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Sample records for neural genes interestingly

  1. Affective neural response to restricted interests in autism spectrum disorders.

    Science.gov (United States)

    Cascio, Carissa J; Foss-Feig, Jennifer H; Heacock, Jessica; Schauder, Kimberly B; Loring, Whitney A; Rogers, Baxter P; Pryweller, Jennifer R; Newsom, Cassandra R; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

    2014-01-01

    Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to the pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals' own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. © 2013 The

  2. CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.

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    Schulz, Yvonne; Wehner, Peter; Opitz, Lennart; Salinas-Riester, Gabriela; Bongers, Ernie M H F; van Ravenswaaij-Arts, Conny M A; Wincent, Josephine; Schoumans, Jacqueline; Kohlhase, Jürgen; Borchers, Annette; Pauli, Silke

    2014-08-01

    Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, cranial nerves and several organ systems. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far, only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition are unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7 (Whi/+) and Chd7 (Whi/Whi)) mouse embryos at day 9.5, a time point of neural crest cell migration. We identified 98 differentially expressed genes between wild-type and Chd7 (Whi/Whi) embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance such as semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 in Xenopus laevis embryos, we found abnormalities in the expression pattern of Sema3a, a protein involved in the pathogenesis of Kallmann syndrome, in vivo. In addition, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7-negative CHARGE patients. In summary, we discovered for the first time that Chd7 regulates genes involved in neural crest cell guidance, demonstrating a new aspect in the pathogenesis of CHARGE syndrome. Furthermore, we showed for Sema3a a conserved regulatory mechanism across different species, highlighting its significance during development. Although we postulated that the non-synonymous SEMA3A variants which we found in CHD7-negative CHARGE patients alone are not sufficient to produce the phenotype, we suggest an important modifier role for SEMA3A in the

  3. 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

  4. Artificial neural networks modeling gene-environment interaction

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    Günther Frauke

    2012-05-01

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

  5. REGION OF NON-INTEREST BASED DIGITAL IMAGE WATERMARKING USING NEURAL NETWORKS

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    Bibi Isac

    2011-11-01

    Full Text Available Copyrights protection of digital data become inevitable in current world. Digital watermarks have been recently proposed as secured scheme for copyright protection, authentication, source tracking, and broadcast monitoring of video, audio, text data and digital images. In this paper a method to embed a watermark in region of non-interest (RONI and a method for adaptive calculation of strength factor using neural network are proposed. The embedding and extraction processes are carried out in the transform domain by using Discrete Wavelet Transform (DWT. Finally, the algorithm robustness is tested against noise addition attacks and geometric distortion attacks. The results authenticate that the proposed watermarking algorithm does not degrade the quality of cover image as the watermark is inserted only in region of non-interest and is resistive to attacks.

  6. Identification of neural outgrowth genes using genome-wide RNAi.

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    Katharine J Sepp

    2008-07-01

    Full Text Available While genetic screens have identified many genes essential for neurite outgrowth, they have been limited in their ability to identify neural genes that also have earlier critical roles in the gastrula, or neural genes for which maternally contributed RNA compensates for gene mutations in the zygote. To address this, we developed methods to screen the Drosophila genome using RNA-interference (RNAi on primary neural cells and present the results of the first full-genome RNAi screen in neurons. We used live-cell imaging and quantitative image analysis to characterize the morphological phenotypes of fluorescently labelled primary neurons and glia in response to RNAi-mediated gene knockdown. From the full genome screen, we focused our analysis on 104 evolutionarily conserved genes that when downregulated by RNAi, have morphological defects such as reduced axon extension, excessive branching, loss of fasciculation, and blebbing. To assist in the phenotypic analysis of the large data sets, we generated image analysis algorithms that could assess the statistical significance of the mutant phenotypes. The algorithms were essential for the analysis of the thousands of images generated by the screening process and will become a valuable tool for future genome-wide screens in primary neurons. Our analysis revealed unexpected, essential roles in neurite outgrowth for genes representing a wide range of functional categories including signalling molecules, enzymes, channels, receptors, and cytoskeletal proteins. We also found that genes known to be involved in protein and vesicle trafficking showed similar RNAi phenotypes. We confirmed phenotypes of the protein trafficking genes Sec61alpha and Ran GTPase using Drosophila embryo and mouse embryonic cerebral cortical neurons, respectively. Collectively, our results showed that RNAi phenotypes in primary neural culture can parallel in vivo phenotypes, and the screening technique can be used to identify many new

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

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    Simmons David K

    2012-01-01

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

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

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    Philippidou, Polyxeni; Dasen, Jeremy S

    2013-10-02

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

  9. A validated gene expression profile for detecting clinical outcome in breast cancer using artificial neural networks.

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    Lancashire, L J; Powe, D G; Reis-Filho, J S; Rakha, E; Lemetre, C; Weigelt, B; Abdel-Fatah, T M; Green, A R; Mukta, R; Blamey, R; Paish, E C; Rees, R C; Ellis, I O; Ball, G R

    2010-02-01

    Gene expression microarrays allow for the high throughput analysis of huge numbers of gene transcripts and this technology has been widely applied to the molecular and biological classification of cancer patients and in predicting clinical outcome. A potential handicap of such data intensive molecular technologies is the translation to clinical application in routine practice. In using an artificial neural network bioinformatic approach, we have reduced a 70 gene signature to just 9 genes capable of accurately predicting distant metastases in the original dataset. Upon validation in a follow-up cohort, this signature was an independent predictor of metastases free and overall survival in the presence of the 70 gene signature and other factors. Interestingly, the ANN signature and CA9 expression also split the groups defined by the 70 gene signature into prognostically distinct groups. Subsequently, the presence of protein for the principal prognosticator gene was categorically assessed in breast cancer tissue of an experimental and independent validation patient cohort, using immunohistochemistry. Importantly our principal prognosticator, CA9, showed that it is capable of selecting an aggressive subgroup of patients who are known to have poor prognosis.

  10. Neural network predicts sequence of TP53 gene based on DNA chip

    DEFF Research Database (Denmark)

    Spicker, J.S.; Wikman, F.; Lu, M.L.

    2002-01-01

    We have trained an artificial neural network to predict the sequence of the human TP53 tumor suppressor gene based on a p53 GeneChip. The trained neural network uses as input the fluorescence intensities of DNA hybridized to oligonucleotides on the surface of the chip and makes between zero...

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

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    Gouti, Mina; Briscoe, James; Gavalas, Anthony

    2011-01-01

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

  12. Power of grammatical evolution neural networks to detect gene-gene interactions in the presence of error

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    Davis Anna C

    2008-08-01

    Full Text Available Abstract Background With the advent of increasingly efficient means to obtain genetic information, a great insurgence of data has resulted, leading to the need for methods for analyzing this data beyond that of traditional parametric statistical approaches. Recently we introduced Grammatical Evolution Neural Network (GENN, a machine-learning approach to detect gene-gene or gene-environment interactions, also known as epistasis, in high dimensional genetic epidemiological data. GENN has been shown to be highly successful in a range of simulated data, but the impact of error common to real data is unknown. In the current study, we examine the power of GENN to detect interesting interactions in the presence of noise due to genotyping error, missing data, phenocopy, and genetic heterogeneity. Additionally, we compare the performance of GENN to that of another computational method – Multifactor Dimensionality Reduction (MDR. Findings GENN is extremely robust to missing data and genotyping error. Phenocopy in a dataset reduces the power of both GENN and MDR. GENN is reasonably robust to genetic heterogeneity and find that in some cases GENN has substantially higher power than MDR to detect functional loci in the presence of genetic heterogeneity. Conclusion GENN is a promising method to detect gene-gene interaction, even in the presence of common types of error found in real data.

  13. Power of grammatical evolution neural networks to detect gene-gene interactions in the presence of error.

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    Motsinger-Reif, Alison A; Fanelli, Theresa J; Davis, Anna C; Ritchie, Marylyn D

    2008-08-13

    With the advent of increasingly efficient means to obtain genetic information, a great insurgence of data has resulted, leading to the need for methods for analyzing this data beyond that of traditional parametric statistical approaches. Recently we introduced Grammatical Evolution Neural Network (GENN), a machine-learning approach to detect gene-gene or gene-environment interactions, also known as epistasis, in high dimensional genetic epidemiological data. GENN has been shown to be highly successful in a range of simulated data, but the impact of error common to real data is unknown. In the current study, we examine the power of GENN to detect interesting interactions in the presence of noise due to genotyping error, missing data, phenocopy, and genetic heterogeneity. Additionally, we compare the performance of GENN to that of another computational method - Multifactor Dimensionality Reduction (MDR). GENN is extremely robust to missing data and genotyping error. Phenocopy in a dataset reduces the power of both GENN and MDR. GENN is reasonably robust to genetic heterogeneity and find that in some cases GENN has substantially higher power than MDR to detect functional loci in the presence of genetic heterogeneity. GENN is a promising method to detect gene-gene interaction, even in the presence of common types of error found in real data.

  14. Optimizationof neural network architecture using genetic programming improvesdetection and modeling of gene-gene interactions in studies of humandiseases

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    Hahn Lance W

    2003-07-01

    Full Text Available Abstract Background Appropriate definitionof neural network architecture prior to data analysis is crucialfor successful data mining. This can be challenging when the underlyingmodel of the data is unknown. The goal of this study was to determinewhether optimizing neural network architecture using genetic programmingas a machine learning strategy would improve the ability of neural networksto model and detect nonlinear interactions among genes in studiesof common human diseases. Results Using simulateddata, we show that a genetic programming optimized neural network approachis able to model gene-gene interactions as well as a traditionalback propagation neural network. Furthermore, the genetic programmingoptimized neural network is better than the traditional back propagationneural network approach in terms of predictive ability and powerto detect gene-gene interactions when non-functional polymorphismsare present. Conclusion This study suggeststhat a machine learning strategy for optimizing neural network architecturemay be preferable to traditional trial-and-error approaches forthe identification and characterization of gene-gene interactionsin common, complex human diseases.

  15. Molecular characterization of neurally expressing genes in the para sodium channel gene cluster of Drosophila

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    Hong, Chang-Sook; Ganetzky, B. [Univ. of Wisconsin, Madison, WI (United States)

    1996-03-01

    To elucidate the mechanisms regulating expression of para, which encodes the major class of sodium channels in the Drosophila nervous system, we have tried to locate upstream cis-acting regulatory elements by mapping the transcriptional start site and analyzing the region immediately upstream of para in region 14D of the polytene chromosomes. From these studies, we have discovered that the region contains a cluster of neurally expressing genes. Here we report the molecular characterization of the genomic organization of the 14D region and the genes within this region, which are: calnexin (Cnx), actin related protein 14D (Arp14D), calcineurin A 14D (CnnA14D), and chromosome associated protein (Cap). The tight clustering of these genes, their neuronal expression patterns, and their potential functions related to expression, modulation, or regulation of sodium channels raise the possibility that these genes represent a functionally related group sharing some coordinate regulatory mechanism. 76 refs., 11 figs.

  16. Interest in politics modulates neural activity in the amygdala and ventral striatum.

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    Gozzi, Marta; Zamboni, Giovanna; Krueger, Frank; Grafman, Jordan

    2010-11-01

    Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. © 2010 Wiley-Liss, Inc.

  17. Improving Maritime Domain Awareness Using Neural Networks for Target of Interest Classification

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    2015-03-01

    Hough transfonnation is used to identify and characterize linear pa.ttenlS exhibited by objects in images. As an alternative to geometric and photometric...interest classification is a. significant result of this thesis. 14. SUBJECT TERMS 15. NUMBER OF Netu·al networks, feature extraction, Hough ...determine if the object belongs to one of four classes specified: warship, cargo ship, small boat, or other. The Hough transformation is used to

  18. Classifying region of interests from mammograms with breast cancer into BIRADS using Artificial Neural Networks

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    Estefanía D. Avalos-Rivera

    2017-05-01

    Full Text Available Breast cancer is one of the most common cancers among female diseases all over the world. Early diagnosis and treatment is particularly important in reducing the mortality rate. This research is focused on the prevention of breast cancer, therefore it is important to detect micro-calcifications (MCs which are a sign of early stage breast cancer. Micro-calcifications are tiny deposits of calcium which are visible on mammograms as they present as tiny white spots. A computer-aided diagnosis system (CAD is created with the development of computer technology that way radiologists are aided improving their diagnostics while using CAD as a second reader. We are aiming to classify into BIRADS 2, 3 and 4 which are the stages when the cancer can be prevented and a fourth category called No lesion which are veins and tissue that our high pass Gaussian filter detects. This research focuses on classification using ANN (Artificial Neural Network. Experimenting with the categories to classify into using ANN, the results were the following: into the four mentioned before an overall accuracy of 71% was obtained, then joining categories BIRADS 2 and 3 into one and classifying into 3 categories gave an 80% of accuracy. Joining this two categories was the result of analizing the ROC curve and observation of the ROI images of the MCs as the regions measured are very alike in this two categories and variation is that MCs are more present in BIRADS 3 than in BIRADS 2. Data matrix was reduced using PCA (Principal Component Analysis but it did not gave better results so it was discarded as the ANN accuracy to classify was reduced to a 69.8%.

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

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    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.

  20. Intellectual Interest Mediates Gene-by-SES Interaction on Adolescent Academic Achievement

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    Tucker-Drob, Elliot M.; Harden, K. Paige

    2011-01-01

    Recent studies have demonstrated that genetic influences on cognitive ability and academic achievement are larger for children raised in higher socioeconomic status (SES) homes. However, little work has been done to document the psychosocial processes that underlie this gene-by-environment interaction. One process may involve the conversion of intellectual interest into academic achievement. Analyses of data from 777 pairs of 17-year-old twins indicated that gene-by-SES effects on achievement scores can be accounted for by stronger influences of genes for intellectual interest on achievement at higher levels of SES. These findings are consistent with the hypothesis that higher SES affords greater opportunity for children to seek out and benefit from learning experiences that are congruent with their genetically influenced intellectual interests. PMID:22288554

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

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    Miki Yamamoto-Hino

    2010-12-01

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

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

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    Leila Dehghani

    2013-01-01

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

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

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    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

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

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    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

  5. Regulators of gene expression in Enteric Neural Crest Cells are putative Hirschsprung disease genes.

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    Schriemer, Duco; Sribudiani, Yunia; IJpma, Arne; Natarajan, Dipa; MacKenzie, Katherine C; Metzger, Marco; Binder, Ellen; Burns, Alan J; Thapar, Nikhil; Hofstra, Robert M W; Eggen, Bart J L

    2016-08-01

    The enteric nervous system (ENS) is required for peristalsis of the gut and is derived from Enteric Neural Crest Cells (ENCCs). During ENS development, the RET receptor tyrosine kinase plays a critical role in the proliferation and survival of ENCCs, their migration along the developing gut, and differentiation into enteric neurons. Mutations in RET and its ligand GDNF cause Hirschsprung disease (HSCR), a complex genetic disorder in which ENCCs fail to colonize variable lengths of the distal bowel. To identify key regulators of ENCCs and the pathways underlying RET signaling, gene expression profiles of untreated and GDNF-treated ENCCs from E14.5 mouse embryos were generated. ENCCs express genes that are involved in both early and late neuronal development, whereas GDNF treatment induced neuronal maturation. Predicted regulators of gene expression in ENCCs include the known HSCR genes Ret and Sox10, as well as Bdnf, App and Mapk10. The regulatory overlap and functional interactions between these genes were used to construct a regulatory network that is underlying ENS development and connects to known HSCR genes. In addition, the adenosine receptor A2a (Adora2a) and neuropeptide Y receptor Y2 (Npy2r) were identified as possible regulators of terminal neuronal differentiation in GDNF-treated ENCCs. The human orthologue of Npy2r maps to the HSCR susceptibility locus 4q31.3-q32.3, suggesting a role for NPY2R both in ENS development and in HSCR. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series.

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    Rubiolo, Mariano; Milone, Diego H; Stegmayer, Georgina

    2015-01-01

    Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles.

  7. Genome-wide gene amplification during differentiation of neural progenitor cells in vitro.

    Directory of Open Access Journals (Sweden)

    Ulrike Fischer

    Full Text Available DNA sequence amplification is a phenomenon that occurs predictably at defined stages during normal development in some organisms. Developmental gene amplification was first described in amphibians during gametogenesis and has not yet been described in humans. To date gene amplification in humans is a hallmark of many tumors. We used array-CGH (comparative genomic hybridization and FISH (fluorescence in situ hybridization to discover gene amplifications during in vitro differentiation of human neural progenitor cells. Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells. We identified several amplified genes in neural progenitor cells that are known to be amplified in malignant tumors. There is also a striking overlap of amplified chromosomal regions between differentiating neural progenitor cells and malignant tumor cells derived from astrocytes. Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

  8. [Cluster ensemble algorithm based on dual neural gas applied to cancer gene expression profiles].

    Science.gov (United States)

    Zhang, Xiaodong; Chen, Hantao

    2015-02-01

    The microarray technology used in biological and medical research provides a new idea for the diagnosis and treatment of cancer. To find different types of cancer and to classify the cancer samples accurately, we propose a new cluster ensemble framework Dual Neural Gas Cluster Ensemble (DNGCE), which is based on neural gas algorithm, to discover the underlying structure of noisy cancer gene expression profiles. This framework DNGCE applies the neural gas algorithm to perform clustering not only on the sample dimension, but also on the attribute dimension. It also adopts the normalized cut algorithm to partition off the consensus matrix constructed from multiple clustering solutions. We obtained the final accurate results. Experiments on cancer gene expression profiles illustrated that the proposed approach could achieve good performance, as it outperforms the single clustering algorithms and most of the existing approaches in the process of clustering gene expression profiles.

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

    Science.gov (United States)

    Fukuchi, Mamoru

    2017-01-01

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

  10. Neural model of gene regulatory network: a survey on supportive meta-heuristics.

    Science.gov (United States)

    Biswas, Surama; Acharyya, Sriyankar

    2016-06-01

    Gene regulatory network (GRN) is produced as a result of regulatory interactions between different genes through their coded proteins in cellular context. Having immense importance in disease detection and drug finding, GRN has been modelled through various mathematical and computational schemes and reported in survey articles. Neural and neuro-fuzzy models have been the focus of attraction in bioinformatics. Predominant use of meta-heuristic algorithms in training neural models has proved its excellence. Considering these facts, this paper is organized to survey neural modelling schemes of GRN and the efficacy of meta-heuristic algorithms towards parameter learning (i.e. weighting connections) within the model. This survey paper renders two different structure-related approaches to infer GRN which are global structure approach and substructure approach. It also describes two neural modelling schemes, such as artificial neural network/recurrent neural network based modelling and neuro-fuzzy modelling. The meta-heuristic algorithms applied so far to learn the structure and parameters of neutrally modelled GRN have been reviewed here.

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

    Science.gov (United States)

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

    2015-01-15

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

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

    Science.gov (United States)

    Miao, Chunyue; Jiang, Qian; Li, Huili; Zhang, Qin; Bai, Baoling; Bao, Yihua; Zhang, Ting

    2016-10-13

    Neural tube defects (NTDs) are severe malformations of the central nervous system caused by complex genetic and environmental factors. Among genes involved in NTD, cilia-related genes have been well defined and found to be essential for the completion of neural tube closure (NTC). We have carried out next-generation sequencing on target genes in 373 NTDs and 222 healthy controls, and discovered eight disease-specific rare mutations in cilia-related gene DNAAF1 DNAAF1 plays a central role in cytoplasmic preassembly of distinct dynein-arm complexes, and is expressed in some key tissues involved in neural system development, such as neural tube, floor plate, embryonic node, and brain ependyma epithelial cells in zebrafish and mouse. Therefore, we evaluated the expression and functions of mutations in DNAAF1 in transfected cells to analyze the potential correlation of these mutants to NTDs in humans. One rare frameshift mutation (p.Gln341Argfs*10) resulted in significantly diminished DNAAF1 protein expression, compared to the wild type. Another mutation, p.Lys231Gln, disrupted cytoplasmic preassembly of the dynein-arm complexes in cellular assay. Furthermore, results from NanoString assay on mRNA from NTD samples indicated that DNAAF1 mutants altered the expression level of NTC-related genes. Altogether, these findings suggest that the rare mutations in DNAAF1 may contribute to the susceptibility for NTDs in humans. Copyright © 2016 Miao et al.

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

    Directory of Open Access Journals (Sweden)

    Chunyue Miao

    2016-10-01

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

  14. 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.

  15. Gene Expression Based Leukemia Sub-Classification Using Committee Neural Networks

    OpenAIRE

    Sewak, Mihir S.; Reddy, Narender P.; Duan, Zhong-Hui

    2009-01-01

    Analysis of gene expression data provides an objective and efficient technique for sub‑classification of leukemia. The purpose of the present study was to design a committee neural networks based classification systems to subcategorize leukemia gene expression data. In the study, a binary classification system was considered to differentiate acute lymphoblastic leukemia from acute myeloid leukemia. A ternary classification system which classifies leukemia expression data into three subclasses...

  16. Neural response to alcohol taste cues in youth : Effects of the OPRM1 gene

    NARCIS (Netherlands)

    Korucuoglu, Ozlem; Gladwin, Thomas E.; Baas, Frank; Mocking, Roel J. T.; Ruhé, Henricus G.; Groot, Paul F. C.; Wiers, Reinout W.

    2017-01-01

    Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively

  17. Gene Expression Based Leukemia Sub‑Classification Using Committee Neural Networks

    Directory of Open Access Journals (Sweden)

    Mihir S. Sewak

    2009-09-01

    Full Text Available Analysis of gene expression data provides an objective and efficient technique for sub‑classification of leukemia. The purpose of the present study was to design a committee neural networks based classification systems to subcategorize leukemia gene expression data. In the study, a binary classification system was considered to differentiate acute lymphoblastic leukemia from acute myeloid leukemia. A ternary classification system which classifies leukemia expression data into three subclasses including B‑cell acute lymphoblastic leukemia, T‑cell acute lymphoblastic leukemia and acute myeloid leukemia was also developed. In each classification system gene expression profiles of leukemia patients were first subjected to a sequence of simple preprocessing steps. This resulted in filtering out approximately 95 percent of the non‑informative genes. The remaining 5 percent of the informative genes were used to train a set of artificial neural networks with different parameters and architectures. The networks that gave the best results during initial testing were recruited into a committee. The committee decision was by majority voting. The committee neural network system was later evaluated using data not used in training. The binary classification system classified microarray gene expression profiles into two categories with 100 percent accuracy and the ternary system correctly predicted the three subclasses of leukemia in over 97 percent of the cases.

  18. Artificial neural network inference (ANNI: a study on gene-gene interaction for biomarkers in childhood sarcomas.

    Directory of Open Access Journals (Sweden)

    Dong Ling Tong

    Full Text Available OBJECTIVE: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI. METHOD: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. RESULTS: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS; FCGRT and OLFM1 in Ewing's sarcoma (EWS suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. CONCLUSIONS: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas.

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

    Directory of Open Access Journals (Sweden)

    Lauren J. Manderfield

    2014-12-01

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

  20. Informational lesions: optical perturbation of spike timing and neural synchrony via microbial opsin gene fusions

    Directory of Open Access Journals (Sweden)

    Xue Han

    2009-08-01

    Full Text Available Synchronous neural activity occurs throughout the brain in association with normal and pathological brain functions. Despite theoretical work exploring how such neural coordination might facilitate neural computation and be corrupted in disease states, it has proven difficult to test experimentally the causal role of synchrony in such phenomena. Attempts to manipulate neural synchrony often alter other features of neural activity such as firing rate. Here we evaluate a single gene which encodes for the blue-light gated cation channel channelrhodopsin-2 and the yellow-light driven chloride pump halorhodopsin from N. pharaonis, linked by a ‘self-cleaving’ 2A peptide. This fusion enables proportional expression of both opsins, sensitizing neurons to being bi-directionally controlled with blue and yellow light, facilitating proportional optical spike insertion and deletion upon delivery of trains of precisely-timed blue and yellow light pulses. Such approaches may enable more detailed explorations of the causal role of specific features of the neural code.

  1. Prediction of Clinical Outcome Using Gene Expression Profiling and Artificial Neural Networks for Patients with Neuroblastoma

    Science.gov (United States)

    Wei, Jun S.; Greer, Braden T.; Westermann, Frank; Steinberg, Seth M.; Son, Chang-Gue; Chen, Qing-Rong; Whiteford, Craig C.; Bilke, Sven; Krasnoselsky, Alexei L.; Cenacchi, Nicola; Catchpoole, Daniel; Berthold, Frank; Schwab, Manfred; Khan, Javed

    2005-01-01

    Currently, patients with neuroblastoma are classified into risk groups (e.g., according to the Children’s Oncology Group risk-stratification) to guide physicians in the choice of the most appropriate therapy. Despite this careful stratification, the survival rate for patients with high-risk neuroblastoma remains artificial neural networks to develop an accurate predictor of survival for each individual patient with neuroblastoma. Using principal component analysis we found that neuroblastoma tumors exhibited inherent prognostic specific gene expression profiles. Subsequent artificial neural network-based prognosis prediction using expression levels of all 37,920 good-quality clones achieved 88% accuracy. Moreover, using an artificial neural network-based gene minimization strategy in a separate analysis we identified 19 genes, including 2 prognostic markers reported previously, MYCN and CD44, which correctly predicted outcome for 98% of these patients. In addition, these 19 predictor genes were able to additionally partition Children’s Oncology Group-stratified high-risk patients into two subgroups according to their survival status (P = 0.0005). Our findings provide evidence of a gene expression signature that can predict prognosis independent of currently known risk factors and could assist physicians in the individual management of patients with high-risk neuroblastoma. PMID:15466177

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Cell cycle-related genes p57kip2, Cdk5 and Spin in the pathogenesis of neural tube defects.

    Science.gov (United States)

    Li, Xinjun; Yang, Zhong; Zeng, Yi; Xu, Hong; Li, Hongli; Han, Yangyun; Long, Xiaodong; You, Chao

    2013-07-15

    In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an important role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

  4. Detection of copy number variants reveals association of cilia genes with neural tube defects.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    Full Text Available BACKGROUND: Neural tube defects (NTDs are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. METHODS: The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. RESULTS: Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV. Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05. Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24-5.87. Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05, corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27-8.01. Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. CONCLUSIONS: Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.

  5. Selection of suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using quantitative real-time polymerase chain reaction

    DEFF Research Database (Denmark)

    Zornhagen, K. W.; Kristensen, A. T.; Hansen, Anders Elias

    2015-01-01

    . The objective of this study was to demonstrate how to identify suitable reference genes for normalization of genes of interest in canine soft tissue sarcomas using RT-qPCR. Primer pairs for 17 potential reference genes were designed and tested in archival tumour biopsies from six dogs. The geNorm algorithm.......053 describing their average stability. We suggest that choice of reference genes should be based on specific testing in every new experimental set-up....

  6. Neural networks for modeling gene-gene interactions in association studies

    Directory of Open Access Journals (Sweden)

    Bammann Karin

    2009-12-01

    Full Text Available Abstract Background Our aim is to investigate the ability of neural networks to model different two-locus disease models. We conduct a simulation study to compare neural networks with two standard methods, namely logistic regression models and multifactor dimensionality reduction. One hundred data sets are generated for each of six two-locus disease models, which are considered in a low and in a high risk scenario. Two models represent independence, one is a multiplicative model, and three models are epistatic. For each data set, six neural networks (with up to five hidden neurons and five logistic regression models (the null model, three main effect models, and the full model with two different codings for the genotype information are fitted. Additionally, the multifactor dimensionality reduction approach is applied. Results The results show that neural networks are more successful in modeling the structure of the underlying disease model than logistic regression models in most of the investigated situations. In our simulation study, neither logistic regression nor multifactor dimensionality reduction are able to correctly identify biological interaction. Conclusions Neural networks are a promising tool to handle complex data situations. However, further research is necessary concerning the interpretation of their parameters.

  7. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans

    National Research Council Canada - National Science Library

    Feng, C; Lori, A; Waldman, I. D; Binder, E. B; Haroon, E; Rilling, J. K

    2015-01-01

    .... However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene ( OXTR...

  8. Identification of cell cycle-regulated genes by convolutional neural network.

    Science.gov (United States)

    Liu, Chenglin; Cui, Peng; Huang, Tao

    2017-04-17

    The cell cycle-regulated genes express periodically with the cell cycle stages, and the identification and study of these genes can provide a deep understanding of the cell cycle process. Large false positives and low overlaps are big problems in cell cycle-regulated gene detection. Here, a computational framework called DLGene was proposed for cell cycle-regulated gene detection. It is based on the convolutional neural network, a deep learning algorithm representing raw form of data pattern without assumption of their distribution. First, the expression data was transformed to categorical state data to denote the changing state of gene expression, and four different expression patterns were revealed for the reported cell cycle-regulated genes. Then, DLGene was applied to discriminate the non-cell cycle gene and the four subtypes of cell cycle genes. Its performances were compared with six traditional machine learning methods. At last, the biological functions of representative cell cycle genes for each subtype were analyzed. Our method showed better and more balanced performance of sensitivity and specificity comparing to other machine learning algorithms. The cell cycle genes had very different expression pattern with non-cell cycle genes and among the cell-cycle genes, there were four subtypes. Our method not only detects the cell cycle genes, but also describes its expression pattern, such as when its highest expression level is reached and how it changes with time. For each type, we analyzed the biological functions of the representative genes and such results provided novel insight of the cell cycle mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis.

    Science.gov (United States)

    Wang, Guang; Li, Yan; Wang, Xiao-Yu; Chuai, Manli; Yeuk-Hon Chan, John; Lei, Jian; Münsterberg, Andrea; Lee, Kenneth Ka Ho; Yang, Xuesong

    2015-03-01

    The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7(+) somite development and directly increased HNK-1(+) neural crest cell (NCC) migration and TuJ-1(+) neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development. © 2015 Wang, Li, Wang, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor

    Science.gov (United States)

    Paonessa, Francesco; Criscuolo, Stefania; Sacchetti, Silvio; Amoroso, Davide; Scarongella, Helena; Pecoraro Bisogni, Federico; Carminati, Emanuele; Pruzzo, Giacomo; Maragliano, Luca; Cesca, Fabrizia; Benfenati, Fabio

    2016-01-01

    Optogenetics provides new ways to activate gene transcription; however, no attempts have been made as yet to modulate mammalian transcription factors. We report the light-mediated regulation of the repressor element 1 (RE1)-silencing transcription factor (REST), a master regulator of neural genes. To tune REST activity, we selected two protein domains that impair REST-DNA binding or recruitment of the cofactor mSin3a. Computational modeling guided the fusion of the inhibitory domains to the light-sensitive Avena sativa light–oxygen–voltage-sensing (LOV) 2-phototrophin 1 (AsLOV2). By expressing AsLOV2 chimeras in Neuro2a cells, we achieved light-dependent modulation of REST target genes that was associated with an improved neural differentiation. In primary neurons, light-mediated REST inhibition increased Na+-channel 1.2 and brain-derived neurotrophic factor transcription and boosted Na+ currents and neuronal firing. This optogenetic approach allows the coordinated expression of a cluster of genes impinging on neuronal activity, providing a tool for studying neuronal physiology and correcting gene expression changes taking place in brain diseases. PMID:26699507

  11. Falling giants and the rise of gene editing: ethics, private interests and the public good.

    Science.gov (United States)

    Capps, Benjamin; Chadwick, Ruth; Joly, Yann; Mulvihill, John J; Lysaght, Tamra; Zwart, Hub

    2017-08-29

    This paper considers the tensions created in genomic research by public and private for-profit ideals. Our intent is to strengthen the public good at a time when doing science is strongly motivated by market possibilities and opportunities. Focusing on the emergence of gene editing, and in particular CRISPR, we consider how commercialisation encourages hype and hope-a sense that only promise and idealism can achieve progress. At this rate, genomic research reinforces structures that promote, above all else, private interests, but that may attenuate conditions for the public good of science. In the first part, we situate genomics using the aphorism that 'on the shoulders of giants we see farther'; these giants are infrastructures and research cultures rather than individual 'heroes' of science. In this respect, private initiatives are not the only pivot for successful discovery, and indeed, fascination in those could impinge upon the fundamental role of public-supported discovery. To redress these circumstances, we define the extent to which progress presupposes research strategies that are for the public good. In the second part, we use a 'falling giant' narrative to illustrate the risks of over-indulging for-profit initiatives. We therefore offer a counterpoint to commercialised science, using three identifiable 'giants'-scientists, publics and cultures-to illustrate how the public good contributes to genomic discovery.

  12. A microarray gene expression data classification using hybrid back propagation neural network

    Directory of Open Access Journals (Sweden)

    Vimaladevi M.

    2014-01-01

    Full Text Available Classification of cancer establishes appropriate treatment and helps to decide the diagnosis. Cancer expands progressively from an alteration in a cell's genetic structure. This change (mutation results in cells with uncontrolled growth patterns. In cancer classification, the approach, Back propagation is sufficient and also it is a universal technique of training artificial neural networks. It is also called supervised learning method. It needs many dataset for input and output for making up the training set. The back propagation method may execute the function of collaborate multiple parties. In existing method, collaborative learning is limited and it considers only two parties. The proposed collaborative function can perform well and problems can be solved by utilizing the power of cloud computing. This technical note applies hybrid models of Back Propagation Neural networks (BPN and fast Genetic Algorithms (GA to estimate the feature selection in gene expression data. The proposed research work examines many feature selection algorithms which are “fragile”; that is, the superiority of their results varies broadly over data sets. By this research, it is suggested that this is due to higherorder interactions between features causing restricted minima in search space in which the algorithm becomes attentive. GAs may escape from such minima by chance, because works are highly stochastic. A neural net classifier with a genetic algorithm, using the GA to select features for classification by the neural net and incorporating the net as part of the objective function of the GA.

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

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    V. Bleu Knight

    2017-01-01

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

  14. atonal- and achaete-scute-related genes in the annelid Platynereis dumerilii: insights into the evolution of neural basic-Helix-Loop-Helix genes

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    Arendt Detlev

    2008-06-01

    Full Text Available Abstract Background Functional studies in model organisms, such as vertebrates and Drosophila, have shown that basic Helix-loop-Helix (bHLH proteins have important roles in different steps of neurogenesis, from the acquisition of neural fate to the differentiation into specific neural cell types. However, these studies highlighted many differences in the expression and function of orthologous bHLH proteins during neural development between vertebrates and Drosophila. To understand how the functions of neural bHLH genes have evolved among bilaterians, we have performed a detailed study of bHLH genes during nervous system development in the polychaete annelid, Platynereis dumerilii, an organism which is evolutionary distant from both Drosophila and vertebrates. Results We have studied Platynereis orthologs of the most important vertebrate neural bHLH genes, i.e. achaete-scute, neurogenin, atonal, olig, and NeuroD genes, the latter two being genes absent of the Drosophila genome. We observed that all these genes have specific expression patterns during nervous system formation in Platynereis. Our data suggest that in Platynereis, like in vertebrates but unlike Drosophila, (i neurogenin is the main proneural gene for the formation of the trunk central nervous system, (ii achaete-scute and olig genes are involved in neural subtype specification in the central nervous system, in particular in the specification of the serotonergic phenotype. In addition, we found that the Platynereis NeuroD gene has a broad and early neuroectodermal expression, which is completely different from the neuronal expression of vertebrate NeuroD genes. Conclusion Our analysis suggests that the Platynereis bHLH genes have both proneural and neuronal specification functions, in a way more akin to the vertebrate situation than to that of Drosophila. We conclude that these features are ancestral to bilaterians and have been conserved in the vertebrates and annelids lineages, but

  15. Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1

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    Sankar, Savita; Yellajoshyula, Dhananjay; Zhang, Bo; Teets, Bryan; Rockweiler, Nicole; Kroll, Kristen L.

    2016-01-01

    Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined. Here, we identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. We determined how Geminin deficiency affected histone acetylation at gene promoters during this process. We integrated these data to demonstrate that Geminin associates with and promotes histone acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system-enriched expression and encode other regulators of neural development. Both Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs, while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co-regulatory potential. Accordingly, we found that Geminin and Zic1 could cooperatively activate the expression of several shared targets encoding transcription factors that control neurogenesis, neural plate patterning, and neuronal differentiation. We used these data to construct gene regulatory networks underlying neural fate acquisition. Establishment of this molecular program in nascent neuroectoderm directly links early neural cell fate acquisition with regulatory control of later neurodevelopment. PMID:27881878

  16. RNA interference machinery-mediated gene regulation in mouse adult neural stem cells.

    Science.gov (United States)

    Cernilogar, Filippo M; Di Giaimo, Rossella; Rehfeld, Frederick; Cappello, Silvia; Lie, D Chichung

    2015-09-19

    Neurogenesis in the brain of adult mammals occurs throughout life in two locations: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. RNA interference mechanisms have emerged as critical regulators of neuronal differentiation. However, to date, little is known about its function in adult neurogenesis. Here we show that the RNA interference machinery regulates Doublecortin levels and is associated with chromatin in differentiating adult neural progenitors. Deletion of Dicer causes abnormal higher levels of Doublecortin. The microRNA pathway plays an important role in Doublecortin regulation. In particular miRNA-128 overexpression can reduce Doublecortin levels in differentiating adult neural progenitors. We conclude that the RNA interference components play an important role, even through chromatin association, in regulating neuron-specific gene expression programs.

  17. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks

    Science.gov (United States)

    Khan, Javed; Wei, Jun S.; Ringnér, Markus; Saal, Lao H.; Ladanyi, Marc; Westermann, Frank; Berthold, Frank; Schwab, Manfred; Antonescu, Cristina R.; Peterson, Carsten; Meltzer, Paul S.

