial cartilages and melanocytes. Neptune MO also suppressed the expression of hatching gland and neural crest markers such as he, snail2, sox9 and msx1 at the neurula stage. Subsequent experiments showed that Neptune is necessary and sufficient for the differentiation of hatching gland cells and that it is located downstream of pax3 in the signal regulating the differentiation of these cells. Thus, Neptune is a new member of hatching gland specifier and plays a physiological role in determination and specification of multiple lineages derived from the NPB region.

  20. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

    Directory of Open Access Journals (Sweden)

    Naosuke Kamei

    2017-01-01

    Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

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

    Directory of Open Access Journals (Sweden)

    Hayato Fukusumi

    2016-01-01

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

  2. Novel nanofibrous spiral scaffolds for neural tissue engineering

    Science.gov (United States)

    Valmikinathan, Chandra M.; Tian, Jingjing; Wang, Junping; Yu, Xiaojun

    2008-12-01

    Due to several drawbacks associated with autografts and allografts, tissue-engineering approaches have been widely used to repair peripheral nerve injuries. Most of the traditional tissue-engineered scaffolds in use are either tubular (single or multi-lumen) or hydrogel-based cylindrical grafts, which provide limited surface area for cell attachment and regeneration. Here, we show a novel poly(lactide-co-glycotide) (PLGA) microsphere-based spiral scaffold design with a nanofibrous surface that has enhanced surface areas and possesses sufficient mechanical properties and porosities to support the nerve regeneration process. These scaffolds have an open architecture that goes evenly throughout the scaffolds hence leaving enough volume for media influx and deeper cell penetration into the scaffolds. The in vitro tests conducted using Schwann cells show that the nanofibrous spiral scaffolds promote higher cell attachment and proliferation when compared to contemporary tubular scaffolds or nanofiber-based tubular scaffolds. Also, the nanofiber coating on the surfaces enhances the surface area, mimics the extracellular matrix and provides unidirectional alignment of cells along its direction. Hence, we propose that these scaffolds could alleviate some drawbacks in current nerve grafts and could potentially be used in nerve regeneration.

  3. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  4. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    Energy Technology Data Exchange (ETDEWEB)

    Campi, G.; Pezzotti, G. [Institute of Crystallography, CNR, via Salaria Km 29.300, I-00015, Monterotondo Roma (Italy); Fratini, M. [Centro Fermi -Museo Storico della Fisica e Centro Studi e Ricerche ' Enrico Fermi' , Roma (Italy); Ricci, A. [Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, D-22607 Hamburg (Germany); Burghammer, M. [European Synchrotron Radiation Facility, B. P. 220, F-38043 Grenoble Cedex (France); Cancedda, R.; Mastrogiacomo, M. [Istituto Nazionale per la Ricerca sul Cancro, and Dipartimento di Medicina Sperimentale dell' Università di Genova and AUO San Martino Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132, Genova (Italy); Bukreeva, I.; Cedola, A. [Institute for Chemical and Physical Process, CNR, c/o Physics Dep. at Sapienza University, P-le A. Moro 5, 00185, Roma (Italy)

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  5. Neural stem cell proliferation and differentiation in the conductive PEDOT-HA/Cs/Gel scaffold for neural tissue engineering.

    Science.gov (United States)

    Wang, Shuping; Guan, Shui; Xu, Jianqiang; Li, Wenfang; Ge, Dan; Sun, Changkai; Liu, Tianqing; Ma, Xuehu

    2017-09-26

    Engineering scaffolds with excellent electro-activity is increasingly important in tissue engineering and regenerative medicine. Herein, conductive poly(3,4-ethylenedioxythiophene) doped with hyaluronic acid (PEDOT-HA) nanoparticles were firstly synthesized via chemical oxidant polymerization. A three-dimensional (3D) PEDOT-HA/Cs/Gel scaffold was then developed by introducing PEDOT-HA nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. HA, as a bridge, not only was used as a dopant, but also combined PEDOT into the Cs/Gel via chemical crosslinking. The PEDOT-HA/Cs/Gel scaffold was used as a conductive substrate for neural stem cell (NSC) culture in vitro. The results demonstrated that the PEDOT-HA/Cs/Gel scaffold had excellent biocompatibility for NSC proliferation and differentiation. 3D confocal fluorescence images showed cells attached on the channel surface of Cs/Gel and PEDOT-HA/Cs/Gel scaffolds with a normal neuronal morphology. Compared to the Cs/Gel scaffold, the PEDOT-HA/Cs/Gel scaffold not only promoted NSC proliferation with up-regulated expression of Ki67, but also enhanced NSC differentiation into neurons and astrocytes with up-regulated expression of β tubulin-III and GFAP, respectively. It is expected that this electro-active and bio-active PEDOT-HA/Cs/Gel scaffold will be used as a conductive platform to regulate NSC behavior for neural tissue engineering.

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

    Science.gov (United States)

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

    2010-11-26

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

  7. Determination of platinum by radiochemical neutron activation analysis in neural tissues from rats, monkeys and patients treated with cisplatin

    DEFF Research Database (Denmark)

    Rietz, B.; Krarup-Hansen, A.; Rorth, M.

    2001-01-01

    of the animals mentioned and in the neural tissues of human patients. For the determination of platinum in the tissues radiochemical neutron activation analysis has been used. The detection limit is 1 ng Pt g(-1). The platinum results indicate that platinum becomes accumulated in the dorsal root ganglia......Cisplatin is one of the most used antineoplastic drugs, essential for the treatment of germ cell tumours. Its use in medical treatment of cancer patients often causes chronic peripheral neuropathy in these patients. The distribution of cisplatin in neural tissues is, therefore, of great interest....... Rats and monkeys were used as animal models for the study of sensory changes in different neural tissues, like spinal cord (ventral and dorsal part), dorsal root ganglia and sural nerve. The study was combined with quantitative measurements of the content of platinum in the neural tissues...

  8. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  9. Trigger Points, Pressure Pain Hyperalgesia, and Mechanosensitivity of Neural Tissue in Women with Chronic Pelvic Pain.

    Science.gov (United States)

    Fuentes-Márquez, Pedro; Valenza, Marie Carmen; Cabrera-Martos, Irene; Ríos-Sánchez, Ana; Ocón-Hernández, Olga

    2017-08-25

    This study aims to evaluate the presence of myofascial trigger points (TrPs), widespread pressure pain sensitivity, and mechanosensitivity of neural tissue in women with chronic pelvic pain. Case-control study. Faculty of Health Sciences. Forty women with chronic pelvic pain between age 18 and 60 years and 40 matched healthy controls were included in the study. TrPs were bilaterally explored in gluteus maximus, gluteus medius, gluteus minimus, quadratus lumborum, and adductor magnus muscles. The referred pain reproduced lumbopelvic symptoms. Pressure pain thresholds (PPTs) were also bilaterally assessed over the Pfannenstiel incision point on the abdominal, C5-C6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle. Mechanosensitivity of neural tissue was assessed with the neurodynamics tests of slump and the straight-leg raising. Significant between-group differences were found in TrP presence in patients with chronic pelvic pain (P Neurodynamics show a significantly decreased value in women with CPP. Patients with chronic pelvic pain presented a high percentage of TrPs that reproduce their symptoms. Patients also showed a widespread pressure pain hyperalgesia and more mechanosensitive neural tissue due to a decrease on the range of motion related to neurodynamics.

  10. On random walks and entropy in diffusion-weighted magnetic resonance imaging studies of neural tissue.

    Science.gov (United States)

    Ingo, Carson; Magin, Richard L; Colon-Perez, Luis; Triplett, William; Mareci, Thomas H

    2014-02-01

    In diffusion-weighted MRI studies of neural tissue, the classical model assumes the statistical mechanics of Brownian motion and predicts a monoexponential signal decay. However, there have been numerous reports of signal decays that are not monoexponential, particularly in the white matter. We modeled diffusion in neural tissue from the perspective of the continuous time random walk. The characteristic diffusion decay is represented by the Mittag-Leffler function, which relaxes a priori assumptions about the governing statistics. We then used entropy as a measure of the anomalous features for the characteristic function. Diffusion-weighted MRI experiments were performed on a fixed rat brain using an imaging spectrometer at 17.6 T with b-values arrayed up to 25,000 s/mm(2). Additionally, we examined the impact of varying either the gradient strength, q, or mixing time, Δ, on the observed diffusion dynamics. In white and gray matter regions, the Mittag-Leffler and entropy parameters demonstrated new information regarding subdiffusion and produced different image contrast from that of the classical diffusion coefficient. The choice of weighting on q and Δ produced different image contrast within the regions of interest. We propose these parameters have the potential as biomarkers for morphology in neural tissue. Copyright © 2013 Wiley Periodicals, Inc.

  11. Comparison of the acute effects of hemostatic agents on neural tissues in spine surgery: Histologic analysis in rat models

    Directory of Open Access Journals (Sweden)

    Gokhan Meric

    2016-03-01

    Conclusion: Both gelatin sponge and oxidized cellulose did not increase the cellular necrosis of neural tissues. However, oxidized cellulose may lead to an increased local inflammatory reaction. [Arch Clin Exp Surg 2016; 5(1.000: 21-26

  12. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

    Directory of Open Access Journals (Sweden)

    Michaela Thomas

    2017-11-01

    Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

  13. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening.

    Science.gov (United States)

    Thomas, Michaela; Willerth, Stephanie M

    2017-01-01

    Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone), and poly(ethylene glycol). This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

  14. 3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration.

    Science.gov (United States)

    Hsieh, Fu-Yu; Hsu, Shan-hui

    2015-01-01

    Acute traumatic injuries and chronic degenerative diseases represent the world's largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37 °C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration.

  15. Improved Selectivity From a Wavelength Addressable Device for Wireless Stimulation of Neural Tissue

    Directory of Open Access Journals (Sweden)

    Elif Ç. Seymour

    2014-02-01

    Full Text Available Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume. Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other.

  16. 3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration

    Science.gov (United States)

    Hsieh, Fu-Yu; Hsu, Shan-hui

    2015-01-01

    ABSTRACT Acute traumatic injuries and chronic degenerative diseases represent the world’s largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37°C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration. PMID:26709633

  17. PANP is a novel O-glycosylated PILR{alpha} ligand expressed in neural tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kogure, Amane [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Shiratori, Ikuo [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Wang, Jing [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Lanier, Lewis L. [Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 (United States); Arase, Hisashi, E-mail: arase@biken.osaka-u.ac.jp [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); JST CREST, Saitama 332-0012 (Japan)

    2011-02-18

    Research highlights: {yields} A Novel molecule, PANP, was identified to be a PILR{alpha} ligand. {yields} Sialylated O-glycan structures on PANP were required for PILR{alpha} recognition. {yields} Transcription of PANP was mainly observed in neural tissues. {yields} PANP seems to be involved in immune regulation as a ligand for PILR{alpha}. -- Abstract: PILR{alpha} is an immune inhibitory receptor possessing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain enabling it to deliver inhibitory signals. Binding of PILR{alpha} to its ligand CD99 is involved in immune regulation; however, whether there are other PILR{alpha} ligands in addition to CD99 is not known. Here, we report that a novel molecule, PILR-associating neural protein (PANP), acts as an additional ligand for PILR{alpha}. Transcription of PANP was mainly observed in neural tissues. PILR{alpha}-Ig fusion protein bound cells transfected with PANP and the transfectants stimulated PILR{alpha} reporter cells. Specific O-glycan structures on PANP were found to be required for PILR recognition of this ligand. These results suggest that PANP is involved in immune regulation as a ligand of the PILR{alpha}.

  18. Binary tissue classification on wound images with neural networks and bayesian classifiers.

    Science.gov (United States)

    Veredas, Francisco; Mesa, Héctor; Morente, Laura

    2010-02-01

    A pressure ulcer is a clinical pathology of localized damage to the skin and underlying tissue caused by pressure, shear, or friction. Diagnosis, treatment, and care of pressure ulcers are costly for health services. Accurate wound evaluation is a critical task for optimizing the efficacy of treatment and care. Clinicians usually evaluate each pressure ulcer by visual inspection of the damaged tissues, which is an imprecise manner of assessing the wound state. Current computer vision approaches do not offer a global solution to this particular problem. In this paper, a hybrid approach based on neural networks and Bayesian classifiers is used in the design of a computational system for automatic tissue identification in wound images. A mean shift procedure and a region-growing strategy are implemented for effective region segmentation. Color and texture features are extracted from these segmented regions. A set of k multilayer perceptrons is trained with inputs consisting of color and texture patterns, and outputs consisting of categorical tissue classes which are determined by clinical experts. This training procedure is driven by a k-fold cross-validation method. Finally, a Bayesian committee machine is formed by training a Bayesian classifier to combine the classifications of the k neural networks. Specific heuristics based on the wound topology are designed to significantly improve the results of the classification. We obtain high efficiency rates from a binary cascade approach for tissue identification. Results are compared with other similar machine-learning approaches, including multiclass Bayesian committee machine classifiers and support vector machines. The different techniques analyzed in this paper show high global classification accuracy rates. Our binary cascade approach gives high global performance rates (average sensitivity =78.7% , specificity =94.7% , and accuracy =91.5% ) and shows the highest average sensitivity score ( =86.3%) when detecting

  19. 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.

  20. Translocation of latex beads after laser ablation of the avian neural crest.

    Science.gov (United States)

    Coulombe, J N; Bronner-Fraser, M

    1984-11-01

    Previous studies from this laboratory (M.E. Bronner-Fraser, 1982, Dev. Biol. 91, 50-63) have demonstrated that latex beads translocate ventrally after injection into avian embryos during the phase of neural crest migration, to settle in the vicinity of neural-crest-derived structures. In order to examine the role of host neural crest cells in the ventral translocation of implanted beads, latex beads have been injected into regions of embryos from which the neural crest cells have been ablated using a laser microbeam. Prior to their migratory phase, neural crest cells reside in the dorsal portion of the neural tube. Laser irradiation of the dorsal neural tube was used to reproducibly achieve either partial or complete ablation of neural crest cells from the irradiated regions. The effectiveness of the ablation was assessed by the degree of reduction in dorsal root ganglia, a neural crest derivative. Because of the rapidity and precision of this technique, it was possible to selectively remove neural crest cells without significantly altering other embryonic structures. The results indicate that, after injection of latex beads into the somites of embryos whose neural crest cells were removed by laser irradiation, the beads translocate ventrally in the absence of the endogenous neural crest.

  1. DNA methyltransferase 3b is dispensable for mouse neural crest development.

    Directory of Open Access Journals (Sweden)

    Bridget T Jacques-Fricke

    Full Text Available The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

  2. Stem Cell Bioprinting: Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells (Adv. Healthcare Mater. 12/2016).

    Science.gov (United States)

    Gu, Qi; Tomaskovic-Crook, Eva; Lozano, Rodrigo; Chen, Yu; Kapsa, Robert M; Zhou, Qi; Wallace, Gordon G; Crook, Jeremy M

    2016-06-01

    On page 1429 G. G. Wallace, J. M. Crook, and co-workers report the first example of fabricating neural tissue by 3D bioprinting human neural stem cells. A novel polysaccharide based bioink preserves stem cell viability and function within the printed construct, enabling self-renewal and differentiation to neurons and supporting neuroglia. Neurons are predominantly GABAergic, establish networks, are spontaneously active, and show a bicuculline induced increased calcium response. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Dental Pulp Stem Cells as a multifaceted tool for bioengineering and the regeneration of craniomaxillofacial tissues

    Directory of Open Access Journals (Sweden)

    Maitane eAurrekoetxea

    2015-10-01

    Full Text Available Dental pulp stem cells, or DPSC, are neural crest-derived cells with an outstanding capacity to differentiate along multiple cell lineages of interest for cell therapy. In particular, highly efficient osteo/dentinogenic differentiation of DPSC can be achieved using simple in vitro protocols, making these cells a very attractive and promising tool for the future treatment of dental and periodontal diseases. Among craniomaxillofacial organs, the tooth and salivary gland are two such cases in which complete regeneration by tissue engineering using DPSC appears to be possible, as research over the last decade has made substantial progress in experimental models of partial or total regeneration of both organs, by cell recombination technology. Moreover, DPSC seem to be a particularly good choice for the regeneration of nerve tissues, including injured or transected cranial nerves. In this context, the oral cavity appears to be an excellent testing ground for new regenerative therapies using DPSC. However, many issues and challenges need yet to be addressed before these cells can be employed in clinical therapy. In this review, we point out some important aspects on the biology of DPSC with regard to their use for the reconstruction of different craniomaxillofacial tissues and organs, with special emphasis on cranial bones, nerves, teeth, and salivary glands. We suggest new ideas and strategies to fully exploit the capacities of DPSC for bioengineering of the aforementioned tissues.

  4. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    Science.gov (United States)

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

  5. New tissue dissociation protocol for scaled-up production of neural stem cells in suspension bioreactors.

    Science.gov (United States)

    Sen, Arindom; Kallos, Michael S; Behie, Leo A

    2004-01-01

    The successful dissociation of mammalian neural stem cell (NSC) aggregates (neurospheres) into a single-cell suspension is an important procedure when expanding NSCs for clinical use, or when performing important assays such as clonal analyses. Until now, researchers have had to rely primarily on destructive mechanical methods such as trituration with a pipette tip to break apart the aggregates. In this study we report on a new chemical dissociation procedure that is efficient, cost effective, reproducible, and much less harmful to murine NSCs than both mechanical and enzymatic techniques. This method, involving the manipulation of environmental pH levels, resulted in 40% higher measured cell densities and 15-20% higher viabilities compared with mechanical dissociation. Moreover, chemical dissociation resulted in the production of significantly less cellular debris. Chemical dissociation was found to have no adverse effects on the long-term proliferation of the NSCs, which retained the ability to proliferate, form neurospheres, self-renew, and exhibit multipotentiality. This chemical method represents a new approach for the dissociation of tissues.

  6. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

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

  7. Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

    Directory of Open Access Journals (Sweden)

    Yike Jiang

    2017-07-01

    Full Text Available While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1, we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG, a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.

  8. Expression of the synaptic vesicle proteins VAMPs/synaptobrevins 1 and 2 in non-neural tissues

    DEFF Research Database (Denmark)

    Ralston, E; Beushausen, S; Ploug, Thorkil

    1994-01-01

    for Vp/Syb 2 detected a protein in the endoplasmic reticulum-Golgi area of skeletal muscle. Thus Vp/Sybs 1 and 2 are not restricted to the nervous system but appear to be co-expressed with cellubrevin in many different tissues. This redundancy of Vp/Sybs in a single cell may be required to control......The VAMPs/synaptobrevins (Vp/Sybs) are small integral membrane proteins. Two isoforms, Vp/Syb 1 and Vp/Syb 2, are considered to be specific to neural tissue. They are associated with synaptic vesicles and are believed to play an important role in neurotransmitter release. A third isoform......, cellubrevin, has recently been found in non-neural tissues. We now report that the distribution of Vp/Syb 1 and Vp/Syb 2 is wider than previously thought. RNA transcripts for both Vp/Syb 1 and Vp/Syb 2 were found in rat skeletal muscle and in several other rat non-neural tissues, and antibodies specific...

  9. Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain

    Science.gov (United States)

    Harris, J. P.; Struzyna, L. A.; Murphy, P. L.; Adewole, D. O.; Kuo, E.; Cullen, D. K.

    2016-02-01

    Objective. Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach. We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results. The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter—white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 μN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance. Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain

  10. 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

  11. Adult bone marrow neural crest stem cells and mesenchymal stem cells are not able to replace lost neurons in acute MPTP-lesioned mice.

    Directory of Open Access Journals (Sweden)

    Virginie Neirinckx

    Full Text Available Adult bone marrow stroma contains multipotent stem cells (BMSC that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC or mesenchymal stem cells (MSC survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management.

  12. Brain tissue aspiration neural tube defect Aspiração de tecido cerebral em casos de defeitos de fechamento do tubo neural

    Directory of Open Access Journals (Sweden)

    Luiz Cesar Peres

    2005-09-01

    Full Text Available The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP. There were 15 (68.2% females and 7 (31.8% males. Age ranged from 18 to 40 weeks of gestation (mean= 31.8. Ten (45.5% were stillborn, the same newborn, and 2 (9.1% were abortuses. Diagnosis were: craniorrhachischisis (9 cases, 40.9%, anencephaly (8 cases, 36,4%, ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each, and early amniotic band disruption sequence (1 case, 4.5%. Only one case (4.5% exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.O objetivo do estudo foi identificar qual a freqüência de aspiração de tecido cerebral e a existência de heterotopia nos pulmões de casos humanos de defeito de fechamento do tubo neural através da reação imuno-histoquímica para proteína fibrilar glial ácida (GFAP em cortes histológicos de todos os lobos de ambos os pulmões de 22 casos de fetos e neonatos com defeito de fechamento do tubo neural. Havia 15 casos femininos (68,2% e 7 masculinos (31,8%, com idade gestacional variando de 18 a 40 semanas (média= 31,8, sendo natimortos e neomortos 10 (45,5% cada e 2 (9,1% abortos. Os diagnósticos foram: Craniorraquisquise (9 casos, 40,9%, anencefalia (8 casos, 36,4%, encefalocele occipital rota e raquisquise (2 casos, 9,1% e 1 (4,5%caso de seqüência de disruptura amniótica precoce. Somente 1 caso (4,5% apresentou células positivas dentro de bronquíolos e alvéolos em meio a células epiteliais

  13. Discriminating solitary cysts from soft tissue lesions in mammography using a pretrained deep convolutional neural network.

    Science.gov (United States)

    Kooi, Thijs; van Ginneken, Bram; Karssemeijer, Nico; den Heeten, Ard

    2017-03-01

    It is estimated that 7% of women in the western world will develop palpable breast cysts in their lifetime. Even though cysts have been correlated with risk of developing breast cancer, many of them are benign and do not require follow-up. We develop a method to discriminate benign solitary cysts from malignant masses in digital mammography. We think a system like this can have merit in the clinic as a decision aid or complementary to specialized modalities. We employ a deep convolutional neural network (CNN) to classify cyst and mass patches. Deep CNNs have been shown to be powerful classifiers, but need a large amount of training data for which medical problems are often difficult to come by. The key contribution of this paper is that we show good performance can be obtained on a small dataset by pretraining the network on a large dataset of a related task. We subsequently investigate the following: (a) when a mammographic exam is performed, two different views of the same breast are recorded. We investigate the merit of combining the output of the classifier from these two views. (b) We evaluate the importance of the resolution of the patches fed to the network. (c) A method dubbed tissue augmentation is subsequently employed, where we extract normal tissue from normal patches and superimpose this onto the actual samples aiming for a classifier invariant to occluding tissue. (d) We combine the representation extracted using the deep CNN with our previously developed features. We show that using the proposed deep learning method, an area under the ROC curve (AUC) value of 0.80 can be obtained on a set of benign solitary cysts and malignant mass findings recalled in screening. We find that it works significantly better than our previously developed approach by comparing the AUC of the ROC using bootstrapping. By combining views, the results can be further improved, though this difference was not found to be significant. We find no significant difference between

  14. Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord.

    Science.gov (United States)

    Lai, Bi-Qin; Che, Ming-Tian; Du, Bao-Ling; Zeng, Xiang; Ma, Yuan-Huan; Feng, Bo; Qiu, Xue-Chen; Zhang, Ke; Liu, Shu; Shen, Hui-Yong; Wu, Jin-Lang; Ling, Eng-Ang; Zeng, Yuan-Shan

    2016-12-01

    Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection. Eight weeks after transplantation, the neural network created a favorable microenvironment for axonal regeneration and for survival and synaptogenesis of NSC-derived neurons. Biotin conjugates of cholera toxin B subunit (b-CTB, a transneuronal tracer) was injected into the crushed sciatic nerve to label spinal cord neurons. Remarkably, not only ascending and descending nerve fibers, but also propriospinal neurons, made contacts with b-CTB positive NSC-derived neurons. Moreover, b-CTB positive NSC-derived neurons extended their axons making contacts with the motor neurons located in areas caudal to the injury/graft site of spinal cord. Further study showed that NT-3/TrkC interactions activated the PI3K/AKT/mTOR pathway and PI3K/AKT/CREB pathway affecting synaptogenesis of NSC-derived neurons. Together, our findings suggest that NT-3-mediated TrkC signaling plays an essential role in constructing a tissue engineering neural network thus representing a promising avenue for effective exogenous neuronal relay-based treatment for SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Fluorescence-Activated Cell Sorting of EGFP-Labeled Neural Crest Cells From Murine Embryonic Craniofacial Tissue

    Directory of Open Access Journals (Sweden)

    Saurabh Singh

    2005-01-01

    Full Text Available During the early stages of embryogenesis, pluripotent neural crest cells (NCC are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR. The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.

  16. Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer's Disease Phenotypes.

    Directory of Open Access Journals (Sweden)

    Waseem K Raja

    Full Text Available The dismal success rate of clinical trials for Alzheimer's disease (AD motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cells (iPSCs allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe. We report brain organoids that use pluripotent stem cells derived from AD patients and recapitulate AD-like pathologies such as amyloid aggregation, hyperphosphorylated tau protein, and endosome abnormalities. These pathologies are observed in an age-dependent manner in organoids derived from multiple familial AD (fAD patients harboring amyloid precursor protein (APP duplication or presenilin1 (PSEN1 mutation, compared to controls. The incidence of AD pathology was consistent amongst several fAD lines, which carried different mutations. Although these are complex assemblies of neural tissue, they are also highly amenable to experimental manipulation. We find that treatment of patient-derived organoids with β- and γ-secretase inhibitors significantly reduces amyloid and tau pathology. Moreover, these results show the potential of this model system to greatly increase the translatability of pre-clinical drug discovery in AD.

  17. The characterization of neural tissue ablation rate and corresponding heat affected zone of a 2 micron Tm3+ doped fiber laser(Conference Presentation)

    Science.gov (United States)

    Marques, Andrew J.; Jivraj, Jamil; Reyes, Robnier; Ramjist, Joel; Gu, Xijia J.; Yang, Victor X. D.

    2017-02-01

    Tissue removal using electrocautery is standard practice in neurosurgery since tissue can be cut and cauterized simultaneously. Thermally mediated tissue ablation using lasers can potentially possess the same benefits but with increased precision. However, given the critical nature of the spine, brain, and nerves, the effects of direct photo-thermal interaction on neural tissue needs to be known, yielding not only high precision of tissue removal but also increased control of peripheral heat damage. The proposed use of lasers as a neurosurgical tool requires that a common ground is found between ablation rates and resulting peripheral heat damage. Most surgical laser systems rely on the conversion of light energy into heat resulting in both desirable and undesirable thermal damage to the targeted tissue. Classifying the distribution of thermal energy in neural tissue, and thus characterizing the extent of undesirable thermal damage, can prove to be exceptionally challenging considering its highly inhomogenous composition when compared to other tissues such as muscle and bone. Here we present the characterization of neural tissue ablation rate and heat affected zone of a 1.94 micron thulium doped fiber laser for neural tissue ablation. In-Vivo ablation of porcine cerebral cortex is performed. Ablation volumes are studied in association with laser parameters. Histological samples are taken and examined to characterize the extent of peripheral heat damage.

  18. ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.

    Science.gov (United States)

    Han, Arum; Zhao, Hu; Li, Jingyuan; Pelikan, Richard; Chai, Yang

    2014-08-01

    The development of the craniofacial muscles requires reciprocal interactions with surrounding craniofacial tissues that originate from cranial neural crest cells (CNCCs). However, the molecular mechanism involved in the tissue-tissue interactions between CNCCs and muscle progenitors during craniofacial muscle development is largely unknown. In the current study, we address how CNCCs regulate the development of the tongue and other craniofacial muscles using Wnt1-Cre; Alk5(fl/fl) mice, in which loss of Alk5 in CNCCs results in severely disrupted muscle formation. We found that Bmp4 is responsible for reduced proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5(fl/fl) mice during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1-Cre; Alk5(fl/fl) mice and are critical for differentiation of the myogenic cells. Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together, our results indicate that CNCCs play critical roles in controlling craniofacial myogenic proliferation and differentiation through tissue-tissue interactions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  19. Neural network-based brain tissue segmentation in MR images using extracted features from intraframe coding in H.264

    Science.gov (United States)

    Jafari, Mehdi; Kasaei, Shohreh

    2012-01-01

    Automatic brain tissue segmentation is a crucial task in diagnosis and treatment of medical images. This paper presents a new algorithm to segment different brain tissues, such as white matter (WM), gray matter (GM), cerebral spinal fluid (CSF), background (BKG), and tumor tissues. The proposed technique uses the modified intraframe coding yielded from H.264/(AVC), for feature extraction. Extracted features are then imposed to an artificial back propagation neural network (BPN) classifier to assign each block to its appropriate class. Since the newest coding standard, H.264/AVC, has the highest compression ratio, it decreases the dimension of extracted features and thus yields to a more accurate classifier with low computational complexity. The performance of the BPN classifier is evaluated using the classification accuracy and computational complexity terms. The results show that the proposed technique is more robust and effective with low computational complexity compared to other recent works.

  20. The influence of a depressed scapular alignment on upper limb neural tissue mechanosensitivity and local pressure pain sensitivity.

    Science.gov (United States)

    Martínez-Merinero, Patricia; Lluch, Enriqe; Gallezo-Izquierdo, Tomas; Pecos-Martín, Daniel; Plaza-Manzano, Gustavo; Nuñez-Nagy, Susana; Falla, Deborah

    2017-06-01

    A depressed scapular alignment could lead to prolonged and repetitive stress or compression of the brachial plexus, resulting in sensitization of neural tissue. However, no study has investigated the influence of alignment of the scapulae on sensitization of upper limb neural tissue in otherwise asymptomatic people. In this case-control study, we investigate the influence of a depressed scapular alignment on mechanosensitivity of the upper limb peripheral nervous system as well as pressure pain thresholds (PPT). Asymptomatic individuals with neutral vertical scapular alignment (n = 25) or depressed scapular alignment (n = 25) participated. We measured the upper limb neurodynamic test (ULNT1), including assessment of symptom response and elbow range of motion (ROM), and PPT measured over upper limb peripheral nerve trunks, the upper trapezius muscle and overlying cervical zygapophyseal joints. Subjects with a depressed scapular reported significantly greater pain intensity (t = 5.7, p < 0.0001) and reduced elbow extension ROM (t = -2.7, p < 0.01) during the ULNT1 compared to those with a normal scapular orientation. Regardless of the location tested, the group presenting with a depressed scapular had significantly lower PPT compared to those with a normal scapular orientation (PPT averaged across all sites: normal orientation: 3.3 ± 0.6 kg/cm(2), depressed scapular: 2.1 ± 0.5 kg/cm(2), p < 0.00001). Despite being asymptomatic, people with a depressed scapular have greater neck and upper limb neural tissue mechanosensitivity when compared to people with a normal scapular orientation. This study offers insight into the potential development of neck-arm pain due to a depressed scapular position. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Travelling waves in models of neural tissue: from localised structures to periodic waves

    NARCIS (Netherlands)

    Meijer, Hil Gaétan Ellart; Coombes, Stephen

    2014-01-01

    We consider travelling waves (fronts, pulses and periodics) in spatially extended one dimensional neural field models. We demonstrate for an excitatory field with linear adaptation that, in addition to an expected stable pulse solution, a stable anti-pulse can exist. Varying the adaptation strength

  2. A fully-automated neural network analysis of AFM force-distance curves for cancer tissue diagnosis

    Science.gov (United States)

    Minelli, Eleonora; Ciasca, Gabriele; Sassun, Tanya Enny; Antonelli, Manila; Palmieri, Valentina; Papi, Massimiliano; Maulucci, Giuseppe; Santoro, Antonio; Giangaspero, Felice; Delfini, Roberto; Campi, Gaetano; De Spirito, Marco

    2017-10-01

    Atomic Force Microscopy (AFM) has the unique capability of probing the nanoscale mechanical properties of biological systems that affect and are affected by the occurrence of many pathologies, including cancer. This capability has triggered growing interest in the translational process of AFM from physics laboratories to clinical practice. A factor still hindering the current use of AFM in diagnostics is related to the complexity of AFM data analysis, which is time-consuming and needs highly specialized personnel with a strong physical and mathematical background. In this work, we demonstrate an operator-independent neural-network approach for the analysis of surgically removed brain cancer tissues. This approach allowed us to distinguish—in a fully automated fashion—cancer from healthy tissues with high accuracy, also highlighting the presence and the location of infiltrating tumor cells.

