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Sample records for histone acetyltransferase p300

  1. The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases

    NARCIS (Netherlands)

    van den Bosch, Thea; Boichenko, Alexander; Leus, Niek G J; Ourailidou, Maria Eleni; Wapenaar, Hannah; Rotili, Dante; Mai, Antonello; Imhof, Axel; Bischoff, Rainer; Haisma, Hidde J; Dekker, Frank J

    2016-01-01

    Lysine acetylations are reversible posttranslational modifications of histone and non-histone proteins that play important regulatory roles in signal transduction cascades and gene expression. Lysine acetylations are regulated by histone acetyltransferases as writers and histone deacetylases as

  2. Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.

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    Banerjee, S; Rakshit, T; Sett, S; Mukhopadhyay, R

    2015-10-22

    One of the important properties of the transcriptional coactivator p300 is histone acetyltransferase (HAT) activity that enables p300 to influence chromatin action via histone modulation. p300 can exert its HAT action upon the other nuclear proteins too--one notable example being the transcription-factor-like protein HMGB1, which functions also as a cytokine, and whose accumulation in the cytoplasm, as a response to tissue damage, is triggered by its acetylation. Hitherto, no information on the structure and stability of the complexes between full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available, probably due to the presence of unstructured regions within p300FL that makes it difficult to be crystallized. Herein, we have adopted the high-resolution atomic force microscopy (AFM) approach, which allows molecularly resolved three-dimensional contour mapping of a protein molecule of any size and structure. From the off-rate and activation barrier values, obtained using single molecule dynamic force spectroscopy, the biochemical proposition of preferential binding of p300FL to histone H3, compared to the octameric histone, can be validated. Importantly, from the energy landscape of the dissociation events, a model for the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be proposed. The lower unbinding forces of the complexes observed in acetylating conditions, compared to those observed in non-acetylating conditions, indicate that upon acetylation, p300 tends to weakly associate, probably as an outcome of charge alterations on the histone/HMGB1 surface and/or acetylation-induced conformational changes. To our knowledge, for the first time, a single molecule level treatment of the interactions of HAT, where the full-length protein is considered, is being reported.

  3. 3D structure prediction of histone acetyltransferase (HAC proteins of the p300/CBP family and their interactome in Arabidopsis thaliana

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    Amar Cemanovic

    2014-09-01

    Full Text Available Histone acetylation is an important posttranslational modification correlated with gene activation. In Arabidopsis thaliana the histone acetyltransferase (HAC proteins of the CBP family are homologous to animal p300/CREB (cAMP-responsive element-binding proteins, which are important histone acetyltransferases participating in many physiological processes, including proliferation, differentiation, and apoptosis. In this study the 3-D structure of all HAC protein subunits in Arabidopsis thaliana: HAC1, HAC2, HAC4, HAC5 and HAC12 is predicted by homology modeling and confirmed by Ramachandran plot analysis. The amino acid sequences HAC family members are highly similar to the sequences of the homologous human p300/CREB protein. Conservation of p300/CBP domains among the HAC proteins was examined further by sequence alignment and pattern search. The domains of p300/CBP required for the HAC function, such as PHD, TAZ and ZZ domains, are conserved in all HAC proteins. Interactome analysis revealed that HAC1, HAC5 and HAC12 proteins interact with S-adenosylmethionine-dependent methyltransferase domaincontaining protein that shows methyltransferase activity, suggesting an additional function of the HAC proteins. Additionally, HAC5 has a strong interaction value for the putative c-myb-like transcription factor MYB3R-4, which suggests that it also may have a function in regulation of DNA replication.

  4. The histone acetyltransferase domains of CREB-binding protein (CBP) and p300/CBP-associated factor are not necessary for cooperativity with the class II transactivator.

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    Harton, J A; Zika, E; Ting, J P

    2001-10-19

    The class II transactivator (CIITA) is a transcriptional co-activator regulating the constitutive and interferon-gamma-inducible expression of class II major histocompatibility complex (MHC) and related genes. Promoter remodeling occurs following CIITA induction, suggesting the involvement of chromatin remodeling factors. Transcription of numerous genes requires the histone acetyltransferase (HAT) activities of CREB-binding protein (CBP), p300, and/or p300/CBP-associated factor (pCAF). These co-activators cooperate with CIITA and are hypothesized to promote class II major histocompatibility complex transcription through their HAT activity. To directly test this, we used HAT-defective CBP and pCAF. We demonstrate that cooperation between CIITA and CBP is independent of CBP HAT activity. Further, although pCAF enhances CIITA-mediated transcription, pCAF HAT domain dependence appears contingent upon the concentration of available CIITA. When HAT-defective CBP and pCAF are both present, cooperativity with CIITA is maintained. Consistent with a recent report, we show that nuclear localization of CIITA is enhanced by lysine 144, an in vitro target of pCAF-mediated HAT. Yet we find that neither mutation of lysine 144 nor deletion of residues 132-209 affects transcriptional cooperation with CBP or pCAF. Thus, acetylation of this residue may not be the primary mechanism for pCAF/CBP cooperation with CIITA. In conclusion, the HAT activities of the co-activators are not necessary for cooperation with CIITA.

  5. Histone Acetyltransferase p300/CREB-binding Protein-associated Factor (PCAF) Is Required for All-trans-retinoic Acid-induced Granulocytic Differentiation in Leukemia Cells.

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    Sunami, Yoshitaka; Araki, Marito; Kan, Shin; Ito, Akihiro; Hironaka, Yumi; Imai, Misa; Morishita, Soji; Ohsaka, Akimichi; Komatsu, Norio

    2017-02-17

    Differentiation therapy with all-trans-retinoic acid (ATRA) improves the treatment outcome of acute promyelocytic leukemia (APL); however, the molecular mechanism by which ATRA induces granulocytic differentiation remains unclear. We previously reported that the inhibition of the NAD-dependent histone deacetylase (HDAC) SIRT2 induces granulocytic differentiation in leukemia cells, suggesting the involvement of protein acetylation in ATRA-induced leukemia cell differentiation. Herein, we show that p300/CREB-binding protein-associated factor (PCAF), a histone acetyltransferase (HAT), is a prerequisite for ATRA-induced granulocytic differentiation in leukemia cells. We found that PCAF expression was markedly increased in leukemia cell lines (NB4 and HL-60) and primary APL cells during ATRA-induced granulocytic differentiation. Consistent with these results, the expression of PCAF was markedly up-regulated in the bone marrow cells of APL patients who received ATRA-containing chemotherapy. The knockdown of PCAF inhibited ATRA-induced granulocytic differentiation in leukemia cell lines and primary APL cells. Conversely, the overexpression of PCAF induced the expression of the granulocytic differentiation marker CD11b at the mRNA level. Acetylome analysis identified the acetylated proteins after ATRA treatment, and we found that histone H3, a known PCAF acetylation substrate, was preferentially acetylated by the ATRA treatment. Furthermore, we have demonstrated that PCAF is required for the acetylation of histone H3 on the promoter of ATRA target genes, such as CCL2 and FGR, and for the expression of these genes in ATRA-treated leukemia cells. These results strongly support our hypothesis that PCAF is induced and activated by ATRA, and the subsequent acetylation of PCAF substrates promotes granulocytic differentiation in leukemia cells. Targeting PCAF and its downstream acetylation targets could serve as a novel therapeutic strategy to overcome all subtypes of AML. Â

  6. Histone deacetylase inhibitors modulate the transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-a gene: interactive roles of modified histones, histone acetyltransferase, p300, AND Sp1.

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    Kumar, Prerna; Tripathi, Satyabha; Pandey, Kailash N

    2014-03-07

    Atrial natriuretic peptide (ANP) binds guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) and produces the intracellular second messenger, cGMP, which regulates cardiovascular homeostasis. We sought to determine the function of histone deacetylases (HDACs) in regulating Npr1 (coding for GC-A/NPRA) gene transcription, using primary mouse mesangial cells treated with class-specific HDAC inhibitors (HDACi). Trichostatin A, a pan inhibitor, and mocetinostat (MGCD0103), a class I HDAC inhibitor, significantly enhanced Npr1 promoter activity (by 8- and 10-fold, respectively), mRNA levels (4- and 5.3-fold, respectively), and NPRA protein (2.7- and 3.5-fold, respectively). However, MC1568 (class II HDAC inhibitor) had no discernible effect. Overexpression of HDAC1 and HDAC2 significantly attenuated Npr1 promoter activity, whereas HDAC3 and HDAC8 had no effect. HDACi-treated cultured cells in vitro and intact animals in vivo showed significantly reduced binding of HDAC1 and -2 and increased accumulation of acetylated H3-K9/14 and H4-K12 at the Npr1 promoter. Deletional analyses of the Npr1 promoter along with ectopic overexpression and inhibition of Sp1 confirmed that HDACi-induced Npr1 gene transcription is accomplished by Sp1 activation. Furthermore, HDACi attenuated the interaction of Sp1 with HDAC1/2 and promoted Sp1 association with p300 and p300/cAMP-binding protein-associated factor; it also promoted the recruitment of p300 and p300/cAMP-binding protein-associated factor to the Npr1 promoter. Our results demonstrate that trichostatin A and MGCD0103 enhanced Npr1 gene expression through inhibition of HDAC1/2 and increased both acetylation of histones (H3-K9/14, H4-K12) and Sp1 by p300, and their recruitment to Npr1 promoter. Our findings define a novel epigenetic regulatory mechanism that governs Npr1 gene transcription.