    2005-01-01

    The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification. Expression of several of these genes has been reported in SRBCTs, but most have not been associated with these cancers. To test the ability of the trained ANN models to recognize SRBCTs, we analyzed additional blinded samples that were not previously used for the training procedure, and correctly classified them in all cases. This study demonstrates the potential applications of these methods for tumor diagnosis and the identification of candidate targets for therapy. PMID:11385503

  18. University Students' Conceptions about the Concept of Gene: Interest of Historical Approach

    Science.gov (United States)

    Boujemaa, Agorram; Pierre, Clement; Sabah, Selmaoui; Salaheddine, Khzami; Jamal, Chafik; Abdellatif, Chiadli

    2010-01-01

    Concepts of genetics are often difficult to teach, specifically the central concept of gene. Even the scientists disagree when defining this concept. This paper investigates university students' understanding about the gene and its functions. The results show the dominance of two conceptions of the gene: the Neoclassical model and the Mendelian…

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

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    Montzka Katrin

    2009-03-01

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

  20. Isolating dividing neural and brain tumour cells for gene expression profiling.

    Science.gov (United States)

    Endaya, Berwini; Cavanagh, Brenton; Alowaidi, Faisal; Walker, Tom; de Pennington, Nicholas; Ng, Jin-Ming A; Lam, Paula Y P; Mackay-Sim, Alan; Neuzil, Jiri; Meedeniya, Adrian C B

    2016-01-15

    The characterisation of dividing brain cells is fundamental for studies ranging from developmental and stem cell biology, to brain cancers. Whilst there is extensive anatomical data on these dividing cells, limited gene transcription data is available due to technical constraints. We focally isolated dividing cells whilst conserving RNA, from culture, primary neural tissue and xenografted glioma tumours, using a thymidine analogue that enables gene transcription analysis. 5-ethynyl-2-deoxyuridine labels the replicating DNA of dividing cells. Once labelled, cultured cells and tissues were dissociated, fluorescently tagged with a revised click chemistry technique and the dividing cells isolated using fluorescence-assisted cell sorting. RNA was extracted and analysed using real time PCR. Proliferation and maturation related gene expression in neurogenic tissues was demonstrated in acutely and 3 day old labelled cells, respectively. An elevated expression of marker and pathway genes was demonstrated in the dividing cells of xenografted brain tumours, with the non-dividing cells showing relatively low levels of expression. BrdU "immune-labelling", the most frequently used protocol for detecting cell proliferation, causes complete denaturation of RNA, precluding gene transcription analysis. This EdU labelling technique, maintained cell integrity during dissociation, minimized copper exposure during labelling and used a cell isolation protocol that avoided cell lysis, thus conserving RNA. The technique conserves RNA, enabling the definition of cell proliferation-related changes in gene transcription of neural and pathological brain cells in cells harvested immediately after division, or following a period of maturation. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells

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    Tsutomu Motohashi

    2016-03-01

    Full Text Available Neural crest cells (NC cells are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+ cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.

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

    Science.gov (United States)

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

    2017-12-20

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

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

    Science.gov (United States)

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

    2013-01-01

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

  4. Delivery of cationic polymer-siRNA nanoparticles for gene therapies in neural regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Yanran [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Liu, Zhonglin, E-mail: zhonglinliu@126.com [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Shuai, Xintao; Wang, Weiwei [School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, People' s Republic of China (China); Liu, Jun [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Bi, Wei [Department of Neurology, The First Affiliated Hospital of Jinan University, No. 613, West Huangpu Road, Guangzhou 510630, People' s Republic of China (China); Wang, Chuanming; Jing, Xiuna; Liu, Yunyun [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China); Tao, Enxiang, E-mail: taoenxiang@yahoo.com.cn [Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, People' s Republic of China (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Nogo receptor can inhibit growth of injured axons, thus affecting neural regeneration. Black-Right-Pointing-Pointer The delivery of siRNA is crucial to inhibit NgR expression in NSCs. Black-Right-Pointing-Pointer Non-viral vector PEG-PEI condensed siRNA targeting NgR into nanoscale particles. Black-Right-Pointing-Pointer PEG-PEI/siRNA at N/P = 15 displayed high transfection efficiency and low cytotoxicity. Black-Right-Pointing-Pointer PEG-PEI has great potential in carrying siRNA to diminish the gene expression in NSCs. -- Abstract: The therapeutic applications of neural stem cells (NSCs) have potential to promote recovery in many obstinate diseases in central nervous system. Regulation of certain gene expressions using siRNA may have significant influence on the fate of NSC. To achieve the optimum gene silencing effect of siRNA, non-viral vector polyethylene glycol-polyethyleneimine (PEG-PEI) was investigated in the delivery of siRNA to NSCs. The characteristics of PEG-PEI/siRNA polyplexes were detected by scanning electron microscopy (SEM). The effects of nanoparticles on cell viability were measured via CCK-8 assay. In addition, the transfection efficiency was evaluated by fluorescence microscope and flow cytometry, and real-time PCR and Western Blot were employed to detect the gene inhibition effect of siRNA delivered by PEG-PEI. The SEM micrographs showed that PEG-PEI could condense siRNA to form diffuse and spherical nanoparticles. The cytotoxicity of PEG-PEI/siRNA nanocomplexes (N/P = 15) was significantly lower when compared with that of Lipofectamine 2000/siRNA (P < 0.05). Moreover, the highest transfection efficiency of PEG-PEI/siRNA nanoparticles was obtained at an N/P ratio of 15, which was better than that achieved in the transfection using Lipofectamine 2000 (P < 0.05). Finally, the gene knockdown effect of PEG-PEI/siRNA nanoparticles was verified at the levels of mRNA and protein. These results suggest that

  5. Speech sound processing deficits and training-induced neural plasticity in rats with dyslexia gene knockdown.

    Directory of Open Access Journals (Sweden)

    Tracy M Centanni

    Full Text Available In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA- degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments.

  6. Distinct actions of ancestral vinclozolin and juvenile stress on neural gene expression in the male rat

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    Ross eGillette

    2015-03-01

    Full Text Available Exposure to the endocrine disrupting chemical vinclozolin during gestation of an F0 generation and/or chronic restraint stress during adolescence of the F3 descendants affects behavior, physiology, and gene expression in the brain. Genes related to the networks of growth factors, signaling peptides and receptors, steroid hormone receptors and enzymes, and epigenetic related factors were measured using quantitative polymerase chain reaction via Taqman low density arrays targeting 48 genes in the central amygdaloid nucleus, medial amygdaloid nucleus, medial preoptic area, lateral hypothalamus, and the ventromedial nucleus of the hypothalamus. We found that growth factors are particularly vulnerable to ancestral exposure in the central and medial amygdala; restraint stress during adolescence affected neural growth factors in the medial amygdala. Signaling peptides were affected by both ancestral exposure and stress during adolescence primarily in hypothalamic nuclei. Steroid hormone receptors and enzymes were strongly affected by restraint stress in the medial preoptic area. Epigenetic related genes were affected by stress in the ventromedial hypothalamus and by both ancestral exposure and stress during adolescence independently in the central amygdala. It is noteworthy that the lateral hypothalamus showed no effects of either manipulation. Gene expression is discussed in the context of behavioral and physiological measures previously published.

  7. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina.

    Science.gov (United States)

    Zhou, Xue-mei; Yuan, Hui-ping; Wu, Dong-lai; Zhou, Xin-rong; Sun, Da-wei; Li, Hong-yi; Shao, Zheng-bo

    2009-07-20

    Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P neuron more efficiently compared with the control NSCs 2 months after transplantation. The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in the normal host retinas.

  8. Viral-mediated gene transfer to mouse primary neural progenitor cells.

    Science.gov (United States)

    Hughes, Stephanie M; Moussavi-Harami, Farid; Sauter, Sybille L; Davidson, Beverly L

    2002-01-01

    Neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. The expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. To address this issue, we cultured cells from embryonic day 16-18 mouse brain in serum-free medium containing epidermal growth factor or basic fibroblast growth factor, and investigated how transduction with recombinant viral vectors affected maintenance and differentiation properties of progenitor cells. Neurosphere cultures were incubated with feline immunodeficiency virus (FIV), adeno-associated virus (AAV) or ade-noviral (Ad) constructs expressing either beta-galactosidase or enhanced green fluorescent protein at low multiplicity of infection. Nestin-positive neurospheres were regenerated after incubation of single progenitor cells with FIV, indicating that FIV-mediated gene transfer did not inhibit progenitor cell self-renewal. In contrast, adenovirus induced differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes. The AAV serotypes tested did not effectively transduce progenitor cells. FIV-transduced progenitors retained the potential for differentiation into neurons and glia in vitro, and when transplanted into the striatum of normal adult C57BL/6 mice differentiated into glia, or remained undifferentiated. In the presence of tumor cells, FIV-transduced progenitors migrated significantly from the injection site. Our results suggest that FIV-based vectors can transduce progenitor cell populations in vitro, with maintenance of their ability to differentiate into multiple cell types or to respond to injury within the central nervous system. These results hold promise for the use of genetically manipulated stem cells for CNS therapies.

  9. Intellectual Interest Mediates Gene x Socioeconomic Status Interaction on Adolescent Academic Achievement

    Science.gov (United States)

    Tucker-Drob, Elliot M.; Harden, K. Paige

    2012-01-01

    Recent studies have demonstrated that genetic influences on cognitive ability and academic achievement are larger for children raised in higher socioeconomic status (SES) homes. However, little work has been done to document the psychosocial processes that underlie this Gene x Environment interaction. One process may involve the conversion of…

  10. Folate-related gene variants in Irish families affected by neural tube defects

    Directory of Open Access Journals (Sweden)

    Ridgely eFisk Green

    2013-11-01

    Full Text Available Periconceptional folic acid use can often prevent neural tube defects (NTDs. Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (risk genotypes and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p=0.017. We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential

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

    Science.gov (United States)

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

    2013-11-01

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

  12. The p53 tumour suppressor gene and the tobacco industry: research, debate, and conflict of interest

    OpenAIRE

    Bitton, A; Neuman, M D; Barnoya, J; Glantz, Stanton A. Ph.D.

    2005-01-01

    Mutations in the p53 tumour suppressor gene lead to uncontrolled cell division and are found in over 50% of all human tumours, including 60% of lung cancers. Research published in 1996 by Denissenko and colleagues demonstrated patterned in-vitro mutagenic effects on p53 of benzo[a]pyrene, a carcinogen present in tobacco smoke. We investigated the tobacco industry's response to p53 research linking smoking to cancer. We searched online tobacco document archives, including the Legacy Tobacco Do...

  13. Recurrent neural network-based modeling of gene regulatory network using elephant swarm water search algorithm.

    Science.gov (United States)

    Mandal, Sudip; Saha, Goutam; Pal, Rajat Kumar

    2017-08-01

    Correct inference of genetic regulations inside a cell from the biological database like time series microarray data is one of the greatest challenges in post genomic era for biologists and researchers. Recurrent Neural Network (RNN) is one of the most popular and simple approach to model the dynamics as well as to infer correct dependencies among genes. Inspired by the behavior of social elephants, we propose a new metaheuristic namely Elephant Swarm Water Search Algorithm (ESWSA) to infer Gene Regulatory Network (GRN). This algorithm is mainly based on the water search strategy of intelligent and social elephants during drought, utilizing the different types of communication techniques. Initially, the algorithm is tested against benchmark small and medium scale artificial genetic networks without and with presence of different noise levels and the efficiency was observed in term of parametric error, minimum fitness value, execution time, accuracy of prediction of true regulation, etc. Next, the proposed algorithm is tested against the real time gene expression data of Escherichia Coli SOS Network and results were also compared with others state of the art optimization methods. The experimental results suggest that ESWSA is very efficient for GRN inference problem and performs better than other methods in many ways.

  14. Genome-wide copy number profiling to detect gene amplifications in neural progenitor cells

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    U. Fischer

    2014-12-01

    Full Text Available DNA sequence amplification occurs at defined stages during normal development in amphibians and flies and seems to be restricted in humans to drug-resistant and tumor cells only. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of human neural progenitor cells. Here, we describe cell culture features, DNA extraction, and comparative genomic hybridization (CGH analysis tailored towards the identification of genomic copy number changes. Further detailed analysis of amplified chromosome regions associated with this experiment, was published by Fischer and colleagues in PLOS One in 2012 (Fischer et al., 2012. We provide detailed information on deleted chromosome regions during differentiation and give an overview on copy number changes during differentiation induction for two representative chromosome regions.

  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. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks | Center for Cancer Research

    Science.gov (United States)

    The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification.

  18. DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects

    OpenAIRE

    Rochtus, Anne; Izzi, Benedetta; Vangeel, Elise; Louwette, Sophie; Wittevrongel, Christine; Lambrechts, Diether; Moreau, Yves; Winand, Raf; Verpoorten, Carla; Jansen, Katrien; van Geet, Chris; Freson, Kathleen

    2015-01-01

    Abstract Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotempo...

  19. An optimized gene set for transcriptomics based neurodevelopmental toxicity prediction in the neural embryonic stem cell test

    NARCIS (Netherlands)

    Pennings, J.L.A.; Theunissen, P.T.; Piersma, A.H.|info:eu-repo/dai/nl/071276947

    2012-01-01

    The murine neural embryonic stem cell test (ESTn) is an in vitro model for neurodevelopmental toxicity testing. Recent studies have shown that application of transcriptomics analyses in the ESTn is useful for obtaining more accurate predictions as well as mechanistic insights. Gene expression

  20. Heterologous Expression of Gene of Interest Using the Marine Protozoan Perkinsus marinus

    Science.gov (United States)

    Cold, E. R.

    2016-02-01

    Perkinsus marinus is a marine protozoan parasite that causes "Dermo" disease in eastern oysters (Crassostrea virginica). P. marinus is closely related to Plasmodium falciparum which causes malaria. A recent study has showed that P. marinus causes no pathology damage but an immune response in humanized mouse, providing the bases for a genetically modified P. marinus expressing Plasmodium genes to be used as a vaccination delivery system for malaria and other pathogenic diseases. A modified plasmid vector (pMOE-GFP) based on highly expressed gene tagged with green fluorescence protein and targeted to P. marinus cell wall was used to clone MSP8 and HAP2. MSP8 encodes for merozoite surface in P. falciparum and HAP2 is essential for fusion of male and female gametes; genetic disruption of the HAP2 locus revealed that parasite fertilization is prevented. Using electroporation, MSP8 and HAP2 plasmid were introduced into the P. marinus trophozoites. As controls pMOE-GFP was transfected into P. mediterraneus, P. atlanticus and P. chesapeaki. Transfection conditions included 5x107 Perkinsus trophozoites and 10 µg of plasmid using Nucleofector® technology (D-023 program). The cells were recovered in 3 mL of Perkinsus culture media and transfected trophozoites were examined for green fluorescence. To facilitate subcloning of cells expressing GFP, we optimized a DME: HAM's F12 -5% FBS -containing agar solid medium for plating Perkinsus. Examination of all transfected cells indicates expression of both MSP8 and HAP2. This is the first time that genes of a protozoan parasite have been expressed in a marine protozoan. It was also concluded that P. mediterraneus, P. atlanticus and P. chesapeaki were stable mutation and can be isolated for further research.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  3. Bioinformatics, interaction network analysis, and neural networks to characterize gene expression of radicular cyst and periapical granuloma.

    Science.gov (United States)

    Poswar, Fabiano de Oliveira; Farias, Lucyana Conceição; Fraga, Carlos Alberto de Carvalho; Bambirra, Wilson; Brito-Júnior, Manoel; Sousa-Neto, Manoel Damião; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; D'Angelo, Marcos Flávio Silveira Vasconcelos; Guimarães, André Luiz Sena

    2015-06-01

    Bioinformatics has emerged as an important tool to analyze the large amount of data generated by research in different diseases. In this study, gene expression for radicular cysts (RCs) and periapical granulomas (PGs) was characterized based on a leader gene approach. A validated bioinformatics algorithm was applied to identify leader genes for RCs and PGs. Genes related to RCs and PGs were first identified in PubMed, GenBank, GeneAtlas, and GeneCards databases. The Web-available STRING software (The European Molecular Biology Laboratory [EMBL], Heidelberg, Baden-Württemberg, Germany) was used in order to build the interaction map among the identified genes by a significance score named weighted number of links. Based on the weighted number of links, genes were clustered using k-means. The genes in the highest cluster were considered leader genes. Multilayer perceptron neural network analysis was used as a complementary supplement for gene classification. For RCs, the suggested leader genes were TP53 and EP300, whereas PGs were associated with IL2RG, CCL2, CCL4, CCL5, CCR1, CCR3, and CCR5 genes. Our data revealed different gene expression for RCs and PGs, suggesting that not only the inflammatory nature but also other biological processes might differentiate RCs and PGs. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Artificial Neural Networks and Gene Expression Programing based age estimation using facial features

    Directory of Open Access Journals (Sweden)

    Baddrud Z. Laskar

    2015-10-01

    Full Text Available This work is about estimating human age automatically through analysis of facial images. It has got a lot of real-world applications. Due to prompt advances in the fields of machine vision, facial image processing, and computer graphics, automatic age estimation via faces in computer is one of the dominant topics these days. This is due to widespread real-world applications, in areas of biometrics, security, surveillance, control, forensic art, entertainment, online customer management and support, along with cosmetology. As it is difficult to estimate the exact age, this system is to estimate a certain range of ages. Four sets of classifications have been used to differentiate a person’s data into one of the different age groups. The uniqueness about this study is the usage of two technologies i.e., Artificial Neural Networks (ANN and Gene Expression Programing (GEP to estimate the age and then compare the results. New methodologies like Gene Expression Programing (GEP have been explored here and significant results were found. The dataset has been developed to provide more efficient results by superior preprocessing methods. This proposed approach has been developed, tested and trained using both the methods. A public data set was used to test the system, FG-NET. The quality of the proposed system for age estimation using facial features is shown by broad experiments on the available database of FG-NET.

  5. CTCF Is Required for Neural Development and Stochastic Expression of Clustered Pcdh Genes in Neurons

    Directory of Open Access Journals (Sweden)

    Teruyoshi Hirayama

    2012-08-01

    Full Text Available The CCCTC-binding factor (CTCF is a key molecule for chromatin conformational changes that promote cellular diversity, but nothing is known about its role in neurons. Here, we produced mice with a conditional knockout (cKO of CTCF in postmitotic projection neurons, mostly in the dorsal telencephalon. The CTCF-cKO mice exhibited postnatal growth retardation and abnormal behavior and had defects in functional somatosensory mapping in the brain. In terms of gene expression, 390 transcripts were expressed at significantly different levels between CTCF-deficient and control cortex and hippocampus. In particular, the levels of 53 isoforms of the clustered protocadherin (Pcdh genes, which are stochastically expressed in each neuron, declined markedly. Each CTCF-deficient neuron showed defects in dendritic arborization and spine density during brain development. Their excitatory postsynaptic currents showed normal amplitude but occurred with low frequency. Our results indicate that CTCF regulates functional neural development and neuronal diversity by controlling clustered Pcdh expression.

  6. Alcohol-induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation.

    Science.gov (United States)

    Veazey, Kylee J; Carnahan, Mindy N; Muller, Daria; Miranda, Rajesh C; Golding, Michael C

    2013-07-01

    From studies using a diverse range of model organisms, we now acknowledge that epigenetic changes to chromatin structure provide a plausible link between environmental teratogens and alterations in gene expression leading to disease. Observations from a number of independent laboratories indicate that ethanol (EtOH) has the capacity to act as a powerful epigenetic disruptor and potentially derail the coordinated processes of cellular differentiation. In this study, we sought to examine whether primary neurospheres cultured under conditions maintaining stemness were susceptible to alcohol-induced alterations in the histone code. We focused our studies on trimethylated histone 3 lysine 4 and trimethylated histone 3 lysine 27, as these are 2 of the most prominent posttranslational histone modifications regulating stem cell maintenance and neural differentiation. Primary neurosphere cultures were maintained under conditions promoting the stem cell state and treated with EtOH for 5 days. Control and EtOH-treated cellular extracts were examined using a combination of quantitative RT-PCR and chromatin immunoprecipitation techniques. We find that the regulatory regions of genes controlling both neural precursor cell identity and processes of differentiation exhibited significant declines in the enrichment of the chromatin marks examined. Despite these widespread changes in chromatin structure, only a small subset of genes including Dlx2, Fabp7, Nestin, Olig2, and Pax6 displayed EtOH-induced alterations in transcription. Unexpectedly, the majority of chromatin-modifying enzymes examined including members of the Polycomb Repressive Complex displayed minimal changes in expression and localization. Only transcripts encoding Dnmt1, Uhrf1, Ehmt1, Ash2 l, Wdr5, and Kdm1b exhibited significant differences. Our results indicate that primary neurospheres maintained as stem cells in vitro are susceptible to alcohol-induced perturbation of the histone code and errors in the epigenetic

  7. CRISPR/Cas9-induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo.

    Science.gov (United States)

    Kalebic, Nereo; Taverna, Elena; Tavano, Stefania; Wong, Fong Kuan; Suchold, Dana; Winkler, Sylke; Huttner, Wieland B; Sarov, Mihail

    2016-03-01

    We have applied the CRISPR/Cas9 system in vivo to disrupt gene expression in neural stem cells in the developing mammalian brain. Two days after in utero electroporation of a single plasmid encoding Cas9 and an appropriate guide RNA (gRNA) into the embryonic neocortex of Tis21::GFP knock-in mice, expression of GFP, which occurs specifically in neural stem cells committed to neurogenesis, was found to be nearly completely (≈ 90%) abolished in the progeny of the targeted cells. Importantly, upon in utero electroporation directly of recombinant Cas9/gRNA complex, near-maximal efficiency of disruption of GFP expression was achieved already after 24 h. Furthermore, by using microinjection of the Cas9 protein/gRNA complex into neural stem cells in organotypic slice culture, we obtained disruption of GFP expression within a single cell cycle. Finally, we used either Cas9 plasmid in utero electroporation or Cas9 protein complex microinjection to disrupt the expression of Eomes/Tbr2, a gene fundamental for neocortical neurogenesis. This resulted in a reduction in basal progenitors and an increase in neuronal differentiation. Thus, the present in vivo application of the CRISPR/Cas9 system in neural stem cells provides a rapid, efficient and enduring disruption of expression of specific genes to dissect their role in mammalian brain development. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  8. Identification of gene expression signatures across different types of neural stem cells with the Monte-Carlo feature selection method.

    Science.gov (United States)

    Chen, Lei; Li, JiaRui; Zhang, Yu-Hang; Feng, KaiYan; Wang, ShaoPeng; Zhang, YunHua; Huang, Tao; Kong, Xiangyin; Cai, Yu-Dong

    2017-11-11

    Adult neural stem cells (NSCs) are a group of multi-potent, self-renewing progenitor cells that contribute to the generation of new neurons and oligodendrocytes. Three subtypes of NSCs can be isolated based on the stages of the NSC lineage, including quiescent neural stem cells (qNSCs), activated neural stem cells (aNSCs) and neural progenitor cells (NPCs). Although it is widely accepted that these three groups of NSCs play different roles in the development of the nervous system, their molecular signatures are poorly understood. In this study, we applied the Monte-Carlo Feature Selection (MCFS) method to identify the gene expression signatures, which can yield a Matthews correlation coefficient (MCC) value of 0.918 with a support vector machine evaluated by ten-fold cross-validation. In addition, some classification rules yielded by the MCFS program for distinguishing above three subtypes were reported. Our results not only demonstrate a high classification capacity and subtype-specific gene expression patterns but also quantitatively reflect the pattern of the gene expression levels across the NSC lineage, providing insight into deciphering the molecular basis of NSC differentiation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-01

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

  10. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

    AbstractBackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate\\/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate\\/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the

  11. Targeted disruption in mice of a neural stem cell-maintaining, KRAB-Zn finger-encoding gene that has rapidly evolved in the human lineage.

    Directory of Open Access Journals (Sweden)

    Huan-Chieh Chien

    Full Text Available Understanding the genetic basis of the physical and behavioral traits that separate humans from other primates is a challenging but intriguing topic. The adaptive functions of the expansion and/or reduction in human brain size have long been explored. From a brain transcriptome project we have identified a KRAB-Zn finger protein-encoding gene (M003-A06 that has rapidly evolved since the human-chimpanzee separation. Quantitative RT-PCR analysis of different human tissues indicates that M003-A06 expression is enriched in the human fetal brain in addition to the fetal heart. Furthermore, analysis with use of immunofluorescence staining, neurosphere culturing and Western blotting indicates that the mouse ortholog of M003-A06, Zfp568, is expressed mainly in the embryonic stem (ES cells and fetal as well as adult neural stem cells (NSCs. Conditional gene knockout experiments in mice demonstrates that Zfp568 is both an NSC maintaining- and a brain size-regulating gene. Significantly, molecular genetic analyses show that human M003-A06 consists of 2 equilibrated allelic types, H and C, one of which (H is human-specific. Combined contemporary genotyping and database mining have revealed interesting genetic associations between the different genotypes of M003-A06 and the human head sizes. We propose that M003-A06 is likely one of the genes contributing to the uniqueness of the human brain in comparison to other higher primates.

  12. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    Directory of Open Access Journals (Sweden)

    Pangilinan Faith

    2012-08-01

    Full Text Available Abstract Background Neural tube defects (NTDs are common birth defects (~1 in 1000 pregnancies in the US and Europe that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T and MTHFD1 rs2236225 (R653Q have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents, including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury and included the known NTD risk factor MTHFD1 R653Q (rs2236225. The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele. Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive

  13. Indoor air pollution and neural tube defects: effect modification by maternal genes.

    Science.gov (United States)

    Wang, Linlin; Li, Zhiwen; Jin, Lei; Li, Kai; Yuan, Yue; Fu, Yunting; Zhang, Yali; Ye, Rongwei; Ren, Aiguo

    2014-09-01

    Gene-environment interactions have been implicated in the development of neural tube defects (NTDs). We conducted a case-control study to investigate (1) the association of aryl hydrocarbon receptor (AHR) genetic variants and phase I metabolic enzymes with the risk of NTDs and (2) the interaction of these variants with maternal exposure to indoor air pollution from smoking and coal combustion or with placental polycyclic aromatic hydrocarbons (PAHs). Blood samples were collected from 534 mothers of fetuses or newborns with NTDs and 534 control mothers who had healthy term newborns and were assayed for 12 polymorphisms in the AHR and cytochrome P450 (CYP) genes. Information on maternal exposure was collected, and placental levels of PAHs were analyzed. Maternal exposure to indoor air pollution was associated with an increased NTD risk. However, no increased NTD risk was observed for individual genetic variants. For mothers with the CYP1B1 rs2855658 GG variant, exposure to indoor air pollution led to a dose-response relationship for NTD risk, with odds ratios (ORs) of 3.0 (95% confidence interval = 1.6-5.7) and 8.1 (3.8-17) for medium and high levels of exposure, respectively. For mothers with GA or AA genotypes, this trend was less apparent. Placental PAHs were associated with an increased risk of NTDs, with an OR of 16 (3.3-75) for high levels compared with low levels of exposure among mothers with the GG genotype; there was no association for mothers with GA or AA genotypes. The CYP1B1 variant modifies the effect of indoor air pollution on NTD risk.

  14. Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Margarita Gutova

    2017-03-01

    Full Text Available Despite improved survival for children with newly diagnosed neuroblastoma (NB, recurrent disease is a significant problem, with treatment options limited by anti-tumor efficacy, patient drug tolerance, and cumulative toxicity. We previously demonstrated that neural stem cells (NSCs expressing a modified rabbit carboxylesterase (rCE can distribute to metastatic NB tumor foci in multiple organs in mice and convert the prodrug irinotecan (CPT-11 to the 1,000-fold more toxic topoisomerase-1 inhibitor SN-38, resulting in significant therapeutic efficacy. We sought to extend these studies by using a clinically relevant NSC line expressing a modified human CE (hCE1m6-NSCs to establish proof of concept and identify an intravenous dose and treatment schedule that gave maximal efficacy. Human-derived NB cell lines were significantly more sensitive to treatment with hCE1m6-NSCs and irinotecan as compared with drug alone. This was supported by pharmacokinetic studies in subcutaneous NB mouse models demonstrating tumor-specific conversion of irinotecan to SN-38. Furthermore, NB-bearing mice that received repeat treatment with intravenous hCE1m6-NSCs and irinotecan showed significantly lower tumor burden (1.4-fold, p = 0.0093 and increased long-term survival compared with mice treated with drug alone. These studies support the continued development of NSC-mediated gene therapy for improved clinical outcome in NB patients.

  15. Interesting Interest Points

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Dahl, Anders Lindbjerg; Pedersen, Kim Steenstrup

    2012-01-01

    Not all interest points are equally interesting. The most valuable interest points lead to optimal performance of the computer vision method in which they are employed. But a measure of this kind will be dependent on the chosen vision application. We propose a more general performance measure based...... position. The LED illumination provides the option for artificially relighting the scene from a range of light directions. This data set has given us the ability to systematically evaluate the performance of a number of interest point detectors. The highlights of the conclusions are that the fixed scale...

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

    Science.gov (United States)

    Kerosuo, Laura; Bronner, Marianne E.

    2014-01-01

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

  17. Global gene expression shift during the transition from early neural development to late neuronal differentiation in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Rafael Cantera

    Full Text Available Regulation of transcription is one of the mechanisms involved in animal development, directing changes in patterning and cell fate specification. Large temporal data series, based on microarrays across the life cycle of the fly Drosophila melanogaster, revealed the existence of groups of genes which expression increases or decreases temporally correlated during the life cycle. These groups of genes are enriched in different biological functions. Here, instead of searching for temporal coincidence in gene expression using the entire genome expression data, we searched for temporal coincidence in gene expression only within predefined catalogues of functionally related genes and investigated whether a catalogue's expression profile can be used to generate larger catalogues, enriched in genes necessary for the same function. We analyzed the expression profiles from genes already associated with early neurodevelopment and late neurodifferentiation, at embryonic stages 16 and 17 of Drosophila life cycle. We hypothesized that during this interval we would find global downregulation of genes important for early neuronal development together with global upregulation of genes necessary for the final differentiation of neurons. Our results were consistent with this hypothesis. We then investigated if the expression profile of gene catalogues representing particular processes of neural development matched the temporal sequence along which these processes occur. The profiles of genes involved in patterning, neurogenesis, axogenesis or synaptic transmission matched the prediction, with largest transcript values at the time when the corresponding biological process takes place in the embryo. Furthermore, we obtained catalogues enriched in genes involved in temporally matching functions by performing a genome-wide systematic search for genes with their highest expression levels at the corresponding embryonic intervals. These findings imply the use of gene

  18. 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.

  19. PosMed (Positional Medline): prioritizing genes with an artificial neural network comprising medical documents to accelerate positional cloning

    Science.gov (United States)

    Yoshida, Yuko; Makita, Yuko; Heida, Naohiko; Asano, Satomi; Matsushima, Akihiro; Ishii, Manabu; Mochizuki, Yoshiki; Masuya, Hiroshi; Wakana, Shigeharu; Kobayashi, Norio; Toyoda, Tetsuro

    2009-01-01

    PosMed (http://omicspace.riken.jp/) prioritizes candidate genes for positional cloning by employing our original database search engine GRASE, which uses an inferential process similar to an artificial neural network comprising documental neurons (or ‘documentrons’) that represent each document contained in databases such as MEDLINE and OMIM. Given a user-specified query, PosMed initially performs a full-text search of each documentron in the first-layer artificial neurons and then calculates the statistical significance of the connections between the hit documentrons and the second-layer artificial neurons representing each gene. When a chromosomal interval(s) is specified, PosMed explores the second-layer and third-layer artificial neurons representing genes within the chromosomal interval by evaluating the combined significance of the connections from the hit documentrons to the genes. PosMed is, therefore, a powerful tool that immediately ranks the candidate genes by connecting phenotypic keywords to the genes through connections representing not only gene–gene interactions but also other biological interactions (e.g. metabolite–gene, mutant mouse–gene, drug–gene, disease–gene and protein–protein interactions) and ortholog data. By utilizing orthologous connections, PosMed facilitates the ranking of human genes based on evidence found in other model species such as mouse. Currently, PosMed, an artificial superbrain that has learned a vast amount of biological knowledge ranging from genomes to phenomes (or ‘omic space’), supports the prioritization of positional candidate genes in humans, mouse, rat and Arabidopsis thaliana. PMID:19468046

  20. Suppression of the SOX2 Neural Effector Gene by PRDM1 Promotes Human Germ Cell Fate in Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    I-Ying Lin

    2014-02-01

    Full Text Available The mechanisms of transcriptional regulation underlying human primordial germ cell (PGC differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developing human gonads and contributes to the determination of germline versus neural fate in early development. We show that knockdown of PRDM1 in human embryonic stem cells (hESCs impairs germline potential and upregulates neural genes. Conversely, ectopic expression of PRDM1 in hESCs promotes the generation of cells that exhibit phenotypic and transcriptomic features of early PGCs. Furthermore, PRDM1 suppresses transcription of SOX2. Overexpression of SOX2 in hESCs under conditions favoring germline differentiation skews cell fate from the germline to the neural lineage. Collectively, our results demonstrate that PRDM1 serves as a molecular switch to modulate the divergence of neural or germline fates through repression of SOX2 during human development.

  1. Inhibition of storage pathology in prenatal CLN5-deficient sheep neural cultures by lentiviral gene therapy.

    Science.gov (United States)

    Hughes, Stephanie M; Hope, Katie M; Xu, Janet Boyu; Mitchell, Nadia L; Palmer, David N

    2014-02-01

    The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are inherited neurodegenerative lysosomal storage diseases caused by mutations in several different genes. Mutations in CLN5 cause a variant late-infantile human disease and some cases of juvenile and adult clinical disease. NCLs also occur in animals, and a flock of New Zealand Borderdale sheep with a CLN5 splice-site mutation has been developed for model studies. Dissociated mixed neural cells from CLN5-deficient foetal sheep brains contained no obvious storage bodies at plating but these accumulated rapidly in culture, mainly in microglial cells and also in neurons and astrocytes. Accumulation was very obvious after a week, as monitored by fluorescent microscopy and immunostaining for subunit c of mitochondrial ATP synthase. Photography at intervals revealed the dynamic nature of the cultures and a flow of storage bodies between cells, specifically the phagocytosis of storage-body containing cells by microglia and incorporation of the storage bodies into the host cells. No storage was observed in cultured control cells. Transduction of cell cultures with a lentiviral vector expressing a C-terminal Myc tagged CLN5 resulted in secretion of post-translationally glycosylated and processed CLN5. Transduction of CLN5-deficient cultures with this construct rapidly reversed storage body accumulation, to less than half in only six days. These results show that storage body accumulation is reversible with enzyme correction and support the use of these cultures for testing of therapeutics prior to whole animal studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.

    Science.gov (United States)

    Corno, Daniela; Daniela, Corno; Pala, Mauro; Cominelli, Manuela; Cipelletti, Barbara; Leto, Ketty; Croci, Laura; Barili, Valeria; Brandalise, Federico; Melzi, Raffaella; Di Gregorio, Alessandra; Sergi, Lucia Sergi; Politi, Letterio Salvatore; Piemonti, Lorenzo; Bulfone, Alessandro; Rossi, Paola; Rossi, Ferdinando; Consalez, Gian Giacomo; Poliani, Pietro Luigi; Galli, Rossella

    2012-06-01

    Medulloblastoma arises from mutations occurring in stem/progenitor cells located in restricted hindbrain territories. Here we report that the mouse postnatal ventricular zone lining the IV ventricle also harbors bona fide stem cells that, remarkably, share the same molecular profile with cerebellar white matter-derived neural stem cells (NSC). To identify novel molecular mediators involved in medulloblastomagenesis, we compared these distinct postnatal hindbrain-derived NSC populations, which are potentially tumor initiating, with murine compound Ptch/p53 mutant medulloblastoma cancer stem cells (CSC) that faithfully phenocopy the different variants of human medulloblastoma in vivo. Transcriptome analysis of both hindbrain NSCs and medulloblastoma CSCs resulted in the generation of well-defined gene signatures, each reminiscent of a specific human medulloblastoma molecular subclass. Most interestingly, medulloblastoma CSCs upregulated developmentally related genes, such as Ebfs, that were shown to be highly expressed in human medulloblastomas and play a pivotal role in experimental medullo-blastomagenesis. These data indicate that gene expression analysis of medulloblastoma CSCs holds great promise not only for understanding functional differences between distinct CSC populations but also for identifying meaningful signatures that might stratify medulloblastoma patients beyond histopathologic staging.

  3. Neural androgen receptors modulate gene expression and social recognition but not social investigation

    Directory of Open Access Journals (Sweden)

    Sara A Karlsson

    2016-03-01

    Full Text Available The role of sex and androgen receptors (ARs for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, ARNesDel, with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Novel object recognition and olfaction were investigated to complement the results from the social tests. Gene expression analysis was performed to reveal molecules involved in the effects of sex and androgens on social behaviors. All three test groups showed social preference in the three-chambered apparatus test. In both social tests an AR-independent sexual dimorphism was seen in the persistence of social investigation of female conspecifics, whereas the social interest towards male stimuli mice was similar in all groups. Male and female controls recognized conspecifics independent of their sex, whereas ARNesDel males recognized female but not male stimuli mice. Moreover, the non-social behaviors were not affected by AR deficiency. The gene expression analyses of hypothalamus and amygdala indicated that Oxtr, Cd38, Esr1, Cyp19a1, Ucn3, Crh and Gtf2i were differentially expressed between the three groups. In conclusion, our results suggest that ARs are required for recognition of male but not female conspecifics, while being dispensable for social investigation towards both sexes. In addition, the AR seems to regulate genes related to oxytocin, estrogen and William’s syndrome.

  4. Temperature based daily incoming solar radiation modeling based on gene expression programming, neuro-fuzzy and neural network computing techniques.

    Science.gov (United States)

    Landeras, G.; López, J. J.; Kisi, O.; Shiri, J.