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

    Science.gov (United States)

    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

  4. Proteomic Profiling of Neuroblastoma Cells Adhesion on Hyaluronic Acid-Based Surface for Neural Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Ming-Hui Yang

    2016-01-01

    Full Text Available The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application.

  5. Development of the trigeminal motor neurons in parrots: implications for the role of nervous tissue in the evolution of jaw muscle morphology.

    Science.gov (United States)

    Tokita, Masayoshi; Nakayama, Tomoki

    2014-02-01

    Vertebrates have succeeded to inhabit almost every ecological niche due in large part to the anatomical diversification of their jaw complex. As a component of the feeding apparatus, jaw muscles carry a vital role for determining the mode of feeding. Early patterning of the jaw muscles has been attributed to cranial neural crest-derived mesenchyme, however, much remains to be understood about the role of nonneural crest tissues in the evolution and diversification of jaw muscle morphology. In this study, we describe the development of trigeminal motor neurons in a parrot species with the uniquely shaped jaw muscles and compare its developmental pattern to that in the quail with the standard jaw muscles to uncover potential roles of nervous tissue in the evolution of vertebrate jaw muscles. In parrot embryogenesis, the motor axon bundles are detectable within the muscular tissue only after the basic shape of the muscular tissue has been established. This supports the view that nervous tissue does not primarily determine the spatial pattern of jaw muscles. In contrast, the trigeminal motor nucleus, which is composed of somata of neurons that innervate major jaw muscles, of parrot is more developed compared to quail, even in embryonic stage where no remarkable interspecific difference in both jaw muscle morphology and motor nerve branching pattern is recognized. Our data suggest that although nervous tissue may not have a large influence on initial patterning of jaw muscles, it may play an important role in subsequent growth and maintenance of muscular tissue and alterations in cranial nervous tissue development may underlie diversification of jaw muscle morphology. Copyright © 2013 Wiley Periodicals, Inc.

  6. Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

    Directory of Open Access Journals (Sweden)

    Paige Snider

    2007-01-01

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

  7. Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells

    Science.gov (United States)

    Schmidt, Jennifer; Piekarski, Nadine; Olsson, Lennart

    2013-01-01

    Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre

  8. Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells.

    Science.gov (United States)

    Schmidt, Jennifer; Piekarski, Nadine; Olsson, Lennart

    2013-01-01

    Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre

  9. Reorganization of pathological control functions of memory-A neural model for tissue healing by shock waves

    Science.gov (United States)

    Wess, Othmar

    2005-04-01

    Since 1980 shock waves have proven effective in the field of extracorporeal lithotripsy. More than 10 years ago shock waves were successfully applied for various indications such as chronic pain, non-unions and, recently, for angina pectoris. These fields do not profit from the disintegration power but from stimulating and healing effects of shock waves. Increased metabolism and neo-vascularization are reported after shock wave application. According to C. J. Wang, a biological cascade is initiated, starting with a stimulating effect of physical energy resulting in increased circulation and metabolism. Pathological memory of neural control patterns is considered the reason for different pathologies characterized by insufficient metabolism. This paper presents a neural model for reorganization of pathological reflex patterns. The model acts on associative memory functions of the brain based on modification of synaptic junctions. Accordingly, pathological memory effects of the autonomous nervous system are reorganized by repeated application of shock waves followed by development of normal reflex patterns. Physiologic control of muscle and vascular tone is followed by increased metabolism and tissue repair. The memory model may explain hyper-stimulation effects in pain therapy.

  10. Transplantation of Xenopus laevis tissues to determine the ability of motor neurons to acquire a novel target.

    Directory of Open Access Journals (Sweden)

    Karen L Elliott

    Full Text Available The evolutionary origin of novelties is a central problem in biology. At a cellular level this requires, for example, molecularly resolving how brainstem motor neurons change their innervation target from muscle fibers (branchial motor neurons to neural crest-derived ganglia (visceral motor neurons or ear-derived hair cells (inner ear and lateral line efferent neurons. Transplantation of various tissues into the path of motor neuron axons could determine the ability of any motor neuron to innervate a novel target. Several tissues that receive direct, indirect, or no motor innervation were transplanted into the path of different motor neuron populations in Xenopus laevis embryos. Ears, somites, hearts, and lungs were transplanted to the orbit, replacing the eye. Jaw and eye muscle were transplanted to the trunk, replacing a somite. Applications of lipophilic dyes and immunohistochemistry to reveal motor neuron axon terminals were used. The ear, but not somite-derived muscle, heart, or liver, received motor neuron axons via the oculomotor or trochlear nerves. Somite-derived muscle tissue was innervated, likely by the hypoglossal nerve, when replacing the ear. In contrast to our previous report on ear innervation by spinal motor neurons, none of the tissues (eye or jaw muscle was innervated when transplanted to the trunk. Taken together, these results suggest that there is some plasticity inherent to motor innervation, but not every motor neuron can become an efferent to any target that normally receives motor input. The only tissue among our samples that can be innervated by all motor neurons tested is the ear. We suggest some possible, testable molecular suggestions for this apparent uniqueness.

  11. The effect of ionic diffusion on extracellular potentials in neural tissue

    CERN Document Server

    Halnes, Geir; Keller, Daniel; Pettersen, Klas H; Eivenoll, Gaute T

    2015-01-01

    In computational neuroscience, it is common to use the simplifying assumption that diffusive currents are negligible compared to Ohmic currents. However, endured periods of intense neural signaling may cause local ion concentration changes in the millimolar range. Theoretical studies have identified scenarios where steep concentration gradients give rise to diffusive currents that are of comparable magnitude with Ohmic currents, and where the simplifying assumption that diffusion can be neglected does not hold. We here propose a novel formalism for computing (1) the ion concentration dynamics and (2) the electrical potential in the extracellular space surrounding multi-compartmental neuron models or networks of such (e.g., the Blue-Brain simulator). We use this formalism to explore the effects that diffusive currents can have on the extracellular (ECS) potential surrounding a small population of active cortical neurons. Our key findings are: (i) Sustained periods of neuronal output (simulations were run for 8...

  12. Outsourcing neural active control to passive composite mechanics: a tissue engineered cyborg ray

    Science.gov (United States)

    Gazzola, Mattia; Park, Sung Jin; Park, Kyung Soo; Park, Shirley; di Santo, Valentina; Deisseroth, Karl; Lauder, George V.; Mahadevan, L.; Parker, Kevin Kit

    2016-11-01

    Translating the blueprint that stingrays and skates provide, we create a cyborg swimming ray capable of orchestrating adaptive maneuvering and phototactic navigation. The impossibility of replicating the neural system of batoids fish is bypassed by outsourcing algorithmic functionalities to the body composite mechanics, hence casting the active control problem into a design, passive one. We present a first step in engineering multilevel "brain-body-flow" systems that couple sensory information to motor coordination and movement, leading to behavior. This work paves the way for the development of autonomous and adaptive artificial creatures able to process multiple sensory inputs and produce complex behaviors in distributed systems and may represent a path toward soft-robotic "embodied cognition".

  13. Deep convolutional neural network and 3D deformable approach for tissue segmentation in musculoskeletal magnetic resonance imaging.

    Science.gov (United States)

    Liu, Fang; Zhou, Zhaoye; Jang, Hyungseok; Samsonov, Alexey; Zhao, Gengyan; Kijowski, Richard

    2017-07-21

    To describe and evaluate a new fully automated musculoskeletal tissue segmentation method using deep convolutional neural network (CNN) and three-dimensional (3D) simplex deformable modeling to improve the accuracy and efficiency of cartilage and bone segmentation within the knee joint. A fully automated segmentation pipeline was built by combining a semantic segmentation CNN and 3D simplex deformable modeling. A CNN technique called SegNet was applied as the core of the segmentation method to perform high resolution pixel-wise multi-class tissue classification. The 3D simplex deformable modeling refined the output from SegNet to preserve the overall shape and maintain a desirable smooth surface for musculoskeletal structure. The fully automated segmentation method was tested using a publicly available knee image data set to compare with currently used state-of-the-art segmentation methods. The fully automated method was also evaluated on two different data sets, which include morphological and quantitative MR images with different tissue contrasts. The proposed fully automated segmentation method provided good segmentation performance with segmentation accuracy superior to most of state-of-the-art methods in the publicly available knee image data set. The method also demonstrated versatile segmentation performance on both morphological and quantitative musculoskeletal MR images with different tissue contrasts and spatial resolutions. The study demonstrates that the combined CNN and 3D deformable modeling approach is useful for performing rapid and accurate cartilage and bone segmentation within the knee joint. The CNN has promising potential applications in musculoskeletal imaging. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  14. Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy.

    Science.gov (United States)

    Pusterla, N; Wilson, W D; Conrad, P A; Barr, B C; Ferraro, G L; Daft, B M; Leutenegger, C M

    2006-09-09

    This study was designed to determine the relative levels of gene transcription of selected pathogens and cytokines in the brain and spinal cord of 12 horses with equine protozoal myeloencephalitis (EPM), 11 with equine herpesvirus type 1 (EHV-1) myeloencephalopathy, and 12 healthy control horses by applying a real time pcr to the formalin-fixed and paraffin-embedded tissues. Total rna was extracted from each tissue, transcribed to complementary dna (cDNA) and assayed for Sarcocystis neurona, Neospora hughesi, EHV-1, equine GAPDH (housekeeping gene), tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10 AND IL-12 p40. S neurona cdna was detected in the neural tissue from all 12 horses with EPM, and two of them also had amplifiable cDNA of N hughesi. The relative levels of transcription of protozoal cdna ranged from 1 to 461 times baseline (mean 123). All the horses with ehv-1 myeloencephalopathy had positive viral signals by PCR with relative levels of transcription ranging from 1 to 1618 times baseline (mean 275). All the control horses tested negative for S neurona, N hughesi and EHV-1 cdna. The cytokine profiles of each disease indicated a balance between pro- and anti-inflammatory markers. In the horses with epm the pro-inflammatory Th1 cytokines (IL-8, TNF-alpha and IFN-gamma) were commonly expressed but the anti-inflammatory Th2 cytokines (IL-4, IL-6 AND IL-10) were absent or rare. In the horses with ehv-1 the proinflammatory cytokine IL-8 was commonly expressed, but IL-10 and IFN-gamma were not, and TNF-alpha was rare. Tissue from the control horses expressed only the gene GAPDH.

  15. Polypyrrole/Alginate Hybrid Hydrogels: Electrically Conductive and Soft Biomaterials for Human Mesenchymal Stem Cell Culture and Potential Neural Tissue Engineering Applications.

    Science.gov (United States)

    Yang, Sumi; Jang, LindyK; Kim, Semin; Yang, Jongcheol; Yang, Kisuk; Cho, Seung-Woo; Lee, Jae Young

    2016-11-01

    Electrically conductive biomaterials that can efficiently deliver electrical signals to cells or improve electrical communication among cells have received considerable attention for potential tissue engineering applications. Conductive hydrogels are desirable particularly for neural applications, as they can provide electrical signals and soft microenvironments that can mimic native nerve tissues. In this study, conductive and soft polypyrrole/alginate (PPy/Alg) hydrogels are developed by chemically polymerizing PPy within ionically cross-linked alginate hydrogel networks. The synthesized hydrogels exhibit a Young's modulus of 20-200 kPa. Electrical conductance of the PPy/Alg hydrogels could be enhanced by more than one order of magnitude compared to that of pristine alginate hydrogels. In vitro studies with human bone marrow-derived mesenchymal stem cells (hMSCs) reveal that cell adhesion and growth are promoted on the PPy/Alg hydrogels. Additionally, the PPy/Alg hydrogels support and greatly enhance the expression of neural differentiation markers (i.e., Tuj1 and MAP2) of hMSCs compared to tissue culture plate controls. Subcutaneous implantation of the hydrogels for eight weeks induces mild inflammatory reactions. These soft and conductive hydrogels will serve as a useful platform to study the effects of electrical and mechanical signals on stem cells and/or neural cells and to develop multifunctional neural tissue engineering scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

    DEFF Research Database (Denmark)

    Venø, Morten Trillingsgaard; Bramsen, Jesper Bertram; Bendixen, Christian

    2012-01-01

    Editing by ADAR enzymes is essential for mammalian life. Still, knowledge of the spatio-temporal editing patterns in mammals is limited. By use of 454 amplicon sequencing we examined the editing status of 12 regionally extracted mRNAs from porcine developing brain encompassing a total of 64...... putative ADAR editing sites. In total 24 brain tissues, dissected from up to five regions from embryonic gestation day 23, 42, 60, 80, 100 and 115, were examined for editing....

  17. Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, P C [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Correia, L [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Salvador, R [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Basser, P J [Section on Tissue Biophysics and Biomimetics, NICHD, National Institutes of Health, Bethesda, MD 20892-1428 (United States)

    2007-09-21

    We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m{sup -1} to 0.333 S m{sup -1}, simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation.

  18. Engineered neural tissue with Schwann cell differentiated human dental pulp stem cells: potential for peripheral nerve repair?

    Science.gov (United States)

    Sanen, Kathleen; Martens, Wendy; Georgiou, Melanie; Ameloot, Marcel; Lambrichts, Ivo; Phillips, James

    2017-01-04

    Despite the spontaneous regenerative capacity of the peripheral nervous system, large gap peripheral nerve injuries (PNIs) require bridging strategies. The limitations and suboptimal results obtained with autografts or hollow nerve conduits in the clinic urge the need for alternative treatments. Recently, we have described promising neuroregenerative capacities of Schwann cells derived from differentiated human dental pulp stem cells (d-hDPSCs) in vitro. Here, we extended the in vitro assays to show the pro-angiogenic effects of d-hDPSCs, such as enhanced endothelial cell proliferation, migration and differentiation. In addition, for the first time we evaluated the performance of d-hDPSCs in an in vivo rat model of PNI. Eight weeks after transplantation of NeuraWrap™ conduits filled with engineered neural tissue (EngNT) containing aligned d-hDPSCs in 15-mm rat sciatic nerve defects, immunohistochemistry and ultrastructural analysis revealed ingrowing neurites, myelinated nerve fibres and blood vessels along the construct. Although further research is required to optimize the delivery of this EngNT, our findings suggest that d-hDPSCs are able to exert a positive effect in the regeneration of nerve tissue in vivo. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    Dana M. Cairns

    2016-09-01

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

  20. EFFECTIVENESS OF NEURAL TISSUE MOBILISATION ON PAIN, PAIN FREE PASSIVE SLR RANGE OF MOTION AND FUNCTIONAL DISABILITY IN LOW BACK ACHE SUBJECTS WITH SCIATICA

    Directory of Open Access Journals (Sweden)

    V. B. Geethika

    2015-10-01

    Full Text Available Background: Low back pain is a common, benign, and self-limiting disease that affects almost all persons, with a lifetime prevalence of up to 84%. In contrast, sciatica affects only 40 % of all persons in the Western industrialized countries. In sciatica, pain radiates down the legs, below the knee along the distribution of sciatic nerve. Nerve root compression is the most common cause of sciatica. Neuro dynamics or Neural Tissue Mobilization is relatively new approach in treatment of neuro musculoskeletal disorders. The aim of the study to determine the effectiveness of Neural Tissue mobilization on pain, pain free passive SLR ROM &functional disability in LBA subjects with Sciatica. Objective of the study is to study and compare the effectiveness of Neural tissue mobilization in LBA subjects with sciatica in terms of pain, pain free SLR ROM and Oswestry Disability Index. Methods: 30 subjects were selected by simple random sampling and assigned in to Control(n=15 &Experimental group(n=15.The subjects in control group were given conventional physiotherapy and those in Experimental group were given Neural Tissue Mobilization in addition to conventional therapy. All the participants were assessed with VAS, ODI and pain free passive SLR ROM. Results: After the analysis, the results were found to be significant improvement in pain, pain free SLR ROM, ODI in both groups (p< 0.00.But there is a high significance in Experimental group when compared to control group. Conclusion: Results suggest that NEURAL TISSUE MOBILIZATION along with conventional therapy is more effective in reducing pain, decreasing disability and improving SLR ROM.

  1. Star poly(ethylene glycol) as a tunable scaffold for neural tissue engineering

    Science.gov (United States)

    Zustiak, Silviya Petrova

    The primary focus of this work was to develop a novel synthetic hydrogel scaffold as an in vitro model to enable future detailed studies of how neurons grow in environments with controllable diffusion profiles of soluble cues and tunable neuronmatrix interactions. The development of in vitro models that enable elucidation of the mechanisms of system performance is a recently emerging goal of tissue engineering. The design of three-dimensional (3D) scaffolds in particular, is motivated by the need to develop model systems that better mimic native tissue as compared to conventional two-dimensional (2D) cell culture substrates. An ideal scaffold is degradable, porous, biocompatible, with mechanical properties to match those of the tissues of interest and with a suitable surface chemistry for cell attachment, proliferation, and differentiation. Although naturally derived materials are more versatile in providing complex biological cues, synthetic polymers are preferable for the design of in vitro models as they provide wider range of properties, controllable degradation rates, and easier processing. Most importantly, their mechanical properties can be decoupled from their biological properties, a crucial issue in interpreting cell responses. The synthetic material provides the structural backbone of the scaffold while biochemical function is added via incorporation of ligands or proteins aimed at triggering specific cell behaviors. As presented in this dissertation, we have developed and characterized a new synthetic 3D hydrogel scaffold from cross-linked poly(ethylene glycol) (PEG). PEG was selected because it is hydrophilic, non-toxic, biocompatible, and inert to protein adhesion. The chosen cross-linking chemistry was a highly specific reaction that occurred under physiological conditions so that cells could be embedded within the gel prior to cross-linking. Controllable degradability was imparted via series of hydrolytically degradable PEG cross-linkers. Thorough

  2. An approach for tissue density classification in mammographic images using artificial neural network based on wavelet and curvelet transforms

    Science.gov (United States)

    Yaşar, Hüseyin; Ceylan, Murat

    2015-03-01

    Breast cancer is one of the types of cancer which is most commonly seen in women. Density of breast is an important indicator for the risk of cancer. In addition, densities of tissue may harden the diagnosis by hiding the abnormalities occurring on the breast. For this reason, during the process of diagnosis, the process of automatic classification of breast density has a significant importance. In this study, a new system with the base of Artificial Neural Network (ANN) and multiple resolution analysis is suggested. Wavelet and curvelet analyses having the most common use have been used as multi resolution analysis. 4 pieces of statistics which are minimum value, maximum value, mean value and standard deviation have been extracted from the images which have been eluted to their sub-bands via multi resolution analysis. For the purpose of testing the success of the system, 322 pieces of images which are in MIAS database have been used. The obtained results for different backgrounds are so satisfying; and the highest classification values have been obtained as 97.16 % with Wavelet transform and ANN for fatty background and 79.80 % with Wavelet transform and ANN for fatty-glanduar background. The same results have been obtained using Wavelet transform and ANN and Curvelet transform and ANN for dense background and accuracy rate of 84.82 % have been reached. The results of mean classification have been obtained, for three pieces of tissue types (fatty, fatty-glanduar, dense), in sequence as 84.47 % with the use of ANN, 85.71 % with the use of curvelet analysis and ANN; and 87.26 % with the use of wavelet analysis and ANN.

  3. Convolutional neural networks for an automatic classification of prostate tissue slides with high-grade Gleason score

    Science.gov (United States)

    Jiménez del Toro, Oscar; Atzori, Manfredo; Otálora, Sebastian; Andersson, Mats; Eurén, Kristian; Hedlund, Martin; Rönnquist, Peter; Müller, Henning

    2017-03-01

    The Gleason grading system was developed for assessing prostate histopathology slides. It is correlated to the outcome and incidence of relapse in prostate cancer. Although this grading is part of a standard protocol performed by pathologists, visual inspection of whole slide images (WSIs) has an inherent subjectivity when evaluated by different pathologists. Computer aided pathology has been proposed to generate an objective and reproducible assessment that can help pathologists in their evaluation of new tissue samples. Deep convolutional neural networks are a promising approach for the automatic classification of histopathology images and can hierarchically learn subtle visual features from the data. However, a large number of manual annotations from pathologists are commonly required to obtain sufficient statistical generalization when training new models that can evaluate the daily generated large amounts of pathology data. A fully automatic approach that detects prostatectomy WSIs with high-grade Gleason score is proposed. We evaluate the performance of various deep learning architectures training them with patches extracted from automatically generated regions-of-interest rather than from manually segmented ones. Relevant parameters for training the deep learning model such as size and number of patches as well as the inclusion or not of data augmentation are compared between the tested deep learning architectures. 235 prostate tissue WSIs with their pathology report from the publicly available TCGA data set were used. An accuracy of 78% was obtained in a balanced set of 46 unseen test images with different Gleason grades in a 2-class decision: high vs. low Gleason grade. Grades 7-8, which represent the boundary decision of the proposed task, were particularly well classified. The method is scalable to larger data sets with straightforward re-training of the model to include data from multiple sources, scanners and acquisition techniques. Automatically

  4. A reduction in DNA damage in neural tissue and peripheral blood of old mice treated with caffeine.

    Science.gov (United States)

    Damiani, Adriani Paganini; Garcez, Michelle Lima; Letieli de Abreu, Larissa; Tavares, Taís Helena; Rodrigues Boeck, Carina; Moraes de Andrade, Vanessa

    2017-01-01

    Studies on caffeine consumption have shown a negative correlation with development of some diseases with subsequent beneficial manifestations. Our aim was to assess the effects of caffeine on peripheral blood and neural tissue DNA in young adult and aged mice. Male Swiss mice (age 2-3 or 16-18 months, respectively) were treated with a caffeine solution (0.3 g/l) for 4 weeks, while controls received water. After the treatments, blood and hippocampal cells (for a comet assay) and femurs (for a micronucleus [MN] test) were collected. The comet assay of peripheral blood and hippocampal cells demonstrated no significant differences between caffeine-treated and control young adult mice in terms of DNA damage index (DI) and frequency. In contrast, when comparing young adult with aged animals, significant differences were observed in DNA damage in blood and hippocampal cells. The differences between aged animals (with or without caffeine) consisted of a significant decrease in DNA DI in the group that received caffeine. In the MN test, an increase in frequency of micronucleated polychromatic (PCE) erythrocytes was noted in aged animals that received water compared to young adult mice. In addition, comparing treated with control aged murine groups, a decrease in frequency of MN was found in PCE erythrocytes of caffeine-treated mice. Chronic caffeine consumption was neither genotoxic nor mutagenic at the dose tested; however, it appears that caffeine actually protected mice from genotoxicity and mutagenicity, consequences attributed to aging.

  5. Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer’s Disease patients: A pilot study

    Science.gov (United States)

    González-Castañeda, Rocío E.; Sánchez-González, Víctor J.; Flores-Soto, Mario; Vázquez-Camacho, Gonzalo; Macías-Islas, Miguel A.; Ortiz, Genaro G.

    2013-01-01

    Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer’s Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels. PMID:23569405

  6. Development of a Multi-Functional Biopolymer Scaffold for Neural Tissue Engineering

    Science.gov (United States)

    Francis, Nicola Louise

    Spinal cord injury (SCI) affects approximately 270,000 people in the U.S., with approximately 12,000 new cases occurring every year. Several strategies have been investigated to enhance axonal regeneration after SCI, however, the resulting growth can be random and disorganized. Bioengineered scaffolds provide a physical substrate for the guidance of regenerating axons towards their targets, and can be produced by freeze casting. This technique involves the controlled directional solidification of an aqueous solution or suspension, resulting in a linearly aligned porous structure caused by ice templating. In this thesis, freeze casting was used to create novel porous chitosan-alginate (C/A) scaffolds with longitudinally aligned channels and a compressive modulus (5.08 ± 0.61 kPa) comparable to that of native spinal cord tissue. These C/A scaffolds supported the viability, attachment, and directionally oriented growth of chick dorsal root ganglia (DRG) neurites in vitro, with surface adsorptions of polycations and laminin promoting significantly longer neurite growth than the uncoated scaffolds (pvitro, while chABC was released for up to 35 days. However, up to 85% of biomolecules emained entrapped within the scaffold walls, due to limitation of diffusion by the scaffold wall mesh size. Release of bioactive chABC and neurotrophins from the multifunctional scaffolds promoted the growth of DRG neurites through an in vitro barrier of chondroitin sulfate proteoglycans, a main inhibitory component of the growth-inhibiting glial scar in the injured spinal cord. The present data suggest these multi-functional scaffolds are suitable for use and future testing in vivo as a combination strategy for spinal cord repair due to their ability to promote the directionally oriented growth of neurites and their ability to provide the sustained release of therapeutic bioactive molecules for the stimulation of axonal growth through the glial scar.

  7. A novel culture method reveals unique neural stem/progenitors in mature porcine iris tissues that differentiate into neuronal and rod photoreceptor-like cells.

    Science.gov (United States)

    Royall, Lars N; Lea, Daniel; Matsushita, Tamami; Takeda, Taka-Aki; Taketani, Shigeru; Araki, Masasuke

    2017-11-15

    Iris neural stem/progenitor cells from mature porcine eyes were investigated using a new protocol for tissue culture, which consists of dispase treatment and Matrigel embedding. We used a number of culture conditions and found an intense differentiation of neuronal cells from both the iris pigmented epithelial (IPE) cells and the stroma tissue cells. Rod photoreceptor-like cells were also observed but mostly in a later stage of culture. Neuronal differentiation does not require any additives such as fetal bovine serum or FGF2, although FGF2 and IGF2 appeared to promote neural differentiation in the IPE cultures. Furthermore, the stroma-derived cells were able to be maintained in vitro indefinitely. The evolutionary similarity between humans and domestic pigs highlight the potential for this methodology in the modeling of human diseases and characterizing human ocular stem cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies.

    Science.gov (United States)

    Hotta, R; Anderson, R B; Kobayashi, K; Newgreen, D F; Young, H M

    2010-03-01

    BACKGROUND Most enteric neurones arise from neural crest cells that originate in the post-otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung's disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin-3 (Et-3). METHODS Co-cultures were used to examine the ability of enteric neural crest-derived cells (ENCCs) from E11.5 mouse gut to colonize a variety of recipient hindguts. KEY RESULTS Enteric neural crest-derived cells migrated and gave rise to neurones in E14.5 and E16.5 aneural colon in which the external muscle layers had differentiated, but they did not migrate as far as in younger colon. There was no evidence of altered ENCC proliferation, cell death or neuronal differentiation in older recipient explants. Enteric neural crest-derived cells failed to enter most recipient E14.5 and E16.5 colon explants already containing enteric neurones, and the few that did showed very limited migration. Finally, ENCCs migrated a shorter distance and a higher proportion expressed the pan-neuronal marker, Hu, in recipient E11.5 Et-3(-/-) colon compared to wild-type recipient colon. CONCLUSIONS & INFERENCES Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration.

  9. Effectiveness of a Treatment Involving Soft Tissue Techniques and/or Neural Mobilization Techniques in the Management of Tension-Type Headache: A Randomized Controlled Trial.

    Science.gov (United States)

    Ferragut-Garcías, Alejandro; Plaza-Manzano, Gustavo; Rodríguez-Blanco, Cleofás; Velasco-Roldán, Olga; Pecos-Martín, Daniel; Oliva-Pascual-Vaca, Jesús; Llabrés-Bennasar, Bartomeu; Oliva-Pascual-Vaca, Ángel

    2017-02-01

    To evaluate the effects of a protocol involving soft tissue techniques and/or neural mobilization techniques in the management of patients with frequent episodic tension-type headache (FETTH) and those with chronic tension-type headache (CTTH). Randomized, double-blind, placebo-controlled before and after trial. Rehabilitation area of the local hospital and a private physiotherapy center. Patients (N=97; 78 women, 19 men) diagnosed with FETTH or CTTH were randomly assigned to groups A, B, C, or D. (A) Placebo superficial massage; (B) soft tissue techniques; (C) neural mobilization techniques; (D) a combination of soft tissue and neural mobilization techniques. The pressure pain threshold (PPT) in the temporal muscles (points 1 and 2) and supraorbital region (point 3), the frequency and maximal intensity of pain crisis, and the score in the Headache Impact Test-6 (HIT-6) were evaluated. All variables were assessed before the intervention, at the end of the intervention, and 15 and 30 days after the intervention. Groups B, C, and D had an increase in PPT and a reduction in frequency, maximal intensity, and HIT-6 values in all time points after the intervention as compared with baseline and group A (P<.001 for all cases). Group D had the highest PPT values and the lowest frequency and HIT-6 values after the intervention. The application of soft tissue and neural mobilization techniques to patients with FETTH or CTTH induces significant changes in PPT, the characteristics of pain crisis, and its effect on activities of daily living as compared with the application of these techniques as isolated interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Histological characterization and quantification of cellular events following neural and fibroblast(-like) stem cell grafting in healty and demyelinated CNS tissue

    OpenAIRE

    Praet, J.; SANTERMANS, Eva; Reekmans, K.; de Vocht, N.; Le Blon, D.; Hoornaert, C.; Daans, J.; Goossens, H.; Berneman, Z.; HENS, Niel; Van der Linden, A.; Ponsaerts, P.

    2014-01-01

    Preclinical animal studies involving intracerebral (stem) cell grafting are gaining popularity in many laboratories due to the reported beneficial effects of cell grafting on various diseases or traumata of the central nervous system (CNS). In this chapter, we describe a histological workflow to characterize and quantify cellular events following neural and fibroblast(-like) stem cell grafting in healthy and demyelinated CNS tissue. First, we provide standardized protocols to isolate and cult...

  11. Anatomically Inspired Three-dimensional Micro-tissue Engineered Neural Networks for Nervous System Reconstruction, Modulation, and Modeling.

    Science.gov (United States)

    Struzyna, Laura A; Adewole, Dayo O; Gordián-Vélez, Wisberty J; Grovola, Michael R; Burrell, Justin C; Katiyar, Kritika S; Petrov, Dmitriy; Harris, James P; Cullen, D Kacy

    2017-05-31

    Functional recovery rarely occurs following injury or disease-induced degeneration within the central nervous system (CNS) due to the inhibitory environment and the limited capacity for neurogenesis. We are developing a strategy to simultaneously address neuronal and axonal pathway loss within the damaged CNS. This manuscript presents the fabrication protocol for micro-tissue engineered neural networks (micro-TENNs), implantable constructs consisting of neurons and aligned axonal tracts spanning the extracellular matrix (ECM) lumen of a preformed hydrogel cylinder hundreds of microns in diameter that may extend centimeters in length. Neuronal aggregates are delimited to the extremes of the three-dimensional encasement and are spanned by axonal projections. Micro-TENNs are uniquely poised as a strategy for CNS reconstruction, emulating aspects of brain connectome cytoarchitecture and potentially providing means for network replacement. The neuronal aggregates may synapse with host tissue to form new functional relays to restore and/or modulate missing or damaged circuitry. These constructs may also act as pro-regenerative "living scaffolds" capable of exploiting developmental mechanisms for cell migration and axonal pathfinding, providing synergistic structural and soluble cues based on the state of regeneration. Micro-TENNs are fabricated by pouring liquid hydrogel into a cylindrical mold containing a longitudinally centered needle. Once the hydrogel has gelled, the needle is removed, leaving a hollow micro-column. An ECM solution is added to the lumen to provide an environment suitable for neuronal adhesion and axonal outgrowth. Dissociated neurons are mechanically aggregated for precise seeding within one or both ends of the micro-column. This methodology reliably produces self-contained miniature constructs with long-projecting axonal tracts that may recapitulate features of brain neuroanatomy. Synaptic immunolabeling and genetically encoded calcium

  12. Neural tissue-spheres

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

    2007-01-01

    -spheres (NTS) in EGF and FGF2 containing medium. The spheres were cut into quarters when passaged every 10-15th day, avoiding mechanical or enzymatic dissociation in order to minimize cellular trauma and preserve intercellular contacts. For analysis of regional differences within the forebrain SVZ, NTS were...