  7. Loss of p300 and CBP disrupts histone acetylation at the mouse Sry promoter and causes XY gonadal sex reversal.

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    Carré, Gwenn-Aël; Siggers, Pam; Xipolita, Marilena; Brindle, Paul; Lutz, Beat; Wells, Sara; Greenfield, Andy

    2018-01-01

    CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex determination, the process by which the embryonic gonad develops into a testis or an ovary. By targeting gene ablation to embryonic gonadal somatic cells using an inducible Cre line, we show that gonads lacking either gene exhibit major abnormalities of XY gonad development at 14.5 dpc, including partial sex reversal. Embryos lacking three out of four functional copies of p300/Cbp exhibit complete XY gonadal sex reversal and have greatly reduced expression of the key testis-determining genes Sry and Sox9. An analysis of histone acetylation at the Sry promoter in mutant gonads at 11.5 dpc shows a reduction in levels of the positive histone mark H3K27Ac. Our data suggest a role for CBP/p300 in testis determination mediated by control of histone acetylation at the Sry locus and reveal a novel element in the epigenetic control of Sry and mammalian sex determination. They also suggest possible novel causes of human disorders of sex development (DSD). © The Author 2017. Published by Oxford University Press.

  8. ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation.

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    Clarke, Christopher J; Shamseddine, Achraf A; Jacob, Joseph J; Khalife, Gabrielle; Burns, Tara A; Hannun, Yusuf A

    2016-05-01

    Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. Reactivity of isothiazolones and isothiazolone-1-oxides in the inhibition of the PCAF histone acetyltransferase

    NARCIS (Netherlands)

    Ghizzoni, Massimo; Haisma, Hidde J.; Dekker, Frank J.

    2009-01-01

    Development of small molecule inhibitors of the histone acetyltransferase p300/CBP associated factor (PCAF) is relevant for oncology. The inhibition of the enzyme PCAF and proliferation of the cancer cell line HEP G2 by a series of 5-chloroisothiazolones was compared to a series of

  10. Structure and function of histone acetyltransferase MOF.

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    Chen, Qiao Yi; Costa, Max; Sun, Hong

    2015-01-01

    MOF was first identified in Drosophila melanogaster as an important component of the dosage compensation complex. As a member of MYST family of histone acetyltransferase, MOF specifically deposits the acetyl groups to histone H4 lysine 16. Throughout evolution, MOF and its mammalian ortholog have retained highly conserved substrate specificity and similar enzymatic activities. MOF plays important roles in dosage compensation, ESC self-renewal, DNA damage and repair, cell survival, and gene expression regulation. Dysregulation of MOF has been implicated in tumor formation and progression of many types of human cancers. This review will discuss the structure and activity of mammalian hMOF as well as its function in H4K16 acetylation, DNA damage response, stem cell pluripotency, and carcinogenesis.

  11. ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation[S

    Science.gov (United States)

    Clarke, Christopher J.; Shamseddine, Achraf A.; Jacob, Joseph J.; Khalife, Gabrielle; Burns, Tara A.; Hannun, Yusuf A.

    2016-01-01

    Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels. PMID:27013100

  12. The histone acetyltransferase MOF overexpression blunts cardiac hypertrophy by targeting ROS in mice.

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    Qiao, Weiwei; Zhang, Weili; Gai, Yusheng; Zhao, Lan; Fan, Juexin

    2014-06-13

    Imbalance between histone acetylation/deacetylation critically participates in the expression of hypertrophic fetal genes and development of cardiac hypertrophy. While histone deacetylases play dual roles in hypertrophy, current evidence reveals that histone acetyltransferase such as p300 and PCAF act as pro-hypertrophic factors. However, it remains elusive whether some histone acetyltransferases can prevent the development of hypertrophy. Males absent on the first (MOF) is a histone acetyltransferase belonging to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. Here in this study, we reported that MOF expression was down-regulated in failing human hearts and hypertrophic murine hearts at protein and mRNA levels. To evaluate the roles of MOF in cardiac hypertrophy, we generated cardiac-specific MOF transgenic mice. MOF transgenic mice did not show any differences from their wide-type littermates at baseline. However, cardiac-specific MOF overexpression protected mice from transverse aortic constriction (TAC)-induced cardiac hypertrophy, with reduced radios of heart weight (HW)/body weight (BW), lung weight/BW and HW/tibia length, decreased left ventricular wall thickness and increased fractional shortening. We also observed lower expression of hypertrophic fetal genes in TAC-challenged MOF transgenic mice compared with that of wide-type mice. Mechanically, MOF overexpression increased the expression of Catalase and MnSOD, which blocked TAC-induced ROS and ROS downstream c-Raf-MEK-ERK pathway that promotes hypertrophy. Taken together, our findings identify a novel anti-hypertrophic role of MOF, and MOF is the first reported anti-hypertrophic histone acetyltransferase. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Ras/MAPK signaling modulates VEGFR-3 expression through Ets-mediated p300 recruitment and histone acetylation on the Vegfr3 gene in lymphatic endothelial cells.

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    Taeko Ichise

    Full Text Available Modulation of VEGFR-3 expression is important for altering lymphatic endothelial cell (LEC characteristics during the lymphangiogenic processes that occur under developmental, physiological, and pathological conditions. However, the mechanisms underlying the modulation of Vegfr3 gene expression remain largely unknown. Using genetically engineered mice and LECs, we demonstrated previously that Ras signaling is involved not only in VEGFR-3-induced signal transduction but also in Vegfr3 gene expression. Here, we investigated the roles of the transcription factor Ets and the histone acetyltransferase p300 in LECs in Ras-mediated transcriptional regulation of Vegfr3. Ras activates Ets proteins via MAPK-induced phosphorylation. Ets knockdown, similar to Ras knockdown, resulted in a decrease in both Vegfr3 transcript levels and acetylated histone H3 on the Vegfr3 gene. Vegfr3 knockdown results in altered LEC phenotypes, such as aberrant cell proliferation and network formation, and Ets knockdown led to milder but similar phenotypic changes. We identified evolutionarily conserved, non-coding regulatory elements within the Vegfr3 gene that harbor Ets-binding motifs and have enhancer activities in LECs. Chromatin immunoprecipitation (ChIP assays revealed that acetylated histone H3 on the regulatory elements of the Vegfr3 gene was decreased following Ras and Ets knockdown, and that activated Ets proteins, together with p300, were associated with these regulatory elements, consistent with a reduction in Vegfr3 gene expression in p300-knockdown LECs. Our findings demonstrate a link between Ras signaling and Ets- and p300-mediated transcriptional regulation of Vegfr3, and provide a potential mechanism by which VEGFR-3 expression levels may be modulated during lymphangiogenesis.

  14. Ras/MAPK signaling modulates VEGFR-3 expression through Ets-mediated p300 recruitment and histone acetylation on the Vegfr3 gene in lymphatic endothelial cells.

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    Ichise, Taeko; Yoshida, Nobuaki; Ichise, Hirotake

    2012-01-01

    Modulation of VEGFR-3 expression is important for altering lymphatic endothelial cell (LEC) characteristics during the lymphangiogenic processes that occur under developmental, physiological, and pathological conditions. However, the mechanisms underlying the modulation of Vegfr3 gene expression remain largely unknown. Using genetically engineered mice and LECs, we demonstrated previously that Ras signaling is involved not only in VEGFR-3-induced signal transduction but also in Vegfr3 gene expression. Here, we investigated the roles of the transcription factor Ets and the histone acetyltransferase p300 in LECs in Ras-mediated transcriptional regulation of Vegfr3. Ras activates Ets proteins via MAPK-induced phosphorylation. Ets knockdown, similar to Ras knockdown, resulted in a decrease in both Vegfr3 transcript levels and acetylated histone H3 on the Vegfr3 gene. Vegfr3 knockdown results in altered LEC phenotypes, such as aberrant cell proliferation and network formation, and Ets knockdown led to milder but similar phenotypic changes. We identified evolutionarily conserved, non-coding regulatory elements within the Vegfr3 gene that harbor Ets-binding motifs and have enhancer activities in LECs. Chromatin immunoprecipitation (ChIP) assays revealed that acetylated histone H3 on the regulatory elements of the Vegfr3 gene was decreased following Ras and Ets knockdown, and that activated Ets proteins, together with p300, were associated with these regulatory elements, consistent with a reduction in Vegfr3 gene expression in p300-knockdown LECs. Our findings demonstrate a link between Ras signaling and Ets- and p300-mediated transcriptional regulation of Vegfr3, and provide a potential mechanism by which VEGFR-3 expression levels may be modulated during lymphangiogenesis.