    2012-04-01

    The correct observation/estimation of surface incoming solar radiation (RS) is very important for many agricultural, meteorological and hydrological related applications. While most weather stations are provided with sensors for air temperature detection, the presence of sensors necessary for the detection of solar radiation is not so habitual and the data quality provided by them is sometimes poor. In these cases it is necessary to estimate this variable. Temperature based modeling procedures are reported in this study for estimating daily incoming solar radiation by using Gene Expression Programming (GEP) for the first time, and other artificial intelligence models such as Artificial Neural Networks (ANNs), and Adaptive Neuro-Fuzzy Inference System (ANFIS). Traditional temperature based solar radiation equations were also included in this study and compared with artificial intelligence based approaches. Root mean square error (RMSE), mean absolute error (MAE) RMSE-based skill score (SSRMSE), MAE-based skill score (SSMAE) and r2 criterion of Nash and Sutcliffe criteria were used to assess the models' performances. An ANN (a four-input multilayer perceptron with ten neurons in the hidden layer) presented the best performance among the studied models (2.93 MJ m-2 d-1 of RMSE). A four-input ANFIS model revealed as an interesting alternative to ANNs (3.14 MJ m-2 d-1 of RMSE). Very limited number of studies has been done on estimation of solar radiation based on ANFIS, and the present one demonstrated the ability of ANFIS to model solar radiation based on temperatures and extraterrestrial radiation. By the way this study demonstrated, for the first time, the ability of GEP models to model solar radiation based on daily atmospheric variables. Despite the accuracy of GEP models was slightly lower than the ANFIS and ANN models the genetic programming models (i.e., GEP) are superior to other artificial intelligence models in giving a simple explicit equation for the

  5. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy.

    NARCIS (Netherlands)

    Jongbloet, P.H.; Verbeek, A.L.M.; Heijer, M. den; Roeleveld, N.

    2008-01-01

    ABSTRACT: Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established

  6. Conditional beta1-integrin gene deletion in neural crest cells causes severe developmental alterations of the peripheral nervous system

    DEFF Research Database (Denmark)

    Pietri, Thomas; Eder, Olivier; Breau, Marie Anne

    2004-01-01

    Integrins are transmembrane receptors that are known to interact with the extracellular matrix and to be required for migration, proliferation, differentiation and apoptosis. We have generated mice with a neural crest cell-specific deletion of the beta1-integrin gene to analyse the role of beta1-....... There was an almost complete absence of Schwann cells and sensory axon segregation and defective maturation in neuromuscular synaptogenesis. Thus, beta1-integrins are important for the control of embryonic and postnatal peripheral nervous system development....

  7. Application of Artificial Neural Networks in Cancer Classification and Diagnosis Prediction of a Subtype of Lymphoma Based on Gene Expression Profile

    Directory of Open Access Journals (Sweden)

    L Ziaei

    2006-01-01

    Full Text Available Background: Diffuse Large B-cell Lymphoma (DLBCL is the most common subtype of non-Hodgkin’s Lymphoma. DLBCL patients have different survivals after diagnosis. 40% of patients respond well to current therapy and have prolonged survival, whereas the remainders survive less than 5 years. In this study, we have applied artificial neural network to classify patients with DLBCL on the basis of their gene expression profiles. Finally, we have attempted to extract a number of genes that their differential expression were significant in DLBCL subtypes. Methods: We studied 40 patients and 4026 genes. In this study, genes were ranked based on their signal to noise (S/N ratios. After selecting a suitable threshold, some of them whose ratios were less than the threshold were removed. Then we used PCA for more reducing and Perceptron neural network for classification of these patients. We extracted some appropriate genes based on their prediction ability. Results: We considered various targets for patients classifying. Thus patients were classified based on their 5 years survival with accuracy of 93%, in regard to Alizadeh et al study results with accuracy of 100%, and regarding with their International Prognosis Index (IPI with accuracy of 89%. Conclusion: Combination of PCA and S/N ratio is an effective method for the reduction of the dimension and neural network is a robust tool for classification of patients according to their gene expression profile. Keywords: classification, gene expression, DLBCL, neural network, Perceptron

  8. Cortical gene expression in spinal cord injury and repair: insight into the functional complexity of the neural regeneration program

    Directory of Open Access Journals (Sweden)

    Fabian eKruse

    2011-09-01

    Full Text Available Traumatic spinal cord injury (SCI results in the formation of a fibrous scar acting as a growth barrier for regenerating axons at the lesion site. We have previously shown (Klapka et al., 2005 that transient suppression of the inhibitory lesion scar in rat spinal cord leads to long distance axon regeneration, retrograde rescue of axotomized cortical motoneurons and improvement of locomotor function. Here we applied a systemic approach to investigate for the first time specific and dynamic alterations in the cortical gene expression profile following both thoracic SCI and regeneration-promoting anti-scarring treatment (AST. In order to monitor cortical gene expression we carried out microarray analyses using total RNA isolated from layer V/VI of rat sensorimotor cortex at 1-60 days post-operation (dpo. We demonstrate that cortical neurons respond to injury by massive changes in gene expression, starting as early as 1 dpo. AST, in turn, results in profound modifications of the lesion-induced expression profile. The treatment attenuates SCI-triggered transcriptional changes of genes related to inhibition of axon growth and impairment of cell survival, while upregulating the expression of genes associated with axon outgrowth, cell protection and neural development. Thus, AST not only modifies the local environment impeding spinal cord regeneration by reduction of fibrous scarring in the injured spinal cord, but, in addition, strikingly changes the intrinsic capacity of cortical pyramidal neurons towards enhanced cell maintenance and axonal regeneration.

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

    Science.gov (United States)

    Maheau, Marissa E.; Ressler, Kerry J.

    2017-01-01

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

  10. Jarid1b targets genes regulating development and is involved in neural differentiation

    DEFF Research Database (Denmark)

    Schmitz, Sandra U; Albert, Mareike; Malatesta, Martina

    2011-01-01

    -renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly...

  11. The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus.

    Science.gov (United States)

    Kudo, Takashi; Block, Gene D; Colwell, Christopher S

    2015-01-01

    The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca(2+)]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca(2+)]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca(2+)]i-activated channel is one of the targets. © The Author(s) 2015.

  12. Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study.

    Science.gov (United States)

    Nishikawa, Saori; Toshima, Tamotsu; Kobayashi, Masao

    2015-01-01

    This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy) during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age = 24.05 years old) provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing]), and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task), and a gene × environment (G × E) interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links.

  13. Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR and Neural System Function during Facial Recognition: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Saori Nishikawa

    Full Text Available This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18 aged between 22 to 37 years old (mean age = 24.05 years old provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing], and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task, and a gene × environment (G × E interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links.

  14. Use of bicistronic retroviral vectors encoding the LacZ gene together with a gene of interest: a method to select producer cells and follow transduced target cells

    NARCIS (Netherlands)

    Staal, F. J.; Bakker, A. Q.; Verkuijlen, M.; van Oort, E.; Spits, H.

    1996-01-01

    The coordinate expression of a marker gene and a therapeutic gene in one retroviral vector has considerable advantages. High-titer producer lines can potentially be selected on the basis of marker gene expression, and the expression of transduced genes in target cells can readily be followed.

  15. Light-dependent transcriptional regulation of genes of biogeochemical interest in the diploid and haploid life cycle stages of Emiliania huxleyi.

    Science.gov (United States)

    Richier, Sophie; Kerros, Marie-Emmanuelle; de Vargas, Colomban; Haramaty, Liti; Falkowski, Paul G; Gattuso, Jean-Pierre

    2009-05-01

    The expression of genes of biogeochemical interest in calcifying and noncalcifying life stages of the coccolithophore Emiliania huxleyi was investigated. Transcripts potentially involved in calcification were tested through a light-dark cycle. These transcripts were more abundant in calcifying cells and were upregulated in the light. Their application as potential candidates for in situ biogeochemical proxies is also suggested.

  16. 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.

  17. Repeated anodal transcranial direct current stimulation induces neural plasticity-associated gene expression in the rat cortex and hippocampus.

    Science.gov (United States)

    Kim, Min Sun; Koo, Ho; Han, Sang Who; Paulus, Walter; Nitsche, Michael A; Kim, Yun-Hee; Yoon, Jin A; Shin, Yong-Il

    2017-01-01

    Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain. The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS. We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days. Levels of mRNA for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), synapsin I, Ca2+/calmodulin-dependent protein kinase II (CaMKII), activity-regulated cytoskeleton-associated protein (Arc), and c-Fos were analyzed using SYBR Green quantitative real-time polymerase chain reaction (PCR). We found that 7 days of unilateral A-tDCS resulted in significant increases in transcription of all plasticity-related genes tested in the ipsilateral cortex. Daily A-tDCS also resulted in a significant increase in c-Fos mRNA in the ipsilateral hippocampus. These results indicate that altered expression of plasticity-associated genes in the cortex and hippocampus is a molecular substrate of A-tDCS-induced neural plasticity.

  18. Enhanced selective gene delivery to neural stem cells in vivo by an adeno-associated viral variant.

    Science.gov (United States)

    Kotterman, Melissa A; Vazin, Tandis; Schaffer, David V

    2015-05-15

    Neural stem cells (NSCs) are defined by their ability to self-renew and to differentiate into mature neuronal and glial cell types. NSCs are the subject of intense investigation, owing to their crucial roles in neural development and adult brain function and because they present potential targets for gene and cell replacement therapies following injury or disease. Approaches to specifically genetically perturb or modulate NSC function would be valuable for either motivation. Unfortunately, most gene delivery vectors are incapable of efficient or specific gene delivery to NSCs in vivo. Vectors based on adeno-associated virus (AAV) present a number of advantages and have proven increasingly successful in clinical trials. However, natural AAV variants are inefficient in transducing NSCs. We previously engineered a novel AAV variant (AAV r3.45) capable of efficient transduction of adult NSCs in vitro. Here, to build upon the initial promise of this variant, we investigated its in vitro and in vivo infectivity. AAV r3.45 was more selective for NSCs than mature neurons in a human embryonic stem cell-derived culture containing a mixture of cell types, including NSCs and neurons. It was capable of more efficient and selective transduction of rat and mouse NSCs in vivo than natural AAV serotypes following intracranial vector administration. Delivery of constitutively active β-catenin yielded insights into mechanisms by which this key regulator modulates NSC function, indicating that this engineered AAV variant can be harnessed for preferential modulation of adult NSCs in the hippocampus. The capacity to rapidly genetically modify these cells might greatly accelerate in vivo investigations of adult neurogenesis. © 2015. Published by The Company of Biologists Ltd.

  19. Falls Risk Prediction for Older Inpatients in Acute Care Medical Wards: Is There an Interest to Combine an Early Nurse Assessment and the Artificial Neural Network Analysis?

    Science.gov (United States)

    Beauchet, O; Noublanche, F; Simon, R; Sekhon, H; Chabot, J; Levinoff, E J; Kabeshova, A; Launay, C P

    2018-01-01

    Identification of the risk of falls is important among older inpatients. This study aims to examine performance criteria (i.e.; sensitivity, specificity, positive predictive value, negative predictive value and accuracy) for fall prediction resulting from a nurse assessment and an artificial neural networks (ANNs) analysis in older inpatients hospitalized in acute care medical wards. A total of 848 older inpatients (mean age, 83.0±7.2 years; 41.8% female) admitted to acute care medical wards in Angers University hospital (France) were included in this study using an observational prospective cohort design. Within 24 hours after admission of older inpatients, nurses performed a bedside clinical assessment. Participants were separated into non-fallers and fallers (i.e.; ≥1 fall during hospitalization stay). The analysis was conducted using three feed forward ANNs (multilayer perceptron [MLP], averaged neural network, and neuroevolution of augmenting topologies [NEAT]). Seventy-three (8.6%) participants fell at least once during their hospital stay. ANNs showed a high specificity, regardless of which ANN was used, and the highest value reported was with MLP (99.8%). In contrast, sensitivity was lower, with values ranging between 98.4 to 14.8%. MLP had the highest accuracy (99.7). Performance criteria for fall prediction resulting from a bedside nursing assessment and an ANNs analysis was associated with a high specificity but a low sensitivity, suggesting that this combined approach should be used more as a diagnostic test than a screening test when considering older inpatients in acute care medical ward.

  20. Rare and private variations in neural crest, apoptosis and sarcomere genes define the polygenic background of isolated Tetralogy of Fallot.

    Science.gov (United States)

    Grunert, Marcel; Dorn, Cornelia; Schueler, Markus; Dunkel, Ilona; Schlesinger, Jenny; Mebus, Siegrun; Alexi-Meskishvili, Vladimir; Perrot, Andreas; Wassilew, Katharina; Timmermann, Bernd; Hetzer, Roland; Berger, Felix; Sperling, Silke R

    2014-06-15

    Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Its genetic basis is demonstrated by an increased recurrence risk in siblings and familial cases. However, the majority of TOF are sporadic, isolated cases of undefined origin and it had been postulated that rare and private autosomal variations in concert define its genetic basis. To elucidate this hypothesis, we performed a multilevel study using targeted re-sequencing and whole-transcriptome profiling. We developed a novel concept based on a gene's mutation frequency to unravel the polygenic origin of TOF. We show that isolated TOF is caused by a combination of deleterious private and rare mutations in genes essential for apoptosis and cell growth, the assembly of the sarcomere as well as for the neural crest and secondary heart field, the cellular basis of the right ventricle and its outflow tract. Affected genes coincide in an interaction network with significant disturbances in expression shared by cases with a mutually affected TOF gene. The majority of genes show continuous expression during adulthood, which opens a new route to understand the diversity in the long-term clinical outcome of TOF cases. Our findings demonstrate that TOF has a polygenic origin and that understanding the genetic basis can lead to novel diagnostic and therapeutic routes. Moreover, the novel concept of the gene mutation frequency is a versatile measure and can be applied to other open genetic disorders. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Promoter sequence of 3-phosphoglycerate kinase gene 2 of lactic acid-producing fungus rhizopus oryzae and a method of expressing a gene of interest in fungal species

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Johnway [Richland, WA; Skeen, Rodney S [Pendleton, OR

    2003-03-04

    The present invention provides the promoter clone discovery of phosphoglycerate kinase gene 2 of a lactic acid-producing filamentous fungal strain, Rhizopus oryzae. The isolated promoter can constitutively regulate gene expression under various carbohydrate conditions. In addition, the present invention also provides a design of an integration vector for the transformation of a foreign gene in Rhizopus oryzae.

  2. Promoter sequence of 3-phosphoglycerate kinase gene 1 of lactic acid-producing fungus rhizopus oryzae and a method of expressing a gene of interest in fungal species

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Johnway [Richland, WA; Skeen, Rodney S [Pendleton, OR

    2002-10-15

    The present invention provides the promoter clone discovery of phosphoglycerate kinase gene 1 of a lactic acid-producing filamentous fungal strain, Rhizopus oryzae. The isolated promoter can constitutively regulate gene expression under various carbohydrate conditions. In addition, the present invention also provides a design of an integration vector for the transformation of a foreign gene in Rhizopus oryzae.

  3. Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer.

    Directory of Open Access Journals (Sweden)

    Sonia Pinho

    2011-04-01

    Full Text Available The amniote organizer (Hensen's node can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct "epochs", or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.

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

    Science.gov (United States)

    Hochgreb-Hägele, Tatiana; Bronner, Marianne E

    2013-02-01

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

  5. Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration

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    Vartak-Sharma Neha

    2012-08-01

    Full Text Available Abstract Background Reactive astrogliosis is a ubiquitous but poorly understood hallmark of central nervous system pathologies such as trauma and neurodegenerative diseases. In vitro and in vivo studies have identified proinflammatory cytokines and chemokines as mediators of astrogliosis during injury and disease; however, the molecular mechanism remains unclear. In this study, we identify astrocyte elevated gene-1 (AEG-1, a human immunodeficiency virus 1 or tumor necrosis factor α-inducible oncogene, as a novel modulator of reactive astrogliosis. AEG-1 has engendered tremendous interest in the field of cancer research as a therapeutic target for aggressive tumors. However, little is known of its role in astrocytes and astrocyte-mediated diseases. Based on its oncogenic role in several cancers, here we investigate the AEG-1-mediated regulation of astrocyte migration and proliferation during reactive astrogliosis. Methods An in vivo brain injury mouse model was utilized to show AEG-1 induction following reactive astrogliosis. In vitro wound healing and cell migration assays following AEG-1 knockdown were performed to analyze the role of AEG-1 in astrocyte migration. AEG-1-mediated regulation of astrocyte proliferation was assayed by quantifying the levels of cell proliferation markers, Ki67 and proliferation cell nuclear antigen, using immunocytochemistry. Confocal microscopy was used to evaluate nucleolar localization of AEG-1 in cultured astrocytes following injury. Results The in vivo mouse model for brain injury showed reactive astrocytes with increased glial fibrillary acidic protein and AEG-1 colocalization at the wound site. AEG-1 knockdown in cultured human astrocytes significantly reduced astrocyte migration into the wound site and cell proliferation. Confocal analysis showed colocalization of AEG-1 to the nucleolus of injured cultured human astrocytes. Conclusions The present findings report for the first time the novel role of AEG-1

  6. Dynamic changes in Ezh2 gene occupancy underlie its involvement in neural stem cell self-renewal and differentiation towards oligodendrocytes.

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    Falak Sher

    Full Text Available The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs. We showed that Ezh2 expression is downregulated during NSC differentiation into astrocytes or neurons. However, high levels of Ezh2 remained present in differentiating oligodendrocytes until myelinating. This study aimed to elucidate the target genes of Ezh2 in NSCs and in premyelinating oligodendrocytes (pOLs.We performed chromatin immunoprecipitation followed by high-throughput sequencing to detect the target genes of Ezh2 in NSCs and pOLs. We found 1532 target genes of Ezh2 in NSCs. During NSC differentiation, the occupancy of these genes by Ezh2 was alleviated. However, when the NSCs differentiated into oligodendrocytes, 393 of these genes remained targets of Ezh2. Analysis of the target genes indicated that the repressive activity of Ezh2 in NSCs concerns genes involved in stem cell maintenance, in cell cycle control and in preventing neural differentiation. Among the genes in pOLs that were still repressed by Ezh2 were most prominently those associated with neuronal and astrocytic committed cell lineages. Suppression of Ezh2 activity in NSCs caused loss of stem cell characteristics, blocked their proliferation and ultimately induced apoptosis. Suppression of Ezh2 activity in pOLs resulted in derangement of the oligodendrocytic phenotype, due to re-expression of neuronal and astrocytic genes, and ultimately in apoptosis.Our data indicate that the epigenetic repressor Ezh2 in NSCs is crucial for proliferative activity and maintenance of neural stemness. During differentiation towards oligodendrocytes, Ezh2 repression continues particularly to suppress other neural fate choices. Ezh2 is completely downregulated during differentiation towards neurons and astrocytes allowing transcription

  7. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

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    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  8. Syndromes and Disorders Associated with Omphalocele (III: Single Gene Disorders, Neural Tube Defects, Diaphragmatic Defects and Others

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-06-01

    Full Text Available Omphalocele can be associated with single gene disorders, neural tube defects, diaphragmatic defects, fetal valproate syndrome, and syndromes of unknown etiology. This article provides a comprehensive review of omphalocele-related disorders: otopalatodigital syndrome type II; Melnick–Needles syndrome; Rieger syndrome; neural tube defects; Meckel syndrome; Shprintzen–Goldberg omphalocele syndrome; lethal omphalocele-cleft palate syndrome; cerebro-costo-mandibular syndrome; fetal valproate syndrome; Marshall–Smith syndrome; fibrochondrogenesis; hydrolethalus syndrome; Fryns syndrome; omphalocele, diaphragmatic defects, radial anomalies and various internal malformations; diaphragmatic defects, limb deficiencies and ossification defects of skull; Donnai–Barrow syndrome; CHARGE syndrome; Goltz syndrome; Carpenter syndrome; Toriello–Carey syndrome; familial omphalocele; Cornelia de Lange syndrome; C syndrome; Elejalde syndrome; Malpuech syndrome; cervical ribs, Sprengel anomaly, anal atresia and urethral obstruction; hydrocephalus with associated malformations; Kennerknecht syndrome; lymphedema, atrial septal defect and facial changes; and craniosynostosis- mental retardation syndrome of Lin and Gettig. Perinatal identification of omphalocele should alert one to the possibility of omphalocele-related disorders and familial inheritance and prompt a thorough genetic counseling for these disorders.

  9. Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells.

    Science.gov (United States)

    Bressan, Raul Bardini; Dewari, Pooran Singh; Kalantzaki, Maria; Gangoso, Ester; Matjusaitis, Mantas; Garcia-Diaz, Claudia; Blin, Carla; Grant, Vivien; Bulstrode, Harry; Gogolok, Sabine; Skarnes, William C; Pollard, Steven M

    2017-02-15

    Mammalian neural stem cell (NSC) lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NSCs are clonally expandable, genetically stable, and easily transfectable - experimental attributes compatible with targeted genetic manipulations. However, gene targeting, which is crucial for functional studies of embryonic stem cells, has not been exploited to date in NSC lines. Here, we deploy CRISPR/Cas9 technology to demonstrate a variety of sophisticated genetic modifications via gene targeting in both mouse and human NSC lines, including: (1) efficient targeted transgene insertion at safe harbour loci (Rosa26 and AAVS1); (2) biallelic knockout of neurodevelopmental transcription factor genes; (3) simple knock-in of epitope tags and fluorescent reporters (e.g. Sox2-V5 and Sox2-mCherry); and (4) engineering of glioma mutations (TP53 deletion; H3F3A point mutations). These resources and optimised methods enable facile and scalable genome editing in mammalian NSCs, providing significant new opportunities for functional genetic analysis. © 2017. Published by The Company of Biologists Ltd.

  10. A Double-Switch Cell Fusion-Inducible Transgene Expression System for Neural Stem Cell-Based Antiglioma Gene Therapy

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    Yumei Luo

    2015-01-01

    Full Text Available Recent progress in neural stem cell- (NSC- based tumor-targeted gene therapy showed that NSC vectors expressing an artificially engineered viral fusogenic protein, VSV-G H162R, could cause tumor cell death specifically under acidic tumor microenvironment by syncytia formation; however, the killing efficiency still had much room to improve. In the view that coexpression of another antitumoral gene with VSV-G can augment the bystander effect, a synthetic regulatory system that triggers transgene expression in a cell fusion-inducible manner has been proposed. Here we have developed a double-switch cell fusion-inducible transgene expression system (DoFIT to drive transgene expression upon VSV-G-mediated NSC-glioma cell fusion. In this binary system, transgene expression is coregulated by a glioma-specific promoter and targeting sequences of a microRNA (miR that is highly expressed in NSCs but lowly expressed in glioma cells. Thus, transgene expression is “switched off” by the miR in NSC vectors, but after cell fusion with glioma cells, the miR is diluted and loses its suppressive effect. Meanwhile, in the syncytia, transgene expression is “switched on” by the glioma-specific promoter. Our in vitro and in vivo experimental data show that DoFIT successfully abolishes luciferase reporter gene expression in NSC vectors but activates it specifically after VSV-G-mediated NSC-glioma cell fusion.

  11. Initialization Parameter Sweep in ATHENA: Optimizing Neural Networks for Detecting Gene-Gene Interactions in the Presence of Small Main Effects.

    Science.gov (United States)

    Holzinger, Emily R; Buchanan, Carrie C; Dudek, Scott M; Torstenson, Eric C; Turner, Stephen D; Ritchie, Marylyn D

    2010-01-01

    Recent advances in genotyping technology have led to the generation of an enormous quantity of genetic data. Traditional methods of statistical analysis have proved insufficient in extracting all of the information about the genetic components of common, complex human diseases. A contributing factor to the problem of analysis is that amongst the small main effects of each single gene on disease susceptibility, there are non-linear, gene-gene interactions that can be difficult for traditional, parametric analyses to detect. In addition, exhaustively searching all multi-locus combinations has proved computationally impractical. Novel strategies for analysis have been developed to address these issues. The Analysis Tool for Heritable and Environmental Network Associations (ATHENA) is an analytical tool that incorporates grammatical evolution neural networks (GENN) to detect interactions among genetic factors. Initial parameters define how the evolutionary process will be implemented. This research addresses how different parameter settings affect detection of disease models involving interactions. In the current study, we iterate over multiple parameter values to determine which combinations appear optimal for detecting interactions in simulated data for multiple genetic models. Our results indicate that the factors that have the greatest influence on detection are: input variable encoding, population size, and parallel computation.

  12. A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data.

    Science.gov (United States)

    Kang, Tianyu; Ding, Wei; Zhang, Luoyan; Ziemek, Daniel; Zarringhalam, Kourosh

    2017-12-19

    Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model. We benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database. In summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

  13. Making Headway: The Roles of Hox Genes and Neural Crest Cells in Craniofacial Development

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    Paul A. Trainor

    2003-01-01

    Full Text Available 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.

  14. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

    Science.gov (United States)

    Lee, Kee Hang; Nam, Hyun; Jeong, Da Eun; Kim, Sung Soo; Song, Hye Jin; Pyeon, Hee Jang; Kang, Kyeongjin; Hong, Seung-Cheol; Nam, Do-Hyun; Joo, Kyeung Min

    2016-01-01

    Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs) immortalized by the human telomerase reverse transcriptase (hTERT) gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM) cells were injected into adult (4-6-week-old) Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old) NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL) were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL), they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  15. A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure.

    Science.gov (United States)

    Fong, Keith S K; Hufnagel, Robert B; Khadka, Vedbar S; Corley, Michael J; Maunakea, Alika K; Fogelgren, Ben; Ahmed, Zubair M; Lozanoff, Scott

    2016-05-01

    Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs) are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1), co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct) cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse. © 2016. Published by The Company of Biologists Ltd.

  16. RNA-Sequencing Analysis of Messenger RNA/MicroRNA in a Rabbit Aneurysm Model Identifies Pathways and Genes of Interest.

    Science.gov (United States)

    Holcomb, M; Ding, Y-H; Dai, D; McDonald, R J; McDonald, J S; Kallmes, D F; Kadirvel, R

    2015-09-01

    Rabbit aneurysm models are used for the testing of embolization devices and elucidating the mechanisms of human intracranial aneurysm growth and healing. We used RNA-sequencing technology to identify genes relevant to induced rabbit aneurysm biology and to identify genes and pathways of potential clinical interest. This process included sequencing microRNAs, which are important regulatory noncoding RNAs. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 6 rabbits. Messenger RNA and microRNA were isolated from the aneurysm and from the control left common carotid artery at 12 weeks and processed by using RNA-sequencing technology. The results from RNA sequencing were analyzed by using the Ingenuity Pathway Analysis tool. A total of 9396 genes were analyzed by using RNA sequencing, 648 (6.9%) of which were found to be significantly differentially expressed between the aneurysms and control tissues (P 2 or rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and antigen presentation. ANKRD1 and TACR1 were identified as genes of interest in the regulation of matrix metalloproteinases. © 2015 by American Journal of Neuroradiology.

  17. Efficient genome editing of genes involved in neural crest development using the CRISPR/Cas9 system in Xenopus embryos.

    Science.gov (United States)

    Liu, Zhongzhen; Cheng, Tina Tsz Kwan; Shi, Zhaoying; Liu, Ziran; Lei, Yong; Wang, Chengdong; Shi, Weili; Chen, Xiongfeng; Qi, Xufeng; Cai, Dongqing; Feng, Bo; Deng, Yi; Chen, Yonglong; Zhao, Hui

    2016-01-01

    The RNA guided CRISPR/Cas9 nucleases have been proven to be effective for gene disruption in various animal models including Xenopus tropicalis. The neural crest (NC) is a transient cell population during embryonic development and contributes to a large variety of tissues. Currently, loss-of-function studies on NC development in X. tropicalis are largely based on morpholino antisense oligonucleotide. It is worthwhile establishing targeted gene knockout X. tropicails line using CRISPR/Cas9 system to study NC development. We utilized CRISPR/Cas9 to disrupt genes that are involved in NC formation in X. tropicalis embryos. A single sgRNA and Cas9 mRNA synthesized in vitro, were co-injected into X. tropicalis embryos at one-cell stage to induce single gene disruption. We also induced duplex mutations, large segmental deletions and inversions in X. tropicalis by injecting Cas9 and a pair of sgRNAs. The specificity of CRISPR/Cas9 was assessed in X. tropicalis embryos and the Cas9 nickase was used to reduce the off-target cleavages. Finally, we crossed the G0 mosaic frogs with targeted mutations to wild type frogs and obtained the germline transmission. Total 16 target sites in 15 genes were targeted by CRISPR/Cas9 and resulted in successful indel mutations at 14 loci with disruption efficiencies in a range from 9.3 to 57.8 %. Furthermore, we demonstrated the feasibility of generation of duplex mutations, large segmental deletions and inversions by using Cas9 and a pair of sgRNAs. We observed that CRISPR/Cas9 displays obvious off-target effects at some loci in X. tropicalis embryos. Such off-target cleavages was reduced by using the D10A Cas9 nickase. Finally, the Cas9 induced indel mutations were efficiently passed to G1 offspring. Our study proved that CRISPR/Cas9 could mediate targeted gene mutation in X. tropicalis with high efficiency. This study expands the application of CRISPR/Cas9 platform in X. tropicalis and set a basis for studying NC development using genetic

  18. Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network Model of Cognitive Development

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    Thomas, Michael S. C.; Forrester, Neil A.; Ronald, Angelica

    2016-01-01

    In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such…

  19. MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

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    Schwartz, C.E.; Wang, Y.; Schroer, R.J.; Stevenson, R.E. [Greenwood Genetic Center, SC (United States)

    1994-09-01

    The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have an altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.

  20. The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan.

    Science.gov (United States)

    Felsky, D; Szeszko, P; Yu, L; Honer, W G; De Jager, P L; Schneider, J A; Malhotra, A K; Lencz, T; Ikuta, T; Pipitone, J; Chakravarty, M M; Lobaugh, N J; Mulsant, B H; Pollock, B G; Kennedy, J L; Bennett, D A; Voineskos, A N

    2014-10-01

    Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.

  1. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

    Science.gov (United States)

    Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa

    2017-01-01

    Abstract Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs—including rs53576 and rs2254298—were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. PMID:27798253

  2. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.

    Science.gov (United States)

    Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa; Yamasue, Hidenori

    2017-03-01

    Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin's effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs-including rs53576 and rs2254298-were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. 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.

  4. Discovering biomarkers from gene expression data for predicting cancer subgroups using neural networks and relational fuzzy clustering

    Directory of Open Access Journals (Sweden)

    Sharma Animesh

    2007-01-01

    Full Text Available Abstract Background The four heterogeneous childhood cancers, neuroblastoma, non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma present a similar histology of small round blue cell tumor (SRBCT and thus often leads to misdiagnosis. Identification of biomarkers for distinguishing these cancers is a well studied problem. Existing methods typically evaluate each gene separately and do not take into account the nonlinear interaction between genes and the tools that are used to design the diagnostic prediction system. Consequently, more genes are usually identified as necessary for prediction. We propose a general scheme for finding a small set of biomarkers to design a diagnostic system for accurate classification of the cancer subgroups. We use multilayer networks with online gene selection ability and relational fuzzy clustering to identify a small set of biomarkers for accurate classification of the training and blind test cases of a well studied data set. Results Our method discerned just seven biomarkers that precisely categorized the four subgroups of cancer both in training and blind samples. For the same problem, others suggested 19–94 genes. These seven biomarkers include three novel genes (NAB2, LSP1 and EHD1 – not identified by others with distinct class-specific signatures and important role in cancer biology, including cellular proliferation, transendothelial migration and trafficking of MHC class antigens. Interestingly, NAB2 is downregulated in other tumors including Non-Hodgkin lymphoma and Neuroblastoma but we observed moderate to high upregulation in a few cases of Ewing sarcoma and Rabhdomyosarcoma, suggesting that NAB2 might be mutated in these tumors. These genes can discover the subgroups correctly with unsupervised learning, can differentiate non-SRBCT samples and they perform equally well with other machine learning tools including support vector machines. These biomarkers lead to four simple human interpretable

  5. Variation in the oxytocin receptor gene is associated with behavioral and neural correlates of empathic accuracy

    DEFF Research Database (Denmark)

    Laursen, Helle Ruff; Siebner, Hartwig Roman; Haren, Tina

    2014-01-01

    The neuromodulators oxytocin and serotonin have been implicated in regulating affective processes underlying empathy. Understanding this dependency, however, has been limited by a lack of objective metrics for measuring empathic performance. Here we employ a novel psychophysical method for measur......The neuromodulators oxytocin and serotonin have been implicated in regulating affective processes underlying empathy. Understanding this dependency, however, has been limited by a lack of objective metrics for measuring empathic performance. Here we employ a novel psychophysical method...... performing an irrelevant attention-demanding task. We investigated the effect of variation in the oxytocin receptor gene (OXTR) and the serotonin transporter gene (SLC6A4) on the psychophysical and neurometric variability associated with empathic performance. The OXTR rs2268498 and rs53576 polymorphisms...

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

    Science.gov (United States)

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

    1996-02-01

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

  7. High-affinity nitrate/nitrite transporter genes (Nrt2) in Tisochrysis lutea: identification and expression analyses reveal some interesting specificities of Haptophyta microalgae.

    Science.gov (United States)

    Charrier, Aurélie; Bérard, Jean-Baptiste; Bougaran, Gaël; Carrier, Grégory; Lukomska, Ewa; Schreiber, Nathalie; Fournier, Flora; Charrier, Aurélie F; Rouxel, Catherine; Garnier, Matthieu; Cadoret, Jean-Paul; Saint-Jean, Bruno

    2015-08-01

    Microalgae have a diversity of industrial applications such as feed, food ingredients, depuration processes and energy. However, microalgal production costs could be substantially improved by controlling nutrient intake. Accordingly, a better understanding of microalgal nitrogen metabolism is essential. Using in silico analysis from transcriptomic data concerning the microalgae Tisochrysis lutea, four genes encoding putative high-affinity nitrate/nitrite transporters (TlNrt2) were identified. Unlike most of the land plants and microalgae, cloning of genomic sequences and their alignment with complementary DNA (cDNA) sequences did not reveal the presence of introns in all TlNrt2 genes. The deduced TlNRT2 protein sequences showed similarities to NRT2 proteins of other phyla such as land plants and green algae. However, some interesting specificities only known among Haptophyta were also revealed, especially an additional sequence of 100 amino acids forming an atypical extracellular loop located between transmembrane domains 9 and 10 and the function of which remains to be elucidated. Analyses of individual TlNrt2 gene expression with different nitrogen sources and concentrations were performed. TlNrt2.1 and TlNrt2.3 were strongly induced by low NO3 (-) concentration and repressed by NH4 (+) substrate and were classified as inducible genes. TlNrt2.2 was characterized by a constitutive pattern whatever the substrate. Finally, TlNrt2.4 displayed an atypical response that was not reported earlier in literature. Interestingly, expression of TlNrt2.4 was rather related to internal nitrogen quota level than external nitrogen concentration. This first study on nitrogen metabolism of T. lutea opens avenues for future investigations on the function of these genes and their implication for industrial applications. © 2015 Scandinavian Plant Physiology Society.

  8. The Xenopus Irx genes are essential for neural patterning and define the border between prethalamus and thalamus through mutual antagonism with the anterior repressors Fezf and Arx.

    Science.gov (United States)

    Rodríguez-Seguel, Elisa; Alarcón, Pilar; Gómez-Skarmeta, José Luis

    2009-05-15

    The Iroquois (Irx) genes encode homeoproteins conserved during evolution. Vertebrate genomes contain six Irx genes organized in two clusters, IrxA (which harbors Irx1, Irx2 and Irx4) and IrxB (which harbors Irx3, Irx5 and Irx6). To determine the precise role of these genes during development and their putative redundancies, we conducted a comparative expression analysis and a comprehensive loss-of-function study of all the early expressed Irx genes (Irx1-5) using specific morpholinos in Xenopus. We found that the five Irx genes display largely overlapping expression patterns and contribute to neural patterning. All Irx genes are required for proper formation of posterior forebrain, midbrain, hindbrain and, to a lesser an extent, spinal cord. Nevertheless, Irx1 and Irx3 seem to have a predominant role during regionalization of the neural plate. In addition, we find that the common anterior limit of Irx gene expression, which will correspond to the future border between the prethalamus and thalamus, is defined by mutual repression between Fezf and Irx proteins. This mutual repression is likely direct. Finally, we show that Arx, another anteriorly expressed repressor, also contribute to delineate the anterior border of Irx expression.

  9. Neural outcome processing of peer-influenced risk-taking behavior in late adolescence: Preliminary evidence for gene × environment interactions.

    Science.gov (United States)

    Webber, Troy A; Soder, Heather E; Potts, Geoffrey F; Park, Jong Y; Bornovalova, Marina A

    2017-02-01

    Adolescent brains are particularly susceptible to the rewarding properties of risky decisions in social contexts. Individual differences in genetic influences on dopamine transmission moderate neural outcome processing of risky decisions and may exert pronounced effects on adolescent risk-taking behavior (RTB) and corresponding neural outcome processing in peer contexts, a process called gene-environment interaction (G × E). Eighty-five undergraduate students completed a behavioral risk task alone and in the presence of a confederate peer providing "risky" feedback. We tested for G × E effects using a polygenic risk index that included 3 candidate genetic variations associated with high dopamine transmission efficiency, as well as the moderating role of family history of behavioral disinhibition. Difference waves for the P300 and FRN (i.e., feedback-related negativity) were examined as indices of neural outcome processing. A G × E effect was observed for RTB and the P300, but not the FRN. Family history of behavioral disinhibition also interacted with peer influence to predict P300 amplitude. These data provide preliminary evidence for G × E for peer-influenced RTB and neural outcome processing during late adolescence. Genetic influences on dopaminergic function may be particularly relevant for attentional and motivational neural systems, as indexed by the P300, which exert downstream effects on peer-influenced RTB. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Extremely low-frequency electromagnetic fields affect transcript levels of neuronal differentiation-related genes in embryonic neural stem cells.