  13. Transplanted neurally modified bone marrow-derived mesenchymal stem cells promote tissue protection and locomotor recovery in spinal cord injured rats.

    Science.gov (United States)

    Alexanian, Arshak R; Fehlings, Michael G; Zhang, Zhiying; Maiman, Dennis J

    2011-01-01

    Stem cell-based therapy for repair and replacement of lost neural cells is a promising treatment for central nervous system (CNS) diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) can differentiate into neural phenotypes and be isolated and expanded for autotransplantation with no risk of rejection. The authors examined whether transplanted neurally induced human MSCs (NI hMSCs), developed by a new procedure, can survive, differentiate, and promote tissue protection and functional recovery in injured spinal cord (ISC) rats. Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation, histone deacetylation, and pharmacological agents that increased cAMP levels. Three groups of adult female Sprague-Dawley rats were injected immediately rostral and caudal to the midline lesion with phosphate-buffered saline, MSCs, or NI hMSCs, 1 week after a spinal cord impact injury at T-8. Functional outcome was measured using the Basso Beattie Bresnahan (BBB) locomotor rating scale and thermal sensitivity test on a weekly basis up to 12 weeks postinjury. Graft integration and anatomy of spinal cord was assessed by stereological, histochemical, and immunohistochemical techniques. The transplanted NI hMSCs survived, differentiated, and significantly improved locomotor recovery of ISC rats. Transplantation also reduced the volume of lesion cavity and white matter loss. This method of hMSC modification may provide an alternative source of autologous adult stem cells for CNS repair.

  14. Electrospun Collagen/Silk Tissue Engineering Scaffolds: Fiber Fabrication, Post-Treatment Optimization, and Application in Neural Differentiation of Stem Cells

    Science.gov (United States)

    Zhu, Bofan

    Biocompatible scaffolds mimicking the locally aligned fibrous structure of native extracellular matrix (ECM) are in high demand in tissue engineering. In this thesis research, unidirectionally aligned fibers were generated via a home-built electrospinning system. Collagen type I, as a major ECM component, was chosen in this study due to its support of cell proliferation and promotion of neuroectodermal commitment in stem cell differentiation. Synthetic dragline silk proteins, as biopolymers with remarkable tensile strength and superior elasticity, were also used as a model material. Good alignment, controllable fiber size and morphology, as well as a desirable deposition density of fibers were achieved via the optimization of solution and electrospinning parameters. The incorporation of silk proteins into collagen was found to significantly enhance mechanical properties and stability of electrospun fibers. Glutaraldehyde (GA) vapor post-treatment was demonstrated as a simple and effective way to tune the properties of collagen/silk fibers without changing their chemical composition. With 6-12 hours GA treatment, electrospun collagen/silk fibers were not only biocompatible, but could also effectively induce the polarization and neural commitment of stem cells, which were optimized on collagen rich fibers due to the unique combination of biochemical and biophysical cues imposed to cells. Taken together, electrospun collagen rich composite fibers are mechanically strong, stable and provide excellent cell adhesion. The unidirectionally aligned fibers can accelerate neural differentiation of stem cells, representing a promising therapy for neural tissue degenerative diseases and nerve injuries.

  15. Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents

    OpenAIRE

    Trolle, Carl; Abrahamsson, Ninnie; König, Niclas; Vasylovska, Svitlana; Kozlova, Elena

    2014-01-01

    The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root ...

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

    Directory of Open Access Journals (Sweden)

    Sujeong Jang

    2015-01-01

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

  17. Connective-Tissue Growth Factor (CTGF/CCN2 Induces Astrogenesis and Fibronectin Expression of Embryonic Neural Cells In Vitro.

    Directory of Open Access Journals (Sweden)

    Fabio A Mendes

    Full Text Available Connective-tissue growth factor (CTGF is a modular secreted protein implicated in multiple cellular events such as chondrogenesis, skeletogenesis, angiogenesis and wound healing. CTGF contains four different structural modules. This modular organization is characteristic of members of the CCN family. The acronym was derived from the first three members discovered, cysteine-rich 61 (CYR61, CTGF and nephroblastoma overexpressed (NOV. CTGF is implicated as a mediator of important cell processes such as adhesion, migration, proliferation and differentiation. Extensive data have shown that CTGF interacts particularly with the TGFβ, WNT and MAPK signaling pathways. The capacity of CTGF to interact with different growth factors lends it an important role during early and late development, especially in the anterior region of the embryo. ctgf knockout mice have several cranio-facial defects, and the skeletal system is also greatly affected due to an impairment of the vascular-system development during chondrogenesis. This study, for the first time, indicated that CTGF is a potent inductor of gliogenesis during development. Our results showed that in vitro addition of recombinant CTGF protein to an embryonic mouse neural precursor cell culture increased the number of GFAP- and GFAP/Nestin-positive cells. Surprisingly, CTGF also increased the number of Sox2-positive cells. Moreover, this induction seemed not to involve cell proliferation. In addition, exogenous CTGF activated p44/42 but not p38 or JNK MAPK signaling, and increased the expression and deposition of the fibronectin extracellular matrix protein. Finally, CTGF was also able to induce GFAP as well as Nestin expression in a human malignant glioma stem cell line, suggesting a possible role in the differentiation process of gliomas. These results implicate ctgf as a key gene for astrogenesis during development, and suggest that its mechanism may involve activation of p44/42 MAPK signaling

  18. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

    Science.gov (United States)

    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

  19. Neural stem cell differentiation by electrical stimulation using a cross-linked PEDOT substrate: Expanding the use of biocompatible conjugated conductive polymers for neural tissue engineering.

    Science.gov (United States)

    Pires, Filipa; Ferreira, Quirina; Rodrigues, Carlos A V; Morgado, Jorge; Ferreira, Frederico Castelo

    2015-06-01

    The use of conjugated polymers allows versatile interactions between cells and flexible processable materials, while providing a platform for electrical stimulation, which is particularly relevant when targeting differentiation of neural stem cells and further application for therapy or drug screening. Materials were tested for cytotoxicity following the ISO10993-5. PSS was cross-linked. ReNcellVM neural stem cells (NSC) were seeded in laminin coated surfaces, cultured for 4 days in the presence of EGF (20 ng/mL), FGF-2 (20 ng/mL) and B27 (20 μg/mL) and differentiated over eight additional days in the absence of those factors under 100Hz pulsed DC electrical stimulation, 1V with 10 ms pulses. NSC and neuron elongation aspect ratio as well as neurite length were assessed using ImageJ. Cells were immune-stained for Tuj1 and GFAP. F8T2, MEH-PPV, P3HT and cross-linked PSS (x PSS) were assessed as non-cytotoxic. L929 fibroblast population was 1.3 higher for x PSS than for glass control, while F8T2 presents moderate proliferation. The population of neurons (Tuj1) was 1.6 times higher with longer neurites (73 vs 108 μm) for cells cultured under electrical stimulus, with cultured NSC. Such stimulus led also to longer neurons. x PSS was, for the first time, used to elongate human NSC through the application of pulsed current, impacting on their differentiation towards neurons and contributing to longer neurites. The range of conductive conjugated polymers known as non-cytotoxic was expanded. x PSS was introduced as a stable material, easily processed from solution, to interface with biological systems, in particular NSC, without the need of in-situ polymerization. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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.

  1. A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not placodal lineage EGFP expression in a transgenic animal.

    Science.gov (United States)

    Lu, Van B; Ikeda, Stephen R; Puhl, Henry L

    2015-05-20

    Under physiological conditions, the voltage-gated sodium channel Nav1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Nav1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Nav1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 μm). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (∼10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Nav1.8 transcript (95%), Nav1.8-immunoreactivity (70%), and TTX-R INa (100%), although not all Nav1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Nav1.8-immunoreactivity confirmed Nav1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R INa recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Nav1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Nav1.8 expression pattern in neural crest-derived sensory neurons. Copyright © 2015 the authors 0270-6474/15/358021-14$15.00/0.

  2. Fabrication of Nerve Growth Factor Encapsulated Aligned Poly(ε-Caprolactone Nanofibers and Their Assessment as a Potential Neural Tissue Engineering Scaffold

    Directory of Open Access Journals (Sweden)

    Jue Hu

    2016-02-01

    Full Text Available Peripheral nerve injury is a serious clinical problem to be solved. There has been no breakthrough so far and neural tissue engineering offers a promising approach to promote the regeneration of peripheral neural injuries. In this study, emulsion electrospinning technique was introduced as a flexible and promising technique for the fabrication of random (R and aligned (A Poly(ε-caprolactone (PCL-Nerve Growth Factor (NGF&Bovine Serum Albumin (BSA nanofibrous scaffolds [(R/A-PCL-NGF&BSA], where NGF and BSA were encapsulated in the core while PCL form the shell. Random and aligned pure PCL, PCL-BSA, and PCL-NGF nanofibers were also produced for comparison. The scaffolds were characterized by Field Emission Scanning Electron Microscopy (FESEM and water contact angle test. Release study showed that, with the addition of stabilizer BSA, a sustained release of NGF from emulsion electrospun PCL nanofibers was observed over 28 days. [3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, inner salt; MTS] assay revealed that (R/A-PCL-NGF and (R/A-PCL-NGF&BSA scaffolds favored cell growth and showed no cytotoxicity to PC12 cells. Laser scanning confocal microscope images exhibited that the A-PCL-NGF&BSA scaffold increased the length of neurites and directed neurites extension along the fiber axis, indicating that the A-PCL-NGF&BSA scaffold has a potential for guiding nerve tissue growth and promoting nerve regeneration.

  3. Histological characterization and quantification of cellular events following neural and fibroblast(-like) stem cell grafting in healthy and demyelinated CNS tissue.

    Science.gov (United States)

    Praet, Jelle; Santermans, Eva; Reekmans, Kristien; de Vocht, Nathalie; Le Blon, Debbie; Hoornaert, Chloé; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Hens, Niel; Van der Linden, Annemie; Ponsaerts, Peter

    2014-01-01

    Preclinical animal studies involving intracerebral (stem) cell grafting are gaining popularity in many laboratories due to the reported beneficial effects of cell grafting on various diseases or traumata of the central nervous system (CNS). In this chapter, we describe a histological workflow to characterize and quantify cellular events following neural and fibroblast(-like) stem cell grafting in healthy and demyelinated CNS tissue. First, we provide standardized protocols to isolate and culture eGFP(+) neural and fibroblast(-like) stem cells from embryonic mouse tissue. Second, we describe flow cytometric procedures to determine cell viability, eGFP transgene expression, and the expression of different stem cell lineage markers. Third, we explain how to induce reproducible demyelination in the CNS of mice by means of cuprizone administration, a validated mouse model for human multiple sclerosis. Fourth, the technical procedures for cell grafting in the CNS are explained in detail. Finally, an optimized and validated workflow for the quantitative histological analysis of cell graft survival and endogenous astroglial and microglial responses is provided.

  4. Poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks for improving optrode-neural tissue interface in optogenetics.

    Science.gov (United States)

    Lu, Yi; Li, Yanling; Pan, Jianqing; Wei, Pengfei; Liu, Nan; Wu, Bifeng; Cheng, Jinbo; Lu, Caiyi; Wang, Liping

    2012-01-01

    The field of optogenetics has been successfully used to understand the mechanisms of neuropsychiatric diseases through the precise spatial and temporal control of specific groups of neurons in a neural circuitry. However, it remains a great challenge to integrate optogenetic modulation with electrophysiological and behavioral read out methods as a means to explore the causal, temporally precise, and behaviorally relevant interactions of neurons in the specific circuits of freely behaving animals. In this study, an eight-channel chronically implantable optrode array was fabricated and modified with poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks (PEDOT/PSS-PVA/PAA IPNs) for improving the optrode-neural tissue interface. The conducting polymer-hydrogel IPN films exhibited a significantly higher capacitance and lower electrochemical impedance at 1 kHz as compared to unmodified optrode sites and showed significantly improved mechanical and electrochemical stability as compared to pure conducting polymer films. The cell attachment and neurite outgrowth of rat pheochromocytoma (PC12) cells on the IPN films were clearly observed through calcein-AM staining. Furthermore, the optrode arrays were chronically implanted into the hippocampus of SD rats after the lentiviral expression of synapsin-ChR2-EYFP, and light-evoked, frequency-dependant action potentials were obtained in freely moving animals. The electrical recording results suggested that the modified optrode arrays showed significantly reduced impedance and RMS noise and an improved SNR as compared to unmodified sites, which may have benefited from the improved electrochemical performance and biocompatibility of the deposited IPN films. All these characteristics are greatly desired in optogenetic applications, and the fabrication method of conducting polymer-hydrogel IPNs can be easily integrated with other modification methods to build a

  5. Novel high-viscosity polyacrylamidated chitosan for neural tissue engineering: fabrication of anisotropic neurodurable scaffold via molecular disposition of persulfate-mediated polymer slicing and complexation.

    Science.gov (United States)

    Kumar, Pradeep; Choonara, Yahya E; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

    2012-10-29

    Macroporous polyacrylamide-grafted-chitosan scaffolds for neural tissue engineering were fabricated with varied synthetic and viscosity profiles. A novel approach and mechanism was utilized for polyacrylamide grafting onto chitosan using potassium persulfate (KPS) mediated degradation of both polymers under a thermally controlled environment. Commercially available high molecular mass polyacrylamide was used instead of the acrylamide monomer for graft copolymerization. This grafting strategy yielded an enhanced grafting efficiency (GE = 92%), grafting ratio (GR = 263%), intrinsic viscosity (IV = 5.231 dL/g) and viscometric average molecular mass (MW = 1.63 × 106 Da) compared with known acrylamide that has a GE = 83%, GR = 178%, IV = 3.901 dL/g and MW = 1.22 × 106 Da. Image processing analysis of SEM images of the newly grafted neurodurable scaffold was undertaken based on the polymer-pore threshold. Attenuated Total Reflectance-FTIR spectral analyses in conjugation with DSC were used for the characterization and comparison of the newly grafted copolymers. Static Lattice Atomistic Simulations were employed to investigate and elucidate the copolymeric assembly and reaction mechanism by exploring the spatial disposition of chitosan and polyacrylamide with respect to the reactional profile of potassium persulfate. Interestingly, potassium persulfate, a peroxide, was found to play a dual role initially degrading the polymers-"polymer slicing"-thereby initiating the formation of free radicals and subsequently leading to synthesis of the high molecular mass polyacrylamide-grafted-chitosan (PAAm-g-CHT)-"polymer complexation". Furthermore, the applicability of the uniquely grafted scaffold for neural tissue engineering was evaluated via PC12 neuronal cell seeding. The novel PAAm-g-CHT exhibited superior neurocompatibility in terms of cell infiltration owing to the anisotropic porous architecture, high molecular mass mediated robustness, superior hydrophilicity as well as

  6. Novel High-Viscosity Polyacrylamidated Chitosan for Neural Tissue Engineering: Fabrication of Anisotropic Neurodurable Scaffold via Molecular Disposition of Persulfate-Mediated Polymer Slicing and Complexation

    Directory of Open Access Journals (Sweden)

    Viness Pillay

    2012-10-01

    Full Text Available Macroporous polyacrylamide-grafted-chitosan scaffolds for neural tissue engineering were fabricated with varied synthetic and viscosity profiles. A novel approach and mechanism was utilized for polyacrylamide grafting onto chitosan using potassium persulfate (KPS mediated degradation of both polymers under a thermally controlled environment. Commercially available high molecular mass polyacrylamide was used instead of the acrylamide monomer for graft copolymerization. This grafting strategy yielded an enhanced grafting efficiency (GE = 92%, grafting ratio (GR = 263%, intrinsic viscosity (IV = 5.231 dL/g and viscometric average molecular mass (MW = 1.63 × 106 Da compared with known acrylamide that has a GE = 83%, GR = 178%, IV = 3.901 dL/g and MW = 1.22 × 106 Da. Image processing analysis of SEM images of the newly grafted neurodurable scaffold was undertaken based on the polymer-pore threshold. Attenuated Total Reflectance-FTIR spectral analyses in conjugation with DSC were used for the characterization and comparison of the newly grafted copolymers. Static Lattice Atomistic Simulations were employed to investigate and elucidate the copolymeric assembly and reaction mechanism by exploring the spatial disposition of chitosan and polyacrylamide with respect to the reactional profile of potassium persulfate. Interestingly, potassium persulfate, a peroxide, was found to play a dual role initially degrading the polymers—“polymer slicing”—thereby initiating the formation of free radicals and subsequently leading to synthesis of the high molecular mass polyacrylamide-grafted-chitosan (PAAm-g-CHT—“polymer complexation”. Furthermore, the applicability of the uniquely grafted scaffold for neural tissue engineering was evaluated via PC12 neuronal cell seeding. The novel PAAm-g-CHT exhibited superior neurocompatibility in terms of cell infiltration owing to the anisotropic porous architecture, high molecular mass mediated robustness

  7. Aebp2 as an epigenetic regulator for neural crest cells.

    Directory of Open Access Journals (Sweden)

    Hana Kim

    Full Text Available Aebp2 is a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2. We generated a mutant mouse line disrupting the transcription of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were embryonic lethal while heterozygotes survived to adulthood with fertility. In developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest origin. In addition, many heterozygotes display a set of phenotypes, enlarged colon and hypopigmentation, similar to those observed in human patients with Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually caused by the absence of the neural crest-derived ganglia in hindguts and melanocytes. ChIP analyses demonstrated that the majority of the genes involved in the migration and development process of neural crest cells are downstream target genes of AEBP2 and PRC2. Furthermore, expression analyses confirmed that some of these genes are indeed affected in the Aebp2 heterozygotes. Taken together, these results suggest that Aebp2 may regulate the migration and development of the neural crest cells through the PRC2-mediated epigenetic mechanism.

  8. The Extent of Tissue Damage in the Epidural Space by Ho / YAG Laser During Epiduroscopic Laser Neural Decompression.

    Science.gov (United States)

    Jo, Daehyun; Lee, Dong Joo

    2016-01-01

    Lasers have recently become very useful for epiduroscopy. As the use of lasers increases, the potential for unwanted complications with direct application of laser energy to nerve tissue has also increased. Even using the lowest laser power to test for nerve stimulation, there are still risks of laser ablation. However, there are no studies investigating tissue damage from laser procedures in the epidural space. This is a study on the risks of Ho/YAG laser usage during epiduroscopy. Observatory cadaver study. Department of anatomy and clinical research institute at the University Hospital. We used 5 cadavers for this study. After removing the dura and nerve root from the spinal column, laser energy from a Ho/YAG laser was applied directly to the dura and nerve root as well as in the virtual epidural space, which mimicked the conditions of epiduroscopy with the dura folded. Tissue destruction at all laser ablation sites was observed with the naked eye as well as with a microscope. Specimens were collected from each site of laser exposure, fixed in 10% neutral formalin, and dyed with H/E staining. Tissue destruction was observed in all laser ablation sites, regardless of the length of exposure and the power of the laser beam. A cadaver is not exactly the same as a living human because dura characteristics change and tissue damage can be influenced by dura thickness according to the spinal level. Even with low power and short duration, a laser can destroy tissue if the laser beam makes direct contact with the tissue.

  9. A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

    Science.gov (United States)

    Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

    2014-06-15

    A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

  10. Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide

    Science.gov (United States)

    Nathanson, James A.; Greengard, Paul

    1974-01-01

    An adenylate cyclase (EC 4.6.1.1) that is activated specifically by low concentrations of serotonin has been identified in homogenates of the thoracic ganglia of an insect nervous system. The activation of this enzyme by serotonin was selectively inhibited by extremely low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, agents which are known to block certain serotonin receptors in vivo. The inhibition was competitive with respect to serotonin, and the calculated inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase was 5 nM. The data are consistent with a model in which the serotonin receptor of neural tissue is intimately associated with a serotonin-sensitive adenylate cyclase which mediates serotonergic neurotransmission. The results are also compatible with the possibility that some of the physiological effects of LSD may be mediated through interaction with serotonin-sensitive adenylate cyclase. PMID:4595572

  11. The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues.

    Science.gov (United States)

    Raport, C J; Schweickart, V L; Eddy, R L; Shows, T B; Gray, P W

    1995-10-03

    A polymerase chain reaction (PCR) strategy with degenerate primers was used to identify novel G-protein-coupled receptor-encoding genes from human genomic DNA. One of the isolated clones, termed V28, showed high sequence similarity to the genes encoding human chemokine receptors for monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1 alpha (MIP-1 alpha)/RANTES, and to the rat orphan receptor-encoding gene RBS11. When RNA was analyzed by Northern blot, V28 was found to be most highly expressed in neural and lymphoid tissues. Myeloid cell lines, particularly THP.1 cells, showed especially high expression of V28. We have mapped V28 to human chromosome 3p21-3pter, near the MIP-1 alpha/RANTES receptor-encoding gene.

  12. The immediate effects of soft tissue mobilization versus therapeutic ultrasound for patients with neck and arm pain with evidence of neural mechanosensitivity: a randomized clinical trial.

    Science.gov (United States)

    Costello, Michael; Puentedura, Emilio 'Louie' J; Cleland, Josh; Ciccone, Charles D

    2016-07-01

    Randomized clinical trial. To investigate the immediate effects of soft tissue mobilization (STM) versus therapeutic ultrasound (US) in patients with neck and arm pain who demonstrate neural mechanical sensitivity. While experts have suggested that individuals with neck and arm pain associated with neural tissue mechanical sensitivity may benefit from STM, there has been little research to investigate this hypothesis. Twenty-three patients with neck and arm pain and a positive upper limb neurodynamic test (ULNT) were randomly assigned to receive STM or therapeutic US during a single session. Outcome measures were collected immediately before and after treatment, and at 2-4 day follow-up. Primary outcomes were the Global Rating of Change (GROC), range of motion (ROM) during the ULNT, and pain rating during the ULNT. Secondary measures included the Neck Disability Index (NDI), Patient-Specific Functional Scale (PSFS), Numeric Pain Rating Scale (NPRS), and active range of shoulder abduction motion combined with the wrist neutral or wrist extension. A greater proportion of patients in the STM group reported a significant improvement on the GROC immediately after treatment (P = 0·003, STM = 75%, US = 9%), and at 2-4 day follow-up (P = 0·027, STM = 58%, US = 9%). Patients who received STM demonstrated greater improvements in ROM during ULNT (P = 0·026), PSFS (P = 0·007), and shoulder active ROM combined with wrist extension (P = 0·028). Improvements in Numeric Pain Rating Scale and pain during the ULNT were observed only in the STM group. There was no difference between groups for the NDI or shoulder abduction ROM with wrist neutral. Patients with neck and arm pain demonstrated greater improvements in ULNT ROM, GROC, and PSFS, and pain following STM than after receiving therapeutic US. Therapy, level 1b.

  13. The immediate effects of soft tissue mobilization versus therapeutic ultrasound for patients with neck and arm pain with evidence of neural mechanosensitivity: a randomized clinical trial

    Science.gov (United States)

    Costello, Michael; Puentedura, Emilio ‘Louie’ J.; Cleland, Josh; Ciccone, Charles D.

    2016-01-01

    Study design Randomized clinical trial. Objectives To investigate the immediate effects of soft tissue mobilization (STM) versus therapeutic ultrasound (US) in patients with neck and arm pain who demonstrate neural mechanical sensitivity. Background While experts have suggested that individuals with neck and arm pain associated with neural tissue mechanical sensitivity may benefit from STM, there has been little research to investigate this hypothesis. Methods Twenty-three patients with neck and arm pain and a positive upper limb neurodynamic test (ULNT) were randomly assigned to receive STM or therapeutic US during a single session. Outcome measures were collected immediately before and after treatment, and at 2–4 day follow-up. Primary outcomes were the Global Rating of Change (GROC), range of motion (ROM) during the ULNT, and pain rating during the ULNT. Secondary measures included the Neck Disability Index (NDI), Patient-Specific Functional Scale (PSFS), Numeric Pain Rating Scale (NPRS), and active range of shoulder abduction motion combined with the wrist neutral or wrist extension. Results A greater proportion of patients in the STM group reported a significant improvement on the GROC immediately after treatment (P = 0·003, STM = 75%, US = 9%), and at 2–4 day follow-up (P = 0·027, STM = 58%, US = 9%). Patients who received STM demonstrated greater improvements in ROM during ULNT (P = 0·026), PSFS (P = 0·007), and shoulder active ROM combined with wrist extension (P = 0·028). Improvements in Numeric Pain Rating Scale and pain during the ULNT were observed only in the STM group. There was no difference between groups for the NDI or shoulder abduction ROM with wrist neutral. Conclusion Patients with neck and arm pain demonstrated greater improvements in ULNT ROM, GROC, and PSFS, and pain following STM than after receiving therapeutic US. Level of evidence Therapy, level 1b. PMID:27559283

  14. Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy.

    Science.gov (United States)

    Schneider, D A; Harrington, R D; Zhuang, D; Yan, H; Truscott, T C; Dassanayake, R P; O'Rourke, K I

    2012-11-01

    Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrP(TME) and of which only the HY strain is associated with accumulation of PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrP(TME) in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum, after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrP(TME) was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrP(TME) was detected readily in the brain and retropharyngeal lymph node during preclinical infection, with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrP(TME) in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrP(TME) accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrP(TME) in the lymphoid

  15. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention.

    Science.gov (United States)

    Heuckeroth, Robert O; Schäfer, Karl-Herbert

    2016-09-15

    Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene-environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention

    Science.gov (United States)

    Heuckeroth, Robert O.; Schäfer, Karl-Herbert

    2016-01-01

    Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene-environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome. PMID:26997034

  17. Automated cancer stem cell recognition in H and E stained tissue using convolutional neural networks and color deconvolution

    Science.gov (United States)

    Aichinger, Wolfgang; Krappe, Sebastian; Cetin, A. Enis; Cetin-Atalay, Rengul; Üner, Aysegül; Benz, Michaela; Wittenberg, Thomas; Stamminger, Marc; Münzenmayer, Christian

    2017-03-01

    The analysis and interpretation of histopathological samples and images is an important discipline in the diagnosis of various diseases, especially cancer. An important factor in prognosis and treatment with the aim of a precision medicine is the determination of so-called cancer stem cells (CSC) which are known for their resistance to chemotherapeutic treatment and involvement in tumor recurrence. Using immunohistochemistry with CSC markers like CD13, CD133 and others is one way to identify CSC. In our work we aim at identifying CSC presence on ubiquitous Hematoxilyn and Eosin (HE) staining as an inexpensive tool for routine histopathology based on their distinct morphological features. We present initial results of a new method based on color deconvolution (CD) and convolutional neural networks (CNN). This method performs favorably (accuracy 0.936) in comparison with a state-of-the-art method based on 1DSIFT and eigen-analysis feature sets evaluated on the same image database. We also show that accuracy of the CNN is improved by the CD pre-processing.

  18. Neuronal regeneration in the newt: a model to study the partly reconstruction of the neural tissue in real and simulated weightles sness

    Science.gov (United States)

    Anton, H.; Grigoryan, E.; Mitashov, V.

    The micro -"g" effect on nervous tissue regeneration in newts has been investigated by our group for many years. It has been performed in real and in simulated microgravity with a clinostat. During limb regeneration the motor - and sensory nerves regrow perfectly within the newly formed limb. Like in `1g' conditions they are responsible for the initiation of blastema formation and continuity of g owth andr differentiation. Except for a general acceleration of growth and differentiation processes no differences became visible. Tail regeneration, which is perfectly regulated in newts during their whole life, includes the restoration of the spinal cord and dorsal root ganglia. They follow or initiate an accelerated growth. Up to the present the cellular derivation of the sensory neurones within the regenerate has not yet been clarified. But growth acceleration comprises the whole nervous system. That means a totally new formation of the sensory connection from the periphery to the whole spinal cord. Regeneration must be initiated by the outgrowth of nerve fibres into the wound area. This may be performed by the remaining cut sensory fibres of the last stump segment and should be followed by the differentiation of undifferentiated cells of neural crest origin nearby the amputation area. Such cells are present in the form of meningeal cells which are the origin of mantle and Schwann cells too. Corresponding to the well proved growth acceleration of lens, retina, connective tissue, muscle and skin, the real and simulated microgravity affects the nervous system in the same manner. Tissues and organs of adult organisms have no chance to remain unaffected by the microgravity effect. We try to find the trigger which initiates the accelerated proliferation of the stem cells of sensory neurons, mantle and sheath cells under micro-"g" conditions.

  19. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues

    KAUST Repository

    Cali, Corrado

    2015-07-14

    Advances for application of electron microscopy to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions (3D). From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here, we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room where we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of electron microscopy (EM) preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to observe a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. This article is protected by copyright. All rights reserved.

  20. Immunohistochemical study of PrPSc distribution in neural and extraneural tissues of two cats with feline spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Wunderlin Sabina S

    2009-03-01

    Full Text Available Abstract Background Two domestic shorthair cats presenting with progressive hind-limb ataxia and increased aggressiveness were necropsied and a post mortem diagnosis of Feline Spongiform Encephalopathy (FSE was made. A wide spectrum of tissue samples was collected and evaluated histologically and immunohistologically for the presence of PrPSc. Results Histopathological examination revealed a diffuse vacuolation of the grey matter neuropil with the following areas being most severely affected: corpus geniculatum medialis, thalamus, gyrus dentatus of the hippocampus, corpus striatum, and deep layers of the cerebral and cerebellar cortex as well as in the brain stem. In addition, a diffuse glial reaction involving astrocytes and microglia and intraneuronal vacuolation in a few neurons in the brain stem was present. Heavy PrPSc immunostaining was detected in brain, retina, optic nerve, pars nervosa of the pituitary gland, trigeminal ganglia and small amounts in the myenteric plexus of the small intestine (duodenum, jejunum and slightly in the medulla of the adrenal gland. Conclusion The PrPSc distribution within the brain was consistent with that described in other FSE-affected cats. The pattern of abnormal PrP in the retina corresponded to that found in a captive cheetah with FSE, in sheep with scrapie and was similar to nvCJD in humans.

  1. Comparative Study of Various Delivery Methods for the Supply of Alpha-Ketoglutarate to the Neural Cells for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Tanushree Vishnoi

    2013-01-01

    Full Text Available Delivery of growth factors or bioactive molecules plays an important role in tissue engineering, as the duration to which these are supplied can modulate the cell fate. Thus, the delivery method plays an important role, and the same is presented in this work wherein the exogenous supply of alpha-ketoglutarate (α-KG gave better results for fast proliferating cells as compared to delivery by microspheres or microspheres incorporated scaffolds which can be used while culturing slow growing cells. All these studies were performed in two dimensional (2D and three dimensional (3D setups in which chitosan-gelatin-polypyrrole has been used as 3-D scaffolds. Chitosan and gelatin microspheres alone as well as incorporated in the cryogels were characterized. MTT assay done using neuro-2a cell line showed approximately 42% and 70% increment in cellular proliferation when gelatin and chitosan microspheres were added in a 3-D setup, respectively, as compared to the control. Biochemical analysis of ammonia showed 6-fold reductions in ammonia level in a 3-D setup compared to the control. We also studied the synthesis of a neurotransmitter-like glutamate and found that its concentration increased up to 0.25 mg/ml when the microspheres were added exogenously in a 3-D system.