  15. Small molecule inhibitors of histone deacetylases and acetyltransferases as potential therapeutics in oncology

    NARCIS (Netherlands)

    van den Bosch, Thea; Leus, Niek; Timmerman, Tirza; Dekker, Frank J

    2016-01-01

    Uncontrolled cell proliferation and resistance to apoptosis in cancer are, among others, regulated by post-translational modifications of histone proteins. The most investigated type of histone modification is lysine acetylation. Histone acetyltransferases (HATs), acetylate histone lysine residues,

  16. Experimental Approaches Toward Histone Acetyltransferase Inhibitors as Therapeutics

    NARCIS (Netherlands)

    Dekker, Frank; Tollefsbol, Trygve

    2016-01-01

    This chapter comprises the most recent developments with respect to the role of human histone acetyltransferases (HATs) in diseases and the potential therapeutic applications of HAT inhibitors. HATs form a diverse group of mainly nuclear enzymes that play an important role in the acetylation of

  17. Dysregulation of Histone Acetyltransferases and Deacetylases in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yonggang Wang

    2014-01-01

    Full Text Available Cardiovascular disease (CVD remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors which contribute to CVD is required in order to develop more effective treatment options. Dysregulation of epigenetic posttranscriptional modifications of histones in chromatin is thought to be associated with the pathology of many disease models, including CVD. Histone acetyltransferases (HATs and deacetylases (HDACs are regulators of histone lysine acetylation. Recent studies have implicated a fundamental role of reversible protein acetylation in the regulation of CVDs such as hypertension, pulmonary hypertension, diabetic cardiomyopathy, coronary artery disease, arrhythmia, and heart failure. This reversible acetylation is governed by enzymes that HATs add or HDACs remove acetyl groups respectively. New evidence has revealed that histone acetylation regulators blunt cardiovascular and related disease states in certain cellular processes including myocyte hypertrophy, apoptosis, fibrosis, oxidative stress, and inflammation. The accumulating evidence of the detrimental role of histone acetylation in cardiac disease combined with the cardioprotective role of histone acetylation regulators suggests that the use of histone acetylation regulators may serve as a novel approach to treating the millions of patients afflicted by cardiac diseases worldwide.

  18. Histone-modifying enzymes, histone modifications and histone chaperones in nucleosome assembly: Lessons learned from Rtt109 histone acetyltransferases

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    Dahlin, Jayme L; Chen, Xiaoyue; Walters, Michael A.; Zhang, Zhiguo

    2015-01-01

    During DNA replication, nucleosomes ahead of replication forks are disassembled to accommodate replication machinery. Following DNA replication, nucleosomes are then reassembled onto replicated DNA using both parental and newly synthesized histones. This process, termed DNA replication-coupled nucleosome assembly (RCNA), is critical for maintaining genome integrity and for the propagation of epigenetic information, dysfunctions of which have been implicated in cancers and aging. In recent years, it has been shown that RCNA is carefully orchestrated by a series of histone modifications, histone chaperones and histone-modifying enzymes. Interestingly, many features of RCNA are also found in processes involving DNA replication-independent nucleosome assembly like histone exchange and gene transcription. In yeast, histone H3 lysine K56 acetylation (H3K56ac) is found in newly synthesized histone H3 and is critical for proper nucleosome assembly and for maintaining genomic stability. The histone acetyltransferase (HAT) regulator of Ty1 transposition 109 (Rtt109) is the sole enzyme responsible for H3K56ac in yeast. Much research has centered on this particular histone modification and histone-modifying enzyme. This Critical Review summarizes much of our current understanding of nucleosome assembly and highlights many important insights learned from studying Rtt109 HATs in fungi. We highlight some seminal features in nucleosome assembly conserved in mammalian systems and describe some of the lingering questions in the field. Further studying fungal and mammalian chromatin assembly may have important public health implications, including deeper understandings of human cancers and aging as well as the pursuit of novel anti-fungal therapies. PMID:25365782

  19. The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis.

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    Su, Jiaming; Wang, Fei; Cai, Yong; Jin, Jingji

    2016-01-14

    Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways.

  20. The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis

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    Jiaming Su

    2016-01-01

    Full Text Available Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60 family of histone acetyltransferases (HATs. As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16; however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8, suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways.

  1. Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative

    NARCIS (Netherlands)

    Ghizzoni, Massimo; Boltjes, Andre; de Graaf, Chris; Haisma, Hidde J.; Dekker, Frank J.

    2010-01-01

    Several lines of evidence indicate that histone acetyltransferases (HATs) are novel drug targets for treatment of diseases like, for example, cancer and inflammation. The natural product anacardic acid is a starting point for development of small molecule inhibitors of the histone acetyltransferase

  2. Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

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    Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Mee-Hee [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Lee, Yoo-Hyun [Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do (Korea, Republic of); Lee, Jeongmin [Department of Medical Nutrition, Kyung Hee University, Kyunggi-do (Korea, Republic of); Jun, Woojin [Department of Food and Nutrition, Chonnam National University, Gwangju (Korea, Republic of); Kim, Sunoh, E-mail: sunoh@korea.ac.kr [Jeollanamdo Institute of Natural Resources Research, Jeonnam (Korea, Republic of); Yoon, Ho-Geun, E-mail: yhgeun@yuhs.ac [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2011-07-08

    Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.

  3. Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

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    Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

    2011-01-01

    Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting


  4. A 6-alkylsalicylate histone acetyltransferase inhibitor inhibits histone acetylation and pro-inflammatory gene expression in murine precision-cut lung slices

    NARCIS (Netherlands)

    Bosch, van den Thea; Leus, Niek G J; Wapenaar, Hannah; Boichenko, Alexander; Hermans, Jos; Bischoff, Rainer; Haisma, Hidde J; Dekker, Frank J

    Lysine acetylations are post-translational modifications of cellular proteins, that are crucial in the regulation of many cellular processes. Lysine acetylations on histone proteins are part of the epigenetic code regulating gene transcription and are installed by histone acetyltransferases.

  5. Chromatin accessibility, p300, and histone acetylation define PML-RARα and AML1-ETO binding sites in acute myeloid leukemia.

    Science.gov (United States)

    Saeed, Sadia; Logie, Colin; Francoijs, Kees-Jan; FrigĂš, Gianmaria; Romanenghi, Mauro; Nielsen, Fiona G; Raats, Lianne; Shahhoseini, Maryam; Huynen, Martijn; Altucci, Lucia; Minucci, Saverio; Martens, Joost H A; Stunnenberg, Hendrik G

    2012-10-11

    Chromatin accessibility plays a key role in regulating cell type specific gene expression during hematopoiesis but has also been suggested to be aberrantly regulated during leukemogenesis. To understand the leukemogenic chromatin signature, we analyzed acute promyelocytic leukemia, a subtype of leukemia characterized by the expression of RARα-fusion proteins, such as PML-RARα. We used nuclease accessibility sequencing in cell lines as well as patient blasts to identify accessible DNA elements and identified > 100 000 accessible regions in each case. Using ChIP-seq, we identified H2A.Z as a histone modification generally associated with these accessible regions, whereas unsupervised clustering analysis of other chromatin features, including DNA methylation, H2A.Zac, H3ac, H3K9me3, H3K27me3, and the regulatory factor p300, distinguished 6 distinct clusters of accessible sites, each with a characteristic functional makeup. Of these, PML-RARα binding was found specifically at accessible chromatin regions characterized by p300 binding and hypoacetylated histones. Identifying regions with a similar epigenetic make up in t(8;21) acute myeloid leukemia (AML) cells, another subtype of AMLs, revealed that these regions are occupied by the oncofusion protein AML1-ETO. Together, our results suggest that oncofusion proteins localize to accessible regions and that chromatin accessibility together with p300 binding and histone acetylation characterize AML1-ETO and PML-RARα binding sites.