    Science.gov (United States)

    Ma, Qinlong; Deng, Ping; Zhu, Gang; Liu, Chuan; Zhang, Lei; Zhou, Zhou; Luo, Xue; Li, Min; Zhong, Min; Yu, Zhengping; Chen, Chunhai; Zhang, Yanwen

    2014-01-01

    Previous studies have reported that extremely low-frequency electromagnetic fields (ELF-EMF) can affect the processes of brain development, but the underlying mechanism is largely unknown. The proliferation and differentiation of embryonic neural stem cells (eNSCs) is essential for brain development during the gestation period. To date, there is no report about the effects of ELF-EMF on eNSCs. In this paper, we studied the effects of ELF-EMF on the proliferation and differentiation of eNSCs. Primary cultured eNSCs were treated with 50 Hz ELF-EMF; various magnetic intensities and exposure times were applied. Our data showed that there was no significant change in cell proliferation, which was evaluated by cell viability (CCK-8 assay), DNA synthesis (Edu incorporation), average diameter of neurospheres, cell cycle distribution (flow cytometry) and transcript levels of cell cycle related genes (P53, P21 and GADD45 detected by real-time PCR). When eNSCs were induced to differentiation, real-time PCR results showed a down-regulation of Sox2 and up-regulation of Math1, Math3, Ngn1 and Tuj1 mRNA levels after 50 Hz ELF-EMF exposure (2 mT for 3 days), but the percentages of neurons (Tuj1 positive cells) and astrocytes (GFAP positive cells) were not altered when detected by immunofluorescence assay. Although cell proliferation and the percentages of neurons and astrocytes differentiated from eNSCs were not affected by 50 Hz ELF-EMF, the expression of genes regulating neuronal differentiation was altered. In conclusion, our results support that 50 Hz ELF-EMF induce molecular changes during eNSCs differentiation, which might be compensated by post-transcriptional mechanisms to support cellular homeostasis.

  11. Extremely low-frequency electromagnetic fields affect transcript levels of neuronal differentiation-related genes in embryonic neural stem cells.

    Directory of Open Access Journals (Sweden)

    Qinlong Ma

    Full Text Available Previous studies have reported that extremely low-frequency electromagnetic fields (ELF-EMF can affect the processes of brain development, but the underlying mechanism is largely unknown. The proliferation and differentiation of embryonic neural stem cells (eNSCs is essential for brain development during the gestation period. To date, there is no report about the effects of ELF-EMF on eNSCs. In this paper, we studied the effects of ELF-EMF on the proliferation and differentiation of eNSCs. Primary cultured eNSCs were treated with 50 Hz ELF-EMF; various magnetic intensities and exposure times were applied. Our data showed that there was no significant change in cell proliferation, which was evaluated by cell viability (CCK-8 assay, DNA synthesis (Edu incorporation, average diameter of neurospheres, cell cycle distribution (flow cytometry and transcript levels of cell cycle related genes (P53, P21 and GADD45 detected by real-time PCR. When eNSCs were induced to differentiation, real-time PCR results showed a down-regulation of Sox2 and up-regulation of Math1, Math3, Ngn1 and Tuj1 mRNA levels after 50 Hz ELF-EMF exposure (2 mT for 3 days, but the percentages of neurons (Tuj1 positive cells and astrocytes (GFAP positive cells were not altered when detected by immunofluorescence assay. Although cell proliferation and the percentages of neurons and astrocytes differentiated from eNSCs were not affected by 50 Hz ELF-EMF, the expression of genes regulating neuronal differentiation was altered. In conclusion, our results support that 50 Hz ELF-EMF induce molecular changes during eNSCs differentiation, which might be compensated by post-transcriptional mechanisms to support cellular homeostasis.

  12. Notch signaling and proneural genes work together to control the neural building blocks for the initial scaffold in the hypothalamus

    Science.gov (United States)

    Ware, Michelle; Hamdi-Rozé, Houda; Dupé, Valérie

    2014-01-01

    The vertebrate embryonic prosencephalon gives rise to the hypothalamus, which plays essential roles in sensory information processing as well as control of physiological homeostasis and behavior. While patterning of the hypothalamus has received much attention, initial neurogenesis in the developing hypothalamus has mostly been neglected. The first differentiating progenitor cells of the hypothalamus will give rise to neurons that form the nucleus of the tract of the postoptic commissure (nTPOC) and the nucleus of the mammillotegmental tract (nMTT). The formation of these neuronal populations has to be highly controlled both spatially and temporally as these tracts will form part of the ventral longitudinal tract (VLT) and act as a scaffold for later, follower axons. This review will cumulate and summarize the existing data available describing initial neurogenesis in the vertebrate hypothalamus. It is well-known that the Notch signaling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. It has only recently been proposed that loss of Notch signaling in the developing chick embryo causes an increase in the number of neurons in the hypothalamus, highlighting an early function of the Notch pathway during hypothalamus formation. Further analysis in the chick and mouse hypothalamus confirms the expression of Notch components and Ascl1 before the appearance of the first differentiated neurons. Many newly identified proneural target genes were also found to be expressed during neuronal differentiation in the hypothalamus. Given the critical role that hypothalamic neural circuitry plays in maintaining homeostasis, it is particularly important to establish the targets downstream of this Notch/proneural network. PMID:25520625

  13. Dynamic Changes in Ezh2 Gene Occupancy Underlie Its Involvement in Neural Stem Cell Self-Renewal and Differentiation towards Oligodendrocytes

    Science.gov (United States)

    Sher, Falak; Boddeke, Erik; Olah, Marta; Copray, Sjef

    2012-01-01

    Background The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs). We showed that Ezh2 expression is downregulated during NSC differentiation into astrocytes or neurons. However, high levels of Ezh2 remained present in differentiating oligodendrocytes until myelinating. This study aimed to elucidate the target genes of Ezh2 in NSCs and in premyelinating oligodendrocytes (pOLs). Methodology/Principal Findings We performed chromatin immunoprecipitation followed by high-throughput sequencing to detect the target genes of Ezh2 in NSCs and pOLs. We found 1532 target genes of Ezh2 in NSCs. During NSC differentiation, the occupancy of these genes by Ezh2 was alleviated. However, when the NSCs differentiated into oligodendrocytes, 393 of these genes remained targets of Ezh2. Analysis of the target genes indicated that the repressive activity of Ezh2 in NSCs concerns genes involved in stem cell maintenance, in cell cycle control and in preventing neural differentiation. Among the genes in pOLs that were still repressed by Ezh2 were most prominently those associated with neuronal and astrocytic committed cell lineages. Suppression of Ezh2 activity in NSCs caused loss of stem cell characteristics, blocked their proliferation and ultimately induced apoptosis. Suppression of Ezh2 activity in pOLs resulted in derangement of the oligodendrocytic phenotype, due to re-expression of neuronal and astrocytic genes, and ultimately in apoptosis. Conclusions/Significance Our data indicate that the epigenetic repressor Ezh2 in NSCs is crucial for proliferative activity and maintenance of neural stemness. During differentiation towards oligodendrocytes, Ezh2 repression continues particularly to suppress other neural fate choices. Ezh2 is completely downregulated during differentiation

  14. Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-12-1-0051 TITLE: Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System ...Central Nervous System Following Neural Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0051 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Robert...mature mammalian central nervous system (CNS), unlike the peripheral nervous system (PNS), is incapable of axon regeneration. There are currently two

  15. Identification and initial characterization of novel neural immediate early genes possibly differentially contributing to foraging-related learning and memory processes in the honeybee.

    Science.gov (United States)

    Ugajin, A; Uchiyama, H; Miyata, T; Sasaki, T; Yajima, S; Ono, M

    2017-11-02

    Despite possessing a limited number of neurones compared to vertebrates, honeybees show remarkable learning and memory performance, an example being 'dance communication'. In this phenomenon, foraging honeybees learn the location of a newly discovered food source and transmit the information to nestmates by symbolic abdomen vibrating behaviour, leading to navigation of nestmates to the new food source. As an initial step toward understanding the detailed molecular mechanisms underlying the sophisticated learning and memory performance of the honeybee, we focused on the neural immediate early genes (IEGs), which are specific genes quickly transcribed after neural activity without de novo protein synthesis. Although these have been reported to play an essential role in learning and memory processes in vertebrates, far fewer studies have been performed in insects in this regard. From RNA-sequencing analysis and subsequent assays, we identified three genes, Src homology 3 (SH3) domain binding kinase, family with sequence similarity 46 and GB47136, as novel neural IEGs in the honeybee. Foragers and/or orientating bees, which fly around their hives to memorize the positional information, showed induced expression of these IEGs in the mushroom body, a higher-order centre essential for learning and memory, indicating a possible role for the novel IEGs in foraging-related learning and memory processes in the honeybee. © 2017 The Royal Entomological Society.

  16. Zebrafish BarH-like genes define discrete neural domains in the early embryo.

    Science.gov (United States)

    Colombo, Alicia; Reig, Germán; Mione, Marina; Concha, Miguel L

    2006-04-01

    BarH (Barhl) genes encode for highly conserved homeodomain-containing transcription factors involved in critical functions during development, including cell fate specification, migration and survival. Here, we report the dynamic and restricted expression of three zebrafish barhl within the developing central nervous system. barhl2 becomes expressed in the late gastrula as a transverse diencephalic domain located immediately caudal to the prospective eyes. At early somitogenesis, barhl1.1 and barhl1.2 are expressed in the diencephalon in domains that partially overlap with the ventral and dorsal aspects of barhl2 expression, respectively. At later stages, expression of all zebrafish barhl shows large extent of overlap in the pretectum, tectum and dorsal hindbrain. The presence of a unique territory of barhl2 expression in the dorsal telencephalon and the high levels of expression in the retina are both consistent with expression reports of other Barhl2 orthologues, and support the subdivision of vertebrate Barhl into two paralogue groups based on the phylogenetic analysis of nucleotide and amino acid sequences.

  17. Differential effects of a polyalanine tract expansion in Arx on neural development and gene expression

    Science.gov (United States)

    Nasrallah, MacLean Pancoast; Cho, Ginam; Simonet, Jacqueline C.; Putt, Mary E.; Kitamura, Kunio; Golden, Jeffrey A.

    2012-01-01

    Polyalanine (poly-A) tracts exist in 494 annotated proteins; to date, expansions in these tracts have been associated with nine human diseases. The pathogenetic mechanism by which a poly-A tract results in these various human disorders remains uncertain. To understand the role of this mutation type, we investigated the change in functional properties of the transcription factor Arx when it has an expanded poly-A tract (ArxE), a mutation associated with infantile spasms and intellectual disabilities in humans. We found that although ArxE functions normally in the dorsal brain, its function in subpallial-derived populations of neurons is compromised. These contrasting functions are associated with the misregulation of Arx targets through the loss of the ability of ArxE to interact with the Arx cofactor Tle1. Our data demonstrate a novel mechanism for poly-A expansion diseases: the misregulation of a subset of target genes normally regulated by a transcription factor. PMID:22108177

  18. The siRNA-mediated knockdown of GluN3A in 46C-derived neural stem cells affects mRNA expression levels of neural genes, including known iGluR interactors

    Science.gov (United States)

    Eilebrecht, Elke; Schöneborn, Hendrik; Neumann, Sebastian; Benecke, Arndt G.; Hollmann, Michael

    2018-01-01

    For years, GluN3A was solely considered to be a dominant-negative modulator of NMDARs, since its incorporation into receptors alters hallmark features of conventional NMDARs composed of GluN1/GluN2 subunits. Only recently, increasing evidence has accumulated that GluN3A plays a more diversified role. It is considered to be critically involved in the maturation of glutamatergic synapses, and it might act as a molecular brake to prevent premature synaptic strengthening. Its expression pattern supports a putative role during neural development, since GluN3A is predominantly expressed in early pre- and postnatal stages. In this study, we used RNA interference to efficiently knock down GluN3A in 46C-derived neural stem cells (NSCs) both at the mRNA and at the protein level. Global gene expression profiling upon GluN3A knockdown revealed significantly altered expression of a multitude of neural genes, including genes encoding small GTPases, retinal proteins, and cytoskeletal proteins, some of which have been previously shown to interact with GluN3A or other iGluR subunits. Canonical pathway enrichment studies point at important roles of GluN3A affecting key cellular pathways involved in cell growth, proliferation, motility, and survival, such as the mTOR pathway. This study for the first time provides insights into transcriptome changes upon the specific knockdown of an NMDAR subunit in NSCs, which may help to identify additional functions and downstream pathways of GluN3A and GluN3A-containing NMDARs. PMID:29438442

  19. Conserved structural domains in FoxD4L1, a neural forkhead box transcription factor, are required to repress or activate target genes.

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    Steven L Klein

    Full Text Available FoxD4L1 is a forkhead transcription factor that expands the neural ectoderm by down-regulating genes that promote the onset of neural differentiation and up-regulating genes that maintain proliferative neural precursors in an immature state. We previously demonstrated that binding of Grg4 to an Eh-1 motif enhances the ability of FoxD4L1 to down-regulate target neural genes but does not account for all of its repressive activity. Herein we analyzed the protein sequence for additional interaction motifs and secondary structure. Eight conserved motifs were identified in the C-terminal region of fish and frog proteins. Extending the analysis to mammals identified a high scoring motif downstream of the Eh-1 domain that contains a tryptophan residue implicated in protein-protein interactions. In addition, secondary structure prediction programs predicted an α-helical structure overlapping with amphibian-specific Motif 6 in Xenopus, and similarly located α-helical structures in other vertebrate FoxD proteins. We tested functionality of this site by inducing a glutamine-to-proline substitution expected to break the predicted α-helical structure; this significantly reduced FoxD4L1's ability to repress zic3 and irx1. Because this mutation does not interfere with Grg4 binding, these results demonstrate that at least two regions, the Eh-1 motif and a more C-terminal predicted α-helical/Motif 6 site, additively contribute to repression. In the N-terminal region we previously identified a 14 amino acid motif that is required for the up-regulation of target genes. Secondary structure prediction programs predicted a short β-strand separating two acidic domains. Mutant constructs show that the β-strand itself is not required for transcriptional activation. Instead, activation depends upon a glycine residue that is predicted to provide sufficient flexibility to bring the two acidic domains into close proximity. These results identify conserved predicted

  20. Effects of high-LET radiation on neural cells in culture: apoptosis induction, cell toxicity and gene expression

    Science.gov (United States)

    Vazquez, M.; Otto, S.; Estevez, L.; Rios, D.; Pena, L.; Anderson, C.

    Despite the fact that some in vivo studies suggest that chronic low-dose exposure to HZE particles might produce effects similar to aging and neurodegeneration, the basic mechanisms of HZE particle neurotoxicity remain to be elucidated. The goal of these experiments is to establish neural cellular models to evaluate the capacity of low- and high-LET radiation, to induce cell damage and apoptosis. In the present study we measured apoptosis, cell toxicity and gene expression induced by low fluences-doses of heavy ions, protons and photons using neuronal precursor cells (NT2, STRATAGENE) and post-mitotic neurons as models for adult neural cell system. Using heavy ions accelerated at AGS (BNL) and HIMAC (Chiba, Japan), and protons (Loma Linda) we study the neurotoxic effects of a variety of heavy particles (1 and 0.6 GeV/n Fe, 580 MeV/n Si, 290 MeV/n C, 550 MeV/n Ar; LET ranging from 13 to148 keV/μm), and 255 MeV/n protons. Apoptosis Induction: We measured the induction of apoptosis by flow cytometry using a FACSCalibur to detect the expression of Annexin V, as an early marker in the apoptotic pathway, in NT-2 cells. The ApoAlert Annexin V assay is based on the observation that soon after initiating apoptosis, most cell types translocate phosphatidylserine (PS) from the inner face of the plasma membrane to the cell surface. Once on the cell surface, PS can be easily detected by staining with a FITC conjugate of Annexin V, a protein that has a strong natural affinity for PS. Externalization of PS occurs earlier than the nuclear changes associated with apoptosis, so the ApoAlert Assay detects apoptotic cells significantly earlier than do DNA-based assays. Exposing NT-2 cells to Fe ions and protons induced a strong dose- and time-dependent induction of apoptosis with the peak of apoptosis appearing at 72 hours post-irradiation. It was determined that Fe ion exposure were more effective to induce apoptosis in comparison to protons and gamma rays, suggesting an high RBE

  1. Candidate Gene Discovery Procedure after Follow-Up Confirmatory Analyses of Candidate Regions of Interests for Alzheimer’s Disease in the NIMH Sibling Dataset

    Directory of Open Access Journals (Sweden)

    Tesfaye M. Baye

    2008-01-01

    Full Text Available The objective of this research was to develop a procedure to identify candidate genes under linkage peaks confirmed in a follow-up of candidate regions of interests (CRIs identified in our original genome scan in the NIMH Alzheimer’s diseases (AD Initiative families (Blacker et al. [1]. There were six CRIs identified that met the threshold of multipoint lod score (MLS of ≥ 2.0 from the original scan. The most significant peak (MLS = 7.7 was at 19q13, which was attributed to APOE. The remaining CRIs with ‘suggestive’ evidence for linkage were identified at 9q22, 6q27, 14q22, 11q25, and 3p26. We have followed up and narrowed the 9q22 CRI signal using simple tandem repeat (STR markers (Perry et al. [2]. In this confirmatory project, we have followed up the 6q27, 14q22, 11q25, and 3p26 CRIs with a total of 24 additional flanking STRs, reducing the mean interval marker distance (MID in each CRI, and substantially increase in the information content (IC. The linkage signals at 6q27, 14q22 and 11q25 remain ‘suggestive’, indicating that these CRIs are promising and worthy of detailed fine mapping and assessment of candidate genes associated with AD.

  2. YB-1 gene expression is kept constant during myocyte differentiation through replacement of different transcription factors and then falls gradually under the control of neural activity.

    Science.gov (United States)

    Kobayashi, Shunsuke; Tanaka, Toru; Moue, Masamitsu; Ohashi, Sachiyo; Nishikawa, Taishi

    2015-11-01

    We have previously reported that translation of acetylcholine receptor α-subunit (AChR α) mRNA in skeletal muscle cells is regulated by Y-box binding protein 1 (YB-1) in response to neural activity, and that in the postnatal mouse developmental changes in the amount of YB-1 mRNA are similar to those of AChR α mRNA, which is known to be regulated by myogenic transcription factors. Here, we examined transcriptional regulation of the YB-1 gene in mouse skeletal muscle and differentiating C2C12 myocytes. Although neither YB-1 nor AChR α was detected at either the mRNA or protein level in adult hind limb muscle, YB-1 expression was transiently activated in response to denervation of the sciatic nerve and completely paralleled that of AChR α, suggesting that these genes are regulated by the same transcription factors. However, during differentiation of C2C12 cells to myotubes, the level of YB-1 remained constant even though the level of AChR α increased markedly. Reporter gene, gel mobility shift and ChIP assays revealed that in the initial stage of myocyte differentiation, transcription of the YB-1 gene was regulated by E2F1 and Sp1, and was then gradually replaced under the control of both MyoD and myogenin through an E-box sequence in the proximal region of the YB-1 gene promoter. These results suggest that transcription factors for the YB-1 gene are exchanged during skeletal muscle cell differentiation, perhaps playing a role in translational control of mRNAs by YB-1 in both myotube formation and the response of skeletal muscle tissues to neural stimulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

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

  4. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.

    Directory of Open Access Journals (Sweden)

    Noa Safra

    Full Text Available Neural tube defects (NTDs is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5, after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525 were found to be significantly over-represented (p=0.036. This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.

  5. Generation of Human Induced Pluripotent Stem Cell‐Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy

    Science.gov (United States)

    Meneghini, Vasco; Sala, Davide; De Cicco, Silvia; Luciani, Marco; Cavazzin, Chiara; Paulis, Marianna; Mentzen, Wieslawa; Morena, Francesco; Giannelli, Serena; Sanvito, Francesca; Villa, Anna; Bulfone, Alessandro; Broccoli, Vania; Martino, Sabata

    2016-01-01

    Abstract Allogeneic fetal‐derived human neural stem cells (hfNSCs) that are under clinical evaluation for several neurodegenerative diseases display a favorable safety profile, but require immunosuppression upon transplantation in patients. Neural progenitors derived from patient‐specific induced pluripotent stem cells (iPSCs) may be relevant for autologous ex vivo gene‐therapy applications to treat genetic diseases with unmet medical need. In this scenario, obtaining iPSC‐derived neural stem cells (NSCs) showing a reliable “NSC signature” is mandatory. Here, we generated human iPSC (hiPSC) clones via reprogramming of skin fibroblasts derived from normal donors and patients affected by metachromatic leukodystrophy (MLD), a fatal neurodegenerative lysosomal storage disease caused by genetic defects of the arylsulfatase A (ARSA) enzyme. We differentiated hiPSCs into NSCs (hiPS‐NSCs) sharing molecular, phenotypic, and functional identity with hfNSCs, which we used as a “gold standard” in a side‐by‐side comparison when validating the phenotype of hiPS‐NSCs and predicting their performance after intracerebral transplantation. Using lentiviral vectors, we efficiently transduced MLD hiPSCs, achieving supraphysiological ARSA activity that further increased upon neural differentiation. Intracerebral transplantation of hiPS‐NSCs into neonatal and adult immunodeficient MLD mice stably restored ARSA activity in the whole central nervous system. Importantly, we observed a significant decrease of sulfatide storage when ARSA‐overexpressing cells were used, with a clear advantage in those mice receiving neonatal as compared with adult intervention. Thus, we generated a renewable source of ARSA‐overexpressing iPSC‐derived bona fide hNSCs with improved features compared with clinically approved hfNSCs. Patient‐specific ARSA‐overexpressing hiPS‐NSCs may be used in autologous ex vivo gene therapy protocols to provide long‐lasting enzymatic

  6. Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees.

    Science.gov (United States)

    Chou, Hsiu-Ling; Yao, Chung-Tay; Su, Sui-Lun; Lee, Chia-Yi; Hu, Kuang-Yu; Terng, Harn-Jing; Shih, Yun-Wen; Chang, Yu-Tien; Lu, Yu-Fen; Chang, Chi-Wen; Wahlqvist, Mark L; Wetter, Thomas; Chu, Chi-Ming

    2013-03-19

    Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann-Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence. The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence.

  7. Role of Reactive Oxygen Species in the Neural and Hormonal Regulation of the PNMT Gene in PC12 Cells

    Directory of Open Access Journals (Sweden)

    James A. G. Crispo

    2011-01-01

    Full Text Available The stress hormone, epinephrine, is produced predominantly by adrenal chromaffin cells and its biosynthesis is regulated by the enzyme phenylethanolamine N-methyltransferase (PNMT. Studies have demonstrated that PNMT may be regulated hormonally via the hypothalamic-pituitary-adrenal axis and neurally via the stimulation of the splanchnic nerve. Additionally, hypoxia has been shown to play a key role in the regulation of PNMT. The purpose of this study was to examine the impact of reactive oxygen species (ROS produced by the hypoxia mimetic agent CoCl2, on the hormonal and neural stimulation of PNMT in an in vitro cell culture model, utilizing the rat pheochromocytoma (PC12 cell line. RT-PCR analyses show inductions of the PNMT intron-retaining and intronless mRNA splice variants by CoCl2 (3.0- and 1.76-fold, respectively. Transient transfection assays of cells treated simultaneously with CoCl2 and the synthetic glucocorticoid, dexamethasone, show increased promoter activity (18.5-fold, while mRNA levels of both splice variants do not demonstrate synergistic effects. Similar results were observed when investigating the effects of CoCl2-induced ROS on the neural stimulation of PNMT via forskolin. Our findings demonstrate that CoCl2-induced ROS have synergistic effects on hormonal and neural activation of the PNMT promoter.

  8. Epigenetic regulation of gene expression in porcine epiblast, hypoblast, trophectoderm and epiblast-derived neural progenitor cells

    National Research Council Canada - National Science Library

    Gao, Yu; Jammes, Helene; Rasmussen, Mikkel Aabech; Oestrup, Olga; Beaujean, Nathalie; Hall, Vanessa; Hyttel, Poul

    2011-01-01

    ...) epiblast, hypoblast, and TE as well as in epiblast-derived neural progenitor cells (NPCs). We found that OCT4, NANOG, and SOX2 were highly expressed in the epiblast and hypoblast, while VIMENTIN was only highly expressed in the epiblast...

  9. Clinical application of modified bag-of-features coupled with hybrid neural-based classifier in dengue fever classification using gene expression data.

    Science.gov (United States)

    Chatterjee, Sankhadeep; Dey, Nilanjan; Shi, Fuqian; Ashour, Amira S; Fong, Simon James; Sen, Soumya

    2017-09-11

    Dengue fever detection and classification have a vital role due to the recent outbreaks of different kinds of dengue fever. Recently, the advancement in the microarray technology can be employed for such classification process. Several studies have established that the gene selection phase takes a significant role in the classifier performance. Subsequently, the current study focused on detecting two different variations, namely, dengue fever (DF) and dengue hemorrhagic fever (DHF). A modified bag-of-features method has been proposed to select the most promising genes in the classification process. Afterward, a modified cuckoo search optimization algorithm has been engaged to support the artificial neural (ANN-MCS) to classify the unknown subjects into three different classes namely, DF, DHF, and another class containing convalescent and normal cases. The proposed method has been compared with other three well-known classifiers, namely, multilayer perceptron feed-forward network (MLP-FFN), artificial neural network (ANN) trained with cuckoo search (ANN-CS), and ANN trained with PSO (ANN-PSO). Experiments have been carried out with different number of clusters for the initial bag-of-features-based feature selection phase. After obtaining the reduced dataset, the hybrid ANN-MCS model has been employed for the classification process. The results have been compared in terms of the confusion matrix-based performance measuring metrics. The experimental results indicated a highly statistically significant improvement with the proposed classifier over the traditional ANN-CS model.

  10. Genetic backgrounds and modifier genes of NTD mouse models: An opportunity for greater understanding of the multifactorial etiology of neural tube defects.

    Science.gov (United States)

    Leduc, Renee Y M; Singh, Parmveer; McDermid, Heather E

    2017-01-30

    Neurulation, the early embryonic process of forming the presumptive brain and spinal cord, is highly complex and involves hundreds of genes in multiple genetic pathways. Mice have long served as a genetic model for studying human neurulation, and the resulting neural tube defects (NTDs) that arise when neurulation is disrupted. Because mice appear to show mostly single gene inheritance for NTDs and humans show multifactorial inheritance, mice sometimes have been characterized as a simpler model for the identification and study of NTD genes. But are they a simple model? When viewed on different genetic backgrounds, many genes show significant variation in the penetrance and expressivity of NTD phenotypes, suggesting the presence of modifier loci that interact with the target gene to affect the phenotypic expression. Looking at mutations on different genetic backgrounds provides us with an opportunity to explore these complex genetic interactions, which are likely to better emulate similar processes in human neurulation. Here, we review NTD genes known to show strain-specific phenotypic variation. We focus particularly on the gene Cecr2, which is studied using both a hypomorphic and a presumptive null mutation on two different backgrounds: one susceptible (BALB/c) and one resistant (FVB/N) to NTDs. This strain difference has led to a search for genetic modifiers within a region on murine chromosome 19. Understanding how genetic variants alter the phenotypic outcome in NTD mouse models will help to direct future studies in humans, particularly now that more genome wide sequencing approaches are being used. Birth Defects Research 109:140-152, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2011-12-01

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

  12. Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

    Science.gov (United States)

    Zhao, Y; Lam, D H; Yang, J; Lin, J; Tham, C K; Ng, W H; Wang, S

    2012-02-01

    Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

  13. Large-Scale Recurrent Neural Network Based Modelling of Gene Regulatory Network Using Cuckoo Search-Flower Pollination Algorithm.

    Science.gov (United States)

    Mandal, Sudip; Khan, Abhinandan; Saha, Goutam; Pal, Rajat K

    2016-01-01

    The accurate prediction of genetic networks using computational tools is one of the greatest challenges in the postgenomic era. Recurrent Neural Network is one of the most popular but simple approaches to model the network dynamics from time-series microarray data. To date, it has been successfully applied to computationally derive small-scale artificial and real-world genetic networks with high accuracy. However, they underperformed for large-scale genetic networks. Here, a new methodology has been proposed where a hybrid Cuckoo Search-Flower Pollination Algorithm has been implemented with Recurrent Neural Network. Cuckoo Search is used to search the best combination of regulators. Moreover, Flower Pollination Algorithm is applied to optimize the model parameters of the Recurrent Neural Network formalism. Initially, the proposed method is tested on a benchmark large-scale artificial network for both noiseless and noisy data. The results obtained show that the proposed methodology is capable of increasing the inference of correct regulations and decreasing false regulations to a high degree. Secondly, the proposed methodology has been validated against the real-world dataset of the DNA SOS repair network of Escherichia coli. However, the proposed method sacrifices computational time complexity in both cases due to the hybrid optimization process.

  14. Large-Scale Recurrent Neural Network Based Modelling of Gene Regulatory Network Using Cuckoo Search-Flower Pollination Algorithm

    Directory of Open Access Journals (Sweden)

    Sudip Mandal

    2016-01-01

    Full Text Available The accurate prediction of genetic networks using computational tools is one of the greatest challenges in the postgenomic era. Recurrent Neural Network is one of the most popular but simple approaches to model the network dynamics from time-series microarray data. To date, it has been successfully applied to computationally derive small-scale artificial and real-world genetic networks with high accuracy. However, they underperformed for large-scale genetic networks. Here, a new methodology has been proposed where a hybrid Cuckoo Search-Flower Pollination Algorithm has been implemented with Recurrent Neural Network. Cuckoo Search is used to search the best combination of regulators. Moreover, Flower Pollination Algorithm is applied to optimize the model parameters of the Recurrent Neural Network formalism. Initially, the proposed method is tested on a benchmark large-scale artificial network for both noiseless and noisy data. The results obtained show that the proposed methodology is capable of increasing the inference of correct regulations and decreasing false regulations to a high degree. Secondly, the proposed methodology has been validated against the real-world dataset of the DNA SOS repair network of Escherichia coli. However, the proposed method sacrifices computational time complexity in both cases due to the hybrid optimization process.

  15. A data science approach to candidate gene selection of pain regarded as a process of learning and neural plasticity.

    Science.gov (United States)

    Ultsch, Alfred; Kringel, Dario; Kalso, Eija; Mogil, Jeffrey S; Lötsch, Jörn

    2016-12-01

    The increasing availability of "big data" enables novel research approaches to chronic pain while also requiring novel techniques for data mining and knowledge discovery. We used machine learning to combine the knowledge about n = 535 genes identified empirically as relevant to pain with the knowledge about the functions of thousands of genes. Starting from an accepted description of chronic pain as displaying systemic features described by the terms "learning" and "neuronal plasticity," a functional genomics analysis proposed that among the functions of the 535 "pain genes," the biological processes "learning or memory" (P = 8.6 × 10) and "nervous system development" (P = 2.4 × 10) are statistically significantly overrepresented as compared with the annotations to these processes expected by chance. After establishing that the hypothesized biological processes were among important functional genomics features of pain, a subset of n = 34 pain genes were found to be annotated with both Gene Ontology terms. Published empirical evidence supporting their involvement in chronic pain was identified for almost all these genes, including 1 gene identified in March 2016 as being involved in pain. By contrast, such evidence was virtually absent in a randomly selected set of 34 other human genes. Hence, the present computational functional genomics-based method can be used for candidate gene selection, providing an alternative to established methods.

  16. Expression of the Lhx genes apterous and lim1 in an errant polychaete: implications for bilaterian appendage evolution, neural development, and muscle diversification

    Directory of Open Access Journals (Sweden)

    Winchell Christopher J

    2013-02-01

    Full Text Available Abstract Background Arthropod and vertebrate appendages appear to have evolved via parallel co-option of a plesiomorphic gene regulatory network. Our previous work implies that annelids evolved unrelated appendage-forming mechanisms; we therefore found no support for homology of parapodia and arthropodia at the level of the whole appendage. We expand on that study here by asking whether expression of the LIM homeobox (Lhx genes apterous and lim1 in the annelid Neanthes arenaceodentata supports homology of the dorsal branches as well as the proximodistal axes of parapodia and arthropodia. In addition, we explore whether the neural expression of apterous and lim1 in Neanthes supports the putative ancestral function of the Lhx gene family in regulating the differentiation and maintenance of neuronal subtypes. Results Both genes exhibit continuous expression in specific portions of the developing central nervous system, from hatching to at least the 13-chaetiger stage. For example, nerve cord expression occurs in segmentally iterated patterns consisting of diffuse sets of many lim1-positive cells and comparatively fewer, clustered pairs of apterous-positive cells. Additionally, continuous apterous expression is observed in presumed neurosecretory ganglia of the posterior brain, while lim1 is continuously expressed in stomatogastric ganglia of the anterior brain. apterous is also expressed in the jaw sacs, dorsal parapodial muscles, and a presumed pair of cephalic sensory organs, whereas lim1 is expressed in multiple pharyngeal ganglia, the segmental peripheral nervous system, neuropodial chaetal sac muscles, and parapodial ligules. Conclusions The early and persistent nervous system expression of apterous and lim1 in Neanthes juveniles supports conservation of Lhx function in bilaterian neural differentiation and maintenance. Our results also suggest that diversification of parapodial muscle precursors involves a complementary LIM code similar to

  17. Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles.

    Science.gov (United States)

    Oh, Jung-Hwa; Son, Mi-Young; Choi, Mi-Sun; Kim, Soojin; Choi, A-Young; Lee, Hyang-Ae; Kim, Ki-Suk; Kim, Janghwan; Song, Chang Woo; Yoon, Seokjoo

    2016-05-15

    Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Transcriptomic profile analysis of mouse neural tube development by RNA-Seq.

    Science.gov (United States)

    Yu, Juan; Mu, Jianbing; Guo, Qian; Yang, Lihong; Zhang, Juan; Liu, Zhizhen; Yu, Baofeng; Zhang, Ting; Xie, Jun

    2017-09-01

    The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA-seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles. Of 45 DEGs, Foxp2, Eomes, Hoxb3, Gpr56, Hap1, Nkx2-1, Sez6l2, Wnt7b, Tbx20, Nfib, Cntn1 and Dcx had different isoforms, and the opposite expression pattern of different isoforms was observed for Gpr56, Nkx2-1 and Sez6l2. In addition, alternative splicing, such as mutually exclusive exon, retained intron, skipped exon and alternative 3' splice site was identified in 10 neural related differentially splicing genes, including Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2, Vcan and App. Moreover, seven neural splicing factors, such as Nova1/2, nSR100/Srrm4, Elavl3/4, Celf3 and Rbfox1 were differentially expressed during mouse neural tube development. Interestingly, nine DEGs identified above were dysregulated in retinoic acid-induced NTDs model, indicating the possible important role of these genes in NTDs. Taken together, our study provides more comprehensive information on mouse neural tube development, which might provide new insights on NTDs occurrence. © 2017 IUBMB Life, 69(9):706-719, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  19. Stressor and glucocorticoid-dependent induction of the immediate early gene kruppel-like factor 9: implications for neural development and plasticity.

    Science.gov (United States)

    Bonett, Ronald M; Hu, Fang; Bagamasbad, Pia; Denver, Robert J

    2009-04-01

    Krüppel-like factor 9 (KLF9) is a thyroid hormone-induced, immediate early gene implicated in neural development in vertebrates. We analyzed stressor and glucocorticoid (GC)-dependent regulation of KLF9 expression in the brain of the frog Xenopus laevis, and investigated a possible role for KLF9 in neuronal differentiation. Exposure to shaking/confinement stressor increased plasma corticosterone (CORT) concentration, and KLF9 immunoreactivity in several brain regions, which included the medial amygdala and bed nucleus of the stria terminalis, anterior preoptic area (homologous to the mammalian paraventricular nucleus), and optic tectum (homologous to the mammalian superior colliculus). The stressor-induced KLF9 mRNA expression in the brain was blocked by pretreatment with the GC receptor antagonist RU486, or mimicked by injection of CORT. Treatment with CORT also caused a rapid and dose-dependent increase in KLF9 mRNA in X. laevis XTC-2 cells that was resistant to inhibition of protein synthesis. The action of CORT on KLF9 expression in XTC-2 cells was blocked by RU486, but not by the mineralocorticoid receptor antagonist spironolactone. To test for functional consequences of up-regulation of KLF9, we introduced a KLF9 expression plasmid into living tadpole brain by electroporation-mediated gene transfer. Forced expression of KLF9 in tadpole brain caused an increase in Golgi-stained cells, reflective of neuronal differentiation/maturation. Our results support that KLF9 is a direct, GC receptor target gene that is induced by stress, and functions as an intermediary in the actions of GCs on brain gene expression and neuronal structure.

  20. Stressor and Glucocorticoid-Dependent Induction of the Immediate Early Gene Krüppel-Like Factor 9: Implications for Neural Development and Plasticity

    Science.gov (United States)

    Bonett, Ronald M.; Hu, Fang; Bagamasbad, Pia; Denver, Robert J.

    2009-01-01

    Krüppel-like factor 9 (KLF9) is a thyroid hormone-induced, immediate early gene implicated in neural development in vertebrates. We analyzed stressor and glucocorticoid (GC)-dependent regulation of KLF9 expression in the brain of the frog Xenopus laevis, and investigated a possible role for KLF9 in neuronal differentiation. Exposure to shaking/confinement stressor increased plasma corticosterone (CORT) concentration, and KLF9 immunoreactivity in several brain regions, which included the medial amygdala and bed nucleus of the stria terminalis, anterior preoptic area (homologous to the mammalian paraventricular nucleus), and optic tectum (homologous to the mammalian superior colliculus). The stressor-induced KLF9 mRNA expression in the brain was blocked by pretreatment with the GC receptor antagonist RU486, or mimicked by injection of CORT. Treatment with CORT also caused a rapid and dose-dependent increase in KLF9 mRNA in X. laevis XTC-2 cells that was resistant to inhibition of protein synthesis. The action of CORT on KLF9 expression in XTC-2 cells was blocked by RU486, but not by the mineralocorticoid receptor antagonist spironolactone. To test for functional consequences of up-regulation of KLF9, we introduced a KLF9 expression plasmid into living tadpole brain by electroporation-mediated gene transfer. Forced expression of KLF9 in tadpole brain caused an increase in Golgi-stained cells, reflective of neuronal differentiation/maturation. Our results support that KLF9 is a direct, GC receptor target gene that is induced by stress, and functions as an intermediary in the actions of GCs on brain gene expression and neuronal structure. PMID:19036875

  1. DNA methylation aberrations rather than polymorphisms of FZD3 gene increase the risk of spina bifida in a high-risk region for neural tube defects.