  2. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues.

    Science.gov (United States)

    Calì, Corrado; Baghabra, Jumana; Boges, Daniya J; Holst, Glendon R; Kreshuk, Anna; Hamprecht, Fred A; Srinivasan, Madhusudhanan; Lehväslaiho, Heikki; Magistretti, Pierre J

    2016-01-01

    Advances in the application of electron microscopy (EM) to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow us to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions. From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room in which we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of EM preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to the observation of a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. © 2015 Wiley Periodicals, Inc.

  3. Development and regeneration of the zebrafish maxillary barbel: a novel study system for vertebrate tissue growth and repair.

    Directory of Open Access Journals (Sweden)

    Elizabeth E LeClair

    2010-01-01

    Full Text Available Barbels are integumentary sense organs found in fishes, reptiles and amphibians. The zebrafish, Danio rerio, develops paired nasal and maxillary barbels approximately one month post fertilization. Small in diameter and optically clear, these adult appendages offer a window on the development, maintenance and function of multiple cell types including skin cells, neural-crest derived pigment cells, circulatory vessels, taste buds and sensory nerves. Importantly, barbels in other otophysan fishes (e.g., catfish are known to regenerate; however, this capacity has not been tested in zebrafish.We describe the development of the maxillary barbel in a staged series of wild type and transgenic zebrafish using light microscopy, histology and immunohistochemistry. By imaging transgenic zebrafish containing fluorescently labeled endothelial cells (Tg(fli1a:EGFP, we demonstrate that the barbel contains a long ( approximately 2-3 mm closed-end vessel that we interpret as a large lymphatic. The identity of this vessel was further supported by live imaging of the barbel circulation, extending recent descriptions of the lymphatic system in zebrafish. The maxillary barbel can be induced to regenerate by proximal amputation. After more than 750 experimental surgeries in which approximately 85% of the barbel's length was removed, we find that wound healing is complete within hours, followed by blastema formation ( approximately 3 days, epithelial redifferentiation (3-5 days and appendage elongation. Maximum regrowth occurs within 2 weeks of injury. Although superficially normal, the regenerates are shorter and thicker than the contralateral controls, have abnormally organized mesenchymal cells and extracellular matrix, and contain prominent connective tissue "stumps" at the plane of section--a mode of regeneration more typical of mammalian scarring than other zebrafish appendages. Finally, we show that the maxillary barbel can regenerate after repeated injury and

  4. 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

  5. Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.

    Directory of Open Access Journals (Sweden)

    Jitender P Dubey

    Full Text Available The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse.Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i. to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25% of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle.This study reevaluated

  6. Effect of Butler's neural tissue mobilization and Mulligan's bent leg raise on pain and straight leg raise in patients of low back ache.

    Science.gov (United States)

    Tambekar, Neha; Sabnis, Shaila; Phadke, Apoorva; Bedekar, Nilima

    2016-04-01

    Low back ache (LBA) is a common musculoskeletal disorder sometimes associated with a positive limited Straight leg raise (SLR) test. Mulligan's bent leg raise (BLR) and Butler's neural tissue mobilization (NTM) are commonly used techniques for the treatment of low back ache where SLR is limited. The aim of this study was to evaluate the effect of both the techniques on pain and limited SLR in patients with LBA. Thirty one patients with LBA with radiculopathy were randomly allocated into 2 groups; BLR [n = 16] NTM [n = 15]. The outcome measures i.e. visual analogue scale (VAS) for pain and universal goniometer for measuring SLR range of motion (SROM) were assessed at the baseline, post intervention and after 24 h (follow up). Within group analysis using paired t-test revealed a significant difference between pre-treatment and post-treatment VAS and SROM score(p  0.05). The study showed that both techniques produce immediate improvement in pain and SLR range but this effect was not maintained during the follow up period. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine.

    Science.gov (United States)

    Schlieve, Christopher R; Fowler, Kathryn L; Thornton, Matthew; Huang, Sha; Hajjali, Ibrahim; Hou, Xiaogang; Grubbs, Brendan; Spence, Jason R; Grikscheit, Tracy C

    2017-09-12

    Acquired or congenital disruption in enteric nervous system (ENS) development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC)-derived tissue-engineered small intestine (TESI) from human intestinal organoids (HIOs). However, HIO-TESI fails to develop an ENS. The purpose of our study is to restore ENS components derived exclusively from hPSCs in HIO-TESI. hPSC-derived enteric neural crest cell (ENCC) supplementation of HIO-TESI establishes submucosal and myenteric ganglia, repopulates various subclasses of neurons, and restores neuroepithelial connections and neuron-dependent contractility and relaxation in ENCC-HIO-TESI. RNA sequencing identified differentially expressed genes involved in neurogenesis, gliogenesis, gastrointestinal tract development, and differentiated epithelial cell types when ENS elements are restored during in vivo development of HIO-TESI. Our findings validate an effective approach to restoring hPSC-derived ENS components in HIO-TESI and may implicate their potential for the treatment of enteric neuropathies. Published by Elsevier Inc.

  8. A two-step convolutional neural network based computer-aided detection scheme for automatically segmenting adipose tissue volume depicting on CT images.

    Science.gov (United States)

    Wang, Yunzhi; Qiu, Yuchen; Thai, Theresa; Moore, Kathleen; Liu, Hong; Zheng, Bin

    2017-06-01

    Accurately assessment of adipose tissue volume inside a human body plays an important role in predicting disease or cancer risk, diagnosis and prognosis. In order to overcome limitation of using only one subjectively selected CT image slice to estimate size of fat areas, this study aims to develop and test a computer-aided detection (CAD) scheme based on deep learning technique to automatically segment subcutaneous fat areas (SFA) and visceral fat areas (VFA) depicting on volumetric CT images. A retrospectively collected CT image dataset was divided into two independent training and testing groups. The proposed CAD framework consisted of two steps with two convolution neural networks (CNNs) namely, Selection-CNN and Segmentation-CNN. The first CNN was trained using 2,240 CT slices to select abdominal CT slices depicting SFA and VFA. The second CNN was trained with 84,000pixel patches and applied to the selected CT slices to identify fat-related pixels and assign them into SFA and VFA classes. Comparing to the manual CT slice selection and fat pixel segmentation results, the accuracy of CT slice selection using the Selection-CNN yielded 95.8%, while the accuracy of fat pixel segmentation using the Segmentation-CNN was 96.8%. This study demonstrated the feasibility of applying a new deep learning based CAD scheme to automatically recognize abdominal section of human body from CT scans and segment SFA and VFA from volumetric CT data with high accuracy or agreement with the manual segmentation results. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Combined Use of Tissue Morphology, Neural Network Analysis of Chromatin Texture and Clinical Variables to Predict Prostate Cancer Agressiveness from Biopsy Water

    National Research Council Canada - National Science Library

    Partin, Alan

    2000-01-01

    Purpose: To combine clinical, serum, pathologic and computer derived information into an artificial neural network to develop/validate a model to predict prostate cancer tumor aggressiveness in both a...

  10. Combined Use of Tissue Morphology, Neural Network Analysis of Chromatin Texture & Clinical Variables to Predict Prostate Cancer Agressiveness from Biopsy Material

    National Research Council Canada - National Science Library

    Partin, Alan

    1999-01-01

    the purpose of this report is to combine clinical, serum, pathological and computer derived information into an artificial neural network to develop/validate a model to predict prostate cancer tumor...

  11. Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

    Science.gov (United States)

    Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

    2017-09-01

    The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-08-01

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

  13. Zebrafish Model of NF1 for Structure-Function Analysis, Mechanisms of Glial Tumorigenesis, and Chemical Biology

    Science.gov (United States)

    2014-05-01

    abnormalities and multiple benign and malignant tumors, including tumors of neural crest origin such as glioma and malignant peripheral nerve sheath...grade gliomas and MPNSTs, but not in the non-malignant neural crest -derived tissues, in the nf1a+/-;nf1b-/-;p53-/-;sox10:GFP adult zebrafish. This...ATRX (a-thalassaemia/mental retardation syndrome X-linked) is a chromatin remodeling factor required for H3.3 incorporation at pericentric

  14. SEGMENTAL NEUROFIBROMATOSIS: A REPORT OF 3 CASES

    OpenAIRE

    Gabhane Sushma; Kotwal Mrunmayi; Bobhate Sudhakar

    2010-01-01

    Neurofibromatosis is a genetic disorder of neural crest-derived cells that primarily affect growth of neural tissues. It is broadly divided into three categories: (a) von Recklinghausen′s neurofibromatosis or NF-1, (b) bilateral acoustic neuroma (NF-2), and (c) all other neurofibromatoses, including alternate or atypical forms of the disease. The patients with generalized form of NF1 are characterized by multiple café-au-lait spots and neurofibromas and diagnosed easily. But when ...

  15. The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders

    Science.gov (United States)

    2013-01-01

    Background We examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF). Methods Rats underwent initial training for 4–6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality. Results Several force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw

  16. Classification of Laser Induced Fluorescence Spectra from Normal and Malignant bladder tissues using Learning Vector Quantization Neural Network in Bladder Cancer Diagnosis

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Mascarenhas, Kim Komal; Patil, Choudhary

    2008-01-01

    In the present work we discuss the potential of recently developed classification algorithm, Learning Vector Quantization (LVQ), for the analysis of Laser Induced Fluorescence (LIF) Spectra, recorded from normal and malignant bladder tissue samples. The algorithm is prototype based and inherently...

  17. Neural repair in the adult brain

    Science.gov (United States)

    Jessberger, Sebastian

    2016-01-01

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

  18. A comparison of the techniques of secondary ion mass spectrometry and resonance ionization mass spectrometry for the analysis of potentially toxic element accumulation in neural tissue.

    Science.gov (United States)

    Jones, O R; Perks, R M; Abraham, C J; Telle, H H; Oakley, A E

    1997-01-01

    A comparison is made of the techniques of secondary ion mass spectrometry (SIMS) and resonance ionization mass spectrometry (RIMS) for the detection of the neuro-toxic element aluminium in cortical tissue. Experiments were performed using a reflectron-type time-of-flight mass spectrometer (TOFMS) in conjunction with an Ar+ source for target sputtering and a pulsed tuneable dye laser system for resonance ionization. It is shown how isobaric interference of species such as CNH and C2H3 in the case of aluminium greatly affect the quantitative accuracy and the detection limit of aluminium in biological samples when analysed using SIMS. In contrast the use of RIMS virtually eliminates this problem, so allowing easier quantification and much lower detection limits to be achieved. Detection limits of approximately 3 ppm for aluminium in brain tissue homogenates were achieved using RIMS, with a spatial resolution of less than 100 microns.

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

    Science.gov (United States)

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

    2015-11-01

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

  20. Tissue segmentation-assisted analysis of fMRI for human motor response: an approach combining artificial neural network and fuzzy C means

    OpenAIRE

    Chiu, MJ; Lin, CC; Chuang, KH; Chen, JH; Huang, KM

    2001-01-01

    The authors have developed an automated algorithm for segmentation of magnetic resonance images (MRI) of the human brain. They investigated the quantitative analysis of tissue-specific human motor response through an approach combining gradient echo functional MRI and automated segmentation analysis. Fifteen healthy volunteers, placed in a 1.5 T clinical MR imager, performed a self-paced finger opposition throughout the activation periods. T1-weighted images (WI), T2WI, and proton density WI ...

  1. Tissue segmentation-assisted analysis of fMRI for human motor response: an approach combining artificial neural network and fuzzy C means.

    Science.gov (United States)

    Chiu, M J; Lin, C C; Chuang, K H; Chen, J H; Huang, K M

    2001-03-01

    The authors have developed an automated algorithm for segmentation of magnetic resonance images (MRI) of the human brain. They investigated the quantitative analysis of tissue-specific human motor response through an approach combining gradient echo functional MRI and automated segmentation analysis. Fifteen healthy volunteers, placed in a 1.5 T clinical MR imager, performed a self-paced finger opposition throughout the activation periods. T1-weighted images (WI), T2WI, and proton density WI were acquired for segmentation analysis. Single-slice axial T2* fast low-angle shot (FLASH) images were obtained during the functional study. Pixelwise cross-correlation analysis was performed to obtain an activation map. A cascaded algorithm, combining Kohonen feature maps and fuzzy C means, was applied for segmentation. After processing, masks for gray matter, white matter, small vessels, and large vessels were generated. Tissue-specific analysis showed a signal change rate of 4.53% in gray matter, 2.98% in white matter, 5.79% in small vessels, and 7.24% in large vessels. Different temporal patterns as well as different levels of activation were identified in the functional response from various types of tissue. High correlation exists between cortical gray matter and subcortical white matter (r = 0.957), while the vessel behaves somewhat different temporally. The cortical gray matter fits best to the assumed input function (r = 0.957) followed by subcortical white matter (r = 0.829) and vessels (r = 0.726). The automated algorithm of tissue-specific analysis thus can assist functional MRI studies with different modalities of response in different brain regions.

  2. Deletion of integrin-linked kinase from neural crest cells in mice results in aortic aneurysms and embryonic lethality

    Directory of Open Access Journals (Sweden)

    Thomas D. Arnold

    2013-09-01

    Neural crest cells (NCCs participate in the remodeling of the cardiac outflow tract and pharyngeal arch arteries during cardiovascular development. Integrin-linked kinase (ILK is a serine/threonine kinase and a major regulator of integrin signaling. It links integrins to the actin cytoskeleton and recruits other adaptor molecules into a large complex to regulate actin dynamics and integrin function. Using the Cre-lox system, we deleted Ilk from NCCs of mice to investigate its role in NCC morphogenesis. The resulting mutants developed a severe aneurysmal arterial trunk that resulted in embryonic lethality during late gestation. Ilk mutants showed normal cardiac NCC migration but reduced differentiation into smooth muscle within the aortic arch arteries and the outflow tract. Within the conotruncal cushions, Ilk-deficient NCCs exhibited disorganization of F-actin stress fibers and a significantly rounder morphology, with shorter cellular projections. Additionally, absence of ILK resulted in reduced in vivo phosphorylation of Smad3 in NCCs, which correlated with reduced αSMA levels. Our findings resemble those seen in Pinch1 and β1 integrin conditional mutant mice, and therefore support that, in neural crest-derived cells, ILK and Pinch1 act as cytoplasmic effectors of β1 integrin in a pathway that protects against aneurysms. In addition, our conditional Ilk mutant mice might prove useful as a model to study aortic aneurysms caused by reduced Smad3 signaling, as occurs in the newly described aneurysms-osteoarthritis syndrome, for example.

  3. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Cécile eCoste

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  4. Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: in vitro studies on neural tissue cells

    Science.gov (United States)

    Murali, Kumarasamy; Kenesei, Kata; Li, Yang; Demeter, Kornél; Környei, Zsuzsanna; Madarász, Emilia

    2015-02-01

    Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of ``aged'' NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with ``identical'' NPs.Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the

  5. 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.

  6. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  7. Neural Crest Cells Isolated from the Bone Marrow of Transgenic Mice Express JCV T-Antigen.

    Directory of Open Access Journals (Sweden)

    Jennifer Gordon

    Full Text Available JC virus (JCV, a common human polyomavirus, is the etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML. In addition to its role in PML, studies have demonstrated the transforming ability of the JCV early protein, T-antigen, and its association with some human cancers. JCV infection occurs in childhood and latent virus is thought to be maintained within the bone marrow, which harbors cells of hematopoietic and non-hematopoietic lineages. Here we show that non-hematopoietic mesenchymal stem cells (MSCs isolated from the bone marrow of JCV T-antigen transgenic mice give rise to JCV T-antigen positive cells when cultured under neural conditions. JCV T-antigen positive cells exhibited neural crest characteristics and demonstrated p75, SOX-10 and nestin positivity. When cultured in conditions typical for mesenchymal cells, a population of T-antigen negative cells, which did not express neural crest markers arose from the MSCs. JCV T-antigen positive cells could be cultured long-term while maintaining their neural crest characteristics. When these cells were induced to differentiate into neural crest derivatives, JCV T-antigen was downregulated in cells differentiating into bone and maintained in glial cells expressing GFAP and S100. We conclude that JCV T-antigen can be stably expressed within a fraction of bone marrow cells differentiating along the neural crest/glial lineage when cultured in vitro. These findings identify a cell population within the bone marrow permissible for JCV early gene expression suggesting the possibility that these cells could support persistent viral infection and thus provide clues toward understanding the role of the bone marrow in JCV latency and reactivation. Further, our data provides an excellent experimental model system for studying the cell-type specificity of JCV T-antigen expression, the role of bone marrow-derived stem cells in the pathogenesis of JCV-related diseases

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

    Science.gov (United States)

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

    2010-09-01

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

  9. Células mesenquimales de médula ósea: Diferenciación y potencial reemplazo neuronal Mesenchymal stem cells: Differentiation and alternative source of neural tissue

    Directory of Open Access Journals (Sweden)

    Catalina C. Bianchi de Di Risio

    2004-12-01

    cells to repair damaged tissues. Particularly neuronal differentiation from progenitors obtained from mesenchymae non hemopoietic cells offers a new possibility in the field of neural transplantation and tissue engineering to repair functional entities in the nervous system.

  10. 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.

  11. 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

  12. 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 ...

  13. Neural recording and modulation technologies

    Science.gov (United States)

    Chen, Ritchie; Canales, Andres; Anikeeva, Polina

    2017-01-01

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

  14. [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.

  15. Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during Embryonic Stem Cell Neural Differentiation.

    Science.gov (United States)

    Xi, Jiajie; Wu, Yukang; Li, Guoping; Ma, Li; Feng, Ke; Guo, Xudong; Jia, Wenwen; Wang, Guiying; Yang, Guang; Li, Ping; Kang, Jiuhong

    2017-08-08

    During gastrulation, the neuroectoderm cells form the neural tube and neural crest. The nervous system contains significantly more microRNAs than other tissues, but the role of microRNAs in controlling the differentiation of neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural differentiation systems, we found that miR-29b was upregulated in NTE cells and downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE cells and inhibited their differentiation into NCCs. Accordingly, the inhibition of miR-29b significantly inhibited the differentiation of NTE cells. A mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a) to regulate neural differentiation. Moreover, miR-29b mediated the function of Pou3f1, a critical neural transcription factor. Therefore, our study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated the determination of cell fate. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Neural plasticity in pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Demir, Ihsan Ekin; Friess, Helmut; Ceyhan, Güralp O

    2015-11-01

    Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain. Instead of being mere histopathological manifestations of disease progression, pancreatic neural plasticity synergizes with the enhanced excitability of sensory neurons, with Schwann cell recruitment toward cancer and with central nervous system alterations. These alterations maintain a bidirectional interaction between nerves and non-neural pancreatic cells, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth. Owing to the prognostic effects of pain and neural invasion in pancreatic cancer, dissecting the mechanism of pancreatic neuroplasticity holds major translational relevance. However, current in vivo models of pancreatic cancer and chronic pancreatitis contain many discrepancies from human disease that overshadow their translational value. The present Review discusses novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression.

  17. EDITORIAL: Focus on the neural interface Focus on the neural interface

    Science.gov (United States)

    Durand, Dominique M.

    2009-10-01

    The possibility of an effective connection between neural tissue and computers has inspired scientists and engineers to develop new ways of controlling and obtaining information from the nervous system. These applications range from `brain hacking' to neural control of artificial limbs with brain signals. Notwithstanding the significant advances in neural prosthetics in the last few decades and the success of some stimulation devices such as cochlear prosthesis, neurotechnology remains below its potential for restoring neural function in patients with nervous system disorders. One of the reasons for this limited impact can be found at the neural interface and close attention to the integration between electrodes and tissue should improve the possibility of successful outcomes. The neural interfaces research community consists of investigators working in areas such as deep brain stimulation, functional neuromuscular/electrical stimulation, auditory prostheses, cortical prostheses, neuromodulation, microelectrode array technology, brain-computer/machine interfaces. Following the success of previous neuroprostheses and neural interfaces workshops, funding (from NIH) was obtained to establish a biennial conference in the area of neural interfaces. The first Neural Interfaces Conference took place in Cleveland, OH in 2008 and several topics from this conference have been selected for publication in this special section of the Journal of Neural Engineering. Three `perspectives' review the areas of neural regeneration (Corredor and Goldberg), cochlear implants (O'Leary et al) and neural prostheses (Anderson). Seven articles focus on various aspects of neural interfacing. One of the most popular of these areas is the field of brain-computer interfaces. Fraser et al, report on a method to generate robust control with simple signal processing algorithms of signals obtained with electrodes implanted in the brain. One problem with implanted electrode arrays, however, is that

  18. Genetic, epigenetic, and environmental contributions to neural tube closure.

    Science.gov (United States)

    Wilde, Jonathan J; Petersen, Juliette R; Niswander, Lee

    2014-01-01

    The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and adhere to close the neural tube. The neural ectoderm and surrounding tissues also coordinate proliferation, differentiation, and patterning. This highly orchestrated process is susceptible to disruption, leading to neural tube defects (NTDs), a common birth defect. Here, we highlight genetic and epigenetic contributions to neural tube closure. We describe an online database we created as a resource for researchers, geneticists, and clinicians. Neural tube closure is sensitive to environmental influences, and we discuss disruptive causes, preventative measures, and possible mechanisms. New technologies will move beyond candidate genes in small cohort studies toward unbiased discoveries in sporadic NTD cases. This will uncover the genetic complexity of NTDs and critical gene-gene interactions. Animal models can reveal the causative nature of genetic variants, the genetic interrelationships, and the mechanisms underlying environmental influences.

  19. The Usage of Neural Networks for the Medical Diagnosis

    OpenAIRE

    Malyshevska, Kateryna

    2009-01-01

    The problem of cancer diagnosis from multi-channel images using the neural networks is investigated. The goal of this work is to classify the different tissue types which are used to determine the cancer risk. The radial basis function networks and backpropagation neural networks are used for classification. The results of experiments are presented.

  20. Numerical continuation of travelling waves and pulses in neural fields

    NARCIS (Netherlands)

    Meijer, Hil Gaétan Ellart; Coombes, Stephen

    2013-01-01

    We study travelling waves and pulses in neural fields. Neural fields are a macroscopic description of the activity of brain tissue, which mathematically are formulated as integro-differential equations. While linear and weakly nonlinear analysis can describe instabilities and small amplitude

  1. 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.

  2. Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function

    Energy Technology Data Exchange (ETDEWEB)

    Ericson, Milton Nance [ORNL; McKnight, Timothy E [ORNL; Melechko, Anatoli Vasilievich [ORNL; Simpson, Michael L [ORNL; Morrison, Barclay [ORNL; Yu, Zhe [Columbia University

    2012-01-01

    Neural chips, which are capable of simultaneous, multi-site neural recording and stimulation, have been used to detect and modulate neural activity for almost 30 years. As a neural interface, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information of neuroplasticity. This novel nano-neuron interface can potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single cell level and even inside the cell.

  3. Neural plasticity after spinal cord injury.

    Science.gov (United States)

    Liu, Jian; Yang, Xiaoyu; Jiang, Lianying; Wang, Chunxin; Yang, Maoguang

    2012-02-15

    Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have been studied, the mechanism and treatment to effectively improve neural plasticity changes remain controversial. The present study reviewed studies regarding plasticity of the central nervous system and methods for promoting plasticity to improve repair of injured central nerves. The results showed that synaptic reorganization, axonal sprouting, and neurogenesis are critical factors for neural circuit reconstruction. Directed functional exercise, neurotrophic factor and transplantation of nerve-derived and non-nerve-derived tissues and cells can effectively ameliorate functional disturbances caused by spinal cord injury and improve quality of life for patients.

  4. 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.

  5. 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.

  6. Microscopic neural image registration based on the structure of mitochondria

    Science.gov (United States)

    Cao, Huiwen; Han, Hua; Rao, Qiang; Xiao, Chi; Chen, Xi

    2017-02-01

    Microscopic image registration is a key component of the neural structure reconstruction with serial sections of neural tissue. The goal of microscopic neural image registration is to recover the 3D continuity and geometrical properties of specimen. During image registration, various distortions need to be corrected, including image rotation, translation, tissue deformation et.al, which come from the procedure of sample cutting, staining and imaging. Furthermore, there is only certain similarity between adjacent sections, and the degree of similarity depends on local structure of the tissue and the thickness of the sections. These factors make the microscopic neural image registration a challenging problem. To tackle the difficulty of corresponding landmarks extraction, we introduce a novel image registration method for Scanning Electron Microscopy (SEM) images of serial neural tissue sections based on the structure of mitochondria. The ellipsoidal shape of mitochondria ensures that the same mitochondria has similar shape between adjacent sections, and its characteristic of broad distribution in the neural tissue guarantees that landmarks based on the mitochondria distributed widely in the image. The proposed image registration method contains three parts: landmarks extraction between adjacent sections, corresponding landmarks matching and image deformation based on the correspondences. We demonstrate the performance of our method with SEM images of drosophila brain.

  7. Microtubules, polarity and vertebrate neural tube morphogenesis.

    Science.gov (United States)

    Cearns, Michael D; Escuin, Sarah; Alexandre, Paula; Greene, Nicholas D E; Copp, Andrew J

    2016-07-01

    Microtubules (MTs) are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of MTs, their effects on cell shape and polarity, and their role in large-scale morphogenesis remain poorly understood. Here, these relationships were examined with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate; and cavitation of the teleost neural rod. The latter process has been compared with 'secondary' neurulation that generates the caudal spinal cord in mammals. MTs align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration, which indirectly impacts on cell shape. Whether MTs play other functional roles in mammalian neurulation remains unclear. In the zebrafish, MTs are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirror-symmetric MT apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of MT functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish 'cause' from 'effect'. Future developments will likely rely on novel ways to selectively impair MT function in order to investigate the roles they play. © 2016 Anatomical Society.

  8. 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

  9. 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.

  10. 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.

  11. Tissue tests

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.

    2009-01-01

    Tissue tests are widely used in horticulture practice and have in comparison with soil or substrate testing advantages as well disadvantages in comparison with soil testing. One of the main advantages of tissue tests is the certainty that analysed nutrients in plant tissues are really present in the

  12. 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...

  13. 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,

  14. 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.

  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. Nano-biotechnology: carbon nanofibres as improved neural and orthopaedic implants

    Science.gov (United States)

    Webster, Thomas J.; Waid, Michael C.; McKenzie, Janice L.; Price, Rachel L.; Ejiofor, Jeremiah U.

    2004-01-01

    For the continuous monitoring, diagnosis, and treatment of neural tissue, implantable probes are required. However, sometimes such neural probes (usually composed of silicon) become encapsulated with non-conductive, undesirable glial scar tissue. Similarly for orthopaedic implants, biomaterials (usually titanium and/or titanium alloys) often become encapsulated with undesirable soft fibrous, not hard bony, tissue. Although possessing intriguing electrical and mechanical properties for neural and orthopaedic applications, carbon nanofibres/nanotubes have not been widely considered for these applications to date. The present work developed a carbon nanofibre reinforced polycarbonate urethane (PU) composite in an attempt to determine the possibility of using carbon nanofibres (CNs) as either neural or orthopaedic prosthetic devices. Electrical and mechanical characterization studies determined that such composites have properties suitable for neural and orthopaedic applications. More importantly, cell adhesion experiments revealed for the first time the promise these materials have to increase neural (nerve cell) and osteoblast (bone-forming cell) functions. In contrast, functions of cells that contribute to glial scar-tissue formation for neural prostheses (astrocytes) and fibrous-tissue encapsulation events for bone implants (fibroblasts) decreased on PU composites containing increasing amounts of CNs. In this manner, this study provided the first evidence of the future that CN formulations may have towards interacting with neural and bone cells which is important for the design of successful neural probes and orthopaedic implants, respectively.

  19. 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

  20. Scaffolds for 3D in vitro culture of neural lineage cells.

    Science.gov (United States)

    Murphy, Ashley R; Laslett, Andrew; O'Brien, Carmel M; Cameron, Neil R

    2017-05-01

    Understanding how neurodegenerative disorders develop is not only a key challenge for researchers but also for the wider society, given the rapidly aging populations in developed countries. Advances in this field require new tools with which to recreate neural tissue in vitro and produce realistic disease models. This in turn requires robust and reliable systems for performing 3D in vitro culture of neural lineage cells. This review provides a state of the art update on three-dimensional culture systems for in vitro development of neural tissue, employing a wide range of scaffold types including hydrogels, solid porous polymers, fibrous materials and decellularised tissues as well as microfluidic devices and lab-on-a-chip systems. To provide some context with in vivo development of the central nervous system (CNS), we also provide a brief overview of the neural stem cell niche, neural development and neural differentiation in vitro. We conclude with a discussion of future directions for this exciting and important field of biomaterials research. Neurodegenerative diseases, including dementia, Parkinson's and Alzheimer's diseases and motor neuron diseases, are a major societal challenge for aging populations. Understanding these conditions and developing therapies against them will require the development of new physical models of healthy and diseased neural tissue. Cellular models resembling neural tissue can be cultured in the laboratory with the help of 3D scaffolds - materials that allow the organization of neural cells into tissue-like structures. This review presents recent work on the development of different types of scaffolds for the 3D culture of neural lineage cells and the generation of functioning neural-like tissue. These in vitro culture systems are enabling the development of new approaches for modelling and tackling diseases of the brain and CNS. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Lack of Motor Neuron Differentiation is an Intrinsic Property of the Mouse Secondary Neural Tube

    Science.gov (United States)

    Shum, Alisa S.W.; Tang, Louisa S.C.; Copp, Andrew J.; Roelink, Henk

    2016-01-01

    The cranial part of the amniote neural tube is formed by folding and fusion of the ectoderm-derived neural plate (primary neurulation). After posterior neuropore closure, however, the caudal neural tube is formed by cavitation of tail bud mesenchyme (secondary neurulation). In mouse embryos, the secondary neural tube expresses several genes important in early patterning and induction, in restricted domains similar to the primary neural tube, yet it does not undergo neuronal differentiation, but subsequently degenerates. Although the secondary neural tube, isolated from surrounding tissues, is responsive to exogenous Sonic Hedgehog proteins in vitro, motor neuron differentiation is never observed. This cannot be attributed to the properties of the secondary notochord, since it is able to induce motor neuron differentiation in naïve chick neural plate explants. Taken together, these results support that the lack of motor neuron differentiation is an intrinsic property of the mouse secondary neural tube. PMID:20960561

  2. Tumor Diagnosis Using Backpropagation Neural Network Method

    Science.gov (United States)

    Ma, Lixing; Looney, Carl; Sukuta, Sydney; Bruch, Reinhard; Afanasyeva, Natalia

    1998-05-01

    For characterization of skin cancer, an artificial neural network (ANN) method has been developed to diagnose normal tissue, benign tumor and melanoma. The pattern recognition is based on a three-layer neural network fuzzy learning system. In this study, the input neuron data set is the Fourier Transform infrared (FT-IR)spectrum obtained by a new Fiberoptic Evanescent Wave Fourier Transform Infrared (FEW-FTIR) spectroscopy method in the range of 1480 to 1850 cm-1. Ten input features are extracted from the absorbency values in this region. A single hidden layer of neural nodes with sigmoids activation functions clusters the feature space into small subclasses and the output nodes are separated in different nonconvex classes to permit nonlinear discrimination of disease states. The output is classified as three classes: normal tissue, benign tumor and melanoma. The results obtained from the neural network pattern recognition are shown to be consistent with traditional medical diagnosis. Input features have also been extracted from the absorbency spectra using chemical factor analysis. These abstract features or factors are also used in the classification.