  6. Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75

    Energy Technology Data Exchange (ETDEWEB)

    Berndsen, Christopher E; Tsubota, Toshiaki; Lindner, Scott E; Lee, Susan; Holton, James M; Kaufman, Paul D; Keck, James L; Denu, John M [UMASS, MED; (UCB); (UW-MED)

    2010-01-12

    Histone acetylation and nucleosome remodeling regulate DNA damage repair, replication and transcription. Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones. In vitro analysis of Rtt109 revealed that Vps75, a Nap1 family histone chaperone, could also stimulate Rtt109-dependent acetylation of H3K56. However, the molecular function of the Rtt109-Vps75 complex remains elusive. Here we have probed the molecular functions of Vps75 and the Rtt109-Vps75 complex through biochemical, structural and genetic means. We find that Vps75 stimulates the kcat of histone acetylation by {approx}100-fold relative to Rtt109 alone and enhances acetylation of K9 in the H3 histone tail. Consistent with the in vitro evidence, cells lacking Vps75 showed a substantial reduction (60%) in H3K9 acetylation during S phase. X-ray structural, biochemical and genetic analyses of Vps75 indicate a unique, structurally dynamic Nap1-like fold that suggests a potential mechanism of Vps75-dependent activation of Rtt109. Together, these data provide evidence for a multifunctional HAT-chaperone complex that acetylates histone H3 and deposits H3-H4 onto DNA, linking histone modification and nucleosome assembly.

  7. Three-dimensional collagen I promotes gemcitabine resistance in vitro in pancreatic cancer cells through HMGA2-dependent histone acetyltransferase expression.

    Directory of Open Access Journals (Sweden)

    Surabhi Dangi-Garimella

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells are resistant to gemcitabine chemotherapy in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2. We have now found that human PDAC tumors display higher levels of histone H3K9 and H3K27 acetylation in fibrotic regions. We show that relative to cells grown on tissue culture plastic, PDAC cells grown in three-dimensional collagen gels demonstrate increased histone H3K9 and H3K27 acetylation, along with increased expression of p300, PCAF and GCN5 histone acetyltransferases (HATs. Knocking down HMGA2 attenuates the effect of collagen on histone H3K9 and H3K27 acetylation and on collagen-induced p300, PCAF and GCN5 expression. We also show that human PDAC tumors with HMGA2 demonstrate increased histone H3K9 and H3K27 acetylation. Additionally, we show that cells in three-dimensional collagen gels demonstrate increased protection against gemcitabine. Significantly, down-regulation of HMGA2 or p300, PCAF and GCN5 HATs sensitizes the cells to gemcitabine in three-dimensional collagen. Overall, our results increase our understanding of how the collagen microenvironment contributes to chemo-resistance in vitro and identify HATs as potential therapeutic targets against this deadly cancer.

  8. p300/CBP Histone Acetyltransferase Activity Is Required for Newly Acquired and Reactivated Fear Memories in the Lateral Amygdala

    Science.gov (United States)

    Maddox, Stephanie A.; Watts, Casey S.; Schafe, Glenn E.

    2013-01-01

    Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation.


  9. Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.

    Science.gov (United States)

    Valerio, Daria G; Xu, Haiming; Eisold, Meghan E; Woolthuis, Carolien M; Pandita, Tej K; Armstrong, Scott A

    2017-01-05

    K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. © 2017 by The American Society of Hematology.

  10. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    DEFF Research Database (Denmark)

    Lasko, Loren M; Jakob, Clarissa G; Edalji, Rohinton P

    2017-01-01

    , selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage...... also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent...... model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases....

  11. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.

    Science.gov (United States)

    Lasko, Loren M; Jakob, Clarissa G; Edalji, Rohinton P; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L; Hansen, T Matt; Risi, Roberto M; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G; Martin, Ruth L; Torrent, Maricel; Chiang, Gary G; Karukurichi, Kannan; Langston, J William; Weinert, Brian T; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A; Rosenberg, Saul H; Michaelides, Michael R; Lai, Albert; Bromberg, Kenneth D

    2017-10-05

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

  12. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L.; Hansen, T. Matt; Risi, Roberto M.; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T.; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G.; Martin, Ruth L.; Torrent, Maricel; Chiang, Gary G.; Karukurichi, Kannan; Langston, J. William; Weinert, Brian T.; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H.; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A.; Rosenberg, Saul H.; Michaelides, Michael R.; Lai, Albert; Bromberg, Kenneth D.

    2017-09-27

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4, bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

  13. Basic nuclear processes affected by histone acetyltransferases and histone deacetylase inhibitors

    NARCIS (Netherlands)

    Legartovå, Soƈa; Stixovå, Lenka; Strnad, Hynek; Kozubek, Stanislav; Martinet, Nadine; Dekker, Frank J; Franek, Michal; Bårtovå, Eva

    AIM: The optimal balance between histone acetylation and deacetylation is important for proper gene function. Therefore, we addressed how inhibitors of histone-modifying enzymes can modulate nuclear events, including replication, transcription, splicing and DNA repair. MATERIALS & METHODS: Changes

  14. Revealing the Protein Propionylation Activity of the Histone Acetyltransferase Males absent on the first (MOF).

    Science.gov (United States)

    Han, Zhen; Wu, Hong; Kim, Sunjoo; Yang, Xiangkun; Li, Qianjin; Huang, He; Cai, Houjian; Bartlett, Michael G; Dong, Aiping; Zeng, Hong; Brown, Peter J; Yang, Xiangjiao; Arrowsmith, Cheryl H; Zhao, Yingming; Zheng, Y George

    2018-01-10

    Short-chain acylation of lysine residues recently emerges as a group of reversible posttranslational modifications in mammalian cells. The diversity of acylation further broadens the landscape and complexity of the proteome. Identification of regulatory enzymes and effector proteins for lysine acylation is critical to understand functions of these novel modifications at the molecular level. Here, we report that the MYST family of lysine acetyltransferases (KATs) possesses strong propionyltransferase activity both in vitro and in cellulo. Particularly, the propionyltransferase activity of MOF, MOZ, and HBO1 is as strong as their acetyltransferase activity. Overexpression of MOF in human embryonic kidney 293T cells induced significantly increased propionylation in multiple histone and non-histone proteins, which manifests that the function of MOF goes far beyond its canonical histone H4 lysine-16 acetylation. We also resolved the X-ray co-crystal structure of MOF bound with propionyl coenzyme A, which provides a direct structural basis for the propionyltransferase activity of the MYST KATs. Our data together defines a novel function for the MYST KATs as lysine propionyltransferases and suggests much broader physiological impacts for this family of enzymes. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

    Directory of Open Access Journals (Sweden)

    Greenblatt Jack F

    2007-09-01

    Full Text Available Abstract Background Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4. Results Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC. While mutational inactivation of the histone acetyltransferase (HAT gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2 exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork. Conclusion We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p. The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

  16. A barcode screen for epigenetic regulators reveals a role for the NuB4/HAT-B histone acetyltransferase complex in histone turnover.

    Directory of Open Access Journals (Sweden)

    Kitty F Verzijlbergen

    2011-10-01

    Full Text Available Dynamic modification of histone proteins plays a key role in regulating gene expression. However, histones themselves can also be dynamic, which potentially affects the stability of histone modifications. To determine the molecular mechanisms of histone turnover, we developed a parallel screening method for epigenetic regulators by analyzing chromatin states on DNA barcodes. Histone turnover was quantified by employing a genetic pulse-chase technique called RITE, which was combined with chromatin immunoprecipitation and high-throughput sequencing. In this screen, the NuB4/HAT-B complex, containing the conserved type B histone acetyltransferase Hat1, was found to promote histone turnover. Unexpectedly, the three members of this complex could be functionally separated from each other as well as from the known interacting factor and histone chaperone Asf1. Thus, systematic and direct interrogation of chromatin structure on DNA barcodes can lead to the discovery of genes and pathways involved in chromatin modification and dynamics.

  17. Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Yong

    2013-02-01

    Full Text Available Abstract Background MYST1 (also known as hMOF, a member of the MYST family of histone acetyltransferases (HATs as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC. Simultaneously, we investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC biomarker carbohydrase IX (CA9 in RCC. Materials and methods The frozen RCC tissues and RCC cell lines as materials, the reverse transcription polymerase chain reaction (RT-PCR, western blotting and immunohistochemical staining approaches were used. Results RT-PCR results indicate that hMOF gene expression levels frequently downregulated in 90.5% of patients (19/21 with RCC. The reduction of hMOF protein in both RCC tissues and RCC cell lines is tightly correlated with acetylation of histone H4K16. In addition, overexpression of CA9 was detected in 100% of ccRCC patients (21/21. However, transient transfection of hMOF in ccRCC 786–0 cells did not affect both the gene and protein expression of CA9. Conclusion hMOF as an acetyltransferase of H4K16 might be involved in the pathogenesis of kidney cancer, and this epigenetic changes might be a new CA9-independent RCC diagnostic maker.