    Science.gov (United States)

    Shangguan, Shaofang; Wang, Li; Chang, Shaoyan; Lu, Xiaoling; Wang, Zhen; Wu, Lihua; Wang, Jianhua; Wang, Xiuwei; Guan, Zhen; Bao, Yihua; Zhao, Huizhi; Zou, Jizhen; Niu, Bo; Zhang, Ting

    2015-01-01

    Animal models of neural tube defects (NTDs) have indicated roles for the Fzd3 gene and the planar cell polarity signaling pathway in convergent extension. We investigated the involvement of FZD3 in genetic and epigenetic mechanisms associated with human NTDs, especially spina bifida. We explored the effects of variants spanning the FZD3 gene in NTDs and examined the role of aberrant methylation of the FZD3 promoter on gene expression in brain tissue in spina bifida. Six FZD3 single nucleotide polymorphisms were genotyped using a MassARRAY system in tissue from 165 NTD fetuses and 152 controls. DNA methylation aberrations in the FZD3 promoter region were detected using a MassARRAY EpiTYPER (17 CpG units from -500 to -2400 bp from the transcription start site) in brain tissue from 77 spina bifida and 74 control fetuses. None of the six single nucleotide polymorphisms evaluated were significantly associated with spina bifida, but the mean methylation level was significantly higher in spina bifida samples (13.70%) compared with control samples (10.91%) (p = 0.001). In terms of specific sites, DNA methylation levels were significantly higher in the spina bifida samples at 14 of the 17 CpG units, which mostly included in R2 region. FZD3 mRNA expression was negatively correlated with methylation of the FZD3 promoter region, especially the R2 region (R = 0.970; p = 0.001) in HeLa cells. The results of this study suggest that DNA methylation plays an important role in FZD3 gene expression regulation and may be associated with an increased risk of spina bifida. © 2014 Wiley Periodicals, Inc.

  2. High throughput analysis reveals dissociable gene expression profiles in two independent neural systems involved in the regulation of social behavior

    Directory of Open Access Journals (Sweden)

    Stevenson Tyler J

    2012-10-01

    Full Text Available Abstract Background Production of contextually appropriate social behaviors involves integrated activity across many brain regions. Many songbird species produce complex vocalizations called ‘songs’ that serve to attract potential mates, defend territories, and/or maintain flock cohesion. There are a series of discrete interconnect brain regions that are essential for the successful production of song. The probability and intensity of singing behavior is influenced by the reproductive state. The objectives of this study were to examine the broad changes in gene expression in brain regions that control song production with a brain region that governs the reproductive state. Results We show using microarray cDNA analysis that two discrete brain systems that are both involved in governing singing behavior show markedly different gene expression profiles. We found that cortical and basal ganglia-like brain regions that control the socio-motor production of song in birds exhibit a categorical switch in gene expression that was dependent on their reproductive state. This pattern is in stark contrast to the pattern of expression observed in a hypothalamic brain region that governs the neuroendocrine control of reproduction. Subsequent gene ontology analysis revealed marked variation in the functional categories of active genes dependent on reproductive state and anatomical localization. HVC, one cortical-like structure, displayed significant gene expression changes associated with microtubule and neurofilament cytoskeleton organization, MAP kinase activity, and steroid hormone receptor complex activity. The transitions observed in the preoptic area, a nucleus that governs the motivation to engage in singing, exhibited variation in functional categories that included thyroid hormone receptor activity, epigenetic and angiogenetic processes. Conclusions These findings highlight the importance of considering the temporal patterns of gene expression

  3. Epigenetic regulation of gene expression in porcine epiblast, hypoblast, trophectoderm and epiblast-derived neural progenitor cells

    DEFF Research Database (Denmark)

    Gao, Yu; Jammes, Helen; Rasmussen, Mikkel Aabech

    2011-01-01

    After fertilization, lineage specification is governed by a complicated molecular network in which permissiveness and repression of expression of pluripotency- and differentiation-associated genes are regulated by epigenetic modifications. DNA methylation operates as a very stable repressive mark...... of its promoter. In conclusion, DNA methylation is an inconsistently operating epigenetic mechanism in porcine E10 blastocysts, whereas in porcine epiblast-derived NPCs, expression of pluripotency-associated and differentiation genes appear to be regulated by this modification.......After fertilization, lineage specification is governed by a complicated molecular network in which permissiveness and repression of expression of pluripotency- and differentiation-associated genes are regulated by epigenetic modifications. DNA methylation operates as a very stable repressive mark...

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

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

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

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

    Science.gov (United States)

    Takada, Masahiko

    2013-06-01

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

  6. 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...

  7. Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition.

    Science.gov (United States)

    van der Meer, Dennis; Hartman, Catharina A; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Buitelaar, Jan K; Hoekstra, Pieter J

    2017-03-01

    Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

  8. Construction of a genetically modified wine yeast strain expressing the Aspergillus aculeatus rhaA gene, encoding an -L-Rhamnosidase of enological interest

    NARCIS (Netherlands)

    Manzanares, P.; Orejas, M.; Vicente Gil, J.; Graaff, de L.H.; Visser, J.; Ramon, D.

    2003-01-01

    The Aspergillus aculeatus rhaA gene encoding an alpha-L-rhamnosidase has been expressed in both laboratory and industrial wine yeast strains. Wines produced in microvinifications, conducted using a combination of the genetically modified industrial strain expressing rhaA and another strain

  9. Construction of a Genetically Modified Wine Yeast Strain Expressing the Aspergillus aculeatus rhaA Gene, Encoding an α-l-Rhamnosidase of Enological Interest

    Science.gov (United States)

    Manzanares, Paloma; Orejas, Margarita; Gil, José Vicente; de Graaff, Leo H.; Visser, Jaap; Ramón, Daniel

    2003-01-01

    The Aspergillus aculeatus rhaA gene encoding an α-l-rhamnosidase has been expressed in both laboratory and industrial wine yeast strains. Wines produced in microvinifications, conducted using a combination of the genetically modified industrial strain expressing rhaA and another strain expressing a β-glucosidase, show increased content mainly of the aromatic compound linalool. PMID:14660415

  10. Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury.

    Science.gov (United States)

    Guo, J-S; Zeng, Y-S; Li, H-B; Huang, W-L; Liu, R-Y; Li, X-B; Ding, Y; Wu, L-Z; Cai, D-Z

    2007-01-01

    An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted neural stem cells (NSCs) and NT-3-SCs promote morphologic and functional recoveries of injured spinal cord. To explore whether cotransplant of NSCs and NT-3-SCs could promote the injured spinal cord repair. Zhongshan Medical College, Sun Yat-sen University, PR China. Female Sprague-Dawley (SD) rats weighing on 200-220 g were used to prepare SCI models. The spinal cord was transected between T(9) and T(10), then NSCs, SCs+NSCs, LacZ-SCs+NSCs, or NT-3-SCs+NSCs were grafted into the transected site. (1) Part of NSCs could differentiate to neuron-like cells in the transected site and the percentage of differentiation was NT-3-SCs+NSCs group>SCs+NSCs group>NSCs group. (2) In the grafted groups, there were 5-HT, CGRP, and SP positive nerve fibres within the transected site. Some fluorogold (FG)-labeled cells were found in the spinal cord rostral to the transected site, the red nuclei and the inner pyramidal layer of sensorimotor cortex. (3) The cells grafted could enhance the injured neurons survival in inner pyramidal layer of sensorimotor cortex, red nuclei of midbrain, and Clark's nuclei of spinal cord's L1 segment, could decrease the latency and increase the amplitude of cortical somatosensory evoked potential (CSEP) and cortical motor evoked potential (CMEP), and could promote partly structural and functional recovery of the SCI rats. These results demonstrate that cografted NT-3-SCs and NSCs is a potential therapy for SCI. This research was supported by Chinese National Key Project for Basic Research (G1999054009), Chinese National Natural Science Foundation (30270700) and Social Developmental Foundation of Guangdong Province (2003C33808) to YS Zeng; Natural Science Foundation of Guangdong Province (04300468) and Medical Science Research Grant of Guangdong Province (A2004081) to JS Guo.

  11. COMT and DRD2/ANKK-1 gene-gene interaction account for resetting of gamma neural oscillations to auditory stimulus-driven attention.

    Directory of Open Access Journals (Sweden)

    Manuel Garcia-Garcia

    Full Text Available Attention capture by potentially relevant environmental stimuli is critical for human survival, yet it varies considerably among individuals. A large series of studies has suggested that attention capture may depend on the cognitive balance between maintenance and manipulation of mental representations and the flexible switch between goal-directed representations and potentially relevant stimuli outside the focus of attention; a balance that seems modulated by a prefrontostriatal dopamine pathway. Here, we examined inter-individual differences in the cognitive control of attention through studying the effects of two single nucleotide polymorphisms regulating dopamine at the prefrontal cortex and the striatum (i.e., COMTMet108/158Val and ANKK1/DRD2TaqIA on stimulus-driven attention capture. Healthy adult participants (N = 40 were assigned to different groups according to the combination of the polymorphisms COMTMet108/158Val and ANKK1/DRD2TaqIA, and were instructed to perform on a well-established distraction protocol. Performance in individuals with a balance between prefrontal dopamine display and striatal receptor density was slowed down by the occurrence of unexpected distracting events, while those with a rather unbalanced dopamine activity were able maintain task performance with no time delay, yet at the expense of a slightly lower accuracy. This advantage, associated to their distinct genetic profiles, was paralleled by an electrophysiological mechanism of phase-resetting of gamma neural oscillation to the novel, distracting events. Taken together, the current results suggest that the epistatic interaction between COMTVal108/158Met and ANKK1/DRD2 TaqIa genetic polymorphisms lies at the basis of stimulus-driven attention capture.

  12. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy.

    Science.gov (United States)

    Jongbloet, Piet Hein; Verbeek, André Lm; den Heijer, Martin; Roeleveld, Nel

    2008-07-10

    Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established for several constitutional chronic diseases in adulthood, such as schizophrenia, cardiovascular diseases, dementia, and even neoplasias in different organ systems. This spectrum of developmental anomalies and constitutional diseases may be linked to high-risk conceptions related to preovulatory overripeness ovopathy (PrOO). Some developmental anomalies, such as NTDs, are to a large extent prevented by supplementation of folic acid before conception, but supplementation does not seem to prevent cardiovascular disease or cognitive decline. These diverging results can be elucidated by introduction of the PrOO concept, as MTHFR polymorphisms and inherent low folate levels induce both non-optimal maturation of the oocyte and unsuccessful DNA methylation and demethylation, i.e. epigenetic mutations. The PrOO concept is testable and predicts in a random population the following: (1) female carriers of specific genetic MTHFR variants exhibit more ovulatory disturbances and inherent subfecundity traits, (2) descendents from a carrier mother, when compared with those from a wild-type mother, are more frequently conceived in PrOO high-risk conditions and, thus, (3) disadvantaged in life expectancy. If so, some MTHFR polymorphisms represent a novel, genetically determined, PrOO high-risk conception category comparable to those which are environmentally and behaviorly influenced. These high-risk conditions may cause developmental anomalies and defective epigenetic reprogramming in progeny. The interaction between genetic and environmental factors is a plausible mechanism of multifactorial inheritance.

  13. The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations.

    Science.gov (United States)

    Dávalos, I P; Olivares, N; Castillo, M T; Cantú, J M; Ibarra, B; Sandoval, L; Morán, M C; Gallegos, M P; Chakraborty, R; Rivas, F

    2000-01-01

    The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, associated with the thermolabile form of the enzyme, has reportedly been found to be increased in neural-tube defects (NTD), though this association is still unclear. A group of 107 mestizo parents of NTD children and five control populations: 101 mestizo (M), 50 Huichol (H), 38 Tarahumara (T), 21 Purepecha (P) and 20 Caucasian (C) individuals were typed for the MTHFR C677T variant by the PCR/RFLP (HinfI) method. Genotype frequencies were in agreement with the Hardy-Weinberg expectations in all six populations. Allele frequency (%) of the C677T variant was 45 in NTD, 44 in M, 56 in H, 36 in T, 57 in P, 35 in C. Pairwise inter-population comparisons of allele frequency disclosed a very similar distribution between NTD and M groups (exact test, P=0.92). Among controls, differences between M and individual native groups were NS (0.06Huichol and Purepecha natives, as compared with other groups world wide.

  14. [Recombinant AAV1 mediated vascular endothelial growth factor gene expression promotes angiogenesis and improves neural function: experiment with rats].

    Science.gov (United States)

    Li, Shi-fang; Meng, Qing-hai; Yao, Wei-cheng; Hu, Guo-jie; Li, Gui-lin; Li, Zhao-jian; Wei, Jun-ji; Bo, Yong-li; Zhang, Zi-heng; Wang, Ren-zhi

    2009-01-20

    To investigate the therapeutic effect of vascular endothelial growth factor (VEGF) gene expression mediated by recombinant AAV1 (rAAV1) vector in brain ischemia and the mechanism thereof. Sixty-four SD rats were randomly divided into 2 equal groups and received intra-ventricular injection with rAAV1-VEGF or rAAV1-lacZ as controls. 21 days later the rats underwent transient middle cerebral artery occlusion (MCAO). Neurological severity score (NSS) was recorded 1, 2, 3, 7, 14, and 21 days after MCAO. 48 rats were sacrificed 21 days after MCAO and brains were taken out from 48 rats. Immune quantitative analysis was used to identify the quantity of VEGF expression. Immunohistochemistry was used to identify the site of VEGF expression. Immunofluorescence double labeling of von Willebrand factor (vWF) and 5-bromodeoxy-uridine (BrdU) was performed to detect the proliferation of endothelial cells. Fluorescein isothiocyanate (FITC)-dextran was infused into the caudal vein of 8 rats from each group and then the rats were killed with their brains taken out to evaluate the cerebral microvessel perfusion and microvessel density. The NSSs of the VEGF group 7, 14, and 21 days after MCAO were all significantly lower than those of the control group (all P < 0.05), and the VEGF165 protein expression quantity was 27 times as that of the control group (P < 0.05). Immunohistochemistry demonstrated that VEGF expression was distributed mainly in the caudate putamen, corpus callosum, choroid plexus, and hippocampus in the VEGF group, while no expression was detected in the control group. The microvessel density of the VEGF group was 157 +/- 13, significantly higher than that of the control group [(89 +/- 9), P < 0.05]. BrdU +/vWF + endothelial cells were detected in the area adjacent to the MCAO. The density of microvessel infused with FITC-dextran was (152,617 +/- 13,076) microm2/mm2 in the VEGF group, significantly higher than that of the control group [(91,658 +/- 6577) microm2/mm2 P

  15. 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

  16. Low-Dose Methylmercury-Induced Genes Regulate Mitochondrial Biogenesis via miR-25 in Immortalized Human Embryonic Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Xinjin Wang

    2016-12-01

    Full Text Available Mitochondria are essential organelles and important targets for environmental pollutants. The detection of mitochondrial biogenesis and generation of reactive oxygen species (ROS and p53 levels following low-dose methylmercury (MeHg exposure could expand our understanding of underlying mechanisms. Here, the sensitivity of immortalized human neural progenitor cells (ihNPCs upon exposure to MeHg was investigated. We found that MeHg altered cell viability and the number of 5-ethynyl-2′-deoxyuridine (EdU-positive cells. We also observed that low-dose MeHg exposure increased the mRNA expression of cell cycle regulators. We observed that MeHg induced ROS production in a dose-dependent manner. In addition, mRNA levels of peroxisome-proliferator-activated receptor gammacoactivator-1α (PGC-1α, mitochondrial transcription factor A (TFAM and p53-controlled ribonucleotide reductase (p53R2 were significantly elevated, which were correlated with the increase of mitochondrial DNA (mtDNA copy number at a concentration as low as 10 nM. Moreover, we examined the expression of microRNAs (miRNAs known as regulatory miRNAs of p53 (i.e., miR-30d, miR-1285, miR-25. We found that the expression of these miRNAs was significantly downregulated upon MeHg treatment. Furthermore, the overexpression of miR-25 resulted in significantly reducted p53 protein levels and decreased mRNA expression of genes involved in mitochondrial biogenesis regulation. Taken together, these results demonstrated that MeHg could induce developmental neurotoxicity in ihNPCs through altering mitochondrial functions and the expression of miRNA.

  17. Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4.

    Science.gov (United States)

    Bergeron, Karl-F; Nguyen, Chloé M A; Cardinal, Tatiana; Charrier, Baptiste; Silversides, David W; Pilon, Nicolas

    2016-11-01

    Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line - obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC) development - is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4. © 2016. Published by The Company of Biologists Ltd.

  18. Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4

    Directory of Open Access Journals (Sweden)

    Karl-F. Bergeron

    2016-11-01

    Full Text Available Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line – obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC development – is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4.

  19. 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.

  20. Interest rate derivatives

    DEFF Research Database (Denmark)

    Svenstrup, Mikkel

    This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered.......This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered....

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  3. The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube

    DEFF Research Database (Denmark)

    Hanotel, Julie; Bessodes, Nathalie; Thélie, Aurore

    2014-01-01

    The basic helix-loop-helix (bHLH) transcriptional activator Ptf1a determines inhibitory GABAergic over excitatory glutamatergic neuronal cell fate in progenitors of the vertebrate dorsal spinal cord, cerebellum and retina. In an in situ hybridization expression survey of PR domain containing genes...... and a reduction of the GABAergic neuronal marker Pax2. It also leads to an upregulation of Prdm13 transcription, suggesting an autonegative regulation. Conversely, in animal caps, Prdm13 blocks the ability of the bHLH factor Neurog2 to activate Tlx3. Additional gain of function experiments in the chick neural...

  4. 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.

  5. Construction of a medicinal leech transcriptome database and its application to the identification of leech homologs of neural and innate immune genes

    Directory of Open Access Journals (Sweden)

    Wincker Patrick

    2010-06-01

    evolutionarily conserved sequences, representing all known pathways involved in these important functions. Conclusions The sequences obtained for Hirudo transcripts represent the first major database of genes expressed in this important model system. Comparison of translated open reading frames (ORFs with the other openly available leech datasets, the genome and transcriptome of Helobdella robusta, shows an average identity at the amino acid level of 58% in matched sequences. Interestingly, comparison with other available Lophotrochozoans shows similar high levels of amino acid identity, where sequences match, for example, 64% with Capitella capitata (a polychaete and 56% with Aplysia californica (a mollusk, as well as 58% with Schistosoma mansoni (a platyhelminth. Phylogenetic comparisons of putative Hirudo innate immune response genes present within the Hirudo transcriptome database herein described show a strong resemblance to the corresponding mammalian genes, indicating that this important physiological response may have older origins than what has been previously proposed.

  6. Points of Interest: What Determines Interest Rates?

    Science.gov (United States)

    Schilling, Tim

    Interest rates can significantly influence people's behavior. When rates decline, homeowners rush to buy new homes and refinance old mortgages; automobile buyers scramble to buy new cars; the stock market soars, and people tend to feel more optimistic about the future. But even though individuals respond to changes in rates, they may not fully…

  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. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  9. Understanding Interest Rate Volatility

    DEFF Research Database (Denmark)

    Volker, Desi

    This thesis is the result of my Ph.D. studies at the Department of Finance of the Copenhagen Business School. It consists of three essays covering topics related to the term structure of interest rates, monetary policy and interest rate volatility. The rst essay, \\Monetary Policy Uncertainty...... and Interest Rates", examines the role of monetary policy uncertainty on the term structure of interest rates. The second essay, \\A Regime-Switching A ne Term Structure Model with Stochastic Volatility" (co-authored with Sebastian Fux), investigates the ability of the class of regime switching models...... with and without stochastic volatility to capture the main stylized features of U.S. interest rates. The third essay, \\Variance Risk Premia in the Interest Rate Swap Market", investigates the time-series and cross-sectional properties of the compensation demanded for holding interest rate variance risk. The essays...

  10. Search for the Missing lncs: Gene Regulatory Networks in Neural Crest Development and Long Non-coding RNA Biomarkers of Hirschsprung's Disease

    Science.gov (United States)

    Hirschsprung’s disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births, and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (S...

  11. Dynamic Changes in Ezh2 Gene Occupancy Underlie Its Involvement in Neural Stem Cell Self-Renewal and Differentiation towards Oligodendrocytes

    NARCIS (Netherlands)

    Sher, Falak; Boddeke, Erik; Olah, Marta; Copray, Sjef

    2012-01-01

    Background: The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs). We showed that Ezh2

  12. Search for the Missing lncs: Gene Regulatory Networks in Neural Crest Development and Long Non-coding RNA Biomarkers of Hirschsprung's Disease

    Science.gov (United States)

    Hirschsprung’s disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births, and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et...

  13. 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.

  14. 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.

  15. 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.

  16. National interest to TLCAN

    OpenAIRE

    Witker Velásquez, Jorge

    2017-01-01

    In this article the author reflects on the concept of national interest, considering its basic referents: State, nation and power. His analysis describes and examines aspects related to the vulnerability of the Mexican national interest on informal policies of the North American Free Trade Agreement (NAFTA.). This article explores, through a series of antithetical elements, such Mexico’s national interest, in the context of NAFTA, producing chiaroscuro effects for the country. The author prov...

  17. Exenatide Alters Gene Expression of Neural Cell Adhesion Molecule (NCAM), Intercellular Cell Adhesion Molecule (ICAM), and Vascular Cell Adhesion Molecule (VCAM) in the Hippocampus of Type 2 Diabetic Model Mice.

    Science.gov (United States)

    Gumuslu, Esen; Cine, Naci; Ertan Gökbayrak, Merve; Mutlu, Oguz; Komsuoglu Celikyurt, Ipek; Ulak, Guner

    2016-07-28

    BACKGROUND Glucagon-like peptide-1 (GLP-1), a potent and selective agonist for the GLP-1 receptor, ameliorates the symptoms of diabetes through stimulation of insulin secretion. Exenatide is a potent and selective agonist for the GLP-1 receptor. Cell adhesion molecules are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. MATERIAL AND METHODS The present study demonstrated the effects of exenatide treatment (0.1 µg/kg, subcutaneously, twice daily for 2 weeks) on the gene expression levels of cell adhesion molecules, neural cell adhesion molecule (NCAM), intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) in the brain tissue of diabetic BALB/c male mice by real-time quantitative polymerase chain reaction (PCR). Diabetes was induced by streptozotocin/nicotinamide (STZ-NA) injection to male mice. RESULTS The results of this study revealed that hippocampal gene expression of NCAM, ICAM, and VCAM were found to be up-regulated in STZ-NA-induced diabetic mice compared to those of controls. A significant decrease in the gene expression levels of NCAM, ICAM, and VCAM were determined after 2 weeks of exenatide administration. CONCLUSIONS Cell adhesion molecules may be involved in the molecular mechanism of diabetes. Exenatide has a strong beneficial action in managing diabetes induced by STZ/NA by altering gene expression of NCAM, ICAM, and VCAM.

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

    Science.gov (United States)

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

    2016-11-03

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

  19. Communication and common interest.

    Directory of Open Access Journals (Sweden)

    Peter Godfrey-Smith

    Full Text Available Explaining the maintenance of communicative behavior in the face of incentives to deceive, conceal information, or exaggerate is an important problem in behavioral biology. When the interests of agents diverge, some form of signal cost is often seen as essential to maintaining honesty. Here, novel computational methods are used to investigate the role of common interest between the sender and receiver of messages in maintaining cost-free informative signaling in a signaling game. Two measures of common interest are defined. These quantify the divergence between sender and receiver in their preference orderings over acts the receiver might perform in each state of the world. Sampling from a large space of signaling games finds that informative signaling is possible at equilibrium with zero common interest in both senses. Games of this kind are rare, however, and the proportion of games that include at least one equilibrium in which informative signals are used increases monotonically with common interest. Common interest as a predictor of informative signaling also interacts with the extent to which agents' preferences vary with the state of the world. Our findings provide a quantitative description of the relation between common interest and informative signaling, employing exact measures of common interest, information use, and contingency of payoff under environmental variation that may be applied to a wide range of models and empirical systems.

  20. Vectors bicistronically linking a gene of interest to the SV40 large T antigen in combination with the SV40 origin of replication enhance transient protein expression and luciferase reporter activity.

    Science.gov (United States)

    Mahon, Matthew J

    2011-08-01

    The simian virus 40 large T antigen (SVLT) induces replication of plasmids bearing the SV40 origin of replication (SV40 ori) within mammalian cells. The internal ribosomal entry site (IRES) is an element that allows for the cotranslation of proteins from one polycistronic mRNA. Through the combination of these elements, IRES-dependent coexpression of a protein of interest and the SVLT, either constitutive or regulated, on plasmids bearing the SV40 ori generates a positive feedback loop, resulting in enhanced expression. A vector linking red fluorescent protein (RFP) to the IRES-SVLT element enhances fluorescence ~10-fold over that demonstrated from a vector lacking this element. In transfection-resistant CV-1 cells, the RFP-IRES-SVLT vector substantially increases the number of cells expressing detectable levels of RFP. Furthermore, inclusion of the IRES-SVLT/SV40 ori elements in standard luciferase-based reporter gene constructs and associated effectors results in marked increases in luminescent output and sensitivity, using the β-catenin/TCF pathway and the mammalian two-hybrid assay as models. Ultimately, vector systems combining these well-established elements (IRES-SVLT/SV40 ori) will increase the utility of transient transfection for the production of recombinant proteins, the use of transfection-resistant cell lines, and the effectiveness of luciferase-based high-throughput screening assays.

  1. 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.

  2. Privatizing Public Interest Law

    OpenAIRE

    Cummings, Scott L

    2011-01-01

    Financial and legal constraints on nonprofit public interest organizations have focused attention on possibilities for pursuing public interest goals from within market-driven private practice. In this context, the private public interest law firm has been held out as an alternative site for “doing well” and “doing good,” allowing lawyers to take on large-scale social change litigation that nonprofit groups cannot because of resource limits—and big-firm pro bono programs will not because of b...

  3. 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 ...

  4. FWS Interest Simplified

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — These boundaries are simplified from the U.S. Fish and Wildlife Service Real Estate Interest data layer containing polygons representing tracts of land (parcels) in...

  5. Debenture Interest Rates

    Data.gov (United States)

    Department of Housing and Urban Development — Interest rates to be paid on debentures issued with respect to a loan or mortgage insured by the Federal Housing Commissioner under the provisions of the National...

  6. Gaps in Political Interest

    DEFF Research Database (Denmark)

    Robison, Joshua

    2015-01-01

    Political interest fundamentally influences political behavior, knowledge, and persuasion (Brady, Verba, & Schlozman, 1995; Delli Carpini & Keeter, 1996; Luskin, 1990; Zukin, Andolina, Keeter, Jenkins, & Delli Carpini, 2006). Since the early 1960s, the American National Election Studies (ANES) has...

  7. Cockayne syndrome b maintains neural precursor function.

    Science.gov (United States)

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

    2013-02-01

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

  8. 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.

  9. [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.

  10. ATHENA: A knowledge-based hybrid backpropagation-grammatical evolution neural network algorithm for discovering epistasis among quantitative trait Loci

    Directory of Open Access Journals (Sweden)

    Turner Stephen D

    2010-09-01

    Full Text Available Abstract Background Growing interest and burgeoning technology for discovering genetic mechanisms that influence disease processes have ushered in a flood of genetic association studies over the last decade, yet little heritability in highly studied complex traits has been explained by genetic variation. Non-additive gene-gene interactions, which are not often explored, are thought to be one source of this "missing" heritability. Methods Stochastic methods employing evolutionary algorithms have demonstrated promise in being able to detect and model gene-gene and gene-environment interactions that influence human traits. Here we demonstrate modifications to a neural network algorithm in ATHENA (the Analysis Tool for Heritable and Environmental Network Associations resulting in clear performance improvements for discovering gene-gene interactions that influence human traits. We employed an alternative tree-based crossover, backpropagation for locally fitting neural network weights, and incorporation of domain knowledge obtainable from publicly accessible biological databases for initializing the search for gene-gene interactions. We tested these modifications in silico using simulated datasets. Results We show that the alternative tree-based crossover modification resulted in a modest increase in the sensitivity of the ATHENA algorithm for discovering gene-gene interactions. The performance increase was highly statistically significant when backpropagation was used to locally fit NN weights. We also demonstrate that using domain knowledge to initialize the search for gene-gene interactions results in a large performance increase, especially when the search space is larger than the search coverage. Conclusions We show that a hybrid optimization procedure, alternative crossover strategies, and incorporation of domain knowledge from publicly available biological databases can result in marked increases in sensitivity and performance of the ATHENA

  11. ATHENA: A knowledge-based hybrid backpropagation-grammatical evolution neural network algorithm for discovering epistasis among quantitative trait Loci.

    Science.gov (United States)

    Turner, Stephen D; Dudek, Scott M; Ritchie, Marylyn D

    2010-09-27

    Growing interest and burgeoning technology for discovering genetic mechanisms that influence disease processes have ushered in a flood of genetic association studies over the last decade, yet little heritability in highly studied complex traits has been explained by genetic variation. Non-additive gene-gene interactions, which are not often explored, are thought to be one source of this "missing" heritability. Stochastic methods employing evolutionary algorithms have demonstrated promise in being able to detect and model gene-gene and gene-environment interactions that influence human traits. Here we demonstrate modifications to a neural network algorithm in ATHENA (the Analysis Tool for Heritable and Environmental Network Associations) resulting in clear performance improvements for discovering gene-gene interactions that influence human traits. We employed an alternative tree-based crossover, backpropagation for locally fitting neural network weights, and incorporation of domain knowledge obtainable from publicly accessible biological databases for initializing the search for gene-gene interactions. We tested these modifications in silico using simulated datasets. We show that the alternative tree-based crossover modification resulted in a modest increase in the sensitivity of the ATHENA algorithm for discovering gene-gene interactions. The performance increase was highly statistically significant when backpropagation was used to locally fit NN weights. We also demonstrate that using domain knowledge to initialize the search for gene-gene interactions results in a large performance increase, especially when the search space is larger than the search coverage. We show that a hybrid optimization procedure, alternative crossover strategies, and incorporation of domain knowledge from publicly available biological databases can result in marked increases in sensitivity and performance of the ATHENA algorithm for detecting and modelling gene-gene interactions that

  12. Neural networks with discontinuous/impact activations

    CERN Document Server

    Akhmet, Marat

    2014-01-01

    This book presents as its main subject new models in mathematical neuroscience. A wide range of neural networks models with discontinuities are discussed, including impulsive differential equations, differential equations with piecewise constant arguments, and models of mixed type. These models involve discontinuities, which are natural because huge velocities and short distances are usually observed in devices modeling the networks. A discussion of the models, appropriate for the proposed applications, is also provided. This book also: Explores questions related to the biological underpinning for models of neural networks\\ Considers neural networks modeling using differential equations with impulsive and piecewise constant argument discontinuities Provides all necessary mathematical basics for application to the theory of neural networks Neural Networks with Discontinuous/Impact Activations is an ideal book for researchers and professionals in the field of engineering mathematics that have an interest in app...

  13. 22nd Italian Workshop on Neural Nets

    CERN Document Server

    Bassis, Simone; Esposito, Anna; Morabito, Francesco

    2013-01-01

    This volume collects a selection of contributions which has been presented at the 22nd Italian Workshop on Neural Networks, the yearly meeting of the Italian Society for Neural Networks (SIREN). The conference was held in Italy, Vietri sul Mare (Salerno), during May 17-19, 2012. The annual meeting of SIREN is sponsored by International Neural Network Society (INNS), European Neural Network Society (ENNS) and IEEE Computational Intelligence Society (CIS). The book – as well as the workshop-  is organized in three main components, two special sessions and a group of regular sessions featuring different aspects and point of views of artificial neural networks and natural intelligence, also including applications of present compelling interest.

  14. Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development.

    Directory of Open Access Journals (Sweden)

    Eric J Hill

    Full Text Available Mood stabilising drugs such as lithium (LiCl and valproic acid (VPA are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4, neurons (Neurofilament M, astrocytes (GFAP or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

  15. Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development.

    Science.gov (United States)

    Hill, Eric J; Nagel, David A; O'Neil, John D; Torr, Elizabeth; Woehrling, Elizabeth K; Devitt, Andrew; Coleman, Michael D

    2013-01-01

    Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

  16. Special Interest Groups.

    Science.gov (United States)

    Degi, Bruce J.

    1999-01-01

    Offers a reflection on the shootings at Columbine High School in Littleton, Colorado, on April 20, 1999. Notes how every special-interest group has used the tragedy to support its own point of view, and concludes that teachers have become bystanders in the education of America's children. (SR)

  17. Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

    Directory of Open Access Journals (Sweden)

    McDonald Karen

    2011-08-01

    Full Text Available Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

  18. Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization.

    Science.gov (United States)

    Jung, Sang-Kyu; McDonald, Karen

    2011-08-16

    Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

  19. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks

    National Research Council Canada - National Science Library

    Tonelli, Paul; Mouret, Jean-Baptiste

    2013-01-01

    .... It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks...

  20. Cancer adjuvant chemotherapy strategic classification by artificial neural network with gene expression data: An example for non-small cell lung cancer.

    Science.gov (United States)

    Chen, Yen-Chen; Chang, Yo-Cheng; Ke, Wan-Chi; Chiu, Hung-Wen

    2015-08-01

    Adjuvant chemotherapy (ACT) is used after surgery to prevent recurrence or metastases. However, ACT for non-small cell lung cancer (NSCLC) is still controversial. This study aimed to develop prediction models to distinguish who is suitable for ACT (ACT-benefit) and who should avoid ACT (ACT-futile) in NSCLC. We identified the ACT correlated gene signatures and performed several types of ANN algorithms to construct the optimal ANN architecture for ACT benefit classification. Reliability was assessed by cross-data set validation. We obtained 2 probes (2 genes) with T-stage clinical data combination can get good prediction result. These genes included 208893_s_at (DUSP6) and 204891_s_at (LCK). The 10-fold cross validation classification accuracy was 65.71%. The best result of ANN models is MLP14-8-2 with logistic activation function. Using gene signature profiles to predict ACT benefit in NSCLC is feasible. The key to this analysis was identifying the pertinent genes and classification. This study maybe helps reduce the ineffective medical practices to avoid the waste of medical resources. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Interesting Questions in Freakonomics

    OpenAIRE

    John DiNardo

    2007-01-01

    Freakonomics is more about "entertainment" than it is a serious attempt at popularization. Consequently, rather than conduct a comprehensive fact check, I use the book as a springboard for a broader inquiry into social science research and take issue with the book's surprising premise that "Economics is a science with excellent tools for gaining answers but a serious shortage of interesting questions." Using examples from Freakonomics , I argue that some of the questions the book addresses ar...

  2. A Novel Mathematical Approach to Define the Genes/SNPs Conferring Risk or Protection in Sporadic Amyotrophic Lateral Sclerosis Based on Auto Contractive Map Neural Networks and Graph Theory.

    Science.gov (United States)

    Buscema, Massimo; Penco, Silvana; Grossi, Enzo

    2012-01-01

    Background. Complex diseases like amyotrophic lateral sclerosis (ALS) implicate phenotypic and genetic heterogeneity. Therefore, multiple genetic traits may show differential association with the disease. The Auto Contractive Map (AutoCM), belonging to the Artificial Neural Network (ANN) architecture, "spatializes" the correlation among variables by constructing a suitable embedding space where a visually transparent and cognitively natural notion such as "closeness" among variables reflects accurately their associations. Results. In this pilot case-control study single nucleotide polymorphism (SNP) in several genes has been evaluated with a novel data mining approach based on an AutoCM. We have divided the ALS dataset into two dataset: Cases and Control dataset; we have applied to each one, independently, the AutoCM algorithm. Six genetic variants were identified which differently contributed to the complexity of the system: three of the above genes/SNPs represent protective factors, APOA4, NOS3, and LPL, since their contribution to the whole complexity resulted to be as high as 0.17. On the other hand ADRB3, LIPC, and MMP3, whose hub relevancies contribution resulted to be as high as 0.13, seem to represent susceptibility factors. Conclusion. The biological information available on these six polymorphisms is consistent with possible pathogenetic pathways related to ALS.

  3. Global and local missions of cAMP signaling in neural plasticity, learning, and memory.

    Science.gov (United States)

    Lee, Daewoo

    2015-01-01

    The fruit fly Drosophila melanogaster has been a popular model to study cAMP signaling and resultant behaviors due to its powerful genetic approaches. All molecular components (AC, PDE, PKA, CREB, etc) essential for cAMP signaling have been identified in the fly. Among them, adenylyl cyclase (AC) gene rutabaga and phosphodiesterase (PDE) gene dunce have been intensively studied to understand the role of cAMP signaling. Interestingly, these two mutant genes were originally identified on the basis of associative learning deficits. This commentary summarizes findings on the role of cAMP in Drosophila neuronal excitability, synaptic plasticity and memory. It mainly focuses on two distinct mechanisms (global versus local) regulating excitatory and inhibitory synaptic plasticity related to cAMP homeostasis. This dual regulatory role of cAMP is to increase the strength of excitatory neural circuits on one hand, but to act locally on postsynaptic GABA receptors to decrease inhibitory synaptic plasticity on the other. Thus the action of cAMP could result in a global increase in the neural circuit excitability and memory. Implications of this cAMP signaling related to drug discovery for neural diseases are also described.

  4. 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.

  5. 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

  6. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone

    NARCIS (Netherlands)

    van de Ven, C.; Bialecka, M.; Neijts, R.; Young, T.; Rowland, J.E.; Stringer, E.J.; van Rooijen, C.R.; Meijlink, F.; Novoa, A.; Freund, J.N.; Mallo, M.; Beck, F.; Deschamps, J.