  3. 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…

  4. 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....

  5. Polymeric Nanofibers in Tissue Engineering

    Science.gov (United States)

    Dahlin, Rebecca L.; Kasper, F. Kurtis

    2011-01-01

    Polymeric nanofibers can be produced using methods such as electrospinning, phase separation, and self-assembly, and the fiber composition, diameter, alignment, degradation, and mechanical properties can be tailored to the intended application. Nanofibers possess unique advantages for tissue engineering. The small diameter closely matches that of extracellular matrix fibers, and the relatively large surface area is beneficial for cell attachment and bioactive factor loading. This review will update the reader on the aspects of nanofiber fabrication and characterization important to tissue engineering, including control of porous structure, cell infiltration, and fiber degradation. Bioactive factor loading will be discussed with specific relevance to tissue engineering. Finally, applications of polymeric nanofibers in the fields of bone, cartilage, ligament and tendon, cardiovascular, and neural tissue engineering will be reviewed. PMID:21699434

  6. Tissue types (image)

    Science.gov (United States)

    ... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

  7. Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

    Science.gov (United States)

    Bond, Allison M.; Ming, Guo-li; Song, Hongjun

    2015-01-01

    Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

  8. Electronic dura mater for long-term multimodal neural interfaces

    Science.gov (United States)

    Minev, Ivan R.; Musienko, Pavel; Hirsch, Arthur; Barraud, Quentin; Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jérôme; Capogrosso, Marco; Milekovic, Tomislav; Asboth, Léonie; Torres, Rafael Fajardo; Vachicouras, Nicolas; Liu, Qihan; Pavlova, Natalia; Duis, Simone; Larmagnac, Alexandre; Vörös, Janos; Micera, Silvestro; Suo, Zhigang; Courtine, Grégoire; Lacour, Stéphanie P.

    2015-01-01

    The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.

  9. Mechanical roles of apical constriction, cell elongation, and cell migration during neural tube formation in Xenopus.

    Science.gov (United States)

    Inoue, Yasuhiro; Suzuki, Makoto; Watanabe, Tadashi; Yasue, Naoko; Tateo, Itsuki; Adachi, Taiji; Ueno, Naoto

    2016-12-01

    Neural tube closure is an important and necessary process during the development of the central nervous system. The formation of the neural tube structure from a flat sheet of neural epithelium requires several cell morphogenetic events and tissue dynamics to account for the mechanics of tissue deformation. Cell elongation changes cuboidal cells into columnar cells, and apical constriction then causes them to adopt apically narrow, wedge-like shapes. In addition, the neural plate in Xenopus is stratified, and the non-neural cells in the deep layer (deep cells) pull the overlying superficial cells, eventually bringing the two layers of cells to the midline. Thus, neural tube closure appears to be a complex event in which these three physical events are considered to play key mechanical roles. To test whether these three physical events are mechanically sufficient to drive neural tube formation, we employed a three-dimensional vertex model and used it to simulate the process of neural tube closure. The results suggest that apical constriction cued the bending of the neural plate by pursing the circumference of the apical surface of the neural cells. Neural cell elongation in concert with apical constriction further narrowed the apical surface of the cells and drove the rapid folding of the neural plate, but was insufficient for complete neural tube closure. Migration of the deep cells provided the additional tissue deformation necessary for closure. To validate the model, apical constriction and cell elongation were inhibited in Xenopus laevis embryos. The resulting cell and tissue shapes resembled the corresponding simulation results.

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

    Science.gov (United States)

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

    2017-01-30

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

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

    Directory of Open Access Journals (Sweden)

    Seunghoon Lee

    2015-08-01

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

  12. 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.

  13. 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.

  14. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

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

    Science.gov (United States)

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

    2002-06-01

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

  16. 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...

  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. A Survey of Neural Front End Amplifiers and Their Requirements toward Practical Neural Interfaces

    Directory of Open Access Journals (Sweden)

    Eric Bharucha

    2014-11-01

    Full Text Available When designing an analog front-end for neural interfacing, it is hard to evaluate the interplay of priority features that one must upkeep. Given the competing nature of design requirements for such systems a good understanding of these trade-offs is necessary. Low power, chip size, noise control, gain, temporal resolution and safety are the salient ones. There is a need to expose theses critical features for high performance neural amplifiers as the density and performance needs of these systems increases. This review revisits the basic science behind the engineering problem of extracting neural signal from living tissue. A summary of architectures and topologies is then presented and illustrated through a rich set of examples based on the literature. A survey of existing systems is presented for comparison based on prevailing performance metrics.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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.)

  5. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...

  6. 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

  7. 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.

  8. Molecular and cellular changes associated with the evolution of novel jaw muscles in parrots.

    Science.gov (United States)

    Tokita, Masayoshi; Nakayama, Tomoki; Schneider, Richard A; Agata, Kiyokazu

    2013-02-07

    Vertebrates have achieved great evolutionary success due in large part to the anatomical diversification of their jaw complex, which allows them to inhabit almost every ecological niche. While many studies have focused on mechanisms that pattern the jaw skeleton, much remains to be understood about the origins of novelty and diversity in the closely associated musculature. To address this issue, we focused on parrots, which have acquired two anatomically unique jaw muscles: the ethmomandibular and the pseudomasseter. In parrot embryos, we observe distinct and highly derived expression patterns for Scx, Bmp4, Tgfβ2 and Six2 in neural crest-derived mesenchyme destined to form jaw muscle connective tissues. Furthermore, immunohistochemical analysis reveals that cell proliferation is more active in the cells within the jaw muscle than in surrounding connective tissue cells. This biased and differentially regulated mode of cell proliferation in cranial musculoskeletal tissues may allow these unusual jaw muscles to extend towards their new attachment sites. We conclude that the alteration of neural crest-derived connective tissue distribution during development may underlie the spatial changes in jaw musculoskeletal architecture found only in parrots. Thus, parrots provide valuable insights into molecular and cellular mechanisms that may generate evolutionary novelties with functionally adaptive significance.

  9. Tissue Classification

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, David Gerald [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    The project began as a e ort to support InLight and Lumidigm. With the sale of the companies to a non-New Mexico entity, the project then focused on supporting a new company Medici Technologies. The Small Business (SB) is attempting to quantify glucose in tissue using a series of short interferometer scans of the nger. Each scan is produced from a novel presentation of the nger to the device. The intent of the project is to identify and, if possible, implement improved methods for classi cation, feature selection, and training to improve the performance of predictive algorithms used for tissue classi cation.

  10. Neural engineering from advanced biomaterials to 3D fabrication techniques

    CERN Document Server

    Kaplan, David

    2016-01-01

    This book covers the principles of advanced 3D fabrication techniques, stem cells and biomaterials for neural engineering. Renowned contributors cover topics such as neural tissue regeneration, peripheral and central nervous system repair, brain-machine interfaces and in vitro nervous system modeling. Within these areas, focus remains on exciting and emerging technologies such as highly developed neuroprostheses and the communication channels between the brain and prostheses, enabling technologies that are beneficial for development of therapeutic interventions, advanced fabrication techniques such as 3D bioprinting, photolithography, microfluidics, and subtractive fabrication, and the engineering of implantable neural grafts. There is a strong focus on stem cells and 3D bioprinting technologies throughout the book, including working with embryonic, fetal, neonatal, and adult stem cells and a variety of sophisticated 3D bioprinting methods for neural engineering applications. There is also a strong focus on b...

  11. Versatile electrochemial sensor for tissue culturing and sample handling

    DEFF Research Database (Denmark)

    Bakmand, Tanya; Kwasny, Dorota; Al Atraktchi, Fatima Al-Zahraa

    2014-01-01

    Culturing of organtypic brain tissues is a routine procedure in neural research. The visual inspection of the medium is the only way of determining the state of the tissue. At the end of culturing, post-processing techniques such as HPLC can be used to measure the concentration of the secreted me...... as a preliminary proof of concept....

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

    Directory of Open Access Journals (Sweden)

    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

  13. Hyperbolic Hopfield neural networks.

    Science.gov (United States)

    Kobayashi, M

    2013-02-01

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

  14. Neural Semantic Encoders.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Yu, Hong

    2017-04-01

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

  15. Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System.

    Science.gov (United States)

    Uesaka, Toshihiro; Nagashimada, Mayumi; Enomoto, Hideki

    2015-07-08

    Elucidation of the cellular identity of neuronal precursors provides mechanistic insights into the development and pathophysiology of the nervous system. In the enteric nervous system (ENS), neurogenesis persists from midgestation to the postnatal period. Cellular mechanism underlying the long-term neurogenesis in the ENS has remained unclear. Using genetic fate mapping in mice, we show here that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate in the postnatal period and contributes to the ENS. We found SCP-derived neurogenesis in the submucosal region of the small intestine in the absence of vagal neural crest-derived ENS precursors. Under physiological conditions, SCPs comprised up to 20% of enteric neurons in the large intestine and gave rise mainly to restricted neuronal subtypes, calretinin-expressing neurons. Genetic ablation of Ret, the signaling receptor for glial cell line-derived neurotrophic factor, in SCPs caused colonic oligoganglionosis, indicating that SCP-derived neurogenesis is essential to ENS integrity. Identification of Schwann cells as a physiological neurogenic source provides novel insight into the development and disorders of neural crest-derived tissues. Elucidating the cellular identity of neuronal precursors provides novel insights into development and function of the nervous system. The enteric nervous system (ENS) is innervated richly by extrinsic nerve fibers, but little is known about the significance of extrinsic innervation to the structural integrity of the ENS. This report reveals that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate and differentiates into specific neuronal subtypes. SCP-specific ablation of the Ret gene leads to colonic oligoganglionosis, demonstrating a crucial role of SCP-derived neurogenesis in ENS development. Cross-lineage differentiation capacity in SCPs suggests

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

    Indian Academy of Sciences (India)

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

  17. Neural correlates of verb argument structure processing.

    Science.gov (United States)

    Thompson, Cynthia K; Bonakdarpour, Borna; Fix, Stephen C; Blumenfeld, Henrike K; Parrish, Todd B; Gitelman, Darren R; Mesulam, M-Marsel

    2007-11-01

    Neuroimaging and lesion studies suggest that processing of word classes, such as verbs and nouns, is associated with distinct neural mechanisms. Such studies also suggest that subcategories within these broad word class categories are differentially processed in the brain. Within the class of verbs, argument structure provides one linguistic dimension that distinguishes among verb exemplars, with some requiring more complex argument structure entries than others. This study examined the neural instantiation of verbs by argument structure complexity: one-, two-, and three-argument verbs. Stimuli of each type, along with nouns and pseudowords, were presented for lexical decision using an event-related functional magnetic resonance imaging design. Results for 14 young normal participants indicated largely overlapping activation maps for verbs and nouns, with no areas of significant activation for verbs compared to nouns, or vice versa. Pseudowords also engaged neural tissue overlapping with that for both word classes, with more widespread activation noted in visual, motor, and peri-sylvian regions. Examination of verbs by argument structure revealed activation of the supramarginal and angular gyri, limited to the left hemisphere only when verbs with two obligatory arguments were compared to verbs with a single argument. However, bilateral activation was noted when both two- and three-argument verbs were compared to one-argument verbs. These findings suggest that posterior peri-sylvian regions are engaged for processing argument structure information associated with verbs, with increasing neural tissue in the inferior parietal region associated with increasing argument structure complexity. These findings are consistent with processing accounts, which suggest that these regions are crucial for semantic integration.

  18. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

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

  19. Deconvolution using a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, S.K.

    1990-11-15

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

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

    Science.gov (United States)

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

    2017-02-01

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

  1. Neural Network Ensembles

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Salamon, Peter

    1990-01-01

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

  2. Neural systems for control

    National Research Council Canada - National Science Library

    Omidvar, Omid; Elliott, David L

    1997-01-01

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

  3. Neural Tube Defects

    Science.gov (United States)

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

  4. Digital tissue and what it may reveal about the brain.

    Science.gov (United States)

    Morgan, Josh L; Lichtman, Jeff W

    2017-10-30

    Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

  5. Neural Tissue And Complete Regeneration Of The Tail Of The ...

    African Journals Online (AJOL)

    Tails of three groups of the Gekkonid lizard, Hemidactylus flavivirdis, were amputated (group I) orautotomized (groups II and III). The animals were exposed to 12 hours of ight and 12 hours of darkness. Ingroup I experiment, previously regenerated tails were amputated (repeated autotomyRA) with a pair of sharp scissors, ...

  6. Neural Control of Hemorrhage-Induced Tissue Cytokine Production

    National Research Council Canada - National Science Library

    Molina, Patrica E

    2007-01-01

    ... to cardiovascular responsiveness. Our studies demonstrated that the intact neuroendocrine response is critical to ensure survival and host defense mechanisms from secondary infectious challenges...

  7. Polypyrrole-Coated Electrospun PLGA Nanofibers for Neural Tissue Applications

    OpenAIRE

    Lee, Jae Young; Bashur, Chris A.; Goldstein, Aaron S.; Christine E Schmidt

    2009-01-01

    Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive mesh...

  8. Engineering reaction-diffusion networks with properties of neural tissue.

    Science.gov (United States)

    Litschel, Thomas; Norton, Michael M; Tserunyan, Vardges; Fraden, Seth

    2018-01-03

    We present an experimental system of networks of coupled non-linear chemical reactors, which we theoretically model within a reaction-diffusion framework. The networks consist of patterned arrays of diffusively coupled nanoliter-scale reactors containing the Belousov-Zhabotinsky (BZ) reaction. Microfluidic fabrication techniques are developed that provide the ability to vary the network topology and the reactor coupling strength and offer the freedom to choose whether an arbitrary reactor is inhibitory or excitatory coupled to its neighbor. This versatile experimental and theoretical framework can be used to create a wide variety of chemical networks. Here we design, construct and characterize chemical networks that achieve the complexity of central pattern generators (CPGs), which are found in the autonomic nervous system of a variety of organisms.

  9. Proliferation and recapitulation of developmental patterning associated with regulative regeneration of the spinal cord neural tube.

    Science.gov (United States)

    Halasi, Gabor; Søviknes, Anne Mette; Sigurjonsson, Olafur; Glover, Joel C

    2012-05-01

    Developmental patterning during regulative regeneration of the chicken embryo spinal neural tube was characterized by assessing proliferation and the expression of transcription factors specific to neural progenitor and postmitotic neuron populations. One to several segments of the thoracolumbar neural tube were selectively excised unilaterally to initiate regeneration. The capacity for regeneration depended on the stage when ablation was performed and the extent of tissue removed. 20% of surviving embryos exhibited complete regulative regeneration, wherein the missing hemi-neural tube was reconstituted to normal size and morphology. Fate-mapping of proliferative adjacent tissue indicated contributions from the opposite side of the neural tube and potentially from the ipsilateral neural tube rostral and caudal to the lesion. Application of the thymidine analog EdU (5-ethynyl-2'-deoxyuridine) demonstrated a moderate increase in cell proliferation in lesioned relative to control embryos, and quantitative PCR demonstrated a parallel moderate increase in transcription of proliferation-related genes. Mathematical calculation showed that such modest increases are sufficient to account for the amount of regenerated tissue. Within the regenerated neural tube the expression pattern of progenitor-specific transcription factors was recapitulated in the separate advancing ventral and dorsal fronts of regeneration, with no evidence of abnormal mixing of progenitor subpopulations, indicating that graded patterning mechanisms do not require continuity of neural tube tissue along the dorsoventral axis and do not involve a sorting out of committed progenitors. Upon completion of the regeneration process, the pattern of neuron-specific transcription factor expression was essentially normal. Modest deficits in the numbers of transcription factor-defined neuron types were evident in the regenerated tissue, increasing particularly in dorsal neuron types with later lesions. These

  10. Piezoelectric materials for tissue regeneration: A review.

    Science.gov (United States)

    Rajabi, Amir Hossein; Jaffe, Michael; Arinzeh, Treena Livingston

    2015-09-01

    The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues raised the question whether or not electric fields play an important role in cell function. It has kindled research and the development of technologies in emulating biological electricity for tissue regeneration. Promising effects of electrical stimulation on cell growth and differentiation and tissue growth has led to interest in using piezoelectric scaffolds for tissue repair. Piezoelectric materials can generate electrical activity when deformed. Hence, an external source to apply electrical stimulation or implantation of electrodes is not needed. Various piezoelectric materials have been employed for different tissue repair applications, particularly in bone repair, where charges induced by mechanical stress can enhance bone formation; and in neural tissue engineering, in which electric pulses can stimulate neurite directional outgrowth to fill gaps in nervous tissue injuries. In this review, a summary of piezoelectricity in different biological tissues, mechanisms through which electrical stimulation may affect cellular response, and recent advances in the fabrication and application of piezoelectric scaffolds will be discussed. The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues has kindled research and the development of technologies using electrical stimulation for tissue regeneration. Piezoelectric materials generate electrical activity in response to deformations and allow for the delivery of an electrical stimulus without the need for an external power source. As a scaffold for tissue engineering, growing interest exists due to its potential of providing electrical stimulation to cells to promote tissue formation. In this review, we cover the discovery of piezoelectricity in biological tissues, its connection to streaming potentials, biological response to electrical stimulation and

  11. Dynamic behaviors of the non-neural ectoderm during mammalian cranial neural tube closure.

    Science.gov (United States)

    Ray, Heather J; Niswander, Lee A

    2016-08-15

    The embryonic brain and spinal cord initially form through the process of neural tube closure (NTC). NTC is thought to be highly similar between rodents and humans, and studies of mouse genetic mutants have greatly increased our understanding of the molecular basis of NTC with relevance for human neural tube defects. In addition, studies using amphibian and chick embryos have shed light into the cellular and tissue dynamics underlying NTC. However, the dynamics of mammalian NTC has been difficult to study due to in utero development until recently when advances in mouse embryo ex vivo culture techniques along with confocal microscopy have allowed for imaging of mouse NTC in real time. Here, we have performed live imaging of mouse embryos with a particular focus on the non-neural ectoderm (NNE). Previous studies in multiple model systems have found that the NNE is important for proper NTC, but little is known about the behavior of these cells during mammalian NTC. Here we utilized a NNE-specific genetic labeling system to assess NNE dynamics during murine NTC and identified different NNE cell behaviors as the cranial region undergoes NTC. These results bring valuable new insight into regional differences in cellular behavior during NTC that may be driven by different molecular regulators and which may underlie the various positional disruptions of NTC observed in humans with neural tube defects. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

    2009-01-01

    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

  13. Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Kazuo, E-mail: knoda@kuhp.kyoto-u.ac.jp [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Nakamura, Tomoyuki [Department of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010 (Japan); Komatsu, Yoshihiro [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Graduate Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States)

    2015-10-23

    Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

  14. Neural network technologies

    Science.gov (United States)

    Villarreal, James A.

    1991-01-01

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

  15. Analysis of neural data

    CERN Document Server

    Kass, Robert E; Brown, Emery N

    2014-01-01

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

  16. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

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

  17. Research Update: Platinum-elastomer mesocomposite as neural electrode coating

    Directory of Open Access Journals (Sweden)

    Ivan R. Minev

    2015-01-01

    Full Text Available Platinum is electrochemically stable and biocompatible, and remains the preferred material for the fabrication of implantable neural electrodes. In a foil or film format, platinum is mechanically stiff compared to interfaced biological tissue. We report a soft, highly stable platinum-elastomer composite that offers both mechanical compliance and the electrochemical properties of platinum. We demonstrate the high-performance of the novel mesocomposite printed on stretchable microelectrodes both in vitro and in vivo. The platinum-elastomer composite is a new promising coating for chronic neural interfaces.

  18. Neural networks for triggering

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  19. Artificial neural network modelling

    CERN Document Server

    Samarasinghe, Sandhya

    2016-01-01

    This book covers theoretical aspects as well as recent innovative applications of Artificial Neural networks (ANNs) in natural, environmental, biological, social, industrial and automated systems. It presents recent results of ANNs in modelling small, large and complex systems under three categories, namely, 1) Networks, Structure Optimisation, Robustness and Stochasticity 2) Advances in Modelling Biological and Environmental Systems and 3) Advances in Modelling Social and Economic Systems. The book aims at serving undergraduates, postgraduates and researchers in ANN computational modelling. .

  20. 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.

  1. The Neural Noisy Channel

    OpenAIRE

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

    2016-01-01

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

  2. FGF-mediated induction of ciliary body tissue in the chick eye

    OpenAIRE

    Dias da Silva, Magnus R.; Tiffin, Nicola; Mima, Tatsuo; Mikawa, Takashi; Hyer, Jeanette

    2007-01-01

    Upon morphogenesis, the simple neuroepithelium of the optic vesicle gives rise to four basic tissues in the vertebrate optic cup: pigmented epithelium, sensory neural retina, secretory ciliary body and muscular iris. Pigmented epithelium and neural retina are established through interactions with specific environments and signals: periocular mesenchyme/BMP specifies pigmented epithelium and surface ectoderm/FGF specifies neural retina. The anterior portions (iris and ciliary body) are specifi...

  3. Neural Based Orthogonal Data Fitting The EXIN Neural Networks

    CERN Document Server

    Cirrincione, Giansalvo

    2008-01-01

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

  4. hmmr mediates anterior neural tube closure and morphogenesis in the frog Xenopus.

    Science.gov (United States)

    Prager, Angela; Hagenlocher, Cathrin; Ott, Tim; Schambony, Alexandra; Feistel, Kerstin

    2017-10-01

    Development of the central nervous system requires orchestration of morphogenetic processes which drive elevation and apposition of the neural folds and their fusion into a neural tube. The newly formed tube gives rise to the brain in anterior regions and continues to develop into the spinal cord posteriorly. Conspicuous differences between the anterior and posterior neural tube become visible already during neural tube closure (NTC). Planar cell polarity (PCP)-mediated convergent extension (CE) movements are restricted to the posterior neural plate, i.e. hindbrain and spinal cord, where they propagate neural fold apposition. The lack of CE in the anterior neural plate correlates with a much slower mode of neural fold apposition anteriorly. The morphogenetic processes driving anterior NTC have not been addressed in detail. Here, we report a novel role for the breast cancer susceptibility gene and microtubule (MT) binding protein Hmmr (Hyaluronan-mediated motility receptor, RHAMM) in anterior neurulation and forebrain development in Xenopus laevis. Loss of hmmr function resulted in a lack of telencephalic hemisphere separation, arising from defective roof plate formation, which in turn was caused by impaired neural tissue narrowing. hmmr regulated polarization of neural cells, a function which was dependent on the MT binding domains. hmmr cooperated with the core PCP component vangl2 in regulating cell polarity and neural morphogenesis. Disrupted cell polarization and elongation in hmmr and vangl2 morphants prevented radial intercalation (RI), a cell behavior essential for neural morphogenesis. Our results pinpoint a novel role of hmmr in anterior neural development and support the notion that RI is a major driving force for anterior neurulation and forebrain morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Neural Correlates of Stimulus Reportability

    OpenAIRE

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

    2009-01-01

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

  6. Symbolic processing in neural networks

    OpenAIRE

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

    2003-01-01

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

  7. [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.

  8. Neural Correlates of Face Detection

    National Research Council Canada - National Science Library

    Xu, Xiaokun; Biederman, Irving

    2014-01-01

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

  9. Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

    Science.gov (United States)

    Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

  10. Graphene-based materials for tissue engineering.

    Science.gov (United States)

    Shin, Su Ryon; Li, Yi-Chen; Jang, Hae Lin; Khoshakhlagh, Parastoo; Akbari, Mohsen; Nasajpour, Amir; Zhang, Yu Shrike; Tamayol, Ali; Khademhosseini, Ali

    2016-10-01

    Graphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two-dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering. In this review, we will highlight the recent applications of graphene-based materials in tissue engineering and regenerative medicine. In particular, we will discuss the application of graphene-based materials in cardiac, neural, bone, cartilage, skeletal muscle, and skin/adipose tissue engineering. We will also discuss the potential risk factors of graphene-based materials in tissue engineering. In conclusion, we will outline the opportunities in the usage of graphene-based materials for clinical applications. Published by Elsevier B.V.

  11. SU-8-based microneedles for in vitro neural applications

    Science.gov (United States)

    Altuna, Ane; Gabriel, Gemma; Menéndez de la Prida, Liset; Tijero, María; Guimerá, Anton; Berganzo, Javier; Salido, Rafa; Villa, Rosa; Fernández, Luis J.

    2010-06-01

    This paper presents novel design, fabrication, packaging and the first in vitro neural activity recordings of SU-8-based microneedles. The polymer SU-8 was chosen because it provides excellent features for the fabrication of flexible and thin probes. A microprobe was designed in order to allow a clean insertion and to minimize the damage caused to neural tissue during in vitro applications. In addition, a tetrode is patterned at the tip of the needle to obtain fine-scale measurements of small neuronal populations within a radius of 100 µm. Impedance characterization of the electrodes has been carried out to demonstrate their viability for neural recording. Finally, probes are inserted into 400 µm thick hippocampal slices, and simultaneous action potentials with peak-to-peak amplitudes of 200-250 µV are detected.

  12. 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

  13. Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmenko, Volodymyr [Wallenberg Wood Science Center, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Department of Microtechnology and Nanoscience, Chalmers University of Technology, Kemivägen 9, SE-412 96 Gothenburg (Sweden); Kalogeropoulos, Theodoros [Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Thunberg, Johannes [Wallenberg Wood Science Center, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Johannesson, Sara; Hägg, Daniel [Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Enoksson, Peter [Wallenberg Wood Science Center, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Department of Microtechnology and Nanoscience, Chalmers University of Technology, Kemivägen 9, SE-412 96 Gothenburg (Sweden); Gatenholm, Paul, E-mail: paul.gatenholm@chalmers.se [Wallenberg Wood Science Center, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden); Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Kemivägen 4, SE-412 96 Gothenburg (Sweden)

    2016-01-01

    The problem of recovery from neurodegeneration needs new effective solutions. Tissue engineering is viewed as a prospective approach for solving this problem since it can help to develop healthy neural tissue using supportive scaffolds. This study presents effective and sustainable tissue engineering methods for creating biomaterials from cellulose that can be used either as scaffolds for the growth of neural tissue in vitro or as drug screening models. To reach this goal, nanofibrous electrospun cellulose mats were made conductive via two different procedures: carbonization and addition of multi-walled carbon nanotubes. The resulting scaffolds were much more conductive than untreated cellulose material and were used to support growth and differentiation of SH-SY5Y neuroblastoma cells. The cells were evaluated by scanning electron microscopy and confocal microscopy methods over a period of 15 days at different time points. The results showed that the cellulose-derived conductive scaffolds can provide support for good cell attachment, growth and differentiation. The formation of a neural network occurred within 10 days of differentiation, which is a promising length of time for SH-SY5Y neuroblastoma cells. - Highlights: • The conductive scaffolds for neural tissue engineering are derived from cellulose. • The scaffolds are used to support growth and differentiation of SH-SY5Y cells. • Distinctive cell differentiation occurs within 10 days on conductive scaffolds. • Electrical conductivity and nanotopography improve neural network formation.

  14. Tumor diagnosis using the backpropagation neural network method

    Science.gov (United States)

    Ma, Lixing; Sukuta, Sydney; Bruch, Reinhard F.; Afanasyeva, Natalia I.; Looney, Carl G.

    1998-04-01

    For characterization of skin cancer, an artificial neural network method has been developed to diagnose normal tissue, benign tumor and melanoma. The pattern recognition is based on a three-layer neural network fuzzy learning system. In this study, the input neuron data set is the Fourier transform IR spectrum obtained by a new fiberoptic evanescent wave Fourier transform IR spectroscopy method in the range of 1480 to 1850 cm-1. Ten input features are extracted from the absorbency values in this region. A single hidden layer of neural nodes with sigmoids activation functions clusters the feature space into small subclasses and the output nodes are separated in different nonconvex classes to permit nonlinear discrimination of disease states. The output is classified as three classes: normal tissue, benign tumor and melanoma. The results obtained from the neural network pattern recognition are shown to be consistent with traditional medical diagnosis. Input features have also been extracted from the absorbency spectra using chemical factor analysis. These abstract features or factors are also used in the classification.

  15. Nano-topography Enhances Communication in Neural Cells Networks

    KAUST Repository

    Onesto, V.

    2017-08-23

    Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can direct nerve cells assembly into computational efficient networks may provide new tools and criteria for tissue engineering and regenerative medicine. In this work, we used information theory approaches and functional multi calcium imaging (fMCI) techniques to examine how information flows in neural networks cultured on surfaces with controlled topography. We found that substrate roughness Sa affects networks topology. In the low nano-meter range, S-a = 0-30 nm, information increases with Sa. Moreover, we found that energy density of a network of cells correlates to the topology of that network. This reinforces the view that information, energy and surface nano-topography are tightly inter-connected and should not be neglected when studying cell-cell interaction in neural tissue repair and regeneration.

  16. Neural substrate expansion for the restoration of brain function

    Directory of Open Access Journals (Sweden)

    Han-Chiao Isaac Chen

    2016-01-01

    Full Text Available Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks.

  17. 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...

  18. The Ap3b1 gene regulates the ocular melanosome biogenesis and tyrosinase distribution differently from the Hps1 gene.

    Science.gov (United States)

    Jing, Renwei; Dong, Xuan; Li, Kailin; Yan, Jie; Chen, Xiangyuan; Feng, Lijun

    2014-11-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. The pearl (pe) mouse, a mouse model for the human HPS-2, bears a mutation in Ap3b1 gene. Here we investigated the pigmentation in eyes of pearl (pe) mice, and compared it with our previously published data in pale ear (ep) mice. We revealed that the hypopigmentation in eyes of pearl mice was more severe than pale ear mice, especially in the neural crest-derived tissues. However, the total tyrosinase activity in eyes of pearl mice was stronger than pale ear mice, suggesting that the degradation of aberrantly transported tyrosinase in eyes of pearl mice was weaker than that of pale ear mice. Furthermore, the pigmentation in eyes of mice doubly heterozygous for Hps1 and Ap3b1 genes was similar to the wild-type, while the hypopigmentation in iris of double mutant mice was more severe than either single mutant. Besides, we found several previously reported characters in pale ear mice, including macromelanosomes in the neural crest-derived melanocytes and increased accumulation of lipofuscin in the RPE, were absent in pearl mice. Our study indicates that Ap3b1 gene play distinct roles in melanin production and tyrosinase distribution compared with Hps1 gene. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Artificial Neural Networks·

    Indian Academy of Sciences (India)

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

  20. Neural Networks for Optimal Control

    DEFF Research Database (Denmark)

    Sørensen, O.

    1995-01-01

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

  1. The Neural Support Vector Machine

    NARCIS (Netherlands)

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

    2013-01-01

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

  2. Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

    Science.gov (United States)

    Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

    1988-11-01

    Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

  3. Neural-network-based fuzzy logic decision systems

    Science.gov (United States)

    Kulkarni, Arun D.; Giridhar, G. B.; Coca, Praveen

    1994-10-01

    During the last few years there has been a large and energetic upswing in research efforts aimed at synthesizing fuzzy logic with neural networks. This combination of neural networks and fuzzy logic seems natural because the two approaches generally attack the design of `intelligent' system from quite different angles. Neural networks provide algorithms for learning, classification, and optimization whereas fuzzy logic often deals with issues such as reasoning in a high (semantic or linguistic) level. Consequently the two technologies complement each other. In this paper, we combine neural networks with fuzzy logic techniques. We propose an artificial neural network (ANN) model for a fuzzy logic decision system. The model consists of six layers. The first three layers map the input variables to fuzzy set membership functions. The last three layers implement the decision rules. The model learns the decision rules using a supervised gradient descent procedure. As an illustration we considered two examples. The first example deals with pixel classification in multispectral satellite images. In our second example we used the fuzzy decision system to analyze data from magnetic resonance imaging (MRI) scans for tissue classification.