  18. Ubiquitination of Notch1 is regulated by MAML1-mediated p300 acetylation of Notch1

    Energy Technology Data Exchange (ETDEWEB)

    Popko-Scibor, Anita E.; Lindberg, Mikael J.; Hansson, Magnus L.; Holmlund, Teresa [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Wallberg, Annika E., E-mail: Annika.Wallberg@ki.se [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer p300 acetylates conserved lysines within Notch1 C-terminal nuclear localization signal. Black-Right-Pointing-Pointer MAML1 and CSL, components of Notch transcription complex, increase Notch acetylation. Black-Right-Pointing-Pointer MAML1-dependent acetylation of Notch1 by p300 decreases the ubiquitination of Notch1. Black-Right-Pointing-Pointer CDK8 inhibits Notch acetylation and Notch transcription enhanced by p300. -- Abstract: Earlier studies demonstrated the involvement of the p300 histone acetyltransferase in Notch signaling but the precise mechanisms by which p300 might modulate Notch function remains to be investigated. In this study, we show that p300 acetylates Notch1 ICD in cell culture assay and in vitro, and conserved lysines located within the Notch C-terminal nuclear localization signal are essential for Notch acetylation. MAML1 and CSL, which are components of the Notch transcription complex, enhance Notch acetylation and we suggest that MAML1 increases Notch acetylation by potentiating p300 autoacetylation. Furthermore, MAML1-dependent acetylation of Notch1 ICD by p300 decreases the ubiquitination of Notch1 ICD in cellular assays. CDK8 has been shown to target Notch1 for ubiquitination and proteosomal degradation. We show that CDK8 inhibits Notch acetylation and Notch transcription enhanced by p300. Therefore, we speculate that acetylation of Notch1 might be a mechanism to regulate Notch activity by interfering with ubiquitin-dependent pathways.

  19. The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice

    Science.gov (United States)

    Brenachot, Xavier; Rigault, Caroline; Nédélec, Emmanuelle; LaderriÚre, Amélie; Khanam, Tasneem; Gouazé, Alexandra; Chaudy, Sylvie; Lemoine, Aleth; Datiche, Frédérique; Gascuel, Jean; Pénicaud, Luc; Benani, Alexandre

    2014-01-01

    Overfeeding causes rapid synaptic remodeling in hypothalamus feeding circuits. Polysialylation of cell surface molecules is a key step in this neuronal rewiring and allows normalization of food intake. Here we examined the role of hypothalamic polysialylation in the long-term maintenance of body weight, and deciphered the molecular sequence underlying its nutritional regulation. We found that upon high fat diet (HFD), reduced hypothalamic polysialylation exacerbated the diet-induced obese phenotype in mice. Upon HFD, the histone acetyltransferase MOF was rapidly recruited on the St8sia4 polysialyltransferase-encoding gene. Mof silencing in the mediobasal hypothalamus of adult mice prevented activation of the St8sia4 gene transcription, reduced polysialylation, altered the acute homeostatic feeding response to HFD and increased the body weight gain. These findings indicate that impaired hypothalamic polysialylation contribute to the development of obesity, and establish a role for MOF in the brain control of energy balance. PMID:25161885

  20. An old HAT in human p300/CBP and yeast Rtt109.

    Science.gov (United States)

    Bazan, J Fernando

    2008-06-15

    The crystal structure of the human p300 histone acetyltransferase (HAT) domain reveals a familiar alpha + beta fold with unique structural elaborations that merit its classification as a third divergent HAT branch alongside the GCN5-related N-acetyltransferase (GNAT) and MYST (MOZ, Ybf2/Sas3, Sas2, Tip60) families. Two key departures from the core GNAT/MYST HAT fold--a long unstructured chain (or "flap") overlaying the acetyl-CoA (AcCoA) binding groove, and a four-alpha-helix "tower" excursion from the main beta-sheet--critically contribute to the recognition and presumptive catalytic machinery of p300/CBP HAT enzymes. Kinetic and mutant analysis of this enlarged residue constellation in p300 (which is distinct from functional fingerprints drawn from GNAT or MYST complexes) led Liu et al., to suggest that p300/CBP works with an unorthodox "hit and run" mechanism that enlists Tyr1467 as the critical catalytic residue. In order to extend the evolutionary testbed for this variant HAT mechanism beyond the thin roll of p300/CBP orthologs, I propose that Rtt109, a novel yeast HAT that has so far eluded classification, is the prototype of a fungal clan of p300-related enzymes that preserve the embellished HAT fold, but further diversify its catalytic options.

  1. 15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} impairs the functions of histone acetyltransferases through their insolubilization in cells

    Energy Technology Data Exchange (ETDEWEB)

    Hironaka, Asako [Department of Biochemistry, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521 (Japan); Morisugi, Toshiaki; Kawakami, Tetsuji [Department of Oral and Maxillofacial Surgery, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521 (Japan); Miyagi, Ikuko [Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215 (Japan); Tanaka, Yasuharu, E-mail: yatanaka@med.u-ryukyu.ac.jp [Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215 (Japan)

    2009-12-11

    The cyclopentenonic prostaglandin 15-deoxy-{Delta}{sup 12,14}-PG J{sub 2} (15d-PGJ{sub 2}) is a metabolite derived from PGD{sub 2}. Although 15d-PGJ{sub 2} has been demonstrated to be a potent ligand for peroxisome proliferator activated receptor {gamma} (PPAR{gamma}), the functions are not fully understood. In order to examine the effect of 15d-PGJ{sub 2} on histone acetyltransferases (HATs), several lines of cell including mouse embryonic fibroblast (MEF) cells were exposed to 15d-PGJ{sub 2}. Three types of HAT, p300, CREB-binding protein (CBP), and p300/CBP-associated factor (PCAF), selectively disappeared from the soluble fraction in time- and dose-dependent manners. Inversely, HATs in the insoluble fraction increased, suggesting their conformational changes. The decrease in the soluble form of HATs resulted in the attenuation of NF-{kappa}B-, p53-, and heat shock factor-dependent reporter gene expressions, implying that the insoluble HATs are inactive. The resultant insoluble PCAF and p300 seemed to be digested by proteasome, because proteasome inhibitors caused the accumulation of insoluble HATs. Taken together, these results indicate that 15d-PGJ{sub 2} attenuates some gene expressions that require HATs. This inhibitory action of 15d-PGJ{sub 2} on the function of HATs was independent of PPAR{gamma}, because PPAR{gamma} agonists could not mimick 15d-PGJ{sub 2} and PPAR{gamma} antagonists did not inhibit 15d-PGJ{sub 2}.

  2. The Histone Acetyltransferase MOF Promotes Induces Generation of Pluripotent Stem Cells.

    Science.gov (United States)

    Mu, Xupeng; Yan, Shaohua; Fu, Changhao; Wei, Anhui

    2015-08-01

    Histone modification plays an important role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). The histone acetyltransferase MOF is a key regulator of ESCs; however, the role of MOF in the process of reprogramming back to induced pluripotent stem cells (iPSCs) remains unclear. In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming. Most importantly, overexpression of MOF improves reprogramming efficiency and facilitates the formation of iPSCs, whereas small hairpin RNA (shRNA)-mediated knockdown of MOF impairs iPSCs generation during reprogramming. Further investigation reveals that MOF interacts with the H3K4 methyltransferase Wdr5 to promote endogenous Oct4 expression during the reprogramming process. Knockdown of MOF reduces H4K16ac and H3K4me3 modification at the Oct4 promoter. In conclusion, our data indicate that MOF is an important epigenetic regulator that is critical for efficient reprogramming.

  3. Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

    Directory of Open Access Journals (Sweden)

    JĂșlia T. Novaes

    2017-10-01

    Full Text Available Tetrahydrocurcumin (THC, curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa. Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC activity, histone acetyltransferase (HAT activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

  4. Garcinol, a Histone Acetyltransferase Inhibitor, Radiosensitizes Cancer Cells by Inhibiting Non-Homologous End Joining

    Energy Technology Data Exchange (ETDEWEB)

    Oike, Takahiro [Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma (Japan); Ogiwara, Hideaki [Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Torikai, Kohta [Gunma University Heavy Ion Medical Center, Maebashi, Gunma (Japan); Nakano, Takashi [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma (Japan); Yokota, Jun [Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Kohno, Takashi, E-mail: tkkohno@ncc.go.jp [Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan)