    2011-01-01

    Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation

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

    Science.gov (United States)

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

    2016-04-15

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

  8. Rangifer and human interests

    Directory of Open Access Journals (Sweden)

    David G. Anderson

    2000-03-01

    Full Text Available This article reviews biological and anthropological literatute on wild and tame Rangifer to demonstrate the powerful effect that this species has had on the imaginations of biologists, social scientists and local hunters. Through identifying a general 'human interest' in Rangifer, the author argues that there is great potential for these three communities to work together. To demonstrate this idea, the paper reviews several examples of successful and unsuccessful 'alliances' between local peoples and both natural and social scientists which have had a fundamental impact upon the history of these sciences. The paper examines recent theorerical models which suggest that human action is a major factor in the behaviour and ecology of the animals. The paper also analyses the ideas of many indigenous people for whom there is no categorical difference between semi-domesticated, semi-sedentary and migratory Rangifer through comparison with many 'anomalous' texts in English and Russian language wildlife biology. By reviewing the history of scholarly interest in Rangifer, the author argues that contemporary models of Rangifer behaviour and identity could be 'revitalised' and 'recalibrated' through the establishment of that dialogue between scientists and local peoples which so characterised the 19th century. Such a dialogue, it is argued, would help mediate many of the political conflicts now appearing in those districts where Rangifer migrate.

  9. 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.

  10. The homeobox gene Gsx2 regulates the self-renewal and differentiation of neural stem cells and the cell fate of postnatal progenitors.

    Directory of Open Access Journals (Sweden)

    Héctor R Méndez-Gómez

    Full Text Available The Genetic screened homeobox 2 (Gsx2 transcription factor is required for the development of olfactory bulb (OB and striatal neurons, and for the regional specification of the embryonic telencephalon. Although Gsx2 is expressed abundantly by progenitor cells in the ventral telencephalon, its precise function in the generation of neurons from neural stem cells (NSCs is not clear. Similarly, the role of Gsx2 in regulating the self-renewal and multipotentiality of NSCs has been little explored. Using retroviral vectors to express Gsx2, we have studied the effect of Gsx2 on the growth of NSCs isolated from the OB and ganglionic eminences (GE, as well as its influence on the proliferation and cell fate of progenitors in the postnatal mouse OB. Expression of Gsx2 reduces proliferation and the self-renewal capacity of NSCs, without significantly affecting cell death. Furthermore, Gsx2 overexpression decreases the differentiation of NSCs into neurons and glia, and it maintains the cells that do not differentiate as cycling progenitors. These effects were stronger in GESCs than in OBSCs, indicating that the actions of Gsx2 are cell-dependent. In vivo, Gsx2 produces a decrease in the number of Pax6+ cells and doublecortin+ neuroblasts, and an increase in Olig2+ cells. In summary, our findings show that Gsx2 inhibits the ability of NSCs to proliferate and self-renew, as well as the capacity of NSC-derived progenitors to differentiate, suggesting that this transcription factor regulates the quiescent and undifferentiated state of NSCs and progenitors. Furthermore, our data indicate that Gsx2 negatively regulates neurogenesis from postnatal progenitor cells.

  11. Globalization, values, interests

    Directory of Open Access Journals (Sweden)

    Radojičić Mirjana S.

    2003-01-01

    Full Text Available The nature of the international politics, after the Cold War directed by the U.S. as the only current super-power, are considered in the text. The author’s intention is to stress the main points of divergence between moralistic-valuable rhetoric and the foreign policy practice of the U.S. In that sense, the examples of the American stand, i.e. the active treatment of the Yugoslav crisis, on the one hand, and the crisis in the Persian Gulf, on the other hand, is considered. The author’s conclusion is that the foreign policy of the only current super-power is still directed by interests rather then by values. In the concluding part, the author presents an anthropologic argument in favor of reestablishing "balance of power" as the only guarantee for peace and stability of the world.

  12. BANKING WITHOUT INTEREST

    Directory of Open Access Journals (Sweden)

    Jana Ilieva

    2017-06-01

    Full Text Available In recent years, there has been increased global awareness of Islamic finance. This topic is mainly opened with respect to the great financial crisis that mostly hit the banking system and the financial markets and caused many bank bankruptcies and state interventions. This paper analyzes the basic principles of Islamic banking. The absolute prohibition of receiving and giving interest (Riba and profit-and-loss sharing (PLS paradigms are elaborated in detail; they are primarily based on mudarabah (profit-sharing and musyarakah (joint venture concepts which nowadays are becoming an accepted way of doing business in several Western multinational banks. An overall comparison of the advantages of Islamic vs. conventional banking is also given. Islamic finance technology solutions have matured and they will face various challenges in the following decades, due to conventional banks offering, increasingly, Islamic products. The need for a more comprehensive environment and regulatory framework is emphasized, so that Islamic banking development can be ensured.

  13. 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.

  14. 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.

  15. PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma

    OpenAIRE

    Tiziana Bachetti; Daniela Di Paolo; Simona Di Lascio; Valentina Mirisola; Chiara Brignole; Marta Bellotti; Irene Caffa; Chiara Ferraris; Michele Fiore; Diego Fornasari; Roberto Chiarle; Silvia Borghini; Ulrich Pfeffer; Mirco Ponzoni; Isabella Ceccherini

    2010-01-01

    BACKGROUND: Neuroblastoma (NB) is a severe pediatric tumor originating from neural crest derivatives and accounting for 15% of childhood cancer mortality. The heterogeneous and complex genetic etiology has been confirmed with the identification of mutations in two genes, encoding for the receptor tyrosine kinase Anaplastic Lymphoma Kinase (ALK) and the transcription factor Paired-like Homeobox 2B (PHOX2B), in a limited proportion of NB patients. Interestingly, these two genes are overexpresse...

  16. ICPD: in whose interest?

    Science.gov (United States)

    Shiva, M

    1994-06-01

    The International Conference on Population and Development (ICPD) is set for September 1994. Arms control and control of military interests are as crucial as population control. The expenditure on the military and arms should go to social measures and true socioeconomic development. Women are leading the movement against war and towards peace. Women make up 70% of current refugees of ethnic conflicts. The conquest of free trade with little or no restriction and globalization trends forces developing countries to accept nonessential luxury items which tend to be irrational, hazardous consumer articles and technologies from industrialized countries. The privileged elite in developing countries and the industrialized countries overconsume, while the basic needs of the poor majority are not being met. The rich view the poor as a global threat and a threat for environmental degradation. They believe that free trade will solve all problems, yet it only marginalizes the poor and the vulnerable. The pattern of overconsumption is the threat. The poor are characterized as demons responsible for the population explosion. Women are angry that population control policies are attempts to control women's fertility. Specifically, most contraceptive technologies and most family planning programs target women. Male responsibility is ignored. Religious fundamentalists tell women not to become pregnant, not to use contraception, and not to seek abortion, yet they allow male sex behavior, e.g., sexual violence. This attitude leaves women vulnerable to unwanted pregnancies, sexually transmitted diseases, and AIDS. Developing countries should be concerned about chapter III on Population, Environment, and Development in the ICPD text. Most countries, including India, have formed a consensus on this chapter. The Vatican and some Latin American countries have objections, however. The meeting in Cairo will likely continue to promote the view that the fertility of women in developing

  17. Neural and extraneural expression of the neuronal ceroid lipofuscinoses genes CLN1, CLN2, and CLN3: functional implications for CLN3.

    Science.gov (United States)

    Chattopadhyay, S; Pearce, D A

    2000-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative disorders of childhood. We have examined mRNA levels of the CLN1, CLN2, and CLN3 genes, which are associated with the infantile, late infantile, and juvenile forms of NCL in 64 different human tissues, and have grouped the results into gastrointestinal tract, central nervous system, glandular/secretory, muscle, and carcinoma tissue types. mRNA levels for CLN3 are highest in gastrointestinal tissue and are also high in glandular/secretory tissue, whereas mRNA levels for CLN1 and CLN2 do not appear to be preferentially elevated in any tissue type. The significance of extraneural expression of CLN3 is reviewed in the context of the function of the protein. Copyright 2000 Academic Press.

  18. Towards a magnetoresistive platform for neural signal recording

    Science.gov (United States)

    Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

    2017-05-01

    A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

  19. 76 FR 77581 - Interest Rates

    Science.gov (United States)

    2011-12-13

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 2.375 (2\\3/8\\) percent for the January-March quarter of FY 2012. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third...

  20. 76 FR 18821 - Interest Rates

    Science.gov (United States)

    2011-04-05

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 3.750 (3\\3/4\\) percent for the April-June quarter of FY 2011. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third party...

  1. 78 FR 18664 - Interest Rates

    Science.gov (United States)

    2013-03-27

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 2.500 (2\\1/2\\) percent for the April-June quarter of FY 2013. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third party...

  2. 75 FR 37872 - Interest Rates

    Science.gov (United States)

    2010-06-30

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 4.000 (4) percent for the July-September quarter of FY 2010. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third party...

  3. 75 FR 17453 - Interest Rates

    Science.gov (United States)

    2010-04-06

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 4.000 (4) percent for the April-June quarter of FY 2010. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third party...

  4. 75 FR 60152 - Interest Rates

    Science.gov (United States)

    2010-09-29

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 3.250 (3\\1/4\\) percent for the October-December quarter of FY 2011. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third...

  5. 77 FR 20476 - Interest Rates

    Science.gov (United States)

    2012-04-04

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 2.250 (2 \\1/4\\) percent for the April-June quarter of FY 2012. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third party...

  6. 77 FR 39560 - Interest Rates

    Science.gov (United States)

    2012-07-03

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 2.500 (2\\1/2\\) percent for the July-September quarter of FY 2012. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third...

  7. 75 FR 81326 - Interest Rates

    Science.gov (United States)

    2010-12-27

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 3.000 (3) percent for the January-March quarter of FY 2011. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third party...

  8. 78 FR 62932 - Interest Rates

    Science.gov (United States)

    2013-10-22

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This rate will be 3.125 (3\\1/8\\) percent for the October-December quarter of FY 2014. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third...

  9. 76 FR 38717 - Interest Rates

    Science.gov (United States)

    2011-07-01

    ... ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional... guaranteed fluctuating interest rate SBA loans. This ] rate will be 3.625 (3\\5/8\\) percent for the July-September quarter of FY 2011. Pursuant to 13 CFR 120.921(b), the maximum legal interest rate for any third...

  10. EDITORIAL: Interesting times

    Science.gov (United States)

    Dobson Honorary Editor, Ken

    1996-01-01

    `May you live in interesting times' - old Chinese curse. First, many thanks to John Avison, the retiring Honorary Editor, for his hard work over the last five years, and the steady development in style and content under his stewardship. I can only hope to live up to the standards that he set. The next five years will take us into a new millenium, an event preceded - in England and Wales at least - by a period of stability, reflection and consolidation in education. Or so we are told - but whether such a self-denying ordinance will actually be maintained by the Government both before and after an election in 1997 remains to be seen. Nevertheless, we shall be thankful for any mercies, however small, that permit forward thinking rather than instant response. One of the things that readers of a journal called Physics Education should be thinking about is the continued decline in the numbers of students studying physics post-16. This is not a purely local phenomenon; most European countries are finding a similar decline. There are exceptions, of course: in Scotland numbers studying physics for Highers are increasing. Is such a decline a good thing or a bad thing? Only a minority of post-16 physics students go on to use the bulk of what they have learned in further studies or vocations. Does a knowledge and understanding of physics contribute to the mental well-being and cultural level - let alone material comfort - of any except those who use physics professionally? Is physics defensible as a contribution to the mental armoury of the educated citizen - compared with chemistry, biology - or Latin, say? Or should one rephrase that last question as `Is physics as we teach it today defensible...?' Such questions, and many others no doubt, may well be in the mind of the new Curriculum Officer appointed by the Institute of Physics `to engage in a wide-ranging consultation throughout the entire physics community on the nature and style of post-16 physics programmes, with a

  11. On the Relationships between Generative Encodings, Regularity, and Learning Abilities when Evolving Plastic Artificial Neural Networks: e79138

    National Research Council Canada - National Science Library

    Paul Tonelli; Jean-Baptiste Mouret

    2013-01-01

    .... It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks...

  12. Indices of Interest Maturity in the Kuder Occupation Interest Survey.

    Science.gov (United States)

    Zytowski, Donald G.; England, Raymond J. L.

    1995-01-01

    A combination of high occupational score and a low men-in-general or women-in-general score on the Kuder Occupational Interest Survey is moderately predictive of interest stability and occupational consistency. (Author)

  13. Interest and Interest-Enhancing Strategies of Adolescent EFL Learners

    Science.gov (United States)

    Wisniewska, Danuta

    2013-01-01

    This paper's focus is on the little researched and sometimes vague concept of interest, discussed here in relation to EFL learning and the potential interest-enhancing strategies that learners may employ if they do not find learning English interesting enough. The study was undertaken to investigate how adolescent EFL learners evaluate the…

  14. Conflict of interests, vested interests and health research.

    Science.gov (United States)

    Little, M

    2000-11-01

    This paper examines conflict of interest as it may arise in the activities of research advisory committees and ethical review committees. It distinguishes between vested interests and true conflict of interest. It also examines the ways in which stakeholdings differ from vested interests and conflicting interests differ from conflicts of interest. It explores the overlapping terrain of corruption and conflict of interest. The paper further examines the ways in which scientists, communities and the subjects of medical research all have legitimate stakeholdings in medical research. Each group thus has differently vested interests in the outcomes of the research. The vested interests of medical scientists are particularly complex because scientists have moral commitments to the welfare of patients that may compete with professional and personal interests in the outcome of research performed on those patients as research subjects. The more these interests diverge, the more opportunity will arise for conflict of interest. These observations have implications for the constitution of research advisory and ethical review committees, and the ways in which their discussions are conducted. Some practical help with protocols of discussion can be gained from philosophical and management writings.

  15. Upper secondary students’ situational interest:

    DEFF Research Database (Denmark)

    Dohn, Niels Bonderup

    2013-01-01

    interest was investigated by a descriptive interpretive approach, based on data from classroom and field trip observations, video recording, and interviews. The findings provided evidence that substantial situational interest can be generated during a fieldtrip to a zoo. Students’ interest was triggered......This paper comprises a presentation of the findings of a case study that investigated how situational factors triggered 12th grade students’ interest during a field trip to a zoo. The purpose was to identify sources of interest and to investigate the attributes that make them interesting. Students...

  16. Social Regulation of Gene Expression in Threespine Sticklebacks.

    Directory of Open Access Journals (Sweden)

    Anna K Greenwood

    Full Text Available Identifying genes that are differentially expressed in response to social interactions is informative for understanding the molecular basis of social behavior. To address this question, we described changes in gene expression as a result of differences in the extent of social interactions. We housed threespine stickleback (Gasterosteus aculeatus females in either group conditions or individually for one week, then measured levels of gene expression in three brain regions using RNA-sequencing. We found that numerous genes in the hindbrain/cerebellum had altered expression in response to group or individual housing. However, relatively few genes were differentially expressed in either the diencephalon or telencephalon. The list of genes upregulated in fish from social groups included many genes related to neural development and cell adhesion as well as genes with functions in sensory signaling, stress, and social and reproductive behavior. The list of genes expressed at higher levels in individually-housed fish included several genes previously identified as regulated by social interactions in other animals. The identified genes are interesting targets for future research on the molecular mechanisms of normal social interactions.

  17. 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.

  18. Diabetic retinopathy screening using deep neural network.

    Science.gov (United States)

    Ramachandran, Nishanthan; Hong, Sheng Chiong; Sime, Mary J; Wilson, Graham A

    2017-09-07

    There is a burgeoning interest in the use of deep neural network in diabetic retinal screening. To determine whether a deep neural network could satisfactorily detect diabetic retinopathy that requires referral to an ophthalmologist from a local diabetic retinal screening programme and an international database. Retrospective audit. Diabetic retinal photos from Otago database photographed during October 2016 (485 photos), and 1200 photos from Messidor international database. Receiver operating characteristic curve to illustrate the ability of a deep neural network to identify referable diabetic retinopathy (moderate or worse diabetic retinopathy or exudates within one disc diameter of the fovea). Area under the receiver operating characteristic curve, sensitivity and specificity. For detecting referable diabetic retinopathy, the deep neural network had an area under receiver operating characteristic curve of 0.901 (95% confidence interval 0.807-0.995), with 84.6% sensitivity and 79.7% specificity for Otago and 0.980 (95% confidence interval 0.973-0.986), with 96.0% sensitivity and 90.0% specificity for Messidor. This study has shown that a deep neural network can detect referable diabetic retinopathy with sensitivities and specificities close to or better than 80% from both an international and a domestic (New Zealand) database. We believe that deep neural networks can be integrated into community screening once they can successfully detect both diabetic retinopathy and diabetic macular oedema. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  19. Four models of family interests.

    Science.gov (United States)

    Groll, Daniel

    2014-10-01

    In this article, I distinguish between 4 models for thinking about how to balance the interests of parents, families, and a sick child: (1) the oxygen mask model; (2) the wide interests model; (3) the family interests model; and (4) the direct model. The oxygen mask model - which takes its name from flight attendants' directives to parents to put on their own oxygen mask before putting on their child's - says that parents should consider their own interests only insofar as doing so is, ultimately, good for the sick child. The wide interests model suggests that in doing well by my child I am at the very same time doing well by myself. My interests can, and plausibly do, encompass the interests of others; they are, to that extent, wide. There is, then, no sharp separation between the interests of the sick child and the interests of other family members. In the family interests model, families themselves are seen as having interests that are neither identical to the sum, nor a simple function, of the interests of individual family members. The family has goals, values, and aspirations that are essentially corporate rather than individual. According to this model, these family interests can explain why sacrifices can sometimes be demanded of some family members for the sake of others in a medical setting. Finally, the direct model takes a simpler view of family members' interests; it claims that these interests matter simply on their own and should be taken into account in making treatment decisions for a sick child. This model openly considers the competing interests that parents and other family members often have when caring for a sick child, and advocates for weighing those interests when making decisions for and about the sick child. While there is room for all four models at the bedside, I argue that the direct model should be highlighted in clinical decision-making. Copyright © 2014 by the American Academy of Pediatrics.

  20. What is interesting? Exploring the appraisal structure of interest.

    Science.gov (United States)

    Silvia, Paul J

    2005-03-01

    Relative to other emotions, interest is poorly understood. On the basis of theories of appraisal process and structure, it was predicted that interest consists of appraisals of novelty (factors related to unfamiliarity and complexity) and appraisals of coping potential (the ability to understand the new, complex thing). Four experiments, using in vivo rather than retrospective methods, supported this appraisal structure. The findings were general across measured and manipulated appraisals, interesting stimuli (random polygons, visual art, poetry), and measures of interest (self-reports, forced-choice, behavioral measures). Furthermore, the appraisal structure was specific to interest (it did not predict enjoyment, a related positive emotion), and appraisals predicted interest beyond relevant traits (curiosity, openness). The appraisal perspective offers a powerful way of construing the causes of interest. Copyright 2005 APA, all rights reserved.

  1. Native Americans' Interest in Horticulture.

    Science.gov (United States)

    Meyer, Mary Hockenberry

    1999-01-01

    Focus groups arranged by local Native American Master Gardeners on two Minnesota reservations determined community interest in extension-horticulture programs. Topics of interest included food preservation and historical Native-American uses of plants. (SK)

  2. 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

  3. Vectors bicistronically linking a gene of interest to the SV40 large T antigen in combination with the SV40 origin of replication enhance transient protein expression and luciferase reporter activity

    OpenAIRE

    Mahon, Matthew J.

    2011-01-01

    The Simian Virus large T antigen (SVLT) induces replication of plasmids bearing the SV40 origin of replication (SV40 ori) within mammalian cells. The internal ribosomal entry site (IRES) is an element that allows for the co-translation of proteins from one polycistronic mRNA. Through the combination of these elements, IRES-dependent co-expression of a protein of interest and the SVLT, either constitutive or regulated, on plasmids bearing the SV40 ori generates a positive feedback loop, result...

  4. 77 FR 59447 - Interest Rates

    Science.gov (United States)

    2012-09-27

    ... Doc No: 2012-23732] SMALL BUSINESS ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional ``peg'' rate (13 CFR 120.214) on a quarterly basis. This rate... direct loan. This rate may be used as a base rate for guaranteed fluctuating interest rate SBA loans...

  5. 78 FR 39434 - Interest Rates

    Science.gov (United States)

    2013-07-01

    ... Doc No: 2013-15648] SMALL BUSINESS ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional ``peg'' rate (13 CFR 120.214) on a quarterly basis. This rate... direct loan. This rate may be used as a base rate for guaranteed fluctuating interest rate SBA loans...

  6. 77 FR 76586 - Interest Rates

    Science.gov (United States)

    2012-12-28

    ... Doc No: 2012-31295] SMALL BUSINESS ADMINISTRATION Interest Rates The Small Business Administration publishes an interest rate called the optional ``peg'' rate (13 CFR 120.214) on a quarterly basis. This rate... direct loan. This rate may be used as a base rate for guaranteed fluctuating interest rate SBA loans...

  7. 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.

  8. 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.

  9. Neural crest development in fetal alcohol syndrome.

    Science.gov (United States)

    Smith, Susan M; Garic, Ana; Flentke, George R; Berres, Mark E

    2014-09-01

    Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disability. Some affected individuals possess distinctive craniofacial deficits, but many more lack overt facial changes. An understanding of the mechanisms underlying these deficits would inform their diagnostic utility. Our understanding of these mechanisms is challenged because ethanol lacks a single receptor when redirecting cellular activity. This review summarizes our current understanding of how ethanol alters neural crest development. Ample evidence shows that ethanol causes the "classic" fetal alcohol syndrome (FAS) face (short palpebral fissures, elongated upper lip, deficient philtrum) because it suppresses prechordal plate outgrowth, thereby reducing neuroectoderm and neural crest induction and causing holoprosencephaly. Prenatal alcohol exposure (PAE) at premigratory stages elicits a different facial appearance, indicating FASD may represent a spectrum of facial outcomes. PAE at this premigratory period initiates a calcium transient that activates CaMKII and destabilizes transcriptionally active β-catenin, thereby initiating apoptosis within neural crest populations. Contributing to neural crest vulnerability are their low antioxidant responses. Ethanol-treated neural crest produce reactive oxygen species and free radical scavengers attenuate their production and prevent apoptosis. Ethanol also significantly impairs neural crest migration, causing cytoskeletal rearrangements that destabilize focal adhesion formation; their directional migratory capacity is also lost. Genetic factors further modify vulnerability to ethanol-induced craniofacial dysmorphology and include genes important for neural crest development, including shh signaling, PDFGA, vangl2, and ribosomal biogenesis. Because facial and brain development are mechanistically and functionally linked, research into ethanol's effects on neural crest also informs our understanding of ethanol's CNS pathologies. © 2014

  10. 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.

  11. 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...

  12. 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...

  13. [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

  14. CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression

    DEFF Research Database (Denmark)

    Egan, Chris M; Nyman, Ulrika; Skotte, Julie

    2013-01-01

    The chromatin remodeler CHD5 is expressed in neural tissue and is frequently deleted in aggressive neuroblastoma. Very little is known about the function of CHD5 in the nervous system or its mechanism of action. Here we report that depletion of Chd5 in the developing neocortex blocks neuronal...... differentiation and leads to an accumulation of undifferentiated progenitors. CHD5 binds a large cohort of genes and is required for facilitating the activation of neuronal genes. It also binds a cohort of Polycomb targets and is required for the maintenance of H3K27me3 on these genes. Interestingly......, the chromodomains of CHD5 directly bind H3K27me3 and are required for neuronal differentiation. In the absence of CHD5, a subgroup of Polycomb-repressed genes becomes aberrantly expressed. These findings provide insights into the regulatory role of CHD5 during neurogenesis and suggest how inactivation...

  15. [Molecular mechanism of brain regeneration and reconstruction of dopaminergic neural network in planarians].

    Science.gov (United States)

    Nishimura, Kaneyasu; Kitamura, Yoshihisa; Agata, Kiyokazu

    2008-04-01

    Recently, planarians have received much attention because of their contributions to research on the basic science of stem cell systems, neural regeneration, and regenerative medicine. Planarians can regenerate complete organs, including a well-organized central nervous system (CNS), within about 7 days. This high regenerative capacity is supported by pluripotent stem cells present in the mesenchymal space throughout the body. Interestingly, planarians can regenerate their brain via a molecular mechanism similar to that of mammalian brain development. The regeneration process of the planarian brain can be divided into five steps: (1) anterior blastema formation, (2) brain rudiment formation, (3) brain pattern formation, (4) neural network formation, and (5) functional recovery, with several kinds of genes and molecular cascades acting at each step. Recently, we have identified a planarian tyrosine hydroxylase (TH) gene, a rate-limiting enzyme for dopamine (DA) biosynthesis, and produced TH-knockdown planarians by the RNA interference technique. Studies of TH-knockdown planarians showed that DA has an important role of the modification in behavioral movement in planarians. Using monoclonal anti-planarian TH antibody, we also found that dopaminergic neurons are mainly localized in the planarian brain. When the planarian body was amputated, newly generated TH-immunopositive neurons were detected in the anterior region at day 3 of regeneration (i.e., the period of neural network formation), and the TH-immunopositive axonal and dendritic neural network in the CNS was reconstructed during day 5-7 of regeneration. In this article, recent advances in elucidating the molecular mechanism of planarian brain regeneration and dopaminergic neurons are reviewed, and its future prospects for contribution of this system to basic science and medical science research are described.

  16. Genetics and development of neural tube defects

    Science.gov (United States)

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

    2014-01-01

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

  17. Neural Networks: Implementations and Applications

    NARCIS (Netherlands)

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

    1996-01-01

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

  18. Cryonics in the Courtroom: Which Interests? Whose Interests?

    Science.gov (United States)

    Huxtable, Richard

    2017-10-25

    In an apparent international first, the High Court has allowed a terminally ill 14-year-old to be cryopreserved after her death. The patient, JS, requested this, as she hoped one day to be reanimated and cured. Jackson J focused on the welfare (or best interests) of JS as she approached the end of her life and particularly on her (apparently) competent wish to be cryopreserved. I consider the interests involved in a decision to undergo cryonics, specifically exploring which interests and whose interests are engaged. Starting with autonomy interests, the judgment implicitly supported a relational account of autonomy, but was dominated by a subjective interpretation of autonomy, which prioritized JS's wishes. Questions nevertheless arise about whether the dying person is entitled to legislate for the reanimated person he or she might become. Temporal concerns also feature when we interpret welfare in terms of happiness, because the dying person and the (potential) future reanimated person might have different interests at different times. Finally, I widen the analysis to accommodate the interests of others, by exploring whether cryonics is in, or contrary to, the public interest. Utilizing different accounts of the public interest, I argue that the case for cryonics is not entirely made out. These observations on autonomy, happiness and the public interest combine to suggest that, although there may not be a decisive case for denying a wish like JS's, there is a case for caution, at least while we seek to clarify and resolve the different interests in issue. © The Author 2017. Published by Oxford University Press.

  19. 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.

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

    Science.gov (United States)

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

    2011-03-24

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

  1. Neural stem cells differentiated from iPS cells spontaneously regain pluripotency.

    Science.gov (United States)

    Choi, Hyun Woo; Kim, Jong Soo; Choi, Sol; Hong, Yean Ju; Kim, Min Jung; Seo, Han Geuk; Do, Jeong Tae

    2014-10-01

    Differentiated somatic cells can be reprogrammed into pluripotent stem cells by transduction of exogenous reprogramming factors. After induced pluripotent stem (iPS) cells are established, exogenous genes are silenced. In the pluripotent state, retroviral genes integrated in the host genome are kept inactive through epigenetic transcriptional regulation. In this study, we tried to determine whether exogenous genes remain silenced or are reactivated upon loss of pluripotency or on differentiation using an in vitro system. We induced differentiation of iPS cells into neural stem cells (NSCs) in vitro; the NSCs appeared morphologically indistinguishable from brain-derived NSCs and stained positive for the NSC markers Nestin and Sox2. These iPS cell-derived NSCs (iPS-NSCs) were also capable of differentiating into all three neural subtypes. Interestingly, iPS-NSCs spontaneously formed aggregates on long-term culture and showed reactivation of the Oct4-GFP marker, which was followed by the formation of embryonic stem cell-like colonies. The spontaneously reverted green fluorescent protein (GFP)-positive (iPS-NSC-GFP(+) ) cells expressed high levels of pluripotency markers (Oct4 and Nanog) and formed germline chimeras, indicating that iPS-NSC-GFP(+) cells had the same pluripotency as the original iPS cells. The reactivation of silenced exogenous genes was tightly correlated with the downregulation of DNA methyltransferases (Dnmts) during differentiation of iPS cells. This phenomenon was not observed in doxycycline-inducible iPS cells, where the reactivation of exogenous genes could be induced only by doxycycline treatment. These results indicate that pluripotency can be regained through reactivation of exogenous genes, which is associated with dynamic change of Dnmt levels during differentiation of iPS cells. © 2014 AlphaMed Press.

  2. Electrospun Nanofibrous Materials for Neural Tissue Engineering

    Directory of Open Access Journals (Sweden)

    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.

  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. Interest Organizations across Economic Sectors

    DEFF Research Database (Denmark)

    Berkhout, Joost; Carroll, Brendan; Braun, Caelesta

    2015-01-01

    on the basis of political and economic institutional factors. Focusing on business interest representation, we show that economic institutions structure the ‘supply’ of interest organizations by affecting the number of potential constituents, the resources available for lobbying and the geographical level......The number of interest organizations (density) varies across policy domains, political issues and economic sectors. This shapes the nature and outcomes of interest representation. In this contribution, we explain the density of interest organizations per economic sector in the European Union...... of collective action of businesses. In contrast, we do not find consistent evidence that political institutions produce ‘demand’ for interest organizations by making laws, developing public policy or spending money. This is in contrast to the extensive evidence that such factors affect lobbying practices...

  6. Upper secondary students’ situational interest:

    DEFF Research Database (Denmark)

    Dohn, Niels Bonderup

    2013-01-01

    This paper comprises a presentation of the findings of a case study that investigated how situational factors triggered 12th grade students’ interest during a field trip to a zoo. The purpose was to identify sources of interest and to investigate the attributes that make them interesting. Students......’ interest was investigated by a descriptive interpretive approach, based on data from classroom and field trip observations, video recording, and interviews. The findings provided evidence that substantial situational interest can be generated during a fieldtrip to a zoo. Students’ interest was triggered....... The study implies that zoo visits can provide students with affective experiences, which can be a powerful way to stimulate students’ learning motivation....

  7. Point of interest to region of interest conversion

    NARCIS (Netherlands)

    de Graaff, V.; de By, R.A.; van Keulen, Maurice; Flokstra, Jan

    2013-01-01

    Trajectories of people contain a vast amount of information on users' interests and popularity of locations. To obtain this information, the places visited by the owner of the device on such a trajectory need to be recognized. However, the location information on a point of interest (POI) in a

  8. Identification of neural transcription factors required for the differentiation of three neuronal subtypes in the sea urchin embryo.

    Science.gov (United States)

    Slota, Leslie A; McClay, David R

    2018-01-10

    Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva. We show that these subtypes are specified through Delta/Notch signaling and identify a different transcription factor required for the development of each neural subtype. Our results show achaete-scute and neurogenin are proneural for the serotonergic neurons of the apical organ and cholinergic neurons of the ciliary band, respectively. We also show that orthopedia is not proneural but is necessary for the differentiation of the cholinergic/catecholaminergic postoral neurons. Interestingly, these transcription factors are used similarly during vertebrate neurogenesis. We believe this study is a starting point for building a neural gene regulatory network in the sea urchin and for finding conserved deuterostome neurogenic mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Which Positive Integers are Interesting?

    Indian Academy of Sciences (India)

    Keywords. Interesting positive integers; idoneal numbers; Carmichael numbers; Wieferich primes; Mersenne primes; Fermat primes; Bernoulli numbers; Kaprekar constant; Skewes constants; look-and-say sequence; Graham's constant.

  10. Nations: Formation and Interest Dynamics

    Directory of Open Access Journals (Sweden)

    A E Kafirin

    2012-06-01

    Full Text Available The article gives a brief description of historic conditions leading to the formation of nations, and on the basis of attributive features of a nation the set of national interests is identified. Considering national interests as a variable, the author stresses that they depend both on the wishes of ordinary people and on the ability of the state to streamline them in a constructive manner. National interests are classified according to their dynamic characteristics, and the special role of the state as the mouthpiece of national interests is pointed out.

  11. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    Science.gov (United States)

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  12. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    Directory of Open Access Journals (Sweden)

    Ubadah Sabbagh

    2016-01-01

    Full Text Available The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES. A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  13. Prototype-Incorporated Emotional Neural Network.

    Science.gov (United States)

    Oyedotun, Oyebade K; Khashman, Adnan

    2017-08-15

    Artificial neural networks (ANNs) aim to simulate the biological neural activities. Interestingly, many ''engineering'' prospects in ANN have relied on motivations from cognition and psychology studies. So far, two important learning theories that have been subject of active research are the prototype and adaptive learning theories. The learning rules employed for ANNs can be related to adaptive learning theory, where several examples of the different classes in a task are supplied to the network for adjusting internal parameters. Conversely, the prototype-learning theory uses prototypes (representative examples); usually, one prototype per class of the different classes contained in the task. These prototypes are supplied for systematic matching with new examples so that class association can be achieved. In this paper, we propose and implement a novel neural network algorithm based on modifying the emotional neural network (EmNN) model to unify the prototype- and adaptive-learning theories. We refer to our new model as ``prototype-incorporated EmNN''. Furthermore, we apply the proposed model to two real-life challenging tasks, namely, static hand-gesture recognition and face recognition, and compare the result to those obtained using the popular back-propagation neural network (BPNN), emotional BPNN (EmNN), deep networks, an exemplar classification model, and k-nearest neighbor.

  14. Cryonics in the courtroom:Which interests? Whose interests?

    OpenAIRE

    Huxtable, Richard

    2017-01-01

    In an apparent international first, the High Court has allowed a terminally ill 14-year-old to be cryopreserved after her death. The patient, JS, requested this, as she hoped one day to be reanimated and cured. Jackson J focused on the welfare (or best interests) of JS as she approached the end of her life and particularly on her (apparently) competent wish to be cryopreserved. I consider the interests involved in a decision to undergo cryonics, specifically exploring which interests and whos...

  15. Medication interest in pregnant women

    Directory of Open Access Journals (Sweden)

    Rok Antolič

    2011-12-01

    Medication interest is comparable to literature data: relatively high for acute problems, relatively low for iron supplementation and extremely low for preventative folic acid intake. As to our knowledge, we were the ones to introduce the term »medication interest« into professional literature in Slovenia.

  16. Interest in Mathematics = Interest in Mathematics? What General Measures of Interest Reflect When the Object of Interest Changes

    Science.gov (United States)

    Ufer, Stefan; Rach, Stefanie; Kosiol, Timo

    2017-01-01

    Students' motivational characteristics, e.g., subject-related interest, are considered important predictors for successful learning processes. However, few empirical studies provide evidence for the assumed chain of effects between high interest and high achievement in mathematics. One reason for this result might be that the applied measures of…

  17. Monitoring Financial Conflict of Interest

    Science.gov (United States)

    Hickson, Lorraine

    2016-01-01

    Conflict of interest is heavily intertwined with research. The purpose of this study was to examine the literature and regulations in order to describe efforts required to properly monitor and disclose conflict of interest as researchers become steadily involved in innovation and discovery. The public assumes that when a conflict is disclosed, it…

  18. Interest Organisations and European Integration

    DEFF Research Database (Denmark)

    Pedersen, Ove K.

    . The paper focuses exclusively on the national policy processes that are involved with managing European Union (EU) issues. More specifically, this paper discusses two aspects of multi-level governance. First is the important role of private interests in the coordination of decision making at the national...... level preceding their government's representation of national interests in the European Council of Ministers and other EU organizations. Second is the effect of all this on national democratic systems.......This paper examines the influence of European integration on the relationship between state administration and private interests in the four Nordic countries - Sweden, Denmark, Norway and Finland. By private interests I mean interest organizations, private corporations and independent experts...

  19. 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

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

    Science.gov (United States)

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

    2017-02-15

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

  1. Short-term synaptic plasticity and heterogeneity in neural systems

    Science.gov (United States)

    Mejias, J. F.; Kappen, H. J.; Longtin, A.; Torres, J. J.

    2013-01-01

    We review some recent results on neural dynamics and information processing which arise when considering several biophysical factors of interest, in particular, short-term synaptic plasticity and neural heterogeneity. The inclusion of short-term synaptic plasticity leads to enhanced long-term memory capacities, a higher robustness of memory to noise, and irregularity in the duration of the so-called up cortical states. On the other hand, considering some level of neural heterogeneity in neuron models allows neural systems to optimize information transmission in rate coding and temporal coding, two strategies commonly used by neurons to codify information in many brain areas. In all these studies, analytical approximations can be made to explain the underlying dynamics of these neural systems.

  2. 23rd Workshop of the Italian Neural Networks Society (SIREN)

    CERN Document Server

    Esposito, Anna; Morabito, Francesco

    2014-01-01

    This volume collects a selection of contributions which has been presented at the 23rd Italian Workshop on Neural Networks, the yearly meeting of the Italian Society for Neural Networks (SIREN). The conference was held in Vietri sul Mare, Salerno, Italy during May 23-24, 2013. The annual meeting of SIREN is sponsored by International Neural Network Society (INNS), European Neural Network Society (ENNS) and IEEE Computational Intelligence Society (CIS). The book – as well as the workshop-  is organized in two main components, a special session and a group of regular sessions featuring different aspects and point of views of artificial neural networks, artificial and natural intelligence, as well as psychological and cognitive theories for modeling human behaviors and human machine interactions, including Information Communication applications of compelling interest.  .

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Shaping the learning curve: epigenetic dynamics in neural plasticity.

    Science.gov (United States)

    Bronfman, Zohar Z; Ginsburg, Simona; Jablonka, Eva

    2014-01-01

    A key characteristic of learning and neural plasticity is state-dependent acquisition dynamics reflected by the non-linear learning curve that links increase in learning with practice. Here we propose that the manner by which epigenetic states of individual cells change during learning contributes to the shape of the neural and behavioral learning curve. We base our suggestion on recent studies showing that epigenetic mechanisms such as DNA methylation, histone acetylation, and RNA-mediated gene regulation are intimately involved in the establishment and maintenance of long-term neural plasticity, reflecting specific learning-histories and influencing future learning. Our model, which is the first to suggest a dynamic molecular account of the shape of the learning curve, leads to several testable predictions regarding the link between epigenetic dynamics at the promoter, gene-network, and neural-network levels. This perspective opens up new avenues for therapeutic interventions in neurological pathologies.