  4. In vivo neural stem cell imaging: current modalities and future directions.

    Science.gov (United States)

    Gera, Atul; Steinberg, Gary K; Guzman, Raphael

    2010-01-01

    Neural stem cells have been proposed as a promising therapy for treating a wide variety of neuropathologies. While several studies have demonstrated the therapeutic benefits of neural stem cells, the exact mechanism remains elusive. In order to facilitate research efforts to understand these mechanisms, and before neural stem cell-based therapies can be utilized in a clinical context, we must develop means of monitoring these cells in vivo. However, because of tissue depth and the blood-brain barrier, in vivo imaging of neural stem cells in the brain has unique challenges that do not apply to stem cells for other purposes. In this paper, we review contemporary methods for in vivo neural stem cell imaging, including MRI, PET and optical imaging techniques.

  5. Neural fields theory and applications

    CERN Document Server

    Graben, Peter; Potthast, Roland; Wright, James

    2014-01-01

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

  6. 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

  7. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

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

  8. Nanobiomaterials for neural regeneration

    Directory of Open Access Journals (Sweden)

    Nuan Chen

    2016-01-01

    Full Text Available Diseases and disorders associated with nervous system such as injuries by trauma and neurodegeneration are shown to be one of the most serious problems in medicine, requiring innovative strategies to trigger and enhance the nerve regeneration. Tissue engineering aims to provide a highly biomimetic environment by using a combination of cells, materials and suitable biological cues, by which the lost body part may be regenerated or even fully rebuilt. Electrospinning, being able to produce extracellular matrix (ECM-like nanostructures with great flexibility in design and choice of materials, have demonstrated their great potential for fabrication of nerve tissue engineered scaffolds. The review here begins with a brief description of the anatomy of native nervous system, which provides basic knowledge and ideas for the design of nerve tissue scaffolds, followed by five main parts in the design of electrospun nerve tissue engineered scaffolds including materials selection, structural design, in vitro bioreactor, functionalization and cellular support. Performances of biomimetic electrospun nanofibrous nerve implant devices are also reviewed. Finally, future directions for advanced electrospun nerve tissue engineered scaffolds are discussed.

  9. Wireless channel characterization for mm-size neural implants.

    Science.gov (United States)

    Mark, Michael; Bjorninen, Toni; Chen, Yuhui David; Venkatraman, Subramaniam; Ukkonen, Leena; Sydanheimo, Lauri; Carmena, Jose M; Rabaey, Jan M

    2010-01-01

    This paper discusses an approach to modeling and characterizing wireless channel properties for mm-size neural implants. Full-wave electromagnetic simulation was employed to model signal propagation characteristics in biological materials. Animal tests were carried out, proving the validity of the simulation model over a wide range of frequency from 100MHz to 6GHz. Finally, effects of variability and uncertainty in human anatomy and dielectric properties of tissues on these radio links are explored.

  10. Stem Cells and Tissue Engineering

    CERN Document Server

    Pavlovic, Mirjana

    2013-01-01

    Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more...

  11. Time to address the problems at the neural interface

    Science.gov (United States)

    Durand, Dominique M.; Ghovanloo, Maysam; Krames, Elliot

    2014-04-01

    Neural engineers have made significant, if not remarkable, progress in interfacing with the nervous system in the last ten years. In particular, neuromodulation of the brain has generated significant therapeutic benefits [1-5]. EEG electrodes can be used to communicate with patients with locked-in syndrome [6]. In the central nervous system (CNS), electrode arrays placed directly over or within the cortex can record neural signals related to the intent of the subject or patient [7, 8]. A similar technology has allowed paralyzed patients to control an otherwise normal skeletal system with brain signals [9, 10]. This technology has significant potential to restore function in these and other patients with neural disorders such as stroke [11]. Although there are several multichannel arrays described in the literature, the workhorse for these cortical interfaces has been the Utah array [12]. This 100-channel electrode array has been used in most studies on animals and humans since the 1990s and is commercially available. This array and other similar microelectrode arrays can record neural signals with high quality (high signal-to-noise ratio), but these signals fade and disappear after a few months and therefore the current technology is not reliable for extended periods of time. Therefore, despite these major advances in communicating with the brain, clinical translation cannot be implemented. The reasons for this failure are not known but clearly involve the interface between the electrode and the neural tissue. The Defense Advanced Research Project Agency (DARPA) as well as other federal funding agencies such as the National Science Foundation (NSF) and the National Institutes of Health have provided significant financial support to investigate this problem without much success. A recent funding program from DARPA was designed to establish the failure modes in order to generate a reliable neural interface technology and again was unsuccessful at producing a robust

  12. CNS immunological modulation of neural graft rejection and survival.

    Science.gov (United States)

    Borlongan, C V; Stahl, C E; Cameron, D F; Saporta, S; Freeman, T B; Cahill, D W; Sanberg, P R

    1996-08-01

    Neural transplantation therapy as a possible alternative treatment for neurological movement disorders, such as in Parkinson's disease (PD), has accentuated research interest on the immune status of the central nervous system (CNS). Most animal studies concerned with neural transplantation for the treatment of PD have utilized dopamine (DA) neurons from tissues of the embryonic ventral mesencephalon. Rat embryonic DA neurons, grafted either as solid blocks or dissociated into a cell suspension and stereotaxically injected intraparenchymally into a rat lesion model of PD, have been shown to survive and form connections with the host brain, and ameliorate the behavioral deficits of PD. Similarly, studies on nonhuman primate models of PD provide considerable support for neural transplantation of DA neurons as an experimental clinical procedure for the treatment of PD. To this end, experimental clinical trials have been centered upon transplantation of the embryonic ventral mesencephalic cells for PD patients. Although not conclusive, the findings from clinical studies have provided some evidence that most patients with marked increases in fluorodopa uptake (indicating graft survival) have been immunosuppressed. Furthermore, immune reactions have been observed in rats xenografted with human embryonic tissue. Of note, embryonic ventral mesencephalic tissues compared to adult tissues produce better morphological and long-lasting behavioral amelioration of the neurobehavioral deficits of PD, thus advocating the use of grafts from young donors (embryo) to circumvent the CNS immune rejection. The possible graft rejection due to CNS immune reactions, coupled with the social and ethical problems surrounding the use of embryonic neural tissue, and the logistical problems concerning tissue availability have prompted the development of alternative sources of DA-secreting cells. To circumvent these obstacles, several methods have been suggested including the use of

  13. Gelatin methacrylamide hydrogel with graphene nanoplatelets for neural cell-laden 3D bioprinting.

    Science.gov (United States)

    Wei Zhu; Harris, Brent T; Zhang, Lijie Grace

    2016-08-01

    Nervous system is extremely complex which leads to rare regrowth of nerves once injury or disease occurs. Advanced 3D bioprinting strategy, which could simultaneously deposit biocompatible materials, cells and supporting components in a layer-by-layer manner, may be a promising solution to address neural damages. Here we presented a printable nano-bioink composed of gelatin methacrylamide (GelMA), neural stem cells, and bioactive graphene nanoplatelets to target nerve tissue regeneration in the assist of stereolithography based 3D bioprinting technique. We found the resultant GelMA hydrogel has a higher compressive modulus with an increase of GelMA concentration. The porous GelMA hydrogel can provide a biocompatible microenvironment for the survival and growth of neural stem cells. The cells encapsulated in the hydrogel presented good cell viability at the low GelMA concentration. Printed neural construct exhibited well-defined architecture and homogenous cell distribution. In addition, neural stem cells showed neuron differentiation and neurites elongation within the printed construct after two weeks of culture. These findings indicate the 3D bioprinted neural construct has great potential for neural tissue regeneration.

  14. An Optoelectronic Neural Network

    Science.gov (United States)

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

    1990-02-01

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

  15. Neural Darwinism and consciousness.

    Science.gov (United States)

    Seth, Anil K; Baars, Bernard J

    2005-03-01

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

  16. Cortical neural prosthetics.

    Science.gov (United States)

    Schwartz, Andrew B

    2004-01-01

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

  17. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  18. Development and Evaluation of Micro-Electrocorticography Arrays for Neural Interfacing Applications

    Science.gov (United States)

    Schendel, Amelia Ann

    Neural interfaces have great promise for both electrophysiological research and therapeutic applications. Whether for the study of neural circuitry or for neural prosthetic or other therapeutic applications, micro-electrocorticography (micro-ECoG) arrays have proven extremely useful as neural interfacing devices. These devices strike a balance between invasiveness and signal resolution, an important step towards eventual human application. The objective of this research was to make design improvements to micro-ECoG devices to enhance both biocompatibility and device functionality. To best evaluate the effectiveness of these improvements, a cranial window imaging method for in vivo monitoring of the longitudinal tissue response post device implant was developed. Employment of this method provided valuable insight into the way tissue grows around micro-ECoG arrays after epidural implantation, spurring a study of the effects of substrate geometry on the meningeal tissue response. The results of the substrate footprint comparison suggest that a more open substrate geometry provides an easy path for the tissue to grow around to the top side of the device, whereas a solid device substrate encourages the tissue to thicken beneath the device, between the electrode sites and the brain. The formation of thick scar tissue between the recording electrode sites and the neural tissue is disadvantageous for long-term recorded signal quality, and thus future micro-ECoG device designs should incorporate open-architecture substrates for enhanced longitudinal in vivo function. In addition to investigating improvements for long-term device reliability, it was also desired to enhance the functionality of micro-ECoG devices for neural electrophysiology research applications. To achieve this goal, a completely transparent graphene-based device was fabricated for use with the cranial window imaging method and optogenetic techniques. The use of graphene as the conductive material provided

  19. Breast tissue segmentation from x-ray radiographs

    NARCIS (Netherlands)

    Chen, C.; Nielsen, M.; Karssemeijer, N.; Brandt, S.S.

    2014-01-01

    In this paper, we propose a robust and accurate method that segments mammograms to three distinct regions: breast tissue, pectoral muscle and background. Our approach is built around a neural, two-layer committee machine. On the first layer, individual experts, each formed by a feature vector and a

  20. Making headway: the roles of Hox genes and neural crest cells in craniofacial development.

    Science.gov (United States)

    Trainor, Paul A

    2003-04-14

    Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

  1. Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord

    Directory of Open Access Journals (Sweden)

    Min-fei Wu

    2015-01-01

    Full Text Available The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco′s modified Eagle′s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem

  2. Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord.

    Science.gov (United States)

    Wu, Min-Fei; Zhang, Shu-Quan; Gu, Rui; Liu, Jia-Bei; Li, Ye; Zhu, Qing-San

    2015-09-01

    The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco's modified Eagle's medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the

  3. Cooperating attackers in neural cryptography.

    Science.gov (United States)

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

    2004-06-01

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

  4. Cooperating attackers in neural cryptography

    Science.gov (United States)

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

    2004-06-01

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

  5. 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.

  6. Review: the role of neural crest cells in the endocrine system.

    Science.gov (United States)

    Adams, Meghan Sara; Bronner-Fraser, Marianne

    2009-01-01

    The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

  7. Photosensitive-polyimide based method for fabricating various neural electrode architectures

    Science.gov (United States)

    Kato, Yasuhiro X.; Furukawa, Shigeto; Samejima, Kazuyuki; Hironaka, Naoyuki; Kashino, Makio

    2012-01-01

    An extensive photosensitive-polyimide (PSPI)-based method for designing and fabricating various neural electrode architectures was developed. The method aims to broaden the design flexibility and expand the fabrication capability for neural electrodes to improve the quality of recorded signals and integrate other functions. After characterizing PSPI's properties for micromachining processes, we successfully designed and fabricated various neural electrodes even on a non-flat substrate using only one PSPI as an insulation material and without the time-consuming dry etching processes. The fabricated neural electrodes were an electrocorticogram (ECoG) electrode, a mesh intracortical electrode with a unique lattice-like mesh structure to fixate neural tissue, and a guide cannula electrode with recording microelectrodes placed on the curved surface of a guide cannula as a microdialysis probe. In vivo neural recordings using anesthetized rats demonstrated that these electrodes can be used to record neural activities repeatedly without any breakage and mechanical failures, which potentially promises stable recordings for long periods of time. These successes make us believe that this PSPI-based fabrication is a powerful method, permitting flexible design, and easy optimization of electrode architectures for a variety of electrophysiological experimental research with improved neural recording performance. PMID:22719725

  8. An electromechanical based deformable model for soft tissue simulation.

    Science.gov (United States)

    Zhong, Yongmin; Shirinzadeh, Bijan; Smith, Julian; Gu, Chengfan

    2009-11-01

    Soft tissue deformation is of great importance to surgery simulation. Although a significant amount of research efforts have been dedicated to simulating the behaviours of soft tissues, modelling of soft tissue deformation is still a challenging problem. This paper presents a new deformable model for simulation of soft tissue deformation from the electromechanical viewpoint of soft tissues. Soft tissue deformation is formulated as a reaction-diffusion process coupled with a mechanical load. The mechanical load applied to a soft tissue to cause a deformation is incorporated into the reaction-diffusion system, and consequently distributed among mass points of the soft tissue. Reaction-diffusion of mechanical load and non-rigid mechanics of motion are combined to govern the simulation dynamics of soft tissue deformation. An improved reaction-diffusion model is developed to describe the distribution of the mechanical load in soft tissues. A three-layer artificial cellular neural network is constructed to solve the reaction-diffusion model for real-time simulation of soft tissue deformation. A gradient based method is established to derive internal forces from the distribution of the mechanical load. Integration with a haptic device has also been achieved to simulate soft tissue deformation with haptic feedback. The proposed methodology does not only predict the typical behaviours of living tissues, but it also accepts both local and large-range deformations. It also accommodates isotropic, anisotropic and inhomogeneous deformations by simple modification of diffusion coefficients.

  9. 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.

  10. Epidemiology of neural tube defects

    National Research Council Canada - National Science Library

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

    2014-01-01

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

  11. 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...

  12. Memristor-based neural networks

    Science.gov (United States)

    Thomas, Andy

    2013-03-01

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

  13. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

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

  14. Neural components of altruistic punishment

    Directory of Open Access Journals (Sweden)

    Emily eDu

    2015-02-01

    Full Text Available Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  15. Complex-Valued Neural Networks

    CERN Document Server

    Hirose, Akira

    2012-01-01

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

  16. Neural components of altruistic punishment.

    Science.gov (United States)

    Du, Emily; Chang, Steve W C

    2015-01-01

    Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  17. Pansharpening by Convolutional Neural Networks

    National Research Council Canada - National Science Library

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

    2016-01-01

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

  18. What are artificial neural networks?

    DEFF Research Database (Denmark)

    Krogh, Anders

    2008-01-01

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

  19. 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 ...

  20. Biologically Inspired Modular Neural Networks

    OpenAIRE

    Azam, Farooq

    2000-01-01

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

  1. Neural crest does not contribute to the neck and shoulder in the axolotl (Ambystoma mexicanum.

    Directory of Open Access Journals (Sweden)

    Hans-Henning Epperlein

    Full Text Available BACKGROUND: A major step during the evolution of tetrapods was their transition from water to land. This process involved the reduction or complete loss of the dermal bones that made up connections to the skull and a concomitant enlargement of the endochondral shoulder girdle. In the mouse the latter is derived from three separate embryonic sources: lateral plate mesoderm, somites, and neural crest. The neural crest was suggested to sustain the muscle attachments. How this complex composition of the endochondral shoulder girdle arose during evolution and whether it is shared by all tetrapods is unknown. Salamanders that lack dermal bone within their shoulder girdle were of special interest for a possible contribution of the neural crest to the endochondral elements and muscle attachment sites, and we therefore studied them in this context. RESULTS: We grafted neural crest from GFP+ fluorescent transgenic axolotl (Ambystoma mexicanum donor embryos into white (d/d axolotl hosts and followed the presence of neural crest cells within the cartilage of the shoulder girdle and the connective tissue of muscle attachment sites of the neck-shoulder region. Strikingly, neural crest cells did not contribute to any part of the endochondral shoulder girdle or to the connective tissue at muscle attachment sites in axolotl. CONCLUSIONS: Our results in axolotl suggest that neural crest does not serve a general function in vertebrate shoulder muscle attachment sites as predicted by the "muscle scaffold theory," and that it is not necessary to maintain connectivity of the endochondral shoulder girdle to the skull. Our data support the possibility that the contribution of the neural crest to the endochondral shoulder girdle, which is observed in the mouse, arose de novo in mammals as a developmental basis for their skeletal synapomorphies. This further supports the hypothesis of an increased neural crest diversification during vertebrate evolution.

  2. Neural-like growing networks

    Science.gov (United States)

    Yashchenko, Vitaliy A.

    2000-03-01

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

  3. Flexibility of neural stem cells

    Directory of Open Access Journals (Sweden)

    Eumorphia eRemboutsika

    2011-04-01

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

  4. Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-balanced, biphasic pulses for 0.566  ⩽  k  ⩽  2.3 in rat subcutaneous tissues

    Science.gov (United States)

    Kumsa, Doe W.; Bhadra, Narendra; Hudak, Eric M.; Mortimer, J. Thomas

    2017-10-01

    Objective. Our mission is twofold: (1) find a way to safely inject more charge through platinum electrodes than the Shannon limit (k  =  1.75) permits and (2) nurture an interest in the neural stimulation community to understand the electron transfer process occurring on neural stimulating electrodes. Approach. We report here on measurements of the electrode potential, performed on platinum neural stimulating electrodes in the subcutaneous space of an anesthetized rat under neural stimulation conditions. Main results. The results for six platinum electrodes with areas ranging from 0.2 mm2 to 12.7 mm2 were similar to prior results in sulfuric acid, except that the measured potentials were shifted negative 0.36 V because of the pH difference between the two media. The anodic ‘end’ potential, measured at t  =  20 ms after the onset of the biphasic current pulse, was the primary focus of the data collected because previous results had shown that as charge injection crosses the Shannon limit (k  =  1.75), this potential moves into a range where platinum surface oxidation and dissolution is likely to occur. The behavior of V e(t  =  20 ms) over a range of electrode surface areas studied was consistent with our sulfuric acid study. Implicit, but little noticed, in Shannon’s formulation is that small and large platinum electrodes behave the same in terms of k value; our data supports this idea. Significance. We hypothesize that the k  =  1.75 Shannon limit for safe stimulation designates a charge-injection boundary above which platinum toxicity becomes a relevant consideration for living cells around an electrode, a possibility that can be directly tested, and is a vital step forward in mission (1).

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

    National Research Council Canada - National Science Library

    Kamban Parasuraman; Amin Elshorbagy; Sean K. Carey

    2006-01-01

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

  6. Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-12-01

    How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

  7. Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

    Science.gov (United States)

    Arendash, Gary W.; Gorski, Roger A.

    1982-09-01

    Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

  8. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues.

    Science.gov (United States)

    Yu, Yao; Xu, Tao; Yu, Yongtao; Hao, Pei; Li, Xuan

    2010-12-14

    Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes.

  9. Tissue bionics: examples in biomimetic tissue engineering.

    Science.gov (United States)

    Green, David W

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  10. Tissue bionics: examples in biomimetic tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  11. Applicability of tooth derived stem cells in neural regeneration

    Directory of Open Access Journals (Sweden)

    Ludovica Parisi

    2016-01-01

    Full Text Available Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many efforts have been done in the research of a cell component that combined with scaffolds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowadays the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we briefly introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in different parts of teeth, and finally we describe some experimental approaches which are exploiting dental stem cells for neural studies.

  12. Mechanotransduction of Neural Cells Through Cell–Substrate Interactions

    Science.gov (United States)

    Stukel, Jessica M.

    2016-01-01

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

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

    Science.gov (United States)

    Stukel, Jessica M; Willits, Rebecca Kuntz

    2016-06-01

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

  14. Early interfaced neural activity from chronic amputated nerves

    Directory of Open Access Journals (Sweden)

    Kshitija Garde

    2009-05-01

    Full Text Available Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation, currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative on-dependent multi-electrode arrays of open design allow the early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. .

  15. Applicability of tooth derived stem cells in neural regeneration.

    Science.gov (United States)

    Parisi, Ludovica; Manfredi, Edoardo

    2016-11-01

    Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many efforts have been done in the research of a cell component that combined with scaffolds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowadays the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we briefly introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in different parts of teeth, and finally we describe some experimental approaches which are exploiting dental stem cells for neural studies.

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

    Science.gov (United States)

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

    2017-10-01

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

  17. American Association of Tissue Banks

    Science.gov (United States)

    ... Brightest in Tissue Banking FIND AATB ACCREDITED TISSUE BANK INSTITUTIONS SEARCH STANDARDS FOR TISSUE BANKING ACCESS CERTIFIED TISSUE BANK SPECIALISTS (CTBS) MANAGE QDEW Workshop | Baltimore, MD Save ...

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

    Science.gov (United States)

    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.

  19. A practical clinical classification of spinal neural tube defects.

    Science.gov (United States)

    McComb, J Gordon

    2015-10-01

    Current commonly used terminology to describe neural tube defects (NTD) is inconsistent, overlapping, contradictory and, at times, inaccurate making it difficult to convey the nature of the malformation and what needs to be done to optimally treat patients with these congenital abnormalities.NTD can be broadly divided into those that are open with exposed neural tissue and leaking cerebrospinal fluid (CSF) and those that are closed with no exposed neural tissue nor loss of CSF. It appears that the loss of CSF during development is the underlying factor that leads to the entire central nervous system involvement with an open NTD and lack thereof with a closed NTD, wherein only the spinal cord is malformed. There are, however, rare transitional cases that bridge the gap between the two forms.Agreeing on a nomenclature that is used in a standard fashion would be of help in addressing this group of congenital anomalies that have a great deal of variability and, at times, can be quite complex.

  20. Drug release from porous silicon for stable neural interface

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Tao, E-mail: taosun@hotmail.com.hk [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Tsang, Wei Mong [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Park, Woo-Tae [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Department of Mechanical and Automotive Engineering, Seoul National University of Science and Technology, Seoul (Korea, Republic of)

    2014-02-15

    70 μm-thick porous Si (PSi) layer with the pore size of 11.1 ± 7.6 nm was formed on an 8-in. Si wafer via an anodization process for the microfabrication of a microelectrode to record neural signals. To reduce host tissue responses to the microelectrode and achieve a stable neural interface, water-soluble dexamethesone (Dex) was loaded into the PSi via incubation with the drug solution overnight. After the drug loading process, the pore size of PSi reduced to 4.7 ± 2.6 nm on the basis of scanning electron microscopic (SEM) images, while its wettability was remarkably enhanced. Fluorescence images demonstrated that Dex was loaded into the porous structure of the PSi. Degradation rate of the PSi was investigated by incubation in distilled water for 21 days. Moreover, the drug release profile of the Dex-loaded PSi was a combination of an initial burst release and subsequent sustained release. To evaluate cellular responses to the drug release from the PSi, primary astrocytes were seeded on the surface of samples. After 2 days of culture, the Dex-loaded PSi could not only moderately prevent astrocyte adhesion in comparison with Si, but also more effectively suppress the activation of primary astrocytes than unloaded PSi due to the drug release. Therefore, it might be an effective method to reduce host tissue responses and stabilize the quality of the recorded neural signal by means of loading drugs into the PSi component of the microelectrode.

  1. Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

    Science.gov (United States)

    Foutz, Thomas J; Ackermann, D Michael; Kilgore, Kevin L; McIntyre, Cameron C

    2012-01-01

    The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

  2. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    Science.gov (United States)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  3. Braided Multi-Electrode Probes (BMEPs) for Neural Interfaces

    Science.gov (United States)

    Kim, Tae Gyo

    Although clinical use of invasive neural interfaces is very limited, due to safety and reliability concerns, the potential benefits of their use in brain machine interfaces (BMIs) seem promising and so they have been widely used in the research field. Microelectrodes as invasive neural interfaces are the core tool to record neural activities and their failure is a critical issue for BMI systems. Possible sources of this failure are neural tissue motions and their interactions with stiff electrode arrays or probes fixed to the skull. To overcome these tissue motion problems, we have developed novel braided multi-electrode probes (BMEPs). By interweaving ultra-fine wires into a tubular braid structure, we obtained a highly flexible multi-electrode probe. In this thesis we described BMEP designs and how to fabricate BMEPs, and explore experiments to show the advantages of BMEPs through a mechanical compliance comparison and a chronic immunohistological comparison with single 50microm nichrome wires used as a reference electrode type. Results from the mechanical compliance test showed that the bodies of BMEPs have 4 to 21 times higher compliance than the single 50microm wire and the tethers of BMEPs were 6 to 96 times higher compliance, depending on combinations of the wire size (9.6microm or 12.7microm), the wire numbers (12 or 24), and the length of tether (3, 5 or 10 mm). Results from the immunohistological comparison showed that both BMEPs and 50microm wires anchored to the skull caused stronger tissue reactions than unanchored BMEPs and 50microm wires, and 50microm wires caused stronger tissue reactions than BMEPs. In in-vivo tests with BMEPs, we succeeded in chronic recordings from the spinal cord of freely jumping frogs and in acute recordings from the spinal cord of decerebrate rats during air stepping which was evoked by mesencephalic locomotor region (MLR) stimulation. This technology may provide a stable and reliable neural interface to spinal cord

  4. Microtubule-associated protein 1b is required for shaping the neural tube.

    Science.gov (United States)

    Jayachandran, Pradeepa; Olmo, Valerie N; Sanchez, Stephanie P; McFarland, Rebecca J; Vital, Eudorah; Werner, Jonathan M; Hong, Elim; Sanchez-Alberola, Neus; Molodstov, Aleksey; Brewster, Rachel M

    2016-01-18

    Shaping of the neural tube, the precursor of the brain and spinal cord, involves narrowing and elongation of the neural tissue, concomitantly with other morphogenetic changes that contribue to this process. In zebrafish, medial displacement of neural cells (neural convergence or NC), which drives the infolding and narrowing of the neural ectoderm, is mediated by polarized migration and cell elongation towards the dorsal midline. Failure to undergo proper NC results in severe neural tube defects, yet the molecular underpinnings of this process remain poorly understood. We investigated here the role of the microtubule (MT) cytoskeleton in mediating NC in zebrafish embryos using the MT destabilizing and hyperstabilizing drugs nocodazole and paclitaxel respectively. We found that MTs undergo major changes in organization and stability during neurulation and are required for the timely completion of NC by promoting cell elongation and polarity. We next examined the role of Microtubule-associated protein 1B (Map1b), previously shown to promote MT dynamicity in axons. map1b is expressed earlier than previously reported, in the developing neural tube and underlying mesoderm. Loss of Map1b function using morpholinos (MOs) or δMap1b (encoding a truncated Map1b protein product) resulted in delayed NC and duplication of the neural tube, a defect associated with impaired NC. We observed a loss of stable MTs in these embryos that is likely to contribute to the NC defect. Lastly, we found that Map1b mediates cell elongation in a cell autonomous manner and polarized protrusive activity, two cell behaviors that underlie NC and are MT-dependent. Together, these data highlight the importance of MTs in the early morphogenetic movements that shape the neural tube and reveal a novel role for the MT regulator Map1b in mediating cell elongation and polarized cell movement in neural progenitor cells.

  5. Resolving time and space constraints during neural crest formation and delamination.

    Science.gov (United States)

    Duband, Jean-Loup; Dady, Alwyn; Fleury, Vincent

    2015-01-01

    A striking feature of neural crest development in vertebrates is that all the specification, delamination, migration, and differentiation steps occur consecutively in distinct areas of the embryo and at different timings of development. The significance and consequences of this partition into clearly separated events are not fully understood yet, but it ought to be related to the necessity of controlling precisely and independently each step, given the wide array of cell types and tissues derived from the neural crest and the long duration of their development spanning almost the entire embryonic life. In this chapter, using the examples of early neural crest induction and delamination, we discuss how time and space constraints influence their development and describe the molecular and cellular responses that are employed by cells to adapt. In the first example, we analyze how cell sorting and cell movements cooperate to allow nascent neural crest cells, which are initially mingled with other neurectodermal progenitors after induction, to segregate from the neural tube and ectoderm populations and settle at the apex of the neural tube prior to migration. In the second example, we examine how cadherins drive the entire process of neural crest segregation from the rest of the neurectoderm by their dual role in mediating first cell sorting and cohesion during specification and later in promoting their delamination. In the third example, we describe how the expression and activity of the transcription factors known to drive epithelium-to-mesenchyme transition (EMT) are regulated timely and spatially by the cellular machinery so that they can alternatively and successively regulate neural crest specification and delamination. In the last example, we briefly tackle the problem of how factors triggering EMT may elicit different cell responses in neural tube and neural crest progenitors. © 2015 Elsevier Inc. All rights reserved.

  6. 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.

  7. Two-photon excitation based photochemistry and neural imaging

    Science.gov (United States)

    Hatch, Kevin Andrew

    Two-photon microscopy is a fluorescence imaging technique which provides distinct advantages in three-dimensional cellular and molecular imaging. The benefits of this technology may extend beyond imaging capabilities through exploitation of the quantum processes responsible for fluorescent events. This study utilized a two-photon microscope to investigate a synthetic photoreactive collagen peptidomimetic, which may serve as a potential material for tissue engineering using the techniques of two-photon photolysis and two-photon polymerization. The combination of these techniques could potentially be used to produce a scaffold for the vascularization of engineered three-dimensional tissues in vitro to address the current limitations of tissue engineering. Additionally, two-photon microscopy was used to observe the effects of the application of the neurotransmitter dopamine to the mushroom body neural structures of Drosophila melanogaster to investigate dopamine's connection to cognitive degeneration.

  8. Multigradient for Neural Networks for Equalizers

    Directory of Open Access Journals (Sweden)

    Chulhee Lee

    2003-06-01

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

  9. 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

  10. 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.

  11. 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.

  12. Role of Rab11 in planar cell polarity and apical constriction during vertebrate neural tube closure.

    Science.gov (United States)

    Ossipova, Olga; Kim, Kyeongmi; Lake, Blue B; Itoh, Keiji; Ioannou, Andriani; Sokol, Sergei Y

    2014-05-13

    Epithelial folding is a critical process underlying many morphogenetic events including vertebrate neural tube closure, however, its spatial regulation is largely unknown. Here we show that during neural tube formation Rab11-positive recycling endosomes acquire bilaterally symmetric distribution in the Xenopus neural plate, being enriched at medial apical cell junctions. This mediolateral polarization was under the control of planar cell polarity (PCP) signalling, was necessary for neural plate folding and was accompanied by the polarization of the exocyst component Sec15. Our further experiments demonstrate that similar PCP-dependent polarization of Rab11 is essential for ectopic apical constriction driven by the actin-binding protein Shroom and during embryonic wound repair. We propose that anisotropic membrane trafficking has key roles in diverse morphogenetic behaviours of individual cells and propagates in a tissue by a common mechanism that involves PCP.

  13. Blood-neural barrier: its diversity and coordinated cell-to-cell communication.

    Science.gov (United States)

    Choi, Yoon Kyung; Kim, Kyu-Won

    2008-05-31

    The cerebral microvessels possess barrier characteristics which are tightly sealed excluding many toxic substances and protecting neural tissues. The specialized blood-neural barriers as well as the cerebral microvascular barrier are recognized in the retina, inner ear, spinal cord, and cerebrospinal fluid. Microvascular endothelial cells in the brain closely interact with other components such as astrocytes, pericytes, perivascular microglia and neurons to form functional 'neurovascular unit'. Communication between endothelial cells and other surrounding cells enhances the barrier functions, consequently resulting in maintenance and elaboration of proper brain homeostasis. Furthermore, the disruption of the neurovascular unit is closely involved in cerebrovascular disorders. In this review, we focus on the location and function of these various blood-neural barriers, and the importance of the cell-to-cell communication for development and maintenance of the barrier integrity at the neurovascular unit. We also demonstrate the close relation between the alteration of the blood-neural barriers and cerebrovascular disorders.