    2012-11-01

    Purpose: Non-homologous end joining (NHEJ), a major pathway used to repair DNA double-strand breaks (DSBs) generated by ionizing radiation (IR), requires chromatin remodeling at DSB sites through the acetylation of histones by histone acetyltransferases (HATs). However, the effect of compounds with HAT inhibitory activities on the DNA damage response (DDR), including the NHEJ and cell cycle checkpoint, as well as on the radiosensitivity of cancer cells, remains largely unclear. Here, we investigated whether garcinol, a HAT inhibitor found in the rinds of Garcinia indica fruit (called mangosteens), has effects on DDR, and whether it can be used for radiosensitization. Methods and Materials: The following assays were used to examine the effect of garcinol on the inhibition of DSB repair, including the following: a conventional neutral comet assay; a cell-based assay recently developed by us, in which NHEJ repair of DSBs on chromosomal DNA was evaluated; the micrococcal nuclease sensitivity assay; and immunoblotting for autophosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We assessed the effect of garcinol on the cell cycle checkpoint after IR treatment by analyzing the phosphorylation levels of checkpoint kinases CHK1 and CHK2 and histone H3, and by cell cycle profile analysis using flow cytometry. The radiosensitizing effect of garcinol was assessed by a clonogenic survival assay, whereas its effects on apoptosis and senescence were examined by annexin V and senescence-associated {beta}-galactosidase (SA-{beta}-Gal) staining, respectively. Results: We found that garcinol inhibits DSB repair, including NHEJ, without affecting cell cycle checkpoint. Garcinol radiosensitized A549 lung and HeLa cervical carcinoma cells with dose enhancement ratios (at 10% surviving fraction) of 1.6 and 1.5, respectively. Cellular senescence induced by IR was enhanced by garcinol. Conclusion: These results suggest that garcinol is a radiosensitizer that

  5. The SAGA Histone Acetyltransferase Complex Regulates Leucine Uptake through the Agp3 Permease in Fission Yeast*

    Science.gov (United States)

    Takahashi, Hidekazu; Sun, Xiaoying; Hamamoto, Makiko; Yashiroda, Yoko; Yoshida, Minoru

    2012-01-01

    Metabolic responses of unicellular organisms are mostly acute, transient, and cell-autonomous. Regulation of nutrient uptake in yeast is one such rapid response. High quality nitrogen sources such as NH4+ inhibit uptake of poor nitrogen sources, such as amino acids. Both transcriptional and posttranscriptional mechanisms operate in nutrient uptake regulation; however, many components of this system remain uncharacterized in the fission yeast, Schizosaccharomyces pombe. Here, we demonstrate that the Spt-Ada-Gcn acetyltransferase (SAGA) complex modulates leucine uptake. Initially, we noticed that a branched-chain amino acid auxotroph exhibits a peculiar adaptive growth phenotype on solid minimal media containing certain nitrogen sources. In fact, the growth of many auxotrophic strains is inhibited by excess NH4Cl, possibly through nitrogen-mediated uptake inhibition of the corresponding nutrients. Surprisingly, DNA microarray analysis revealed that the transcriptional reprogramming during the adaptation of the branched-chain amino acid auxotroph was highly correlated with reprogramming observed in deletions of the SAGA histone acetyltransferase module genes. Deletion of gcn5+ increased leucine uptake in the prototrophic background and rendered the leucine auxotroph resistant to NH4Cl. Deletion of tra1+ caused the opposite phenotypes. The increase in leucine uptake in the gcn5Δ mutant was dependent on an amino acid permease gene, SPCC965.11c+. The closest budding yeast homolog of this permease is a relatively nonspecific amino acid permease AGP3, which functions in poor nutrient conditions. Our analysis identified the regulation of nutrient uptake as a physiological function for the SAGA complex, providing a potential link between cellular metabolism and chromatin regulation. PMID:22992726

  6. Targeting histone-acetyltransferase Tat-interactive protein 60 inhibits intestinal allergy.

    Science.gov (United States)

    Yang, G; Cheng, B-H; Yang, S-B; Liu, Z-Q; Qiu, S-Q; Yang, L-T; Xie, R-D; Geng, X-R; Li, M-G; Gao, L; Liu, Z-G; Yang, P-C

    2018-02-01

    The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone-acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body. This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy. The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE-mediated allergic inflammation. High levels of Tip60 were observed in the peripheral B cells of patients with FA. Tat-interactive protein 60 (Tip60) was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6), and nuclear factor-ÎșB at the locus of IΔ promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa. Tat-interactive protein 60 (Tip60) plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti-allergy drug. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  7. The MYST histone acetyltransferases are essential for gametophyte development in Arabidopsis

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    Zhou Dao-Xiu

    2008-11-01

    Full Text Available Abstract Background Histone acetyltransferases (HATs play critical roles in the regulation of chromatin structure and gene expression. Arabidopsis genome contains 12 HAT genes, but the biological functions of many of them are still unknown. In this work, we studied the evolutionary relationship and cellular functions of the two Arabidopsis HAT genes homologous to the MYST family members. Results An extensive phylogenetic analysis of 105 MYST proteins revealed that they can be divided into 5 classes, each of which contains a specific combination of protein modules. The two Arabidopsis MYST proteins, HAM1 and HAM2, belong to a "green clade", clearly separated from other families of HATs. Using a reverse genetic approach, we show that HAM1 and HAM2 are a functionally redundant pair of genes, as single Arabidopsis ham1 and ham2 mutants displayed a wild-type phenotype, while no double mutant seedling could be recovered. Genetic analysis and cytological study revealed that ham1ham2 double mutation induced severe defects in the formation of male and female gametophyte, resulting in an arrest of mitotic cell cycle at early stages of gametogenesis. RT-PCR experiments and the analysis of transgenic plants expressing the GUS reporter gene under the HAM1 or the HAM2 promoter showed that both genes displayed an overlapping expression pattern, mainly in growing organs such as shoots and flower buds. Conclusion The work presented here reveals novel properties for MYST HATs in Arabidopsis. In addition to providing an evolutionary relationship of this large protein family, we show the evidence of a link between MYST and gamete formation as previously suggested in mammalian cells. A possible function of the Arabidopsis MYST protein-mediated histone acetylation during cell division is suggested.

  8. Epigenetic Regulation of Axonal Growth of Drosophila Pacemaker Cells by Histone Acetyltransferase Tip60 Controls Sleep

    Science.gov (United States)

    Pirooznia, Sheila K.; Chiu, Kellie; Chan, May T.; Zimmerman, John E.; Elefant, Felice

    2012-01-01

    Tip60 is a histone acetyltransferase (HAT) enzyme that epigenetically regulates genes enriched for neuronal functions through interaction with the amyloid precursor protein (APP) intracellular domain. However, whether Tip60-mediated epigenetic dysregulation affects specific neuronal processes in vivo and contributes to neurodegeneration remains unclear. Here, we show that Tip60 HAT activity mediates axonal growth of the Drosophila pacemaker cells, termed “small ventrolateral neurons” (sLNvs), and their production of the neuropeptide pigment-dispersing factor (PDF) that functions to stabilize Drosophila sleep–wake cycles. Using genetic approaches, we show that loss of Tip60 HAT activity in the presence of the Alzheimer’s disease-associated APP affects PDF expression and causes retraction of the sLNv synaptic arbor required for presynaptic release of PDF. Functional consequence of these effects is evidenced by disruption of the sleep–wake cycle in these flies. Notably, overexpression of Tip60 in conjunction with APP rescues these sleep–wake disturbances by inducing overelaboration of the sLNv synaptic terminals and increasing PDF levels, supporting a neuroprotective role for dTip60 in sLNv growth and function under APP-induced neurodegenerative conditions. Our findings reveal a novel mechanism for Tip60 mediated sleep–wake regulation via control of axonal growth and PDF levels within the sLNv-encompassing neural network and provide insight into epigenetic-based regulation of sleep disturbances observed in neurodegenerative diseases like Alzheimer’s disease. PMID:22982579

  9. The Histone Acetyltransferase MOF is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network

    Science.gov (United States)

    Li, Xiangzhi; Li, Li; Pandey, Ruchi; Byun, Jung S.; Gardner, Kevin; Qin, Zhaohui; Dou, Yali

    2012-01-01

    SUMMARY Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining and differentiation potential. They also have aberrant expression of core transcription factors Nanog, Oct4 and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP sequencing and transcriptome analyses further demonstrate that Mof is an integral component of ESC core transcription network and Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3 K4 methylation at key regulatory loci, highlighting complexity and interconnectivity of various chromatin regulators in ESCs. PMID:22862943

  10. Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation.

    Science.gov (United States)

    Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

    2016-02-01

    Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms. © 2016 Merschbaecher et al.; Published by Cold Spring Harbor Laboratory Press.