  8. Making working in retailing interesting

    DEFF Research Database (Denmark)

    Esbjerg, Lars; Buck, Nuka; Grunert, Klaus G.

    2010-01-01

    This paper is about how five retail chains in the Danish grocery industry attempt to make low-wage, low-status store-level retail jobs as checkout operators and sales assistants interesting from the perspective of both retailers and employees. Following analysis of the social and institutional...... and make store-level retail jobs interesting to them. Although retailers mainly focus their attention on career seekers, we find that working in retailing is interesting for all employee types because the retailers are currently able to meet their respective motivations and aspirations. Nevertheless, we...

  9. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as ...

  10. Defining and Classifying Interest Groups

    DEFF Research Database (Denmark)

    Baroni, Laura; Carroll, Brendan; Chalmers, Adam

    2014-01-01

    The interest group concept is defined in many different ways in the existing literature and a range of different classification schemes are employed. This complicates comparisons between different studies and their findings. One of the important tasks faced by interest group scholars engaged...... in large-N studies is therefore to define the concept of an interest group and to determine which classification scheme to use for different group types. After reviewing the existing literature, this article sets out to compare different approaches to defining and classifying interest groups with a sample...... of lobbying actors coded according to different coding schemes. We systematically assess the performance of different schemes by comparing how actor types in the different schemes differ with respect to a number of background characteristics. This is done in a two-stage approach where we first cluster actors...

  11. Interests diffusion in social networks

    Science.gov (United States)

    D'Agostino, Gregorio; D'Antonio, Fulvio; De Nicola, Antonio; Tucci, Salvatore

    2015-10-01

    We provide a model for diffusion of interests in Social Networks (SNs). We demonstrate that the topology of the SN plays a crucial role in the dynamics of the individual interests. Understanding cultural phenomena on SNs and exploiting the implicit knowledge about their members is attracting the interest of different research communities both from the academic and the business side. The community of complexity science is devoting significant efforts to define laws, models, and theories, which, based on acquired knowledge, are able to predict future observations (e.g. success of a product). In the mean time, the semantic web community aims at engineering a new generation of advanced services by defining constructs, models and methods, adding a semantic layer to SNs. In this context, a leapfrog is expected to come from a hybrid approach merging the disciplines above. Along this line, this work focuses on the propagation of individual interests in social networks. The proposed framework consists of the following main components: a method to gather information about the members of the social networks; methods to perform some semantic analysis of the Domain of Interest; a procedure to infer members' interests; and an interests evolution theory to predict how the interests propagate in the network. As a result, one achieves an analytic tool to measure individual features, such as members' susceptibilities and authorities. Although the approach applies to any type of social network, here it is has been tested against the computer science research community. The DBLP (Digital Bibliography and Library Project) database has been elected as test-case since it provides the most comprehensive list of scientific production in this field.

  12. 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...

  13. [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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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.)

  20. ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate.

    Science.gov (United States)

    Morales Diaz, Heidi; Mejares, Emil; Newman-Smith, Erin; Smith, William C

    2016-01-01

    The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Neural Stem Cell Differentiation Is Dictated by Distinct Actions of Nuclear Receptor Corepressors and Histone Deacetylases

    Directory of Open Access Journals (Sweden)

    Gonçalo Castelo-Branco

    2014-09-01

    Full Text Available Signaling factors including retinoic acid (RA and thyroid hormone (T3 promote neuronal, oligodendrocyte, and astrocyte differentiation of cortical neural stem cells (NSCs. However, the functional specificity of transcriptional repressor checkpoints controlling these differentiation programs remains unclear. Here, we show by genome-wide analysis that histone deacetylase (HDAC2 and HDAC3 show overlapping and distinct promoter occupancy at neuronal and oligodendrocyte-related genes in NSCs. The absence of HDAC3, but not HDAC2, initiated a neuronal differentiation pathway in NSCs. The ablation of the corepressor NCOR or HDAC2, in conjunction with T3 treatment, resulted in increased expression of oligodendrocyte genes, revealing a direct HDAC2-mediated repression of Sox8 and Sox10 expression. Interestingly, Sox10 was required also for maintaining the more differentiated state by repression of stem cell programming factors such as Sox2 and Sox9. Distinct and nonredundant actions of NCORs and HDACs are thus critical for control of lineage progression and differentiation programs in neural progenitors.

  2. Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.

    Science.gov (United States)

    Tovar, Juan A

    2007-06-01

    This review highlights the relevance of the neural crest (NC) as a developmental control mechanism involved in several pediatric surgical conditions and the investigative interest of following some of its known signaling pathways. The participation of the NC in facial clefts, ear defects, branchial fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular anomalies is briefly reviewed. Then, the literature on clinical and experimental esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects. Finally, some of the molecular signaling pathways involved in both conditions (sonic hedgehog, Hox genes, and retinoids) are summarized. The association of facial, cardiovascular, thymic, parathyroid, and C-cell defects together with anomalies of extrinsic and intrinsic esophageal innervation in babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis that NC is involved in the pathogenesis of these malformative clusters. On the other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in the previously mentioned signaling pathways. The investigation of NC-related molecular pathogenic pathways involved in malformative associations like EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens, and engineered mutations is a promising way of clarifying why and how some pediatric surgical conditions occur. Pediatric surgeons should be actively involved in these investigations.

  3. Foetal ECG recovery using dynamic neural networks.

    Science.gov (United States)

    Camps-Valls, Gustavo; Martínez-Sober, Marcelino; Soria-Olivas, Emilio; Magdalena-Benedito, Rafael; Calpe-Maravilla, Javier; Guerrero-Martínez, Juan

    2004-07-01

    Non-invasive electrocardiography has proven to be a very interesting method for obtaining information about the foetus state and thus to assure its well-being during pregnancy. One of the main applications in this field is foetal electrocardiogram (ECG) recovery by means of automatic methods. Evident problems found in the literature are the limited number of available registers, the lack of performance indicators, and the limited use of non-linear adaptive methods. In order to circumvent these problems, we first introduce the generation of synthetic registers and discuss the influence of different kinds of noise to the modelling. Second, a method which is based on numerical (correlation coefficient) and statistical (analysis of variance, ANOVA) measures allows us to select the best recovery model. Finally, finite impulse response (FIR) and gamma neural networks are included in the adaptive noise cancellation (ANC) scheme in order to provide highly non-linear, dynamic capabilities to the recovery model. Neural networks are benchmarked with classical adaptive methods such as the least mean squares (LMS) and the normalized LMS (NLMS) algorithms in simulated and real registers and some conclusions are drawn. For synthetic registers, the most determinant factor in the identification of the models is the foetal-maternal signal-to-noise ratio (SNR). In addition, as the electromyogram contribution becomes more relevant, neural networks clearly outperform the LMS-based algorithm. From the ANOVA test, we found statistical differences between LMS-based models and neural models when complex situations (high foetal-maternal and foetal-noise SNRs) were present. These conclusions were confirmed after doing robustness tests on synthetic registers, visual inspection of the recovered signals and calculation of the recognition rates of foetal R-peaks for real situations. Finally, the best compromise between model complexity and outcomes was provided by the FIR neural network. Both

  4. Interest Traitedness as a Moderator of Interest-Occupation Congruence.

    Science.gov (United States)

    Tracey, Terence J. G.

    2003-01-01

    The Unisex Edition of ACT Interest Inventory and career choice certainty measure were completed by 4,676 12th-graders. Hierarchical regressions were conducted on traitedness, measured by interitem consistency and construct similarity using Holland's personality types. All traitedness indices showed a significant moderating effect on…

  5. 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.

  6. The Optimal Interest Rates and the Current Interest Rate System

    Directory of Open Access Journals (Sweden)

    Ioannis N. Kallianiotis

    2014-12-01

    Full Text Available The paper discusses the current target interest rate, which is closed to zero with the new experiment of quantitative easing since 2009 and has reduced the rate of return and the income and has made the real savings rate negative. This target rate has not reduced unemployment and has not improved growth (it is not optimal, but has increased the debt of individuals and the low taxes on businesses have magnified the budget deficits and the national debt. People were borrowing the present value of their uncertain future wealth and their high debt and low income raise the risk and this high risk premium heighten the interest rate on loans, especially on credit cards. The current monetary system needs to be changed and an interest rate floor on deposits (savings and an interest rate ceiling on individuals‟ loans (borrowings is necessary to improve social welfare, fairness, and justice in our society and not to support only disintermediation (financial markets. The middle class cannot work only to pay taxes and interest on its debt (redistribution of their wealth to government and banks or worse to be in chronic unemployment. Many home owners defaulted on their loans payments and their homes are foreclosed. They will end up without property (real assets. The unconcern towards the middle class will affect negatively the entire socio-economic structure of the nation and after losing its productive power, it will start declining, as history has shown to us with so many empires that do not exist anymore. We hope the leaders (the democratic governments to improve public policies, to regulate the financial market and institutions, and to satisfy their policy ultimate objective, which is citizens‟ perfection and the nation‟s highest point of prosperity.

  7. Federal Debt and Interests Costs

    Science.gov (United States)

    1993-05-01

    rowing at lower rates would save $0.6 billion The feedback effect of 5 basis points was arbi- in the first year, growing to $3 billion in 1998 trarily...estimate assumes no feedback effects in 1994 and $0.8 billion smaller in 1998 than on interest rates. Some analysts argue, they would have been with no...bread and butter of the Trea- in Britain (which, like other British govern- sury’s financing. Nominal interest rates are ment bonds, are nicknamed gilts

  8. 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.

  9. Predicting complex quantitative traits with Bayesian neural networks: a case study with Jersey cows and wheat

    Directory of Open Access Journals (Sweden)

    Okut Hayrettin

    2011-10-01

    Full Text Available Abstract Background In the study of associations between genomic data and complex phenotypes there may be relationships that are not amenable to parametric statistical modeling. Such associations have been investigated mainly using single-marker and Bayesian linear regression models that differ in their distributions, but that assume additive inheritance while ignoring interactions and non-linearity. When interactions have been included in the model, their effects have entered linearly. There is a growing interest in non-parametric methods for predicting quantitative traits based on reproducing kernel Hilbert spaces regressions on markers and radial basis functions. Artificial neural networks (ANN provide an alternative, because these act as universal approximators of complex functions and can capture non-linear relationships between predictors and responses, with the interplay among variables learned adaptively. ANNs are interesting candidates for analysis of traits affected by cryptic forms of gene action. Results We investigated various Bayesian ANN architectures using for predicting phenotypes in two data sets consisting of milk production in Jersey cows and yield of inbred lines of wheat. For the Jerseys, predictor variables were derived from pedigree and molecular marker (35,798 single nucleotide polymorphisms, SNPS information on 297 individually cows. The wheat data represented 599 lines, each genotyped with 1,279 markers. The ability of predicting fat, milk and protein yield was low when using pedigrees, but it was better when SNPs were employed, irrespective of the ANN trained. Predictive ability was even better in wheat because the trait was a mean, as opposed to an individual phenotype in cows. Non-linear neural networks outperformed a linear model in predictive ability in both data sets, but more clearly in wheat. Conclusion Results suggest that neural networks may be useful for predicting complex traits using high

  10. Predicting complex quantitative traits with Bayesian neural networks: a case study with Jersey cows and wheat.

    Science.gov (United States)

    Gianola, Daniel; Okut, Hayrettin; Weigel, Kent A; Rosa, Guilherme Jm

    2011-10-07

    In the study of associations between genomic data and complex phenotypes there may be relationships that are not amenable to parametric statistical modeling. Such associations have been investigated mainly using single-marker and Bayesian linear regression models that differ in their distributions, but that assume additive inheritance while ignoring interactions and non-linearity. When interactions have been included in the model, their effects have entered linearly. There is a growing interest in non-parametric methods for predicting quantitative traits based on reproducing kernel Hilbert spaces regressions on markers and radial basis functions. Artificial neural networks (ANN) provide an alternative, because these act as universal approximators of complex functions and can capture non-linear relationships between predictors and responses, with the interplay among variables learned adaptively. ANNs are interesting candidates for analysis of traits affected by cryptic forms of gene action. We investigated various Bayesian ANN architectures using for predicting phenotypes in two data sets consisting of milk production in Jersey cows and yield of inbred lines of wheat. For the Jerseys, predictor variables were derived from pedigree and molecular marker (35,798 single nucleotide polymorphisms, SNPS) information on 297 individually cows. The wheat data represented 599 lines, each genotyped with 1,279 markers. The ability of predicting fat, milk and protein yield was low when using pedigrees, but it was better when SNPs were employed, irrespective of the ANN trained. Predictive ability was even better in wheat because the trait was a mean, as opposed to an individual phenotype in cows. Non-linear neural networks outperformed a linear model in predictive ability in both data sets, but more clearly in wheat. Results suggest that neural networks may be useful for predicting complex traits using high-dimensional genomic information, a situation where the number of unknowns

  11. Organizational Change and Vested Interest

    NARCIS (Netherlands)

    Hendrikse, G.W.J.

    1996-01-01

    The nature of organizational change and the value of headquarters is derived from a model with costs of delay, vested interests and costs of organizational change.The value of headquarters is derived from imposed organizational change. It is viewed as an institution which is able to prevent surplus

  12. Forecasting Interest Rates and Inflation

    DEFF Research Database (Denmark)

    Chun, Albert Lee

    the best overall for short horizon forecasts of short to medium term yields and inflation. Econometric models with shrinkage perform the best over longer horizons and maturities. Aggregating over a larger set of analysts improves inflation surveys while generally degrading interest rates surveys. We...

  13. CENTRE OF THE MAIN INTERESTS

    Directory of Open Access Journals (Sweden)

    DIANA DELEANU

    2013-05-01

    Full Text Available The centre of the main interests of the debtor is a legal tool meant to settle conflicts that can arise between jurisdictions in cross-border insolvencies, based on the principles of mutual recognition and co-operation.

  14. Preventing Trustee Conflicts of Interest.

    Science.gov (United States)

    Harpool, David

    1998-01-01

    The potential for conflict of interest in college and university trustees is high. A 1974 court decision (Stern vs. Sibley Memorial Hospital) established guidelines for trustees of nonprofit organizations, and a survey of 566 colleges and universities reveals how institutions are managing such conflicts through policy statements and…

  15. VOCATIONAL INTEREST, COUNSELLING, SOCIO- ECONOMIC ...

    African Journals Online (AJOL)

    Elizabeth

    contribute towards national development. Moreover, the concept of age is attracting more attention from educational psychologists. The girl child is expected to show some level of readiness, and interest in pursuing a vocation with increasing age. Super (1957) reported that reality factors play an increasingly important role ...

  16. Speculation, Hedging, and Interest Rates

    DEFF Research Database (Denmark)

    Buraschi, Andrea; Whelan, Paul

    of Treasury bond markets that the singleagent paradigm finds difficult to reconcile. Empirically, we test predictions from themodel using a large dataset on beliefs about fundamentals and find that: (i) shocksto disagreement lower short term interest rates; (ii) raise the slope of the yield curve;and (iii...

  17. Novel Mutation of LRP6 Identified in Chinese Han Population Links Canonical WNT Signaling to Neural Tube Defects.

    Science.gov (United States)

    Shi, Zhiwen; Yang, Xueyan; Li, Bin-Bin; Chen, Shuxia; Yang, Luming; Cheng, Liangping; Zhang, Ting; Wang, Hongyan; Zheng, Yufang

    2017-09-29

    Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//β-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/β-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling. In this study, we screened mutations in the LRP6 gene in 343 NTDs and 215 ethnically matched normal controls of Chinese Han population. Three rare missense mutations (c.1514A>G, p.Y505C); c.2984A>G, p.D995G; and c.4280C>A, p.P1427Q) of the LRP6 gene were identified in Chinese NTD patients. The Y505C mutation is a loss-of-function mutation on both WNT/β-catenin and PCP signaling. The D995G mutation only partially lost inhibition on PCP signaling without affecting WNT/β-catenin signaling. The P1427Q mutation dramatically increased WNT/β-catenin signaling but only mildly loss of inhibition on PCP signaling. All three mutations failed to rescue CE defects caused by lrp6 morpholino oligos knockdown in zebrafish. Of interest, when overexpressed, D995G did not induce any defects, but Y505C and P1427Q caused more severe CE defects in zebrafish. Our results suggested that over-active canonical WNT signaling induced by gain-of-function mutation in LRP6 could also contribute to human NTDs, and a balanced WNT/β-catenin and PCP signaling is probably required for proper neural tube development. Birth Defects Research, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. 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

  19. Neural bases of congenital amusia in tonal language speakers.

    Science.gov (United States)

    Zhang, Caicai; Peng, Gang; Shao, Jing; Wang, William S-Y

    2017-03-01

    Congenital amusia is a lifelong neurodevelopmental disorder of fine-grained pitch processing. In this fMRI study, we examined the neural bases of congenial amusia in speakers of a tonal language - Cantonese. Previous studies on non-tonal language speakers suggest that the neural deficits of congenital amusia lie in the music-selective neural circuitry in the right inferior frontal gyrus (IFG). However, it is unclear whether this finding can generalize to congenital amusics in tonal languages. Tonal language experience has been reported to shape the neural processing of pitch, which raises the question of how tonal language experience affects the neural bases of congenital amusia. To investigate this question, we examined the neural circuitries sub-serving the processing of relative pitch interval in pitch-matched Cantonese level tone and musical stimuli in 11 Cantonese-speaking amusics and 11 musically intact controls. Cantonese-speaking amusics exhibited abnormal brain activities in a widely distributed neural network during the processing of lexical tone and musical stimuli. Whereas the controls exhibited significant activation in the right superior temporal gyrus (STG) in the lexical tone condition and in the cerebellum regardless of the lexical tone and music conditions, no activation was found in the amusics in those regions, which likely reflects a dysfunctional neural mechanism of relative pitch processing in the amusics. Furthermore, the amusics showed abnormally strong activation of the right middle frontal gyrus and precuneus when the pitch stimuli were repeated, which presumably reflect deficits of attending to repeated pitch stimuli or encoding them into working memory. No significant group difference was found in the right IFG in either the whole-brain analysis or region-of-interest analysis. These findings imply that the neural deficits in tonal language speakers might differ from those in non-tonal language speakers, and overlap partly with the

  20. Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases.

    Science.gov (United States)

    Valensisi, Cristina; Andrus, Colin; Buckberry, Sam; Doni Jayavelu, Naresh; Lund, Riikka J; Lister, Ryan; Hawkins, R David

    2017-08-08

    We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation. Epigenomic maps reveal enhancer elements unique to NRs relative to 2D systems. A master regulatory network illustrates that key NR properties are related to their epigenomic landscapes. We found that folate-associated DNA methylation changes were enriched within NR regulatory elements near genes involved in neural tube formation and metabolism. Our comprehensive regulatory maps offer insights into the mechanisms by which folate may prevent NTDs. Lastly, our distal regulatory maps provide a better understanding of the potential role of neurological-disorder-associated SNPs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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 ...

  4. Interests versus morality in politics

    Directory of Open Access Journals (Sweden)

    Radojčić Mirjana S.

    2002-01-01

    Full Text Available In this individual project the relationship between interests and moral in politics will be considered, taking into consideration the disintegration of former Yugoslavia and the processes of globalization. The starting thesis of the research is that the main actors of global politics are still guided by the modern principles of real-politics with interests as its basic category and power as its supreme value. In that context the main elements of external politics of USA as the key actor of the processes will be specially considered. In the concluding part of the research author will be argue in favor of the affirmation of a new model of global politics, matching the character and scope of the problems faced by humanity at the turn of the century and the millenium.

  5. Informational pathologies and interest bubbles

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella; Wiewiura, Joachim Schmidt

    2017-01-01

    This article contends that certain configurations of information networks facilitate specific cognitive states that are instrumental for decision and action on social media. Group-related knowledge and belief states—in particular common knowledge and pluralistic ignorance—may enable strong public...... signals. Indeed, some network configurations and attitude states foster informational pathologies that may fuel interest bubbles affecting agenda-setting and the generation of narratives in public spheres....

  6. 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....

  7. 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.

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

    Science.gov (United States)

    Anderson, Michael L

    2010-08-01

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

  9. Identifying the neural substrates of intrinsic motivation during task performance.

    Science.gov (United States)

    Lee, Woogul; Reeve, Johnmarshall

    2017-10-01

    Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

  10. Beyond Pattern Recognition With Neural Nets

    Science.gov (United States)

    Arsenault, Henri H.; Macukow, Bohdan

    1989-02-01

    Neural networks are finding many areas of application. Although they are particularly well-suited for applications related to associative recall such as content-addressable memories, neural nets can perform many other applications ranging from logic operations to the solution of optimization problems. The training of a recently introduced model to perform boolean logical operations such as XOR is described. Such simple systems can be combined to perform any complex boolean operation. Any complex task consisting of parallel and serial operations including fuzzy logic that can be described in terms of input-output relations can be accomplished by combining modules such as the ones described here. The fact that some modules can carry out their functions even when their inputs contain erroneous data, and the fact that each module can carry out its functions in parallel with itself and other modules promises some interesting applications.

  11. 27 CFR 70.93 - Interest rate.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Interest rate. 70.93... Excise and Special (Occupational) Tax Interest § 70.93 Interest rate. (a) In general. The interest rate... annual percentage rate of interest will exceed the prescribed rate of interest. (b) Applicability of...

  12. Neural tube defects: recent advances, unsolved questions, and controversies.

    Science.gov (United States)

    Copp, Andrew J; Stanier, Philip; Greene, Nicholas D E

    2013-08-01

    Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kong Lingxin

    2008-04-01

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

  14. 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....

  15. 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...

  16. 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 ...

  17. The neural correlates of temporal reward discounting.

    Science.gov (United States)

    Scheres, Anouk; de Water, Erik; Mies, Gabry W

    2013-09-01

    Temporal reward discounting (TD) refers to the decrease in subjective value of a reward when the delay to that reward increases. In recent years, a growing number of studies on the neural correlates of temporal reward discounting have been conducted. This article focuses on functional magnetic resonance imaging (fMRI) studies on TD in humans. First, we describe the different types of tasks (also from behavioral studies) and the dependent variables. Subsequently, we discuss the evidence for three neurobiological models of TD: the dual-systems model, the single-system model and the self-control model. Further, studies in which nontraditional tasks (e.g., with nonmonetary rewards) were used to study TD are reviewed. Finally, we discuss the neural correlates of individual differences in discounting, and its development across the lifespan. We conclude that the evidence for each of the three neurobiological models of TD is mixed, in that all models receive (partial) support, and several studies provide support for multiple models. Because of large differences between studies in task design and analytical approach, it is difficult to draw a firm conclusion regarding which model provides the best explanation of the neural correlates of temporal discounting. We propose that some components of these models can complement each other, and future studies should test the predictions offered by different models against each other. Several future research directions are suggested, including studying the connectivity between brain regions in relation to discounting, and directly comparing the neural mechanisms involved in discounting of monetary and primary rewards. WIREs Cogn Sci 2013, 4:523-545. doi: 10.1002/wcs.1246 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

  18. Advances in neural networks computational and theoretical issues

    CERN Document Server

    Esposito, Anna; Morabito, Francesco

    2015-01-01

    This book collects research works that exploit neural networks and machine learning techniques from a multidisciplinary perspective. Subjects covered include theoretical, methodological and computational topics which are grouped together into chapters devoted to the discussion of novelties and innovations related to the field of Artificial Neural Networks as well as the use of neural networks for applications, pattern recognition, signal processing, and special topics such as the detection and recognition of multimodal emotional expressions and daily cognitive functions, and  bio-inspired memristor-based networks.  Providing insights into the latest research interest from a pool of international experts coming from different research fields, the volume becomes valuable to all those with any interest in a holistic approach to implement believable, autonomous, adaptive, and context-aware Information Communication Technologies.

  19. Special Interests and the Media

    Science.gov (United States)

    Shapiro, Jesse M.

    2017-01-01

    A journalist reports to a voter on an unknown, policy-relevant state. Competing special interests can make claims that contradict the facts but seem credible to the voter. A reputational incentive to avoid taking sides leads the journalist to report special interests’ claims to the voter. In equilibrium, the voter can remain uninformed even when the journalist is perfectly informed. Communication is improved if the journalist discloses her partisan leanings. The model provides an account of persistent public ignorance on climate change that is consistent with narrative and quantitative evidence. PMID:28725092

  20. Epigenetic regulation of adult neural stem cells: implications for Alzheimer's disease

    NARCIS (Netherlands)

    Fitzsimons, C.P.; van Bodegraven, E.; Schouten, M.; Lardenoije, R.; Kompotis, K.; Kenis, G.; van den Hurk, M.; Boks, M.P.; Biojone, C.; Joca, S.; Steinbusch, H.W.; Lunnon, K.; Mastroeni, D.F.; Mill, J.; Lucassen, P.J.; Coleman, P.D.; Van den Hove, D.L.; Rutten, B.P.F.

    2014-01-01

    Experimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those

  1. Training Convolutional Neural Networks for Translational Invariance on SAR ATR

    DEFF Research Database (Denmark)

    Malmgren-Hansen, David; Engholm, Rasmus; Østergaard Pedersen, Morten

    2016-01-01

    In this paper we present a comparison of the robustness of Convolutional Neural Networks (CNN) to other classifiers in the presence of uncertainty of the objects localization in SAR image. We present a framework for simulating simple SAR images, translating the object of interest systematically...

  2. Neural networks for predictive control of the mechanism of ...

    African Journals Online (AJOL)

    In this paper, we are interested in the study of the control of orientation of a wind turbine like means of optimization of his output/input ratio (efficiency). The approach suggested is based on the neural predictive control which is justified by the randomness of the wind on the one hand, and on the other hand by the capacity of ...

  3. 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.

  4. 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.

  5. Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage

    OpenAIRE

    Jackson, Steven A.; Zachariah P.G. Olufs; Tran, Khoa A.; Zaidan, Nur Zafirah; Sridharan, Rupa

    2016-01-01

    Summary During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expres...

  6. Astrophysically Interesting Resonances; Another Approach

    Science.gov (United States)

    Austin, Roby; Jenkins, David

    2008-10-01

    R.A.E. Austin, R. Kanungo, A. Campbell, S. Colosimo, S. Reeve Saint Mary's University; D.G. Jenkins, C.Aa.Diget, A. Robinson, University of York, UK; P.J. Woods T. Davinson University of Edinburgh; C.-Y. Wu A. Hurst J.A. Becker Lawrence Livermore National Laboratory; G.C. Ball M. Djongolov G. Hackman A.C. Morton, C. Pearson, S.J. Williams TRIUMF; A.A. Phillips, M. Schumaker, University of Guelph H.Boston, A. Grint, D. Oxley, University of Liverpool; D. Cline, A. Hayes, University of Rochester; We describe a prototype experiment to measure resonances of interest in astrophysical reactions. We use the TIGRESS to detect gamma rays in coincidence with charged particles, inelastically scattered in inverse kinematics. The particles are detected with the Bambino detector modified to a δE-E silicon telescope spanning 15-40 degrees in the lab.

  7. Information, Interests, and Environmental Regulation

    DEFF Research Database (Denmark)

    Winter, Søren; May, Peter J.

    2002-01-01

    This study contributes to the understanding of informational approaches to bringing about compliance with environmental regulations with particular attention to differences in the influence of information provided by different information sources. Based on theorizing from a combination of informa......This study contributes to the understanding of informational approaches to bringing about compliance with environmental regulations with particular attention to differences in the influence of information provided by different information sources. Based on theorizing from a combination...... of information processing and interest group literatures, we develop hypotheses about regulatees' reliance upon and the influence of different sources of information. We test these hypotheses for Danish farmers’ compliance with agro-environmental rules. Our findings show that information plays a role in bringing...

  8. Methylenetetrahydrofolate reductase (MTHFR) C677T gene ...

    Indian Academy of Sciences (India)

    including cardiovascular diseases, pregnancy complications, neural tube defects, Alzheimer disease, schizophrenia, cancer, etc. Available literatures elucidated that both gene and. Keywords. homocysteine; MTHFR; Mendelian population; gene–environment interaction. Journal of Genetics, Vol. 94, No. 1, March 2015. 121 ...

  9. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  10. 24 CFR 206.21 - Interest rate.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Interest rate. 206.21 Section 206... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgages § 206.21 Interest rate. (a) Fixed interest rate. A fixed interest rate is agreed upon by the mortgagor and mortgagee. (b) Adjustable interest...

  11. Toward a Neural Basis for Social Behavior

    OpenAIRE

    Stanley, Damian A.; Adolphs, Ralph

    2013-01-01

    Nearly 25 years ago, the shared interests of psychologists and biologists in understanding the neural basis of social behavior led to the inception of social neuroscience. In the past decade, this field has exploded, in large part due to the infusion of studies that use fMRI. At the same time, tensions have arisen about how to prioritize a diverse range of questions and about the authority of neurobiological data in answering them. The field is now poised to tackle some of the most interestin...

  12. Changes in the osmolarity of the embryonic microenvironment induce neural tube defects.

    Science.gov (United States)

    Jin, Yi-Mei; Wang, Guang; Zhang, Nuan; Wei, Yi-Fan; Li, Shuai; Chen, You-Peng; Chuai, Manli; Lee, Henry Siu Sum; Hocher, Berthold; Yang, Xuesong

    2015-05-01

    Many maternal disorders that modify the embryonic microenvironment, such as a change in osmolarity, can affect development, but how these changes influence the early embryo remains obscure. Neural tube defects, for example, are common congenital disorders found in fetus and neonates. In this study, we investigated the impact of anisotonic osmolarity (unequal osmotic pressures) on neural tube development in the early chick embryo, finding that neuronal cell differentiation was impaired in the neural tube due to enhanced apoptosis and repressed cell proliferation. Anisotonic osmolarity also affected normal development of the neural crest, which in turn influenced abnormal development of the neural tube. As neural tube development is highly dependent on the proper expression of bone morphogenetic protein 4 (BMP4), paired box 7 (PAX7), and sonic hedgehog (SHH) genes in the dorsal and ventral regions along the tube, we investigated the impact of anisotonic osmolarity on their expression. Indeed, small changes in osmolarity could positively and negatively impact the expression of these regulatory genes, which profoundly affected neural tube development. Thus, both the central and peripheral nervous systems were perturbed by anisotonic consitions as a consequence of the abnormal expression of key genes within the developing neural tube. © 2015 Wiley Periodicals, Inc.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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. .

  18. 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.

  19. 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 ...

  20. Neural remodeling in retinal degeneration.

    Science.gov (United States)

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  1. Identifying Broadband Rotational Spectra with Neural Networks

    Science.gov (United States)

    Zaleski, Daniel P.; Prozument, Kirill

    2017-06-01

    A typical broadband rotational spectrum may contain several thousand observable transitions, spanning many species. Identifying the individual spectra, particularly when the dynamic range reaches 1,000:1 or even 10,000:1, can be challenging. One approach is to apply automated fitting routines. In this approach, combinations of 3 transitions can be created to form a "triple", which allows fitting of the A, B, and C rotational constants in a Watson-type Hamiltonian. On a standard desktop computer, with a target molecule of interest, a typical AUTOFIT routine takes 2-12 hours depending on the spectral density. A new approach is to utilize machine learning to train a computer to recognize the patterns (frequency spacing and relative intensities) inherit in rotational spectra and to identify the individual spectra in a raw broadband rotational spectrum. Here, recurrent neural networks have been trained to identify different types of rotational spectra and classify them accordingly. Furthermore, early results in applying convolutional neural networks for spectral object recognition in broadband rotational spectra appear promising. Perez et al. "Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer." Chem. Phys. Lett., 2013, 571, 1-15. Seifert et al. "AUTOFIT, an Automated Fitting Tool for Broadband Rotational Spectra, and Applications to 1-Hexanal." J. Mol. Spectrosc., 2015, 312, 13-21. Bishop. "Neural networks for pattern recognition." Oxford university press, 1995.

  2. Neural basis of multisensory looming signals.

    Science.gov (United States)

    Tyll, Sascha; Bonath, Björn; Schoenfeld, Mircea Ariel; Heinze, Hans-Jochen; Ohl, Frank W; Noesselt, Tömme

    2013-01-15

    Approaching or looming signals are often related to extremely relevant environmental events (e.g. threats or collisions) making these signals critical for survival. However, the neural network underlying multisensory looming processing is not yet fully understood. Using functional magnetic resonance imaging (fMRI) we identified the neural correlates of audiovisual looming processing in humans: audiovisual looming (vs. receding) signals enhance fMRI-responses in low-level visual and auditory areas plus multisensory cortex (superior temporal sulcus; plus parietal and frontal structures). When characterizing the fMRI-response profiles for multisensory looming stimuli, we found significant enhancements relative to the mean and maximum of unisensory responses in looming-sensitive visual and auditory cortex plus STS. Superadditive enhancements were observed in visual cortex. Subject-specific region-of-interest analyses further revealed superadditive response profiles within all sensory-specific looming-sensitive structures plus bilateral STS for audiovisual looming vs. summed unisensory looming conditions. Finally, we observed enhanced connectivity of bilateral STS with low-level visual areas in the context of looming processing. This enhanced coupling of STS with unisensory regions might potentially serve to enhance the salience of unisensory stimulus features and is accompanied by superadditive fMRI-responses. We suggest that this preference in neural signaling for looming stimuli effectively informs animals to avoid potential threats or collisions. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Common approach to common interests

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-06-01

    In referring to issues confronting the energy field in this region and options to be exercised in the future, I would like to mention the fundamental condition of the utmost importance. That can be summed up as follows: any subject in energy area can never be solved by one country alone, given the geographical and geopolitical characteristics intrinsically possessed by energy. So, a regional approach is needed and it is especially necessary for the main players in the region to jointly address problems common to them. Though it may be a matter to be pursued in the distant future, I am personally dreaming a 'Common Energy Market for Northeast Asia,' in which member countries' interests are adjusted so that the market can be integrated and the region can become a most economically efficient market, thus formulating an effective power to encounter the outside. It should be noted that Europe needed forty years to integrate its market as the unified common market. It is necessary for us to follow a number of steps over the period to eventually materialize our common market concept, too. Now is the time for us to take a first step to lay the foundation for our descendants to enjoy prosperity from such a common market.

  4. Balancing commercial and public interests

    Directory of Open Access Journals (Sweden)

    Sevick Mary

    2004-07-01

    Full Text Available Abstract A large number of randomized clinical trials with important health outcomes are completed each year. Those with favorable findings are typically reported and published rapidly, while the publication of those with unfavorable results is often delayed or given a positive "spin." This observation applies primarily to industry-sponsored trials. Our objectives are to discuss the responsibility of pharmaceutical firms to the public with respect to timely, complete, and unbiased information from all randomized clinical trials and to propose solutions for improvements. We believe that in addition to financial obligations to their shareholders, pharmaceutical companies have social responsibilities to the public and to health care providers. However, private markets do not reward or compel optimal disclosure of drug safety or inferiority information on a voluntary basis. A problem which has not previously been identified relates to non-comparability of drugs. A case report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT illustrates how public interests may be violated due to failure to inform about drug inferiority. The current system for dissemination of relevant medical information could be improved if all involved parties collaborated fully. However, full disclosure of trial results is unlikely when research results are unfavorable to the firm. We conclude that expanded government regulations will be required for a satisfactory solution to the problem.

  5. Balancing commercial and public interests.

    Science.gov (United States)

    Furberg, Curt D; Hall, Mark A; Sevick, Mary Ann

    2004-07-07

    Alarge number of randomized clinical trials with important health outcomes are completed each year. Those with favorable findings are typically reported and published rapidly, while the publication of those with unfavorable results is often delayed or given a positive "spin." This observation applies primarily to industry-sponsored trials. Our objectives are to discuss the responsibility of pharmaceutical firms to the public with respect to timely, complete, and unbiased information from all randomized clinical trials and to propose solutions for improvements. We believe that in addition to financial obligations to their shareholders, pharmaceutical companies have social responsibilities to the public and to health care providers. However, private markets do not reward or compel optimal disclosure of drug safety or inferiority information on a voluntary basis.A problem which has not previously been identified relates to non-comparability of drugs. A case report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates how public interests may be violated due to failure to inform about drug inferiority. The current system for dissemination of relevant medical information could be improved if all involved parties collaborated fully. However, full disclosure of trial results is unlikely when research results are unfavorable to the firm. We conclude that expanded government regulations will be required for a satisfactory solution to the problem.

  6. 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

  7. Neural Tube Defects, Folic Acid and Methylation

    Science.gov (United States)

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

    2013-01-01

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

  8. Neural Plasticity: For Good and Bad

    Science.gov (United States)

    Møller, A. R.

    The brain's ability to change its organization and function is necessary for normal development of the nervous system and it makes it possible to adapt to changing demands but it can also cause disorders when going awry. This property, known as neural plasticity, is only evident when induced, very much like genes. Plastic changes may be programmed and providing a ``midcourse correction" during childhood development. If that is not executed in the normal way severe developmental disorders such as autism may results. Normal development of functions and anatomical organization of the brain and the spinal cord depend on appropriate sensory stimulation and motor activations. So-called enriched sensory environments have been shown to be beneficial for cognitive development and enriched acoustic environment may even slow the progression of age-related hearing loss. It is possible that the beneficial effect of physical exercise is achieved through activation of neural plasticity. The beneficial effect of training after trauma to the brain or spinal cord is mainly achieved through shifting functions from damaged brain area to other parts of the central nervous system and adapting these parts to take over the functions that are lost. This is accomplished through activation of neural plasticity. Plastic changes can also be harmful and cause symptoms and signs of disorders such as some forms of chronic pain (central neuropathic pain) and severe tinnitus. We will call such disorders ``plasticity disorders".

  9. Neural Tube Defects, Folic Acid and Methylation

    Directory of Open Access Journals (Sweden)

    Henk J. Blom

    2013-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Rajalaxmi Natarajan

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

  11. Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

    Directory of Open Access Journals (Sweden)

    Olivier Brock

    Full Text Available The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus, as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

  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. 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...