  14. The mych gene is required for neural crest survival during zebrafish development.

    Directory of Open Access Journals (Sweden)

    Sung-Kook Hong

    2008-04-01

    Full Text Available Among Myc family genes, c-Myc is known to have a role in neural crest specification in Xenopus and in craniofacial development in the mouse. There is no information on the function of other Myc genes in neural crest development, or about any developmental role of zebrafish Myc genes.We isolated the zebrafish mych (myc homologue gene. Knockdown of mych leads to severe defects in craniofacial development and in certain other tissues including the eye. These phenotypes appear to be caused by cell death in the neural crest and in the eye field in the anterior brain.Mych is a novel factor required for neural crest cell survival in zebrafish.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Shingo Kanao

    2017-01-01

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

  17. The anatomy of the bifurcated neural spine and its occurrence within Tetrapoda.

    Science.gov (United States)

    Woodruff, D Cary

    2014-09-01

    Vertebral neural spine bifurcation has been historically treated as largely restrictive to sauropodomorph dinosaurs; wherein it is inferred to be an adaptation in response to the increasing weight from the horizontally extended cervical column. Because no extant terrestrial vertebrates have massive, horizontally extended necks, extant forms with large cranial masses were examined for the presence of neural spine bifurcation. Here, I report for the first time on the soft tissue surrounding neural spine bifurcation in a terrestrial quadruped through the dissection of three Ankole-Watusi cattle. With horns weighing up to a combined 90 kg, the Ankole-Watusi is unlike any other breed of cattle in terms of cranial weight and presence of neural spine bifurcation. Using the Ankole-Watusi as a model, it appears that neural spine bifurcation plays a critical role in supporting a large mobile weight adjacent to the girdles. In addition to neural spine bifurcation being recognized within nonavian dinosaurs, this vertebral feature is also documented within many members of temnospondyls, captorhinids, seymouriamorphs, diadectomorphs, Aves, marsupials, artiodactyls, perissodactyls, and Primates, amongst others. This phylogenetic distribution indicates that spine bifurcation is more common than previously thought, and that this vertebral adaptation has contributed throughout the evolutionary history of tetrapods. Neural spine bifurcation should now be recognized as an anatomical component adapted by some vertebrates to deal with massive, horizontal, mobile weights adjacent the girdles. © 2014 Wiley Periodicals, Inc.

  18. A hybrid hardware and software approach for cancelling stimulus artifacts during same-electrode neural stimulation and recording.

    Science.gov (United States)

    Culaclii, Stanislav; Kim, Brian; Yi-Kai Lo; Wentai Liu

    2016-08-01

    Recovering neural responses from electrode recordings is fundamental for understanding the dynamics of neural networks. This effort is often obscured by stimulus artifacts in the recordings, which result from stimuli injected into the electrode-tissue interface. Stimulus artifacts, which can be orders of magnitude larger than the neural responses of interest, can mask short-latency evoked responses. Furthermore, simultaneous neural stimulation and recording on the same electrode generates artifacts with larger amplitudes compared to a separate electrode setup, which inevitably overwhelm the amplifier operation and cause unrecoverable neural signal loss. This paper proposes an end-to-end system combining hardware and software techniques for actively cancelling stimulus artifacts, avoiding amplifier saturation, and recovering neural responses during current-controlled in-vivo neural stimulation and recording. The proposed system is tested in-vitro under various stimulation settings by stimulating and recording on the same electrode with a superimposed pre-recorded neural signal. Experimental results show that neural responses can be recovered with minimal distortion even during stimulus artifacts that are several orders greater in magnitude.

  19. Inclusion mechanical property estimation using tactile images, finite element method, and artificial neural network.

    Science.gov (United States)

    Lee, Jong-Ha; Won, Chang-Hee

    2011-01-01

    In this paper, we developed a methodology for estimating three parameters of tissue inclusion: size, depth, and Young's modulus from the tactile data obtained at the tissue surface with the tactile sensation imaging system. The estimation method consists of the forward algorithm using finite element method, and inversion algorithm using artificial neural network. The forward algorithm is designed to comprehensively predict the tactile data based on the mechanical properties of the tissue inclusion. This forward information is used to develop an inversion algorithm that will be used to extract the size, depth, and Young's modulus of a tissue inclusion from the tactile image. The proposed method is then validated with custom made tissue phantoms with matching elasticities of typical human breast tissues. The experimental results showed that the proposed estimation method estimates the size, depth, and Young's modulus of tissue inclusions with root mean squared errors of 1.25 mm, 2.09 mm, and 28.65 kPa, respectively.

  20. Dietary blueberry supplementation affects growth but not vascularization of neural transplants

    OpenAIRE

    Willis, Lauren M; Small, Brent J.; Bickford, Paula C.; Umphlet, Claudia D; Moore, Alfred B.; Granholm, Ann-Charlotte E.

    2008-01-01

    Transplantation of neural tissue has been attempted as a treatment method for neurodegenerative disorders. Grafted neurons survive to a lesser extent into middle-aged or aged hosts, and survival rates of < 10% of grafted neurons is common. Antioxidant diets, such as blueberry, can exert powerful effects on developing neurons and blood vessels in vitro, but studies are lacking that examine the effects of these diets on transplanted tissues. In this study, we examined the effects of a blueberry...

  1. Insights from amphioxus into the evolution of vertebrate cartilage.

    Directory of Open Access Journals (Sweden)

    Daniel Meulemans

    2007-08-01

    Full Text Available Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm.

  2. Improved diagnostics using polarization imaging and artificial neural networks

    Science.gov (United States)

    Klimach, Uwe; Zhao, Hongzhi; Chen, Qiushui; Zou, Yingyin Kevin; Wang, Yue; Xuan, Jianhua

    2006-03-01

    In recent years there has been an increasing interest in studying the propagation of polarized light in randomly scattering media. This paper presents a novel approach for cell and tissue imaging by using full Stokes imaging and for its improved diagnostics by using artificial neural networks (ANNs). Phantom experiments have been conducted using a prototyped Stokes polarization imaging device. Several types of phantoms, consisting of polystyrene latex spheres in various diameters, were prepared to simulate different conditions of epidermal layer of skin. Several sets of four images that contain not only the intensity, but also the polarization information were taken for analysis. Wavelet transforms are first applied to the Stokes components for initial feature analysis and extraction. Artificial neural networks (ANNs) are then used to extract diagnostic features for improved classification and prediction. The experimental results show that the classification performance using Stokes images is significantly improved over that using the intensity image only.

  3. Neural prostheses and biomedical microsystems in neurological rehabilitation.

    Science.gov (United States)

    Koch, K P

    2007-01-01

    Interfaces between electrodes and the neural system differ with respect to material and shape depending on their intended application and fabrication method. This chapter will review the different electrode designs regarding the technological implementation and fabrication process. Furthermore this book chapter will describe electrodes for interfacing the peripheral nerves like cuff, book or helix as well as electrodes for interfacing the cortex like needle arrays. The implantation method and mechanical interaction between the electrode and the nervous tissue were taken into consideration. To develop appropriate microtechnological assembling strategies that ensure proper interfacing between the tiny electrodes and microelectronics or connectors is one of the major challenges. The integration of electronics into the system helps to improve the reliability of detecting neural signals and reduces the size of the implants. Promising results with these novel electrodes will pave the road for future developments such as visual prosthetics or improved control of artificial limbs in paralyzed patients.

  4. Development of bioactive conducting polymers for neural interfaces.

    Science.gov (United States)

    Poole-Warren, Laura; Lovell, Nigel; Baek, Sungchul; Green, Rylie

    2010-01-01

    Bioelectrodes for neural recording and neurostimulation are an integral component of a number of neuroprosthetic devices, including the commercially available cochlear implant, and developmental devices, such as the bionic eye and brain-machine interfaces. Current electrode designs limit the application of such devices owing to suboptimal material properties that lead to minimal interaction with the target neural tissue and the formation of fibrotic capsules. In designing an ideal bioelectrode, a number of design criteria must be considered with respect to physical, mechanical, electrical and biological properties. Conducting polymers have the potential to address the synergistic interaction of these properties and show promise as superior coatings for next-generation electrodes in implant devices.

  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. Review of transplantation of neural stem/progenitor cells for spinal cord injury.

    Science.gov (United States)

    Mothe, Andrea J; Tator, Charles H

    2013-11-01

    Spinal cord injury (SCI) is a debilitating condition often resulting in paralysis, yet currently there is no effective treatment. Stem cell transplantation is a promising therapeutic strategy for promoting tissue repair after SCI. Stem cells offer a renewable source of cells with inherent plasticity for tissue regeneration. Neural stem/progenitor cells (NSPCs) are multipotent cells that self-renew and are committed to the neural lineage, and thus, they are especially suited to SCI repair. NSPCs may differentiate into neural cells after transplantation into the injured spinal cord, replacing lost or damaged cells, providing trophic support, restoring connectivity, and facilitating regeneration. Here, we review experimental studies and considerations for clinical translation of NSPC transplantation for SCI. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. Neural networks and statistical learning

    CERN Document Server

    Du, Ke-Lin

    2014-01-01

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

  8. Multiprocessor Neural Network in Healthcare.

    Science.gov (United States)

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

    2015-01-01

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

  9. Principles of neural information processing

    CERN Document Server

    Seelen, Werner v

    2016-01-01

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

  10. Mechanics of neurulation: From classical to current perspectives on the physical mechanics that shape, fold, and form the neural tube.

    Science.gov (United States)

    Vijayraghavan, Deepthi S; Davidson, Lance A

    2017-01-30

    Neural tube defects arise from mechanical failures in the process of neurulation. At the most fundamental level, formation of the neural tube relies on coordinated, complex tissue movements that mechanically transform the flat neural epithelium into a lumenized epithelial tube (Davidson, 2012). The nature of this mechanical transformation has mystified embryologists, geneticists, and clinicians for more than 100 years. Early embryologists pondered the physical mechanisms that guide this transformation. Detailed observations of cell and tissue movements as well as experimental embryological manipulations allowed researchers to generate and test elementary hypotheses of the intrinsic and extrinsic forces acting on the neural tissue. Current research has turned toward understanding the molecular mechanisms underlying neurulation. Genetic and molecular perturbation have identified a multitude of subcellular components that correlate with cell behaviors and tissue movements during neural tube formation. In this review, we focus on methods and conceptual frameworks that have been applied to the study of amphibian neurulation that can be used to determine how molecular and physical mechanisms are integrated and responsible for neurulation. We will describe how qualitative descriptions and quantitative measurements of strain, force generation, and tissue material properties as well as simulations can be used to understand how embryos use morphogenetic programs to drive neurulation. Birth Defects Research 109:153-168, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Performance sustaining intracortical neural prostheses

    Science.gov (United States)

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

    2014-12-01

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

  12. FGF-mediated induction of ciliary body tissue in the chick eye.

    Science.gov (United States)

    Dias da Silva, Magnus R; Tiffin, Nicola; Mima, Tatsuo; Mikawa, Takashi; Hyer, Jeanette

    2007-04-01

    Upon morphogenesis, the simple neuroepithelium of the optic vesicle gives rise to four basic tissues in the vertebrate optic cup: pigmented epithelium, sensory neural retina, secretory ciliary body and muscular iris. Pigmented epithelium and neural retina are established through interactions with specific environments and signals: periocular mesenchyme/BMP specifies pigmented epithelium and surface ectoderm/FGF specifies neural retina. The anterior portions (iris and ciliary body) are specified through interactions with lens although the molecular mechanisms of induction have not been deciphered. As lens is a source of FGF, we examined whether this factor was involved in inducing ciliary body. We forced the pigmented epithelium of the embryonic chick eye to express FGF4. Infected cells and their immediate neighbors were transformed into neural retina. At a distance from the FGF signal, the tissue transitioned back into pigmented epithelium. Ciliary body tissue was found in the transitioning zone. The ectopic ciliary body was never in contact with the lens tissue. In order to assess the contribution of the lens on the specification of normal ciliary body, we created optic cups in which the lens had been removed while still pre-lens ectoderm. Ciliary body tissue was identified in the anterior portion of lens-less optic cups. We propose that the ciliary body may be specified at optic vesicle stages, at the same developmental stage when the neural retina and pigmented epithelium are specified and we present a model as to how this could be accomplished through overlapping BMP and FGF signals.

  13. Current approaches to model extracellular electrical neural microstimulation

    Directory of Open Access Journals (Sweden)

    Sébastien eJoucla

    2014-02-01

    Full Text Available Nowadays, high-density microelectrode arrays provide unprecedented possibilities to precisely activate spatially well-controlled central nervous system (CNS areas. However, this requires optimizing stimulating devices, which in turn requires a good understanding of the effects of microstimulation on cells and tissues. In this context, modeling approaches provide flexible ways to predict the outcome of electrical stimulation in terms of CNS activation. In this paper, we present state-of-the-art modeling methods with sufficient details to allow the reader to rapidly build numerical models of neuronal extracellular microstimulation. These include 1 the computation of the electrical potential field created by the stimulation in the tissue, and 2 the response of a target neuron to this field. Two main approaches are described: First we describe the classical hybrid approach that combines the finite element modeling of the potential field with the calculation of the neuron’s response in a cable equation framework (compartmentalized neuron models. Then, we present a whole finite element approach allows the simultaneous calculation of the extracellular and intracellular potentials, by representing the neuronal membrane with a thin-film approximation. This approach was previously introduced in the frame of neural recording, but has never been implemented to determine the effect of extracellular stimulation on the neural response at a sub-compartment level. Here, we show on an example that the latter modeling scheme can reveal important sub-compartment behavior of the neural membrane that cannot be resolved using the hybrid approach. The goal of this paper is also to describe in detail the practical implementation of these methods to allow the reader to easily build new models using standard software packages. These modeling paradigms, depending on the situation, should help build more efficient high-density neural prostheses for CNS rehabilitation.

  14. Exploring infrared neural stimulation with multimodal nonlinear imaging (Conference Presentation)

    Science.gov (United States)

    Adams, Wilson R.; Mahadevan-Jansen, Anita

    2017-02-01

    Infrared neural stimulation (INS) provides optical control of neural excitability using near to mid-infrared (mid-IR) light, which allows for spatially selective, artifact-free excitation without the introduction of exogenous agents or genetic modification. Although neural excitability is mediated by a transient temperature increase due to water absorption of IR energy, the molecular nature of IR excitability in neural tissue remains unknown. Current research suggests that transient changes in local tissue temperature give rise to a myriad of cellular responses that have been individually attributed to IR mediated excitability. To further elucidate the underlying biophysical mechanisms, we have begun work towards employing a novel multimodal nonlinear imaging platform to probe the molecular underpinnings of INS. Our imaging system performs coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG) and thermal imaging into a single platform that allows for unprecedented co-registration of thermal and biochemical information in real-time. Here, we present our work leveraging CARS and SRS in acute thalamocortical brain slice preparations. We observe the evolution of lipid and protein-specific Raman bands during INS and electrically evoked activity in real-time. Combined with two-photon fluorescence and second harmonic generation, we offer insight to cellular metabolism and membrane dynamics during INS. Thermal imaging allows for the coregistration of acquired biochemical information with temperature information. Our work previews the versatility and capabilities of coherent Raman imaging combined with multiphoton imaging to observe biophysical phenomena for neuroscience applications.

  15. Multiplexed lasing in tissues

    Science.gov (United States)

    Chen, Yu-Cheng; Chen, Qiushu; Fan, Xudong

    2017-02-01

    Biolasers are an emerging technology for next generation biochemical detection and clinical applications. Progress has recently been made to achieve lasing from biomolecules and single living cells. Tissues, which consist of cells embedded in extracellular matrix, mimic more closely the actual complex biological environment in a living body and therefore are of more practical significance. Here, we developed a highly versatile tissue laser platform, in which tissues stained with fluorophores are sandwiched in a high-Q Fabry-Pérot microcavity. Distinct lasing emissions from muscle and adipose tissues stained respectively with fluorescein isothiocyanate (FITC) and boron-dipyrromethene (BODIPY), and hybrid muscle/adipose tissue with dual-staining were achieved with a threshold of only 10 μJ/mm2. Additionally, we investigated how tissue structure/geometry, tissue thickness, and staining dye concentration affect the tissue laser. It is further found that, despite large fluorescence spectral overlap between FITC and BODIPY in tissues, their lasing emissions could be clearly distinguished and controlled due to their narrow lasing bands and different lasing thresholds, thus enabling highly multiplexed detection. Our tissue laser platform can be broadly applicable to various types of tissues/diseases. It provides a new tool for a wide range of biological and biomedical applications, such as diagnostics/screening of tissues and identification/monitoring of biological transformations in tissue engineering.

  16. Roles of FGFs as Adipokines in Adipose Tissue Development, Remodeling, and Metabolism

    OpenAIRE

    Nobuyuki eItoh; Hiroya eOhta

    2014-01-01

    White and brown adipose tissues, which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among twenty-two FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and brown adipose tissues. FGF1 is a critical transducer in white adipose tissue remodeling. The PPARγ–F...

  17. Neural Decoder for Topological Codes

    Science.gov (United States)

    Torlai, Giacomo; Melko, Roger G.

    2017-07-01

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

  18. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  19. Classification of clinical autofluorescence spectra of oral leukoplakia using an artificial neural network : a pilot study

    NARCIS (Netherlands)

    van Staveren, HJ; van Veen, RLP; Speelman, OC; Witjes, MJH; Roodenburg, JLN

    The performance of an artificial neural network was evaluated as an alternative classification technique of autofluorescence spectra of oral leukoplakia, which may reflect the grade of tissue dysplasia. Twenty-two visible lesions of 21 patients suffering from oral leukoplakia and six locations on

  20. Xeya3 regulates survival and proliferation of neural progenitor cells within the anterior neural plate of Xenopus embryos.

    Science.gov (United States)

    Kriebel, Martin; Müller, Frank; Hollemann, Thomas

    2007-06-01

    The transcriptional coactivater and tyrosine phosphatase eyes absent (eya) is vital for eye development in Drosophila. We identified a vertebrate member of the Eya family, Xeya3, which is expressed in the anterior neural plate, including the eye field. Overexpression of wild-type Xeya3 or of a phosphatase-negative version of Xeya3 creates massive enlargements of brain and retinal tissues, mainly caused by overproliferation of neural precursor cells. On the other hand, suppression of Xeya3 function induces local apoptosis within the sensorial layer of the anterior neuroectoderm. Thus, Xeya3 is key factor for the formation and size control of brain and eyes in vertebrates. Copyright 2007 Wiley-Liss, Inc.

  1. Wireless gigabit data telemetry for large-scale neural recording.

    Science.gov (United States)

    Kuan, Yen-Cheng; Lo, Yi-Kai; Kim, Yanghyo; Chang, Mau-Chung Frank; Liu, Wentai

    2015-05-01

    Implantable wireless neural recording from a large ensemble of simultaneously acting neurons is a critical component to thoroughly investigate neural interactions and brain dynamics from freely moving animals. Recent researches have shown the feasibility of simultaneously recording from hundreds of neurons and suggested that the ability of recording a larger number of neurons results in better signal quality. This massive recording inevitably demands a large amount of data transfer. For example, recording 2000 neurons while keeping the signal fidelity ( > 12 bit, > 40 KS/s per neuron) needs approximately a 1-Gb/s data link. Designing a wireless data telemetry system to support such (or higher) data rate while aiming to lower the power consumption of an implantable device imposes a grand challenge on neuroscience community. In this paper, we present a wireless gigabit data telemetry for future large-scale neural recording interface. This telemetry comprises of a pair of low-power gigabit transmitter and receiver operating at 60 GHz, and establishes a short-distance wireless link to transfer the massive amount of neural signals outward from the implanted device. The transmission distance of the received neural signal can be further extended by an externally rendezvous wireless transceiver, which is less power/heat-constraint since it is not at the immediate proximity of the cortex and its radiated signal is not seriously attenuated by the lossy tissue. The gigabit data link has been demonstrated to achieve a high data rate of 6 Gb/s with a bit-error-rate of 10(-12) at a transmission distance of 6 mm, an applicable separation between transmitter and receiver. This high data rate is able to support thousands of recording channels while ensuring a low energy cost per bit of 2.08 pJ/b.

  2. Generalization performance of regularized neural network models

    DEFF Research Database (Denmark)

    Larsen, Jan; Hansen, Lars Kai

    1994-01-01

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

  3. voltage compensation using artificial neural network

    African Journals Online (AJOL)

    Offor Theophilos

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

  4. Plant Growth Models Using Artificial Neural Networks

    Science.gov (United States)

    Bubenheim, David

    1997-01-01

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

  5. Neural circulatory control in vasovagal syncope

    NARCIS (Netherlands)

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

    1997-01-01

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

  6. Neural overlap in processing music and speech

    Science.gov (United States)

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

    2015-01-01

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

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

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

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

  8. Analysis of the scattering performance of human retinal tissue layers

    Science.gov (United States)

    Zhu, Dan; Gao, Zhisan; Ye, Haishui; Yuan, Qun

    2017-02-01

    Human retina is different from other ocular tissues, such as cornea, crystalline lens and vitreous because of high scattering performance. As an anisotropic tissue, we cannot neglect its impact on the polarization state of the scattered light. In this paper, Mie scattering and radiative transfer theory are applied to analyze the polarization state of backscattered light from four types of retinal tissues, including neural retina, retinal pigment epithelial (RPE), choroid and sclera. The results show that the most backscattered zones in different depths have almost the same electrical fields of Jones vector, which represents the polarization state of light, whether neural retina layer is under normal incidence or oblique incidence. Very little change occurs in the polarization of backscattered light compared to that of the incident light. Polarization distribution of backward scattered light from neural retina layer doesn't make apparent effects on polarization phase shifting in spectral domain OCT because its thickness is far less than photon mean free path, while other retinal tissues do not meet this rule.

  9. Laser/tissue interaction.

    Science.gov (United States)

    Dederich, D N

    1991-01-01

    When laser light impinges on tissue, it can reflect, scatter, be absorbed, or transmit to the surrounding tissue. Absorption controls to a great degree the extent to which reflection, scattering and transmission occur, and wavelength is the primary determinant of absorption. The CO2 laser is consistently absorbed by most materials and tissues and the Nd-YAG laser wavelength is preferentially absorbed in pigmented tissues. The factors which determine the initial tissue effect include the laser wavelength, laser power, laser waveform, tissue optical properties, and tissue thermal properties. There are almost an infinite number of combinations of these factors possible, many of which would result in unacceptable damage to the tissues. This underscores the need to thoroughly test any particular combination of these factors on the conceptual, in-vitro, and in-vivo level before a treatment is offered.

  10. Plant tissue culture techniques

    Directory of Open Access Journals (Sweden)

    Rolf Dieter Illg

    1991-01-01

    Full Text Available Plant cell and tissue culture in a simple fashion refers to techniques which utilize either single plant cells, groups of unorganized cells (callus or organized tissues or organs put in culture, under controlled sterile conditions.

  11. FRD tissue archive

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The fishery genetics tissue collection has over 80,000 tissues stored in 95% ethanol representing fishes and invertebrates collected globally but with a focus on the...

  12. MEMBRAIN NEURAL NETWORK FOR VISUAL PATTERN RECOGNITION

    Directory of Open Access Journals (Sweden)

    Artur Popko

    2013-06-01

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

  13. Adipose tissue fibrosis

    OpenAIRE

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-01-01

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. The...

  14. Bioreactors for tissue engineering.

    Science.gov (United States)

    Chen, Huang-Chi; Hu, Yu-Chen

    2006-09-01

    Bioreactors are essential in tissue engineering, not only because they provide an in vitro environment mimicking in vivo conditions for the growth of tissue substitutes, but also because they enable systematic studies of the responses of living tissues to various mechanical and biochemical cues. The basic principles of bioreactor design are reviewed, the bioreactors commonly used for the tissue engineering of cartilage, bone and cardiovascular systems are assessed in terms of their performance and usefulness. Several novel bioreactor types are also reviewed.

  15. Vascularization Tissue Engineering

    NARCIS (Netherlands)

    Rouwkema, Jeroen; Rivron, N.C.; van Blitterswijk, Clemens

    2008-01-01

    Tissue engineering has been an active field of research for several decades now. However, the amount of clinical applications in the field of tissue engineering is still limited. One of the current limitations of tissue engineering is its inability to provide sufficient blood supply in the initial

  16. Tertiary lymphoid tissue

    Science.gov (United States)

    Di Caro, Giuseppe; Marchesi, Federica

    2014-01-01

    Tumor-infiltrating lymphocytes influence colorectal cancer progression. We have recently documented that tertiary lymphoid tissue in the colorectal cancer microenvironment orchestrates lymphocyte infiltration and that tertiary lymphoid tissue and lymphocytes cooperate in a coordinated antitumor immune response to improve patient outcome. Thus, tertiary lymphoid tissue represents a potential target in the design of tailored immune-based therapeutic approaches. PMID:25083321

  17. Development of tissue bank

    Directory of Open Access Journals (Sweden)

    R P Narayan

    2012-01-01

    Full Text Available The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

  18. Radioactive fallout and neural tube defects

    African Journals Online (AJOL)

    Nejat Akar

    2015-07-10

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

  19. Analysis of neural networks through base functions

    NARCIS (Netherlands)

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

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

  20. Simplified LQG Control with Neural Networks

    DEFF Research Database (Denmark)

    Sørensen, O.

    1997-01-01

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

  1. Novel quantum inspired binary neural network algorithm

    Indian Academy of Sciences (India)

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

  2. Degenerate coding in neural systems.

    Science.gov (United States)

    Leonardo, Anthony

    2005-11-01

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

  3. Optoelectronic Implementation of Neural Networks

    Indian Academy of Sciences (India)

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

  4. Aphasia Classification Using Neural Networks

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  5. Memory Storage and Neural Systems.

    Science.gov (United States)

    Alkon, Daniel L.

    1989-01-01

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

  6. Neural Control of the Circulation

    Science.gov (United States)

    Thomas, Gail D.

    2011-01-01

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

  7. Classification using Bayesian neural nets

    NARCIS (Netherlands)

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

    1995-01-01

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

  8. Vitamins and neural tube defects

    OpenAIRE

    Harris, Rodney

    1988-01-01

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

  9. Neural Mechanisms of Conceptual Relations

    Science.gov (United States)

    Lewis, Gwyneth A.

    2017-01-01

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

  10. Neural mechanisms for voice recognition

    NARCIS (Netherlands)

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

    2010-01-01

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

  11. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

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

  12. Non-invasive neural stimulation

    Science.gov (United States)

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

    2017-05-01

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

  13. Neural networks and applications tutorial

    Science.gov (United States)

    Guyon, I.

    1991-09-01

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

  14. Adipose tissue fibrosis.

    Science.gov (United States)

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-05-15

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases.

  15. Cell and Tissue Engineering

    CERN Document Server

    2012-01-01

    “Cell and Tissue Engineering” introduces the principles and new approaches in cell and tissue engineering. It includes both the fundamentals and the current trends in cell and tissue engineering, in a way useful both to a novice and an expert in the field. The book is composed of 13 chapters all of which are written by the leading experts. It is organized to gradually assemble an insight in cell and tissue function starting form a molecular nano-level, extending to a cellular micro-level and finishing at the tissue macro-level. In specific, biological, physiological, biophysical, biochemical, medical, and engineering aspects are covered from the standpoint of the development of functional substitutes of biological tissues for potential clinical use. Topics in the area of cell engineering include cell membrane biophysics, structure and function of the cytoskeleton, cell-extracellular matrix interactions, and mechanotransduction. In the area of tissue engineering the focus is on the in vitro cultivation of ...

  16. The Pursuit of Chronically Reliable Neural Interfaces: A Materials Perspective.

    Science.gov (United States)

    Guo, Liang

    2016-01-01

    Brain-computer interfaces represent one of the most astonishing technologies in our era. However, the grand challenge of chronic instability and limited throughput of the electrode-tissue interface has significantly hindered the further development and ultimate deployment of such exciting technologies. A multidisciplinary research workforce has been called upon to respond to this engineering need. In this paper, I briefly review this multidisciplinary pursuit of chronically reliable neural interfaces from a materials perspective by analyzing the problem, abstracting the engineering principles, and summarizing the corresponding engineering strategies. I further draw my future perspectives by extending the proposed engineering principles.

  17. Yes-associated protein 65 (YAP expands neural progenitors and regulates Pax3 expression in the neural plate border zone.

    Directory of Open Access Journals (Sweden)

    Stephen T Gee

    Full Text Available Yes-associated protein 65 (YAP contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein. Mouse embryos lacking YAP did not survive past embryonic day 8.5 and showed signs of defective yolk sac vasculogenesis, chorioallantoic fusion, and anterior-posterior (A-P axis elongation. Given that the YAP knockout mouse defects might be due in part to nutritional deficiencies, we sought to better characterize a role for YAP during early development using embryos that develop externally. YAP morpholino (MO-mediated loss-of-function in both frog and fish resulted in incomplete epiboly at gastrulation and impaired axis formation, similar to the mouse phenotype. In frog, germ layer specific genes were expressed, but they were temporally delayed. YAP MO-mediated partial knockdown in frog allowed a shortened axis to form. YAP gain-of-function in Xenopus expanded the progenitor populations in the neural plate (sox2(+ and neural plate border zone (pax3(+, while inhibiting the expression of later markers of tissues derived from the neural plate border zone (neural crest, pre-placodal ectoderm, hatching gland, as well as epidermis and somitic muscle. YAP directly regulates pax3 expression via association with TEAD1 (N-TEF at a highly conserved, previously undescribed, TEAD-binding site within the 5' regulatory region of pax3. Structure/function analyses revealed that the PDZ-binding motif of YAP contributes to the inhibition of epidermal and somitic muscle differentiation, but a complete, intact YAP protein is required for expansion of the neural plate and neural plate border zone progenitor pools. These results provide a thorough analysis of YAP mediated gene expression changes in loss- and gain-of-function experiments. Furthermore, this is the first report to use YAP structure-function analyzes to determine which portion of YAP is involved in specific gene expression changes and the

  18. Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10

    DEFF Research Database (Denmark)

    Sonnenberg-Riethmacher, Eva; Miehe, Michaela; Stolt, Claus C.

    2001-01-01

    Abstract The HMG-domain transcription factor Sox10 is essential for the development of various neural crest derived lineages including glia and neurons of the peripheral nervous system (PNS). Within the PNS the most striking defect is the complete absence of glial differentiation whereas neurogen......Abstract The HMG-domain transcription factor Sox10 is essential for the development of various neural crest derived lineages including glia and neurons of the peripheral nervous system (PNS). Within the PNS the most striking defect is the complete absence of glial differentiation whereas...

  19. Dynamic properties of cellular neural networks

    Directory of Open Access Journals (Sweden)

    Angela Slavova

    1993-01-01

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

  20. Micro- and Nanotechnologies for Optical Neural Interfaces

    Science.gov (United States)

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

    2016-01-01

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

  1. Distinct intracellular Ca(2+) dynamics regulate apical constriction and differentially contribute to neural tube closure.

    Science.gov (United States)

    Suzuki, Makoto; Sato, Masanao; Koyama, Hiroshi; Hara, Yusuke; Hayashi, Kentaro; Yasue, Naoko; Imamura, Hiromi; Fujimori, Toshihiko; Nagai, Takeharu; Campbell, Robert E; Ueno, Naoto

    2017-04-01

    Early in the development of the central nervous system, progenitor cells undergo a shape change, called apical constriction, that triggers the neural plate to form a tubular structure. How apical constriction in the neural plate is controlled and how it contributes to tissue morphogenesis are not fully understood. In this study, we show that intracellular calcium ions (Ca(2+)) are required for Xenopus neural tube formation and that there are two types of Ca(2+)-concentration changes, a single-cell and a multicellular wave-like fluctuation, in the developing neural plate. Quantitative imaging analyses revealed that transient increases in Ca(2+) concentration induced cortical F-actin remodeling, apical constriction and accelerations of the closing movement of the neural plate. We also show that extracellular ATP and N-cadherin (cdh2) participate in the Ca(2+)-induced apical constriction. Furthermore, our mathematical model suggests that the effect of Ca(2+) fluctuations on tissue morphogenesis is independent of fluctuation frequency and that fluctuations affecting individual cells are more efficient than those at the multicellular level. We propose that distinct Ca(2+) signaling patterns differentially modulate apical constriction for efficient epithelial folding and that this mechanism has a broad range of physiological outcomes. © 2017. Published by The Company of Biologists Ltd.