  11. The Candida albicans Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways.

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    Michael Tscherner

    2015-10-01

    Full Text Available Human fungal pathogens like Candida albicans respond to host immune surveillance by rapidly adapting their transcriptional programs. Chromatin assembly factors are involved in the regulation of stress genes by modulating the histone density at these loci. Here, we report a novel role for the chromatin assembly-associated histone acetyltransferase complex NuB4 in regulating oxidative stress resistance, antifungal drug tolerance and virulence in C. albicans. Strikingly, depletion of the NuB4 catalytic subunit, the histone acetyltransferase Hat1, markedly increases resistance to oxidative stress and tolerance to azole antifungals. Hydrogen peroxide resistance in cells lacking Hat1 results from higher induction rates of oxidative stress gene expression, accompanied by reduced histone density as well as subsequent increased RNA polymerase recruitment. Furthermore, hat1Δ/Δ cells, despite showing growth defects in vitro, display reduced susceptibility to reactive oxygen-mediated killing by innate immune cells. Thus, clearance from infected mice is delayed although cells lacking Hat1 are severely compromised in killing the host. Interestingly, increased oxidative stress resistance and azole tolerance are phenocopied by the loss of histone chaperone complexes CAF-1 and HIR, respectively, suggesting a central role for NuB4 in the delivery of histones destined for chromatin assembly via distinct pathways. Remarkably, the oxidative stress phenotype of hat1Δ/Δ cells is a species-specific trait only found in C. albicans and members of the CTG clade. The reduced azole susceptibility appears to be conserved in a wider range of fungi. Thus, our work demonstrates how highly conserved chromatin assembly pathways can acquire new functions in pathogenic fungi during coevolution with the host.

  12. Asynchronous P300 BCI

    DEFF Research Database (Denmark)

    Panicker, Rajesh; Puthusserypady, Sadasivan; Sun, Ying

    2010-01-01

    An asynchronous hybrid brain-computer interface (BCI) system combining the P300 and steady-state visually evoked potentials (SSVEP) paradigms is introduced. A P300 base system is used for information transfer, and is augmented to include SSVEP for control state detection. The proposed system has...

  13. Histone acetyl transferases CBP and p300 are necessary for maintenance of renin cell identity and transformation of smooth muscle cells to the renin phenotype

    Science.gov (United States)

    Pentz, Ellen Steward; Cordaillat, Magali; Carretero, Oscar A.; Tucker, Ana E.; Sequeira Lopez, Maria Luisa S.

    2012-01-01

    In response to a homeostatic threat circulating renin increases by increasing the number of cells expressing renin by dedifferentiation and re-expression of renin in arteriolar smooth muscle cells (aSMCs) that descended from cells that expressed renin in early life. However, the mechanisms that govern the maintenance and reacquisition of the renin phenotype are not well understood. The cAMP pathway is important for renin synthesis and release: the transcriptional effects are mediated by binding of cAMP responsive element binding protein with its co-activators, CBP and p300, to the cAMP response element in the renin promoter. We have shown previously that mice with conditional deletion of CBP and p300 (cKO) in renin cells had severely reduced renin expression in adult life. In this study we investigated when the loss of renin-expressing cells in the cKO occurred and found that the loss of renin expression becomes evident after differentiation of the kidney is completed during postnatal life. To determine whether CBP/p300 is necessary for re-expression of renin we subjected cKO mice to low sodium diet + captopril to induce retransformation of aSMCs to the renin phenotype. The cKO mice did not increase circulating renin, their renin mRNA and protein expression were greatly diminished compared with controls, and only a few aSMCs re-expressed renin. These studies underline the crucial importance of the CREB/CBP/p300 complex for the ability of renin cells to retain their cellular memory and regain renin expression, a fundamental survival mechanism, in response to a threat to homeostasis. PMID:22523253

  14. Histone Acetyltransferase Activity of MOF Is Required forMLL-AF9Leukemogenesis.

    Science.gov (United States)

    Valerio, Daria G; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J; Huang, Chun-Hao; Lujambio, Amaia; Zheng, YuJun George; Zuber, Johannes; Pandita, Tej K; Lowe, Scott W; Armstrong, Scott A

    2017-04-01

    Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9 -driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof -deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9 -driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL -rearranged leukemias. Cancer Res; 77(7); 1753-62. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. HIV-1 Resistance to Dolutegravir Is Affected by Cellular Histone Acetyltransferase Activity.

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    Anstett, Kaitlin; Brenner, Bluma; MesplĂšde, Thibault; Wainberg, Mark A

    2017-11-01

    Integrase strand transfer inhibitors (INSTIs) are the newest class of antiretrovirals to be approved for the treatment of HIV infection. Canonical resistance to these competitive inhibitors develops through substitutions in the integrase active site that disrupt drug-protein interactions. However, resistance against the newest integrase inhibitor, dolutegravir (DTG), is associated with an R263K substitution at the C terminus of integrase that causes resistance through an unknown mechanism. The integrase C-terminal domain is involved in many processes over the course of infection and is posttranslationally modified via acetylation of three lysine residues that are important for enzyme activity, integrase multimerization, and protein-protein interactions. Here we report that regulation of the acetylation of integrase is integral to the replication of HIV in the presence of DTG and that the R263K mutation specifically disrupts this regulation, likely due to enhancement of interactions with the histone deacetylase I complex, as suggested by coimmunoprecipitation assays. Although no detectable differences in the levels of cell-free acetylation of the wild-type (WT) and mutated R263K enzymes were observed, the inhibition of cellular histone acetyltransferase enzymes sensitized the NL4.3WT virus to DTG, while NL4.3R263K was almost completely unaffected. When levels of endogenous acetylation were manipulated in virus-producing cells, inhibitors of acetylation enhanced the replication of NL4.3R263K, whereas inhibition of deacetylation greatly diminished the replication of NL4.3WT Taken together, these results point to a pivotal role of acetylation in the resistance mechanism of HIV to some second-generation integrase strand transfer inhibitors, such as DTG.IMPORTANCE This is, to our knowledge, the first report of the influence of posttranslational modifications on HIV drug resistance. Both viral replication and resistance to second-generation integrase strand transfer

  16. Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase in Saccharomyces cerevisiae.

    Science.gov (United States)

    Martin, Benjamin J E; McBurney, Kristina L; Maltby, Vicki E; Jensen, Kristoffer N; Brind'Amour, Julie; Howe, LeAnn J

    2017-03-01

    Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatin-modifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. In Saccharomyces cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14; which in vitro bind to H3K4 methylation, H3K36 methylation, and acetylated and crotonylated H3K9, respectively. While the in vitro binding has been well characterized, the relative in vivo contributions of these histone PTMs in targeting NuA3 is unknown. Here, through genome-wide colocalization and by mutational interrogation, we demonstrate that the PHD finger of Yng1, and the PWWP domain of Pdp3 independently target NuA3 to H3K4 and H3K36 methylated chromatin, respectively. In contrast, we find no evidence to support the YEATS domain of Taf14 functioning in NuA3 recruitment. Collectively our results suggest that the presence of multiple histone PTM binding domains within NuA3, rather than restricting it to nucleosomes containing distinct combinations of histone PTMs, can serve to increase the range of nucleosomes bound by the complex. Interestingly, however, the simple presence of NuA3 is insufficient to ensure acetylation of the associated nucleosomes, suggesting a secondary level of acetylation regulation that does not involve control of HAT-nucleosome interactions. Copyright © 2017 by the Genetics Society of America.

  17. Metabolic regulation of histone acetyltransferases by endogenous Acyl-CoA cofactors | Center for Cancer Research

    Science.gov (United States)

    Unraveling the metabolic regulation of lysine acetyltransferases (KATs). Montgomery et al. detail the application of a competitive chemoproteomic strategy to quantitatively characterize the interactions of acyl-CoA metabolites with cellular KAT enzymes.

  18. Widespread colocalization of the Drosophila histone acetyltransferase homolog MYST5 with DREF and insulator proteins at active genes.

    Science.gov (United States)

    Heseding, Christiane; Saumweber, Harald; Rathke, Christina; Ehrenhofer-Murray, Ann E

    2017-02-01

    MYST family histone acetyltransferases play important roles in gene regulation. Here, we have characterized the Drosophila MYST histone acetyltransferase (HAT) encoded by cg1894, whose closest homolog is Drosophila MOF, and which we have termed MYST5. We found it localized to a large number of interbands as well as to the telomeres of polytene chromosomes, and it showed strong colocalization with the interband protein Z4/Putzig and RNA polymerase II. Accordingly, genome-wide location analysis by ChIP-seq showed co-occurrence of MYST5 with the Z4-interacting partner Chriz/Chromator. Interestingly, MYST5 bound to the promoter of actively transcribed genes, and about half of MYST5 sites colocalized with the transcription factor DNA replication-related element-binding factor (DREF), indicating a role for MYST5 in gene expression. Moreover, we observed substantial overlap of MYST5 binding with that of the insulator proteins CP190, dCTCF, and BEAF-32, which mediate the organization of the genome into functionally distinct topological domains. Altogether, our data suggest a broad role for MYST5 both in gene-specific transcriptional regulation and in the organization of the genome into chromatin domains, with the two roles possibly being functionally interconnected.