  14. 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...

  15. Stability and synchronization control of stochastic neural networks

    CERN Document Server

    Zhou, Wuneng; Zhou, Liuwei; Tong, Dongbing

    2016-01-01

    This book reports on the latest findings in the study of Stochastic Neural Networks (SNN). The book collects the novel model of the disturbance driven by Levy process, the research method of M-matrix, and the adaptive control method of the SNN in the context of stability and synchronization control. The book will be of interest to university researchers, graduate students in control science and engineering and neural networks who wish to learn the core principles, methods, algorithms and applications of SNN.

  16. Adaptive Synchronization of Memristor-based Chaotic Neural Systems

    Directory of Open Access Journals (Sweden)

    Xiaofang Hu

    2014-11-01

    Full Text Available Chaotic neural networks consisting of a great number of chaotic neurons are able to reproduce the rich dynamics observed in biological nervous systems. In recent years, the memristor has attracted much interest in the efficient implementation of artificial synapses and neurons. This work addresses adaptive synchronization of a class of memristor-based neural chaotic systems using a novel adaptive backstepping approach. A systematic design procedure is presented. Simulation results have demonstrated the effectiveness of the proposed adaptive synchronization method and its potential in practical application of memristive chaotic oscillators in secure communication.

  17. [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.

  18. 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...

  19. 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.

  20. 7 CFR 3565.211 - Interest credit.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Interest credit. 3565.211 Section 3565.211... AGRICULTURE GUARANTEED RURAL RENTAL HOUSING PROGRAM Loan Requirements § 3565.211 Interest credit. (a... assistance in the form of interest credit, to the extent necessary to reduce the agreed-upon rate of interest...

  1. 7 CFR 4279.125 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Interest rates. 4279.125 Section 4279.125 Agriculture... Interest rates. The interest rate for the guaranteed loan will be negotiated between the lender and the applicant and may be either fixed or variable as long as it is a legal rate. Interest rates will not be more...

  2. 24 CFR 200.83 - Interest rate.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Interest rate. 200.83 Section 200... Eligibility Requirements for Existing Projects Mortgage Provisions § 200.83 Interest rate. (a) The mortgage shall bear interest at the rate agreed upon by the mortgagee and the mortgagor. (b) Interest shall be...

  3. 7 CFR 4274.325 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Interest rates. 4274.325 Section 4274.325 Agriculture... (IRP) § 4274.325 Interest rates. (a) Loans made by the Agency pursuant to this subpart shall bear interest at a fixed rate of 1 percent per annum over the term of the loan. (b) Interest rates charged by...

  4. 7 CFR 4280.124 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Interest rates. 4280.124 Section 4280.124 Agriculture... Improvements Program Section B. Guaranteed Loans § 4280.124 Interest rates. (a) The interest rate for the... in similar circumstances in the ordinary course of business. The interest rate charged is subject to...

  5. 24 CFR 232.560 - Interest rate.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Interest rate. 232.560 Section 232... Equipment Eligible Security Instruments § 232.560 Interest rate. (a) The loan shall bear interest at the rate agreed upon by the lender and the borrower. (b) Interest shall be payable in monthly installments...

  6. 7 CFR 1980.320 - Interest rate.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Interest rate. 1980.320 Section 1980.320 Agriculture... REGULATIONS (CONTINUED) GENERAL Rural Housing Loans § 1980.320 Interest rate. The interest rate must not... interest rate over the life of the loan. The rate shall be agreed upon by the borrower and the Lender and...

  7. Maximum Entropy Approaches to Living Neural Networks

    Directory of Open Access Journals (Sweden)

    John M. Beggs

    2010-01-01

    Full Text Available Understanding how ensembles of neurons collectively interact will be a key step in developing a mechanistic theory of cognitive processes. Recent progress in multineuron recording and analysis techniques has generated tremendous excitement over the physiology of living neural networks. One of the key developments driving this interest is a new class of models based on the principle of maximum entropy. Maximum entropy models have been reported to account for spatial correlation structure in ensembles of neurons recorded from several different types of data. Importantly, these models require only information about the firing rates of individual neurons and their pairwise correlations. If this approach is generally applicable, it would drastically simplify the problem of understanding how neural networks behave. Given the interest in this method, several groups now have worked to extend maximum entropy models to account for temporal correlations. Here, we review how maximum entropy models have been applied to neuronal ensemble data to account for spatial and temporal correlations. We also discuss criticisms of the maximum entropy approach that argue that it is not generally applicable to larger ensembles of neurons. We conclude that future maximum entropy models will need to address three issues: temporal correlations, higher-order correlations, and larger ensemble sizes. Finally, we provide a brief list of topics for future research.

  8. 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.

  9. 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

  10. Age-related gene expression analysis in enteric ganglia of human colon after laser microdissection

    Directory of Open Access Journals (Sweden)

    Susan eHetz

    2014-10-01

    Full Text Available The enteric nervous system (ENS poses the intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. There is increasing scientific and clinical interest in acquired or age-related gastrointestinal dysfunctions that can be manifested in diseases such as gut constipation or fecal incontinence. In this study, we sought to analyze age-dependent changes in the gene expression profile of the human ENS, particularly in the myenteric plexus. Therefore, we used the laser microdissection technique which has been proven as a feasible tool to analyze distinct cell populations within heterogeneously composed tissues.Full biopsy gut samples were prepared from children (4-12 months, middle aged (48-58 years and aged donors (70-95 years. Cryosections were histologically stained with H&E, the ganglia of the myenteric plexus identified and RNA isolated using laser microdissection technique. Quantitative PCR was performed for selected neural genes, neurotransmitters and receptors. Data were confirmed on protein level using NADPH-diaphorase staining and immunohistochemistry.As result, we demonstrate age-associated alterations in site-specific gene expression pattern of the ENS. Thus, in the adult and aged distal parts of the colon a marked decrease in relative gene expression of neural key genes like NGFR, RET, NOS1 and a concurrent increase of CHAT were observed. Further, we detected notable regional differences of RET, CHAT, TH and S100B comparing gene expression in aged proximal and distal colon. Interestingly, markers indicating cellular senescence or oxidative stress (SNCA, CASP3, CAT, SOD2 and TERT were largely unchanged within the ENS. For the first time, our study also describes the age-dependent expression pattern of all major sodium channels within the ENS.Our results are in line with previous studies showing spatio-temporal differences within the mammalian ENS.

  11. 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...

  12. Neural networks for process control and optimization: two industrial applications.

    Science.gov (United States)

    Bloch, Gérard; Denoeux, Thierry

    2003-01-01

    The two most widely used neural models, multilayer perceptron (MLP) and radial basis function network (RBFN), are presented in the framework of system identification and control. The main steps for building such nonlinear black box models are regressor choice, selection of internal architecture, and parameter estimation. The advantages of neural network models are summarized: universal approximation capabilities, flexibility, and parsimony. Two applications are described in steel industry and water treatment, respectively, the control of alloying process in a hot dipped galvanizing line and the control of a coagulation process in a drinking water treatment plant. These examples highlight the interest of neural techniques, when complex nonlinear phenomena are involved, but the empirical knowledge of control operators can be learned.

  13. Audience preferences are predicted by temporal reliability of neural processing.

    Science.gov (United States)

    Dmochowski, Jacek P; Bezdek, Matthew A; Abelson, Brian P; Johnson, John S; Schumacher, Eric H; Parra, Lucas C

    2014-07-29

    Naturalistic stimuli evoke highly reliable brain activity across viewers. Here we record neural activity from a group of naive individuals while viewing popular, previously-broadcast television content for which the broad audience response is characterized by social media activity and audience ratings. We find that the level of inter-subject correlation in the evoked encephalographic responses predicts the expressions of interest and preference among thousands. Surprisingly, ratings of the larger audience are predicted with greater accuracy than those of the individuals from whom the neural data is obtained. An additional functional magnetic resonance imaging study employing a separate sample of subjects shows that the level of neural reliability evoked by these stimuli covaries with the amount of blood-oxygenation-level-dependent (BOLD) activation in higher-order visual and auditory regions. Our findings suggest that stimuli which we judge favourably may be those to which our brains respond in a stereotypical manner shared by our peers.

  14. Statistical modelling of neural networks in {gamma}-spectrometry applications

    Energy Technology Data Exchange (ETDEWEB)

    Vigneron, V.; Martinez, J.M. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. de Mecanique et de Technologie; Morel, J.; Lepy, M.C. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. des Applications et de la Metrologie des Rayonnements Ionisants

    1995-12-31

    Layered Neural Networks, which are a class of models based on neural computation, are applied to the measurement of uranium enrichment, i.e. the isotope ratio {sup 235} U/({sup 235} U + {sup 236} U + {sup 238} U). The usual method consider a limited number of {Gamma}-ray and X-ray peaks, and require previously calibrated instrumentation for each sample. But, in practice, the source-detector ensemble geometry conditions are critically different, thus a means of improving the above convention methods is to reduce the region of interest: this is possible by focusing on the K{sub {alpha}} X region where the three elementary components are present. Real data are used to study the performance of neural networks. Training is done with a Maximum Likelihood method to measure uranium {sup 235} U and {sup 238} U quantities in infinitely thick samples. (authors). 18 refs., 6 figs., 3 tabs.

  15. KCNQ potassium channels in sensory system and neural circuits.

    Science.gov (United States)

    Wang, Jing-jing; Li, Yang

    2016-01-01

    M channels, an important regulator of neural excitability, are composed of four subunits of the Kv7 (KCNQ) K(+) channel family. M channels were named as such because their activity was suppressed by stimulation of muscarinic acetylcholine receptors. These channels are of particular interest because they are activated at the subthreshold membrane potentials. Furthermore, neural KCNQ channels are drug targets for the treatments of epilepsy and a variety of neurological disorders, including chronic and neuropathic pain, deafness, and mental illness. This review will update readers on the roles of KCNQ channels in the sensory system and neural circuits as well as discuss their respective mechanisms and the implications for physiology and medicine. We will also consider future perspectives and the development of additional pharmacological models, such as seizure, stroke, pain and mental illness, which work in combination with drug-design targeting of KCNQ channels. These models will hopefully deepen our understanding of KCNQ channels and provide general therapeutic prospects of related channelopathies.

  16. Structured learning via convolutional neural networks for vehicle detection

    Science.gov (United States)

    Maqueda, Ana I.; del Blanco, Carlos R.; Jaureguizar, Fernando; García, Narciso

    2017-05-01

    One of the main tasks in a vision-based traffic monitoring system is the detection of vehicles. Recently, deep neural networks have been successfully applied to this end, outperforming previous approaches. However, most of these works generally rely on complex and high-computational region proposal networks. Others employ deep neural networks as a segmentation strategy to achieve a semantic representation of the object of interest, which has to be up-sampled later. In this paper, a new design for a convolutional neural network is applied to vehicle detection in highways for traffic monitoring. This network generates a spatially structured output that encodes the vehicle locations. Promising results have been obtained in the GRAM-RTM dataset.

  17. Genetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome.

    Science.gov (United States)

    Di Napoli, Agnese; Warrier, Varun; Baron-Cohen, Simon; Chakrabarti, Bhismadev

    2015-01-01

    Autism Spectrum Conditions (ASC) are neurodevelopmental conditions characterized by difficulties in communication and social interaction, alongside unusually repetitive behaviours and narrow interests. Asperger Syndrome (AS) is one subgroup of ASC and differs from classic autism in that in AS there is no language or general cognitive delay. Genetic, epigenetic and environmental factors are implicated in ASC and genes involved in neural connectivity and neurodevelopment are good candidates for studying the susceptibility to ASC. The aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) gene encodes a transcription factor involved in neurodevelopmental processes, neuronal connectivity and cellular responses to hypoxia. A mutation in this gene has been identified in individuals with ASC and single nucleotide polymorphisms (SNPs) have been nominally associated with AS and autistic traits in previous studies. In this study, we tested 34 SNPs in ARNT2 for association with AS in 118 cases and 412 controls of Caucasian origin. P values were adjusted for multiple comparisons, and linkage disequilibrium (LD) among the SNPs analysed was calculated in our sample. Finally, SNP annotation allowed functional and structural analyses of the genetic variants in ARNT2. We tested the replicability of our result using the genome-wide association studies (GWAS) database of the Psychiatric Genomics Consortium (PGC). We report statistically significant association of rs17225178 with AS. This SNP modifies transcription factor binding sites and regions that regulate the chromatin state in neural cell lines. It is also included in a LD block in our sample, alongside other genetic variants that alter chromatin regulatory regions in neural cells. These findings demonstrate that rs17225178 in the ARNT2 gene is associated with AS and support previous studies that pointed out an involvement of this gene in the predisposition to ASC.

  18. 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.

  19. 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....

  20. 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

  1. Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

    Science.gov (United States)

    Lau, Jennifer Y. F.; Guyer, Amanda E.; Tone, Erin B.; Jenness, Jessica; Parrish, Jessica M.; Pine, Daniel S.; Nelson, Eric E.

    2012-01-01

    Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and twelve age-, gender- and IQ-matched, psychiatrically healthy adolescents received "not interested" and "interested" feedback from unknown peers during a…

  2. Critical Aspects of Clinical Trial Design for Novel Cell and Gene Therapies

    Directory of Open Access Journals (Sweden)

    Zinovia Kefalopoulou

    2011-01-01

    Full Text Available Neural cell transplantation and gene therapy have attracted considerable interest as promising therapeutic alternatives for patients with Parkinson's disease (PD. Preclinical and open-label studies have suggested that grafted fetal neural tissue or viral vector gene transfer can achieve considerable biochemical and clinical improvements, whereas subsequent double-blind, placebo-controlled protocols have produced rather more modest and variable results. Detailed evaluation of these discordant findings has highlighted several crucial issues such as patient selection criteria, details surrounding transplantation or gene therapy methodologies, as well as the study designs themselves that ought to be carefully considered in the planning phases of future clinical trials. Beyond the provision of symptomatic efficacy and safety data, it also remains to be identified whether the possibilities offered by stem cell and gene therapy technological advances might translate to meaningful neuroprotection and/or disease-modifying effects or alleviate the nonmotor aspects of PD and thus offer additional benefits beyond those achieved through conventional pharmacotherapy or deep brain stimulation (DBS.

  3. 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 ...

  4. 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

  5. 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...

  6. Identification of a novel intronic enhancer responsible for the transcriptional regulation of musashi1 in neural stem/progenitor cells

    Directory of Open Access Journals (Sweden)

    Kawase Satoshi

    2011-04-01

    Full Text Available Abstract Background The specific genetic regulation of neural primordial cell determination is of great interest in stem cell biology. The Musashi1 (Msi1 protein, which belongs to an evolutionarily conserved family of RNA-binding proteins, is a marker for neural stem/progenitor cells (NS/PCs in the embryonic and post-natal central nervous system (CNS. Msi1 regulates the translation of its downstream targets, including m-Numb and p21 mRNAs. In vitro experiments using knockout mice have shown that Msi1 and its isoform Musashi2 (Msi2 keep NS/PCs in an undifferentiated and proliferative state. Msi1 is expressed not only in NS/PCs, but also in other somatic stem cells and in tumours. Based on previous findings, Msi1 is likely to be a key regulator for maintaining the characteristics of self-renewing stem cells. However, the mechanisms regulating Msi1 expression are not yet clear. Results To identify the DNA region affecting Msi1 transcription, we inserted the fusion gene ffLuc, comprised of the fluorescent Venus protein and firefly Luciferase, at the translation initiation site of the mouse Msi1 gene locus contained in a 184-kb bacterial artificial chromosome (BAC. Fluorescence and Luciferase activity, reflecting the Msi1 transcriptional activity, were observed in a stable BAC-carrying embryonic stem cell line when it was induced toward neural lineage differentiation by retinoic acid treatment. When neuronal differentiation was induced in embryoid body (EB-derived neurosphere cells, reporter signals were detected in Msi1-positive NSCs and GFAP-positive astrocytes, but not in MAP2-positive neurons. By introducing deletions into the BAC reporter gene and conducting further reporter experiments using a minimized enhancer region, we identified a region, "D5E2," that is responsible for Msi1 transcription in NS/PCs. Conclusions A regulatory element for Msi1 transcription in NS/PCs is located in the sixth intron of the Msi1 gene. The 595-bp D5E2 intronic

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

    Science.gov (United States)

    Kobayashi, Kenta; Kato, Shigeki; Kobayashi, Kazuto

    2017-01-05

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

  8. miR-381 Regulates Neural Stem Cell Proliferation and Differentiation via Regulating Hes1 Expression.

    Directory of Open Access Journals (Sweden)

    Xiaodong Shi

    Full Text Available Neural stem cells are self-renewing, multipotent and undifferentiated precursors that retain the capacity for differentiation into both glial (astrocytes and oligodendrocytes and neuronal lineages. Neural stem cells offer cell-based therapies for neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and spinal cord injuries. However, their cellular behavior is poorly understood. MicroRNAs (miRNAs are a class of small noncoding RNAs involved in cell development, proliferation and differentiation through regulating gene expression at post-transcriptional level. The role of miR-381 in the development of neural stem cells remains unknown. In this study, we showed that overexpression of miR-381 promoted neural stem cells proliferation. It induced the neural stem cells differentiation to neurons and inhibited their differentiation to astrocytes. Furthermore, we identified HES1 as a direct target of miR-381 in neural stem cells. Moreover, re-expression of HES1 impaired miR-381-induced promotion of neural stem cells proliferation and induce neural stem cells differentiation to neurons. In conclusion, miR-381 played important role in neural stem cells proliferation and differentiation.

  9. Association between competing interests and authors' conclusions

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Als-Nielsen, Bodil

    2002-01-01

    To assess the association between competing interests and authors' conclusions in randomised clinical trials.......To assess the association between competing interests and authors' conclusions in randomised clinical trials....

  10. Development of a Career Interest Inventory

    Science.gov (United States)

    Thomas, Hollie B.

    1974-01-01

    The educational significance of the present study lies in the potential use of the Career Interest by career educators needing to identify students with interests in particular career areas and to counselors placing students into various career courses. (BP)

  11. 37 CFR 251.31 - Financial interests.

    Science.gov (United States)

    2010-07-01

    ... or blind trust which might have an interest in a prohibited entity but whose decisions to invest or... own interests: (1) The arbitrator's spouse; (2) The arbitrator's minor child; (3) The arbitrator's...

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

    Science.gov (United States)

    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.

  13. Developmental plasticity in neural circuits for a learned behavior.

    Science.gov (United States)

    Bottjer, S W; Arnold, A P

    1997-01-01

    The neural substrate underlying learned vocal behavior in songbirds provides a textbook illustration of anatomical localization of function for a complex learned behavior in vertebrates. The song-control system has become an important model for studying neural systems related to learning, behavior, and development. The song system of zebra finches is characterized by a heightened capacity for both neural and behavioral change during development and has taught us valuable information regarding sensitive periods, rearrangement of synaptic connections, topographic specificity, cell death and neurogenesis, experience-dependent neural plasticity, and sexual differentiation. The song system differs in some interesting ways from some well-studied mammalian model systems and thus offers fresh perspectives on specific theoretical issues. In this highly selective review, we concentrate on two major questions: What are the developmental changes in the song system responsible for song learning and the restriction of learning to a sensitive period, and what factors explain the highly sexually dimorphic development of this system? We discuss the important role of sex steroid hormones and of neurotrophins in creating a male-typical neural song circuit (which can learn to produce complex vocalizations) instead of a reduced, female-typical song circuit that does not produce learned song.

  14. The Complexity of Dynamics in Small Neural Circuits.

    Directory of Open Access Journals (Sweden)

    Diego Fasoli

    2016-08-01

    Full Text Available Mean-field approximations are a powerful tool for studying large neural networks. However, they do not describe well the behavior of networks composed of a small number of neurons. In this case, major differences between the mean-field approximation and the real behavior of the network can arise. Yet, many interesting problems in neuroscience involve the study of mesoscopic networks composed of a few tens of neurons. Nonetheless, mathematical methods that correctly describe networks of small size are still rare, and this prevents us to make progress in understanding neural dynamics at these intermediate scales. Here we develop a novel systematic analysis of the dynamics of arbitrarily small networks composed of homogeneous populations of excitatory and inhibitory firing-rate neurons. We study the local bifurcations of their neural activity with an approach that is largely analytically tractable, and we numerically determine the global bifurcations. We find that for strong inhibition these networks give rise to very complex dynamics, caused by the formation of multiple branching solutions of the neural dynamics equations that emerge through spontaneous symmetry-breaking. This qualitative change of the neural dynamics is a finite-size effect of the network, that reveals qualitative and previously unexplored differences between mesoscopic cortical circuits and their mean-field approximation. The most important consequence of spontaneous symmetry-breaking is the ability of mesoscopic networks to regulate their degree of functional heterogeneity, which is thought to help reducing the detrimental effect of noise correlations on cortical information processing.

  15. Environmental enrichment promotes neural plasticity and cognitive ability in fish.

    Science.gov (United States)

    Salvanes, Anne Gro Vea; Moberg, Olav; Ebbesson, Lars O E; Nilsen, Tom Ole; Jensen, Knut Helge; Braithwaite, Victoria A

    2013-09-22

    Different kinds of experience during early life can play a significant role in the development of an animal's behavioural phenotype. In natural contexts, this influences behaviours from anti-predator responses to navigation abilities. By contrast, for animals reared in captive environments, the homogeneous nature of their experience tends to reduce behavioural flexibility. Studies with cage-reared rodents indicate that captivity often compromises neural development and neural plasticity. Such neural and behavioural deficits can be problematic if captive-bred animals are being reared with the intention of releasing them as part of a conservation strategy. Over the last decade, there has been growing interest in the use of environmental enrichment to promote behavioural flexibility in animals that are bred for release. Here, we describe the positive effects of environmental enrichment on neural plasticity and cognition in juvenile Atlantic salmon (Salmo salar). Exposing fish to enriched conditions upregulated the forebrain expression of NeuroD1 mRNA and improved learning ability assessed in a spatial task. The addition of enrichment to the captive environment thus promotes neural and behavioural changes that are likely to promote behavioural flexibility and improve post-release survival.

  16. Pricing Interest-Rate-Derivative Securities.

    OpenAIRE

    Hull, John; White, Alan

    1990-01-01

    This article shows that the one-state-variable interest-rate models of Vasicek (1977) and Cox, Ingersoll, and Ross (1985b) can be extended so that they are consistent with both the current term structure of interest rates and either the current volatilities of all spot interest rates or the current volatilities of all forward interest rates. The extended Vasicek model is shown to be very tractable analytically. The article compares option prices obtained using the extended Vasicek model with ...

  17. Effective learning in recurrent max-min neural networks.

    Science.gov (United States)

    Loe, Kia Fock; Teow, Loo Nin

    1998-04-01

    Max and min operations have interesting properties that facilitate the exchange of information between the symbolic and real-valued domains. As such, neural networks that employ max-min activation functions have been a subject of interest in recent years. Since max-min functions are not strictly differentiable, we propose a mathematically sound learning method based on using Fourier convergence analysis of side-derivatives to derive a gradient descent technique for max-min error functions. We then propose a novel recurrent max-min neural network model that is trained to perform grammatical inference as an application example. Comparisons made between this model and recurrent sigmoidal neural networks show that our model not only performs better in terms of learning speed and generalization, but that its final weight configuration allows a deterministic finite automation (DFA) to be extracted in a straightforward manner. In essence, we are able to demonstrate that our proposed gradient descent technique does allow max-min neural networks to learn effectively.

  18. 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.

  19. 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.

  20. 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.

  1. Can Animals have preference-interests?

    OpenAIRE

    Julia Tanne

    2007-01-01

    It has been argued that only moral agents can have preference-interests and this therefore excludes animals. I will present two objections to this argument. The first will show that moral agency is not necessary to have preference-interests. The second will assert that the argument that animals cannot have preference-interests has unwelcome consequences.

  2. Reading Interest in a Digital Age

    Science.gov (United States)

    Putro, Nur Hidayanto Pancoro Setyo; Lee, Jihyun

    2017-01-01

    The era of "digital literacy" raises the question of whether the meaning of reading interest may have changed. This study examined psycho-behavioral dimensions of reading interest as these relate to different reading modes and different purposes of reading. Findings show that reading interest is best represented by its subcomponents of…

  3. Interest prohibition and financial product innovation

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2011-01-01

    We give a rough sketch of the Judaic, Greek, Islamic and Christian positions in the matter of interest prohibition during the last few millennia and discuss the way in which interest prohibition is dealt with in Islamic finance, the problems with authority-based arguments for interest prohibition,

  4. Items of interest from recent ornithological literature

    African Journals Online (AJOL)

    hereby introduce a new feature for Scopus: Items of interest from recent ornithological literature. We hope to have this feature in all forthcoming issues of Scopus, switching between topics based on interest and articles received. Besides the Editorial Board occasionally soliciting articles, we welcome pieces from interested ...

  5. ESTIMATING THE EFFECTS OF EXCHANGE AND INTEREST ...

    African Journals Online (AJOL)

    Common stock value is affected by two important economic and financial risk factors namely interest rate and exchange rate. Interest rate which reflects the price of money also affects other variables in the financial market. Valuation of stock prices is indirectly affected by interest rates while directly its volatility causes a shift ...

  6. 5 CFR 1655.7 - Interest rate.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Interest rate. 1655.7 Section 1655.7 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD LOAN PROGRAM § 1655.7 Interest rate. (a... interest rate established by the Department of the Treasury in effect on the date the TSP record keeper...

  7. 7 CFR 3575.33 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Interest rates. 3575.33 Section 3575.33 Agriculture... GENERAL Community Programs Guaranteed Loans § 3575.33 Interest rates. (a) General. Rates will be negotiated between the lender and the borrower. They may be either fixed or variable rates. Interest rates...

  8. 7 CFR 3550.66 - Interest rate.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Interest rate. 3550.66 Section 3550.66 Agriculture... DIRECT SINGLE FAMILY HOUSING LOANS AND GRANTS Section 502 Origination § 3550.66 Interest rate. Loans will be written using the applicable RHS interest rate in effect at loan approval or loan closing...

  9. 38 CFR 36.4312 - Interest rates.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Interest rates. 36.4312... GUARANTY Guaranty or Insurance of Loans to Veterans With Electronic Reporting § 36.4312 Interest rates. (a... such loans either bear interest at a rate that is agreed upon by the veteran and the lender, or bear...

  10. 7 CFR 1950.105 - Interest rate.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Interest rate. 1950.105 Section 1950.105 Agriculture... rate. (a) The Soldiers and Sailors Relief Act requires that the effective interest rate charged a... Supervisor will send the borrower a letter which states that the interest rate on the borrower's FmHA or its...

  11. 13 CFR 120.932 - Interest rate.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Interest rate. 120.932 Section 120.932 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) 504 Loans and Debentures § 120.932 Interest rate. The interest rate of the 504 Loan...

  12. 76 FR 16570 - Interest Rate Risk

    Science.gov (United States)

    2011-03-24

    ... ADMINISTRATION 12 CFR Part 741 RIN 3133-AD66 Interest Rate Risk AGENCY: National Credit Union Administration... insured credit unions to have a written policy addressing interest rate risk (IRR) management and an... (FICUs) to have a written policy and an effective program addressing interest rate risk (IRR) as part of...

  13. 7 CFR 1714.4 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Interest rates. 1714.4 Section 1714.4 Agriculture... PRE-LOAN POLICIES AND PROCEDURES FOR INSURED ELECTRIC LOANS General § 1714.4 Interest rates. (a) Municipal rate loans. Each advance of funds on a municipal rate loan shall bear interest at a single rate...

  14. 8 CFR 293.2 - Interest rate.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Interest rate. 293.2 Section 293.2 Aliens... CASH RECEIVED TO SECURE IMMIGRATION BONDS § 293.2 Interest rate. The Secretary of the Treasury has determined that effective from date of deposit occurring after April 27, 1966, the interest rate shall be 3...

  15. 12 CFR 614.4155 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Interest rates. 614.4155 Section 614.4155 Banks... Policies for Banks and Associations § 614.4155 Interest rates. Loans made by each bank and direct lender association shall bear interest at a rate or rates as may be determined by the institution board. The board...

  16. 7 CFR 1779.33 - Interest rates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Interest rates. 1779.33 Section 1779.33 Agriculture... (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.33 Interest rates. (a) General. Rates.... Interest rates will be those rates customarily charged borrowers in similar circumstances in the ordinary...

  17. 76 FR 59767 - Interest Rates; Notice

    Science.gov (United States)

    2011-09-27

    ... ADMINISTRATION Interest Rates; Notice AGENCY: Small Business Administration. The Small Business Administration publishes an interest rate called the optional ``peg'' rate (13 CFR 120.214) on a quarterly basis. This rate... direct loan. This rate may be used as a base rate for guaranteed fluctuating interest rate SBA loans...

  18. 7 CFR 29.28 - Interested party.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Interested party. 29.28 Section 29.28 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.28 Interested party. The owner or other financially interested person...

  19. Following Passionate Interests to Well-Being

    Science.gov (United States)

    Dik, Bryan J.; Hansen, Jo-Ida C.

    2008-01-01

    This article describes the relationship between interests and well-being by conceptualizing interest as both an emotional state and a stable disposition. First, interest is explored as a distinct emotion or affective state, itself a form of well-being that also leads to other forms of well-being by facilitating the development of diverse life…

  20. Dialectical roots for interest prohibition theory

    NARCIS (Netherlands)

    Bergstra, J.A.

    2011-01-01

    It is argued that arguments for strict prohibition of interests must be based on the use of arguments from authority. This is carried out by first making a survey of so-called dialectical roots for interest prohibition and then demonstrating that for at least one important positive interest bearing

  1. 31 CFR 10.29 - Conflicting interests.

    Science.gov (United States)

    2010-07-01

    ... conflict of interest. A conflict of interest exists if— (1) The representation of one client will be... more clients will be materially limited by the practitioner's responsibilities to another client, a... existence of a conflict of interest under paragraph (a) of this section, the practitioner may represent a...

  2. 76 FR 61046 - TARP Conflicts of Interest

    Science.gov (United States)

    2011-10-03

    ... conflicts of interest. (a) Retained entity's responsibility. A retained entity working under an arrangement... responsibility. A retained entity shall ensure that all key individuals have no personal conflicts of interest... 31 CFR Part 31 RIN 1505-AC05 TARP Conflicts of Interest AGENCY: Departmental Offices, Treasury...

  3. Genome-Wide Definition of Promoter and Enhancer Usage during Neural Induction of Human Embryonic Stem Cells

    National Research Council Canada - National Science Library

    Poletti, Valentina; Delli Carri, Alessia; Malagoli Tagliazucchi, Guidantonio; Faedo, Andrea; Petiti, Luca; Mazza, Emilia Maria Cristina; Peano, Clelia; De Bellis, Gianluca; Bicciato, Silvio; Miccio, Annarita; Cattaneo, Elena; Mavilio, Fulvio

    2015-01-01

    ... are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs...

  4. Genome-Wide Definition of Promoter and Enhancer Usage during Neural Induction of Human Embryonic Stem Cells: e0126590

    National Research Council Canada - National Science Library

    Valentina Poletti; Alessia Delli Carri; Guidantonio Malagoli Tagliazucchi; Andrea Faedo; Luca Petiti; Emilia Maria Cristina Mazza; Clelia Peano; Gianluca De Bellis; Silvio Bicciato; Annarita Miccio; Elena Cattaneo; Fulvio Mavilio

    2015-01-01

    ... are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs...

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

    Science.gov (United States)

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

    2015-10-06

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

  6. 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.

  7. 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.

  8. 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.

  9. Data Mining of Gene Arrays for Biomarkers of Survival in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Clare Coveney

    2015-07-01

    Full Text Available The expected five-year survival rate from a stage III ovarian cancer diagnosis is a mere 22%; this applies to the 7000 new cases diagnosed yearly in the UK. Stratification of patients with this heterogeneous disease, based on active molecular pathways, would aid a targeted treatment improving the prognosis for many cases. While hundreds of genes have been associated with ovarian cancer, few have yet been verified by peer research for clinical significance. Here, a meta-analysis approach was applied to two carefully selected gene expression microarray datasets. Artificial neural networks, Cox univariate survival analyses and T-tests identified genes whose expression was consistently and significantly associated with patient survival. The rigor of this experimental design increases confidence in the genes found to be of interest. A list of 56 genes were distilled from a potential 37,000 to be significantly related to survival in both datasets with a FDR of 1.39859 × 10−11, the identities of which both verify genes already implicated with this disease and provide novel genes and pathways to pursue. Further investigation and validation of these may lead to clinical insights and have potential to predict a patient’s response to treatment or be used as a novel target for therapy.

  10. Diagnosis of Cervical Cancer Using the Median M-Type Radial Basis Function (MMRBF) Neural Network

    Science.gov (United States)

    Gómez-Mayorga, Margarita E.; Gallegos-Funes, Francisco J.; de-La-Rosa-Vázquez, José M.; Cruz-Santiago, Rene; Ponomaryov, Volodymyr

    The automatic analysis of Pap smear microscopic images is one of the most interesting fields in biomedical image processing. In this paper we present the capability of the Median M-Type Radial Basis Function (MMRBF) neural network in the classification of cervical cancer cells. From simulation results we observe that the MMRBF neural network has better classification capabilities in comparison with the Median RBF algorithm used as comparative.

  11. Cognitive Psychology for Deep Neural Networks: A Shape Bias Case Study

    OpenAIRE

    Ritter, Samuel; Barrett, David G. T.; Santoro, Adam; Botvinick, Matt M.

    2017-01-01

    Deep neural networks (DNNs) have achieved unprecedented performance on a wide range of complex tasks, rapidly outpacing our understanding of the nature of their solutions. This has caused a recent surge of interest in methods for rendering modern neural systems more interpretable. In this work, we propose to address the interpretability problem in modern DNNs using the rich history of problem descriptions, theories and experimental methods developed by cognitive psychologists to study the hum...

  12. Learning of N-layers neural network

    Directory of Open Access Journals (Sweden)

    Vladimír Konečný

    2005-01-01

    Full Text Available In the last decade we can observe increasing number of applications based on the Artificial Intelligence that are designed to solve problems from different areas of human activity. The reason why there is so much interest in these technologies is that the classical way of solutions does not exist or these technologies are not suitable because of their robustness. They are often used in applications like Business Intelligence that enable to obtain useful information for high-quality decision-making and to increase competitive advantage.One of the most widespread tools for the Artificial Intelligence are the artificial neural networks. Their high advantage is relative simplicity and the possibility of self-learning based on set of pattern situations.For the learning phase is the most commonly used algorithm back-propagation error (BPE. The base of BPE is the method minima of error function representing the sum of squared errors on outputs of neural net, for all patterns of the learning set. However, while performing BPE and in the first usage, we can find out that it is necessary to complete the handling of the learning factor by suitable method. The stability of the learning process and the rate of convergence depend on the selected method. In the article there are derived two functions: one function for the learning process management by the relative great error function value and the second function when the value of error function approximates to global minimum.The aim of the article is to introduce the BPE algorithm in compact matrix form for multilayer neural networks, the derivation of the learning factor handling method and the presentation of the results.

  13. Workshop on Thermal Field Theory to Neural Networks

    CERN Document Server

    Veneziano, Gabriele; Aurenche, Patrick

    1996-01-01

    Tanguy Altherr was a Fellow in the Theory Division at CERN, on leave from LAPP (CNRS) Annecy. At the time of his accidental death in July 1994, he was only 31.A meeting was organized at CERN, covering the various aspects of his scientific interests: thermal field theory and its applications to hot or dense media, neural networks and its applications to high energy data analysis. Speakers were among his closest collaborators and friends.

  14. A Fast C++ Implementation of Neural Network Backpropagation Training Algorithm: Application to Bayesian Optimal Image Demosaicing

    Directory of Open Access Journals (Sweden)

    Yi-Qing Wang

    2015-09-01

    Full Text Available Recent years have seen a surge of interest in multilayer neural networks fueled by their successful applications in numerous image processing and computer vision tasks. In this article, we describe a C++ implementation of the stochastic gradient descent to train a multilayer neural network, where a fast and accurate acceleration of tanh(· is achieved with linear interpolation. As an example of application, we present a neural network able to deliver state-of-the-art performance in image demosaicing.

  15. Bayesian neural networks for detecting epistasis in genetic association studies.

    Science.gov (United States)

    Beam, Andrew L; Motsinger-Reif, Alison; Doyle, Jon

    2014-11-21

    Discovering causal genetic variants from large genetic association studies poses many difficult challenges. Assessing which genetic markers are involved in determining trait status is a computationally demanding task, especially in the presence of gene-gene interactions. A non-parametric Bayesian approach in the form of a Bayesian neural network is proposed for use in analyzing genetic association studies. Demonstrations on synthetic and real data reveal they are able to efficiently and accurately determine which variants are involved in determining case-control status. By using graphics processing units (GPUs) the time needed to build these models is decreased by several orders of magnitude. In comparison with commonly used approaches for detecting interactions, Bayesian neural networks perform very well across a broad spectrum of possible genetic relationships. The proposed framework is shown to be a powerful method for detecting causal SNPs while being computationally efficient enough to handle large datasets.

  16. 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.

  17. Neural correlates of threat perception: neural equivalence of conspecific and heterospecific mobbing calls is learned.

    Science.gov (United States)

    Avey, Marc T; Hoeschele, Marisa; Moscicki, Michele K; Bloomfield, Laurie L; Sturdy, Christopher B

    2011-01-01

    Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators. Mobbing calls produced in response to smaller, higher-threat predators contain more "D" notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned.

  18. Neural correlates of threat perception: neural equivalence of conspecific and heterospecific mobbing calls is learned.

    Directory of Open Access Journals (Sweden)

    Marc T Avey

    Full Text Available Songbird auditory areas (i.e., CMM and NCM are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators. Mobbing calls produced in response to smaller, higher-threat predators contain more "D" notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned.

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

    Science.gov (United States)

    Shimada, Issei S; Mukhopadhyay, Saikat

    2017-01-30

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

  20. 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.