  2. Implications of the Dependence of Neuronal Activity on Neural Network States for the Design of Brain-Machine Interfaces.

    Science.gov (United States)

    Panzeri, Stefano; Safaai, Houman; De Feo, Vito; Vato, Alessandro

    2016-01-01

    Brain-machine interfaces (BMIs) can improve the quality of life of patients with sensory and motor disabilities by both decoding motor intentions expressed by neural activity, and by encoding artificially sensed information into patterns of neural activity elicited by causal interventions on the neural tissue. Yet, current BMIs can exchange relatively small amounts of information with the brain. This problem has proved difficult to overcome by simply increasing the number of recording or stimulating electrodes, because trial-to-trial variability of neural activity partly arises from intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation, and so is shared among neurons. Here we review recent progress in characterizing the state dependence of neural responses, and in particular of how neural responses depend on endogenous slow fluctuations of network excitability. We then elaborate on how this knowledge may be used to increase the amount of information that BMIs exchange with brain. Knowledge of network state can be used to fine-tune the stimulation pattern that should reliably elicit a target neural response used to encode information in the brain, and to discount part of the trial-by-trial variability of neural responses, so that they can be decoded more accurately.

  3. Implications of the dependence of neuronal activity on neural network states for the design of brain-machine interfaces

    Directory of Open Access Journals (Sweden)

    Stefano ePanzeri

    2016-04-01

    Full Text Available Brain-machine interfaces (BMIs can improve the quality of life of patients with sensory and motor disabilities by both decoding motor intentions expressed by neural activity, and by encoding artificially sensed information into patterns of neural activity elicited by causal interventions on the neural tissue. Yet, current BMIs can exchange relatively small amounts of information with the brain. This problem has proved difficult to overcome by simply increasing the number of recording or stimulating electrodes, because trial-to-trial variability of neural activity partly arises from intrinsic factors (collectively known as the network state that include ongoing spontaneous activity and neuromodulation, and so is shared among neurons. Here we review recent progress in characterizing the state dependence of neural responses, and in particular of how neural responses depend on endogenous slow fluctuations of network excitability. We then elaborate on how this knowledge may be used to increase the amount of information that BMIs exchange with brains. Knowledge of network state can be used to fine-tune the stimulation pattern that should reliably elicit a target neural response used to encode information in the brain, and to discount part of the trial-by-trial variability of neural responses, so that they can be decoded more accurately.

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

    Directory of Open Access Journals (Sweden)

    Usue Etxaniz

    2014-11-01

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

  5. Spike Neural Models Part II: Abstract Neural Models

    OpenAIRE

    Johnson, Melissa G.; Chartier, Sylvain

    2018-01-01

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

  6. Deep convolutional neural networks for classifying head and neck cancer using hyperspectral imaging

    Science.gov (United States)

    Halicek, Martin; Lu, Guolan; Little, James V.; Wang, Xu; Patel, Mihir; Griffith, Christopher C.; El-Deiry, Mark W.; Chen, Amy Y.; Fei, Baowei

    2017-06-01

    Surgical cancer resection requires an accurate and timely diagnosis of the cancer margins in order to achieve successful patient remission. Hyperspectral imaging (HSI) has emerged as a useful, noncontact technique for acquiring spectral and optical properties of tissue. A convolutional neural network (CNN) classifier is developed to classify excised, squamous-cell carcinoma, thyroid cancer, and normal head and neck tissue samples using HSI. The CNN classification was validated by the manual annotation of a pathologist specialized in head and neck cancer. The preliminary results of 50 patients indicate the potential of HSI and deep learning for automatic tissue-labeling of surgical specimens of head and neck patients.

  7. Regeneration of periodontal tissues: guided tissue regeneration.

    Science.gov (United States)

    Villar, Cristina C; Cochran, David L

    2010-01-01

    The concept that only fibroblasts from the periodontal ligament or undifferentiated mesenchymal cells have the potential to re-create the original periodontal attachment has been long recognized. Based on this concept, guided tissue regeneration has been applied with variable success to regenerate periodontal defects. Quantitative analysis of clinical outcomes after guided tissue regeneration suggests that this therapy is a successful and predictable procedure to treat narrow intrabony defects and class II mandibular furcations, but offers limited benefits in the treatment of other types of periodontal defects.

  8. Towards the fabrication of artificial 3D microdevices for neural cell networks.

    Science.gov (United States)

    Gill, Andrew A; Ortega, Ílida; Kelly, Stephen; Claeyssens, Frederik

    2015-04-01

    This work reports first steps towards the development of artificial neural stem cell microenvironments for the control and assessment of neural stem cell behaviour. Stem cells have been shown to be found in specific, supportive microenvironments (niches) and are believed to play an important role in tissue regeneration mechanisms. These environments are intricate spaces with chemical and biological features. Here we present work towards the development of physically defined microdevices in which neural and neural stem cells can be studied in 3-dimensions. We have approached this challenge by creating bespoke, microstructured polymer environments using both 2-photon polymerisation and soft lithography techniques. Specifically, we have designed and fabricated biodegradable microwell-shaped devices using an in house synthetized polymer (4-arm photocurable poly-lactid acid) on a bespoke 2-photon polymerisation (2PP) set-up. We have studied swelling and degradation of the constructs as well as biocompatibility. Moreover, we have explored the potential of these constructs as artificial neural cell substrates by culturing NG108-15 cells (mouse neuroblastoma; rat glioma hybrid) and human neural progenitor cells on the microstructures. Finally, we have studied the effects of our artificial microenvironments upon neurite length and cell density.

  9. 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

  10. Nanoelectronics enabled chronic multimodal neural platform in a mouse ischemic model.

    Science.gov (United States)

    Luan, Lan; Sullender, Colin T; Li, Xue; Zhao, Zhengtuo; Zhu, Hanlin; Wei, Xiaoling; Xie, Chong; Dunn, Andrew K

    2017-12-04

    Despite significant advancements of optical imaging techniques for mapping hemodynamics in small animal models, it remains challenging to combine imaging with spatially resolved electrical recording of individual neurons especially for longitudinal studies. This is largely due to the strong invasiveness to the living brain from the penetrating electrodes and their limited compatibility with longitudinal imaging. We implant arrays of ultraflexible nanoelectronic threads (NETs) in mice for neural recording both at the brain surface and intracortically, which maintain great tissue compatibility chronically. By mounting a cranial window atop of the NET arrays that allows for chronic optical access, we establish a multimodal platform that combines spatially resolved electrical recording of neural activity and laser speckle contrast imaging (LSCI) of cerebral blood flow (CBF) for longitudinal studies. We induce peri-infarct depolarizations (PIDs) by targeted photothrombosis, and show the ability to detect its occurrence and propagation through spatiotemporal variations in both extracellular potentials and CBF. We also demonstrate chronic tracking of single-unit neural activity and CBF over days after photothrombosis, from which we observe reperfusion and increased firing rates. This multimodal platform enables simultaneous mapping of neural activity and hemodynamic parameters at the microscale for quantitative, longitudinal comparisons with minimal perturbation to the baseline neurophysiology. The ability to spatiotemporally resolve and chronically track CBF and neural electrical activity in the same living brain region has broad applications for studying the interplay between neural and hemodynamic responses in health and in cerebrovascular and neurological pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Physical principles for scalable neural recording.

    Science.gov (United States)

    Marblestone, Adam H; Zamft, Bradley M; Maguire, Yael G; Shapiro, Mikhail G; Cybulski, Thaddeus R; Glaser, Joshua I; Amodei, Dario; Stranges, P Benjamin; Kalhor, Reza; Dalrymple, David A; Seo, Dongjin; Alon, Elad; Maharbiz, Michel M; Carmena, Jose M; Rabaey, Jan M; Boyden, Edward S; Church, George M; Kording, Konrad P

    2013-01-01

    Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power-bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and

  12. Computational models of the neural control of breathing.

    Science.gov (United States)

    Molkov, Yaroslav I; Rubin, Jonathan E; Rybak, Ilya A; Smith, Jeffrey C

    2017-03-01

    The ongoing process of breathing underlies the gas exchange essential for mammalian life. Each respiratory cycle ensues from the activity of rhythmic neural circuits in the brainstem, shaped by various modulatory signals, including mechanoreceptor feedback sensitive to lung inflation and chemoreceptor feedback dependent on gas composition in blood and tissues. This paper reviews a variety of computational models designed to reproduce experimental findings related to the neural control of breathing and generate predictions for future experimental testing. The review starts from the description of the core respiratory network in the brainstem, representing the central pattern generator (CPG) responsible for producing rhythmic respiratory activity, and progresses to encompass additional complexities needed to simulate different metabolic challenges, closed-loop feedback control including the lungs, and interactions between the respiratory and autonomic nervous systems. The integrated models considered in this review share a common framework including a distributed CPG core network responsible for generating the baseline three-phase pattern of rhythmic neural activity underlying normal breathing. WIREs Syst Biol Med 2017, 9:e1371. doi: 10.1002/wsbm.1371 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  13. DNA from keratinous tissue

    DEFF Research Database (Denmark)

    Bengtsson, Camilla F.; Olsen, Maja E.; Brandt, Luise Ørsted

    2011-01-01

    Keratinous tissues such as nail, hair, horn, scales and feather have been used as a source of DNA for over 20 years. Particular benefits of such tissues include the ease with which they can be sampled, the relative stability of DNA in such tissues once sampled, and, in the context of ancient...... genetic analyses, the fact that sampling generally causes minimal visual damage to valuable specimens. Even when freshly sampled, however, the DNA quantity and quality in the fully keratinized parts of such tissues is extremely poor in comparison to other tissues such as blood and muscle – although little...... systematic research has been undertaken to characterize how such degradation may relate to sample source. In this review paper we present the current understanding of the quality and limitations of DNA in two key keratinous tissues, nail and hair. The findings indicate that although some fragments of nuclear...

  14. [Management of severe soft-tissue trauma in the upper extremity - shoulder, upper and lower arm].

    Science.gov (United States)

    Mittlmeier, Thomas; Krapohl, Björn Dirk; Schaser, Klaus-Dieter

    2010-05-01

    Salvage of the respective extremity. Standardized approach to adequate soft-tissue coverage (isolated severe soft-tissue trauma) and preconditioning for fracture healing (in complex trauma) as a basis for functional restoration. Limitation of secondary soft-tissue loss. Prevention of infection. Isolated extended severe soft-tissue trauma (crush trauma, degloving injury) in the region of the shoulder and the upper extremity. Complex trauma with soft-tissue involvement Gustilo IIIB/C or Tscherne GIII/IV. Segmental soft-tissue/bone loss. Subtotal or partial amputations. Unstable polytraumatized patient with vital hazards and the priority for lifesaving measures. Irretrievable devascularization or unreconstructable neural destruction, extended severe loss of multiple muscular units. Systematic, eventually serial debridement, temporary joint transfixation, reconstruction of macrocirculation, dermatofasciotomy in compartment syndrome, preferably primary shortening in segmental soft-tissue/bone loss, temporary soft-tissue coverage, systematic conditioning of soft tissues, postprimary or secondary soft-tissue reconstruction, secondary change to preferably internal fixation techniques. Individualized earliest possible passive or assisted mobilization of nontransfixed joints, early removal of transfixation and change to internal fixation modes, eventually secondary reconstructive measures (e.g., augmentation of bone defects, flap correction, secondary nerve reconstruction, functional muscle transposition procedures, arthrolyses). Patency rate after vascular reconstruction > 90%, flap survival > 95%, need for amputation is a rare entity; main determinants of prognosis: severity of soft-tissue trauma, neural damage, and potential for reconstruction.

  15. Polymer Composite with Carbon Nanofibers Aligned during Thermal Drawing as a Microelectrode for Chronic Neural Interfaces.

    Science.gov (United States)

    Guo, Yuanyuan; Jiang, Shan; Grena, Benjamin J B; Kimbrough, Ian F; Thompson, Emily G; Fink, Yoel; Sontheimer, Harald; Yoshinobu, Tatsuo; Jia, Xiaoting

    2017-07-25

    Microelectrodes provide a direct pathway to investigate brain activities electrically from the external world, which has advanced our fundamental understanding of brain functions and has been utilized for rehabilitative applications as brain-machine interfaces. However, minimizing the tissue response and prolonging the functional durations of these devices remain challenging. Therefore, the development of next-generation microelectrodes as neural interfaces is actively progressing from traditional inorganic materials toward biocompatible and functional organic materials with a miniature footprint, good flexibility, and reasonable robustness. In this study, we developed a miniaturized all polymer-based neural probe with carbon nanofiber (CNF) composites as recording electrodes via the scalable thermal drawing process. We demonstrated that in situ CNF unidirectional alignment can be achieved during the thermal drawing, which contributes to a drastic improvement of electrical conductivity by 2 orders of magnitude compared to a conventional polymer electrode, while still maintaining the mechanical compliance with brain tissues. The resulting neural probe has a miniature footprint, including a recording site with a reduced size comparable to a single neuron and maintained impedance that was able to capture neural activities. Its stable functionality as a chronic implant has been demonstrated with the long-term reliable electrophysiological recording with single-spike resolution and the minimal tissue response over the extended period of implantation in wild-type mice. Technology developed here can be applied to basic chronic electrophysiological studies as well as clinical implementation for neuro-rehabilitative applications.

  16. Tissue engineering in dentistry.

    Science.gov (United States)

    Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Salih, Vehid M; Kim, Hae-Won; Knowles, Jonathan C

    2014-08-01

    of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. Only those articles that dealt with the tissue engineering in dentistry were selected. There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. Considering the

  17. Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

    Science.gov (United States)

    Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

    2016-09-15

    Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

  18. Tissue elasticity measurement method using forward and inversion algorithms

    Science.gov (United States)

    Lee, Jong-Ha; Won, Chang-Hee; Park, Hee-Jun; Ku, Jeonghun; Heo, Yun Seok; Kim, Yoon-Nyun

    2013-03-01

    Elasticity is an important indicator of tissue health, with increased stiffness pointing to an increased risk of cancer. We investigated a tissue elasticity measurement method using forward and inversion algorithms for the application of early breast tumor identification. An optical based elasticity measurement system is developed to capture images of the embedded lesions using total internal reflection principle. From elasticity images, we developed a novel method to estimate the elasticity of the embedded lesion using 3-D finite-element-model-based forward algorithm, and neural-network-based inversion algorithm. The experimental results showed that the proposed characterization method can be diffierentiate the benign and malignant breast lesions.

  19. Genetic attack on neural cryptography.

    Science.gov (United States)

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

    2006-03-01

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

  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 Networks Methodology and Applications

    CERN Document Server

    Dreyfus, Gérard

    2005-01-01

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

  2. Autonomic neural functions in space.

    Science.gov (United States)

    Mano, T

    2005-08-01

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

  3. A novel wavelet neural network based pathological stage detection technique for an oral precancerous condition

    Science.gov (United States)

    Paul, R R; Mukherjee, A; Dutta, P K; Banerjee, S; Pal, M; Chatterjee, J; Chaudhuri, K; Mukkerjee, K

    2005-01-01

    Aim: To describe a novel neural network based oral precancer (oral submucous fibrosis; OSF) stage detection method. Method: The wavelet coefficients of transmission electron microscopy images of collagen fibres from normal oral submucosa and OSF tissues were used to choose the feature vector which, in turn, was used to train the artificial neural network. Results: The trained network was able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. Conclusions: The results obtained from this proposed technique were promising and suggest that with further optimisation this method could be used to detect and stage OSF, and could be adapted for other conditions. PMID:16126873

  4. Treatment of spinal cord injury: a review of engineering using neural and mesenchymal stem cells.

    Science.gov (United States)

    Mortazavi, Martin M; Harmon, Olivia A; Adeeb, Nimer; Deep, Aman; Tubbs, R Shane

    2015-01-01

    Over time, various treatment modalities for spinal cord injury have been trialed, including pharmacological and nonpharmacological methods. Among these, replacement of the injured neural and paraneural tissues via cellular transplantation of neural and mesenchymal stem cells has been the most attractive. Extensive experimental studies have been done to identify the safety and effectiveness of this transplantation in animal and human models. Herein, we review the literature for studies conducted, with a focus on the human-related studies, recruitment, isolation, and transplantation, of these multipotent stem cells, and associated outcomes. © 2014 Wiley Periodicals, Inc.

  5. Adaptive Regularization of Neural Classifiers

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  6. 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.

  7. Handbook on neural information processing

    CERN Document Server

    Maggini, Marco; Jain, Lakhmi

    2013-01-01

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

  8. [Glutamate signaling and neural plasticity].

    Science.gov (United States)

    Watanabe, Masahiko

    2013-07-01

    Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting

  9. Implantable liquid metal-based flexible neural microelectrode array and its application in recovering animal locomotion functions

    Science.gov (United States)

    Guo, Rui; Liu, Jing

    2017-10-01

    With significant advantages in rapidly restoring the nerve function, electrical stimulation of nervous tissue is a crucial treatment of peripheral nerve injuries leading to common movement disorder. However, the currently available stimulating electrodes generally based on rigid conductive materials would cause a potential mechanical mismatch with soft neural tissues which thus reduces long-term effects of electrical stimulation. Here, we proposed and fabricated a flexible neural microelectrode array system based on the liquid metal GaIn alloy (75.5% Ga and 24.5% In by weight) and via printing approach. Such an alloy with a unique low melting point (10.35 °C) owns excellent electrical conductivity and high compliance, which are beneficial to serve as implantable flexible neural electrodes. The flexible neural microelectrode array embeds four liquid metal electrodes and stretchable interconnects in a PDMS membrane (500 µm in thickness) that possess a lower elastic modulus (1.055 MPa), which is similar to neural tissues with elastic moduli in the 0.1-1.5 MPa range. The electrical experiments indicate that the liquid metal interconnects could sustain over 7000 mechanical stretch cycles with resistance approximately staying at 4 Ω. Over the conceptual experiments on animal sciatic nerve electrical stimulation, the dead bullfrog implanted with flexible neural microelectrode array could even rhythmically contract and move its lower limbs under the electrical stimulations from the implant. This demonstrates a highly efficient way for quickly recovering biological nerve functions. Further, the good biocompatibility of the liquid metal material was justified via a series of biological experiments. This liquid metal modality for neural stimulation is expected to play important roles as biologic electrodes to overcome the fundamental mismatch in mechanics between biological tissues and electronic devices in the coming time.

  10. Neural prostheses and brain plasticity

    Science.gov (United States)

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

    2009-12-01

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

  11. 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.

  12. Three dimensional living neural networks

    Science.gov (United States)

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

    2015-08-01

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

  13. 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.

  14. Neural Correlates of Predictive Saccades.

    Science.gov (United States)

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

    2016-08-01

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

  15. Fuzzy neural networks: theory and applications

    Science.gov (United States)

    Gupta, Madan M.

    1994-10-01

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

  16. Pulp tissue from primary teeth: new source of stem cells

    Directory of Open Access Journals (Sweden)

    Paloma Dias Telles

    2011-06-01

    Full Text Available SHED (stem cells from human exfoliated deciduous teeth represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells and discuss tissue engineering approaches that use SHED to replace irreversibly inflamed or necrotic pulps with a healthy and functionally competent tissue that is capable of forming new dentin.

  17. Robotic multimodality stereotactic brain tissue identification: work in progress

    Science.gov (United States)

    Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

    1997-01-01

    Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

  18. Modeling the Insertion Mechanics of Flexible Neural Probes Coated with Sacrificial Polymers for Optimizing Probe Design

    Science.gov (United States)

    Singh, Sagar; Lo, Meng-Chen; Damodaran, Vinod B.; Kaplan, Hilton M.; Kohn, Joachim; Zahn, Jeffrey D.; Shreiber, David I.

    2016-01-01

    Single-unit recording neural probes have significant advantages towards improving signal-to-noise ratio and specificity for signal acquisition in brain-to-computer interface devices. Long-term effectiveness is unfortunately limited by the chronic injury response, which has been linked to the mechanical mismatch between rigid probes and compliant brain tissue. Small, flexible microelectrodes may overcome this limitation, but insertion of these probes without buckling requires supporting elements such as a stiff coating with a biodegradable polymer. For these coated probes, there is a design trade-off between the potential for successful insertion into brain tissue and the degree of trauma generated by the insertion. The objective of this study was to develop and validate a finite element model (FEM) to simulate insertion of coated neural probes of varying dimensions and material properties into brain tissue. Simulations were performed to predict the buckling and insertion forces during insertion of coated probes into a tissue phantom with material properties of brain. The simulations were validated with parallel experimental studies where probes were inserted into agarose tissue phantom, ex vivo chick embryonic brain tissue, and ex vivo rat brain tissue. Experiments were performed with uncoated copper wire and both uncoated and coated SU-8 photoresist and Parylene C probes. Model predictions were found to strongly agree with experimental results (probe length were the most important features in influencing insertion potential. The model also revealed the effects of manufacturing flaws on insertion potential. PMID:26959021

  19. ORGANIC ELECTRODE COATINGS FOR NEXT-GENERATION NEURAL INTERFACES

    Directory of Open Access Journals (Sweden)

    Ulises A Aregueta-Robles

    2014-05-01

    Full Text Available Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Regional differences in the expression of laminin isoforms during mouse neural tube development

    Science.gov (United States)

    Copp, Andrew J.; Carvalho, Rita; Wallace, Adam; Sorokin, Lydia; Sasaki, Takako; Greene, Nicholas D.E.; Ybot-Gonzalez, Patricia

    2013-01-01

    Many significant human birth defects originate around the time of neural tube closure or early during post-closure nervous system development. For example, failure of the neural tube to close generates anencephaly and spina bifida, faulty cell cycle progression is implicated in primary microcephaly, while defective migration of neuroblasts can lead to neuronal migration disorders such as lissencephaly. At the stage of neural tube closure, basement membranes are becoming organised around the neuroepithelium, and beneath the adjacent non-neural surface ectoderm. While there is circumstantial evidence to implicate basement membrane dynamics in neural tube and surface ectodermal development, we have an incomplete understanding of the molecular composition of basement membranes at this stage. In the present study, we examined the developing basement membranes of the mouse embryo at mid-gestation (embryonic day 9.5), with particular reference to laminin composition. We performed in situ hybridization to detect the mRNAs of all eleven individual laminin chains, and immunohistochemistry to identify which laminin chains are present in the basement membranes. From this information, we inferred the likely laminin variants and their tissues of origin: that is, whether a given basement membrane laminin is contributed by epithelium, mesenchyme, or both. Our findings reveal major differences in basement composition along the body axis, with the rostral neural tube (at mandibular arch and heart levels) exhibiting many distinct laminin variants, while the lumbar level where the neural tube is just closing shows a much simpler laminin profile. Moreover, there appears to be a marked difference in the extent to which the mesenchyme contributes laminin variants to the basement membrane, with potential contribution of several laminins rostrally, but no contribution caudally. This information paves the way towards a mechanistic analysis of basement membrane laminin function during early

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

    Directory of Open Access Journals (Sweden)

    Callihan Phillip

    2008-12-01

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

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

    Science.gov (United States)

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

    2015-05-15

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

  4. Toward multi-area distributed network of implanted neural interrogators

    Science.gov (United States)

    Powell, Marc P.; Hou, Xiaoxiao; Galligan, Craig; Ashe, Jeffrey; Borton, David A.

    2017-08-01

    As we aim to improve our understanding of the brain, it is critical that researchers have simultaneous multi-area, large-scale access to the brain. Information processing in the brain occurs through close and distant coupling of functional sub-domains, as opposed to within isolated single neurons. However, commercially available neural interfaces capable of sensing electrophysiology of single neurons, currently allow access to only a small, mm3 volume of cortical cells, are not scalable to recording from orders of magnitude more neurons, and leverage bulky, skull mounted hardware and cabling sensitive to relative movements of the skull and brain. In this work, we propose a system capable of recording from many individual distributed neural interrogator nodes, untethered from any external electronics. Using an array of epidural inductive coils to wirelessly power the implanted electronics, the system is intended to be agnostic to the surgical placement of any individual node. Here, we demonstrate the ability to transmit nearly 15mW of power with greater than 50% power transfer efficiency, benchtop testing of individual subcircuit system components showing successful digitization of neural signals, and wireless transmission currently supporting a data rate of 3.84Mbps. We leverage a software defined radio based RF receiver to demodulate the data which can be stored in memory for later retrieval. Finally, we introduce a packaging technology capable of isolating active electronics from the surrounding tissue while providing capability for electrical feed-through assemblies for external neural interfacing. We expect, based on the presented preliminary findings, that the system can be integrated into a platform technology for the study of the intricate interactions between cortical domains.

  5. Neuronal spike sorting based on radial basis function neural networks

    Directory of Open Access Journals (Sweden)

    Taghavi Kani M

    2011-02-01

    Full Text Available "nBackground: Studying the behavior of a society of neurons, extracting the communication mechanisms of brain with other tissues, finding treatment for some nervous system diseases and designing neuroprosthetic devices, require an algorithm to sort neuralspikes automatically. However, sorting neural spikes is a challenging task because of the low signal to noise ratio (SNR of the spikes. The main purpose of this study was to design an automatic algorithm for classifying neuronal spikes that are emitted from a specific region of the nervous system."n "nMethods: The spike sorting process usually consists of three stages: detection, feature extraction and sorting. We initially used signal statistics to detect neural spikes. Then, we chose a limited number of typical spikes as features and finally used them to train a radial basis function (RBF neural network to sort the spikes. In most spike sorting devices, these signals are not linearly discriminative. In order to solve this problem, the aforesaid RBF neural network was used."n "nResults: After the learning process, our proposed algorithm classified any arbitrary spike. The obtained results showed that even though the proposed Radial Basis Spike Sorter (RBSS reached to the same error as the previous methods, however, the computational costs were much lower compared to other algorithms. Moreover, the competitive points of the proposed algorithm were its good speed and low computational complexity."n "nConclusion: Regarding the results of this study, the proposed algorithm seems to serve the purpose of procedures that require real-time processing and spike sorting.

  6. Electrical Impedance Tomography: Tissue Properties to Image Measures.

    Science.gov (United States)

    Adler, Andy; Boyle, Alistair

    Electrical impedance tomography (EIT) uses electrical stimulation and measurement at the body surface to image the electrical properties of internal tissues. It has the advantage of noninvasiveness and high temporal resolution but suffers from poor spatial resolution and sensitivity to electrode movement and contact quality. EIT can be useful to applications, where there are conductive contrasts between tissues, fluids, or gasses, such as imaging of cancerous or ischemic tissue or functional monitoring of breathing, blood flow, gastric motility, and neural activity. The past decade has seen clinical application and commercial activity using EIT for ventilation monitoring. Interpretation of EIT-based measures is complex, and this review paper focuses on describing the image interpretation "pathway." We review this pathway, from Tissue Electrical Properties, EIT Electrodes & Hardware, Sensitivity, Image Reconstruction, Image Processing to EIT Measures. The relationship is discussed between the clinically relevant parameters and the reconstructed properties. An overview is given of areas of EIT application and of our perspectives for research and development.Electrical impedance tomography (EIT) uses electrical stimulation and measurement at the body surface to image the electrical properties of internal tissues. It has the advantage of noninvasiveness and high temporal resolution but suffers from poor spatial resolution and sensitivity to electrode movement and contact quality. EIT can be useful to applications, where there are conductive contrasts between tissues, fluids, or gasses, such as imaging of cancerous or ischemic tissue or functional monitoring of breathing, blood flow, gastric motility, and neural activity. The past decade has seen clinical application and commercial activity using EIT for ventilation monitoring. Interpretation of EIT-based measures is complex, and this review paper focuses on describing the image interpretation "pathway." We review this

  7. Microchip-Embedded Capacitors for Implantable Neural Stimulators

    Science.gov (United States)

    Auciello, Orlando

    Miniaturization of microchips for implantation in the human body (e.g., microchip for the artificial retina to restore sight to people blinded by retina photoreceptors degeneration) requires the integration of high-capacitance (≥ 10 μF) energy-storage capacitors into the microchip. These capacitors would be based on high-dielectric constant layers, preferably made of materials that are bioinert (not affected by human body fluids) and are biocompatible (do not elicit adverse reactions in the human body). This chapter focuses on reviewing the work being done at Argonne National Laboratory (Materials Science Division and Center for Nanoscale Materials) to develop high-capacitance microchip-embedded capacitors based on novel high-K dielectric layers (TiAlOx or TiO2/Al2O3 superlattices). The microchip-embedded capacitor provides energy storage and electromagnetic signal coupling needed for neural stimulations. Advances in neural prostheses such as artificial retinas and cochlear implants require miniaturization of device size to minimize tissue damage and improve device/tissue interfaces in the human body. Therefore, development of microchip-embedded capacitors is critical to achieve full-implantable biomedical device miniaturization.

  8. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

  9. Undifferentiated Connective Tissue Disease

    Science.gov (United States)

    ... Examples of connective tissue diseases include lupus , scleroderma , rheumatoid arthritis , Sjögren's syndrome , myositis and vasculitis . There are many people who have features of connective tissue disease, however, they do not fulfill the diagnostic criteria established for any one disease. In such ...

  10. Engineering Vascularized Adipose Tissue

    NARCIS (Netherlands)

    F. Verseijden (Femke)

    2011-01-01

    textabstractA large portion of the plastic and reconstructive surgical procedures performed each year is aimed at repairing soft tissue defects, which result for example from traumatic injury or tumor resections. Large soft tissue defects, lead to a change in function and ‘normal’ body contour,

  11. Tissue engineered aortic valve

    OpenAIRE

    Dohmen, P M

    2012-01-01

    Several prostheses are available to replace degenerative diseased aortic valves with unique advantages and disadvantages. Bioprotheses show excellent hemodynamic behavior and low risk of thromboembolic complications, but are limited by tissue deterioration. Mechanical heart valves have extended durability, but permanent anticoagulation is mandatory. Tissue engineering created a new generation heart valve, which overcome limitations of biological and mechanical heart valves due to remodelling,...

  12. Satellite image analysis using neural networks

    Science.gov (United States)

    Sheldon, Roger A.

    1990-01-01

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

  13. Neural plasticity of development and learning.

    Science.gov (United States)

    Galván, Adriana

    2010-06-01

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

  14. Neurosecurity: security and privacy for neural devices.

    Science.gov (United States)

    Denning, Tamara; Matsuoka, Yoky; Kohno, Tadayoshi

    2009-07-01

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

  15. Flexible and Organic Neural Interfaces: A Review

    Directory of Open Access Journals (Sweden)

    Nicolò Lago

    2017-12-01

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

  16. Person Movement Prediction Using Neural Networks

    OpenAIRE

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

    2006-01-01

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

  17. Pediatric Nutritional Requirements Determination with Neural Networks

    OpenAIRE

    Karlık, Bekir; Ece, Aydın

    1998-01-01

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

  18. Adaptive optimization and control using neural networks

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-10-22

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

  19. Initialization of multilayer forecasting artifical neural networks

    OpenAIRE

    Bochkarev, Vladimir V.; Maslennikova, Yulia S.

    2014-01-01

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

  20. Texture Based Image Analysis With Neural Nets

    Science.gov (United States)

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

    1990-03-01

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