  19. MicroRNA-20a constrains p300-driven myocardial angiogenic transcription by direct targeting of p300.

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    Lina A Shehadeh

    Full Text Available To characterize downstream effectors of p300 acetyltransferase in the myocardium.Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known.Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17∌92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17∌92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3'UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts.p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a.

  20. Histone acetyltransferases are crucial regulators in NF-kappa B mediated inflammation

    NARCIS (Netherlands)

    Ghizzoni, Massimo; Haisma, Hidde J.; Maarsingh, Harm; Dekker, Frank J.

    Post-translational modifications of proteins, such as acetylation, are important regulatory events in eukaryotic cells. Reversible acetylations of histones and non-histone proteins regulate gene expression and protein activity. Acetylation levels of proteins are regulated by a dynamic equilibrium

  1. The UmGcn5 gene encoding histone acetyltransferase from Ustilago maydis is involved in dimorphism and virulence.

    Science.gov (United States)

    Gonzålez-Prieto, Juan Manuel; Rosas-Quijano, Raymundo; Domínguez, Angel; Ruiz-Herrera, José

    2014-10-01

    We isolated a gene encoding a histone acetyltransferase from Ustilago maydis (DC.) Cda., which is orthologous to the Saccharomyces cerevisiae GCN5 gene. The gene was isolated from genomic clones identified by their specific hybridization to a gene fragment obtained by the polymerase chain reaction (PCR). This gene (Umgcn5; um05168) contains an open reading frame (ORF) of 1421bp that encodes a putative protein of 473 amino acids with a Mr. of 52.6kDa. The protein exhibits a high degree of homology with histone acetyltransferases from different organisms. Null a2b2 ΔUmgcn5 mutants were constructed by substitution of the region encoding the catalytic site with a hygromycin B resistance cassette. Null a1b1 ΔUmgcn5 mutants were isolated from genetic crosses of a2b2 ΔUmgcn5 and a1b1 wild-type strains in maize. Mutants displayed a slight reduction in growth rate under different conditions, and were more sensitive than the wild type to stress conditions, but more important, they grew as long mycelial cells, and formed fuzz-like colonies under all conditions where wild-type strains grew in the yeast-like morphology and formed smooth colonies. This phenotype was not reverted by cAMP addition. Mutants were not virulent to maize plants, and were unable to form teliospores. These phenotypic alterations of the mutants were reverted by their transformation with the wild-type gene. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila

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    Belikoff Esther J

    2010-11-01

    Full Text Available Abstract Background In male Drosophila melanogaster, the male specific lethal (MSL complex is somehow responsible for a two-fold increase in transcription of most X-linked genes, which are enriched for histone H4 acetylated at lysine 16 (H4K16ac. This acetylation requires MOF, a histone acetyltransferase that is a component of the MSL complex. MOF also associates with the non-specific lethal or NSL complex. The MSL complex is bound within active genes on the male X chromosome with a 3' bias. In contrast, the NSL complex is enriched at promoter regions of many autosomal and X-linked genes in both sexes. In this study we have investigated the role of MOF as a transcriptional activator. Results MOF was fused to the DNA binding domain of Gal4 and targeted to the promoter region of UAS-reporter genes in Drosophila. We found that expression of a UAS-red fluorescent protein (DsRed reporter gene was strongly induced by Gal4-MOF. However, DsRed RNA levels were about seven times higher in female than male larvae. Immunostaining of polytene chromosomes showed that Gal4-MOF co-localized with MSL1 to many sites on the X chromosome in male but not female nuclei. However, in female nuclei that express MSL2, Gal4-MOF co-localized with MSL1 to many sites on polytene chromosomes but DsRed expression was reduced. Mutation of conserved active site residues in MOF (Glu714 and Cys680 reduced HAT activity in vitro and UAS-DsRed activation in Drosophila. In the presence of Gal4-MOF, H4K16ac levels were enriched over UAS-lacZ and UAS-arm-lacZ reporter genes. The latter utilizes the constitutive promoter from the arm gene to drive lacZ expression. In contrast to the strong induction of UAS-DsRed expression, UAS-arm-lacZ expression increased by about 2-fold in both sexes. Conclusions Targeting MOF to reporter genes led to transcription enhancement and acetylation of histone H4 at lysine 16. Histone acetyltransferase activity was required for the full transcriptional

  3. Absence of Rtt109p, a fungal-specific histone acetyltransferase, results in improved acetic acid tolerance of Saccharomyces cerevisiae.

    Science.gov (United States)

    Cheng, Cheng; Zhao, Xinqing; Zhang, Mingming; Bai, Fengwu

    2016-03-01

    RTT109 is a histone acetyltransferase for the acetylation of histone H3. It is still not clear whether RTT109 plays a role in regulation of gene expression under environmental stresses. In this study, the involvement of RTT109 in acetic acid stress tolerance of Saccharomyces cerevisiae was investigated. It was revealed that the absence of RTT109 enhanced resistance to 5.5 g L(-1) acetic acid, which was indicated by improved growth of RTT109Δ mutant compared with that of the wild-type BY4741 strain. Meanwhile, the lag phase was shortened for 48 h and glucose consumption completed 36 h in advance for RTT109Δ mutant compared to the wild-type strain, with ethanol production rate increased from 0.39 to 0.60 g L(-1) h(-1). Significantly, elevated transcription levels of HSP12, CTT1 and GSH1, as well as increased activities of antioxidant enzymes were observed in RTT109Δ under acetic acid stress. Improved flocculation of RTT109Δ compared to that of the control strain BY4741 under the acetic acid stress was also observed. These results suggest that the absence of RTT109 not only activates transcription of stress responsive genes, but also improves resistance to oxidative stress, which ultimately contributes to improved acetic acid tolerance in S. cerevisiae. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. A naturally-occurring histone acetyltransferase inhibitor derived from Garcinia indica impairs newly acquired and reactivated fear memories.

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    Stephanie A Maddox

    Full Text Available The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD. Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica, to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.

  5. Elongator subunit 3 positively regulates plant immunity through its histone acetyltransferase and radical S-adenosylmethionine domains

    Science.gov (United States)

    2013-01-01

    Background Pathogen infection triggers a large-scale transcriptional reprogramming in plants, and the speed of this reprogramming affects the outcome of the infection. Our understanding of this process has significantly benefited from mutants that display either delayed or accelerated defense gene induction. In our previous work we demonstrated that the Arabidopsis Elongator complex subunit 2 (AtELP2) plays an important role in both basal immunity and effector-triggered immunity (ETI), and more recently showed that AtELP2 is involved in dynamic changes in histone acetylation and DNA methylation at several defense genes. However, the function of other Elongator subunits in plant immunity has not been characterized. Results In the same genetic screen used to identify Atelp2, we found another Elongator mutant, Atelp3-10, which mimics Atelp2 in that it exhibits a delay in defense gene induction following salicylic acid treatment or pathogen infection. Similarly to AtELP2, AtELP3 is required for basal immunity and ETI, but not for systemic acquired resistance (SAR). Furthermore, we demonstrate that both the histone acetyltransferase and radical S-adenosylmethionine domains of AtELP3 are essential for its function in plant immunity. Conclusion Our results indicate that the entire Elongator complex is involved in basal immunity and ETI, but not in SAR, and support that Elongator may play a role in facilitating the transcriptional induction of defense genes through alterations to their chromatin. PMID:23856002

  6. p300-mediated acetylation of TRF2 is required for maintaining functional telomeres.

    Science.gov (United States)

    Her, Yoon Ra; Chung, In Kwon

    2013-02-01

    The human telomeric protein TRF2 is required to protect chromosome ends by facilitating their organization into the protective capping structure. Post-translational modifications of TRF2 such as phosphorylation, ubiquitination, SUMOylation, methylation and poly(ADP-ribosyl)ation have been shown to play important roles in telomere function. Here we show that TRF2 specifically interacts with the histone acetyltransferase p300, and that p300 acetylates the lysine residue at position 293 of TRF2. We also report that p300-mediated acetylation stabilizes the TRF2 protein by inhibiting its ubiquitin-dependent proteolysis and is required for efficient telomere binding of TRF2. Furthermore, overexpression of the acetylation-deficient mutant, K293R, induces DNA-damage response foci at telomeres, thereby leading to induction of impaired cell growth, cellular senescence and altered cell cycle distribution. A small but significant number of metaphase chromosomes show no telomeric signals at chromatid ends, suggesting an aberrant telomere structure. These findings demonstrate that acetylation of TRF2 by p300 plays a crucial role in the maintenance of functional telomeres as well as in the regulation of the telomere-associated DNA-damage response, thus providing a new route for modulating telomere protection function.

  7. Structure and Histone Binding Properties of the Vps75-Rtt109 Chaperone-Lysine Acetyltransferase Complex

    Energy Technology Data Exchange (ETDEWEB)

    Su, Dan; Hu, Qi; Zhou, Hui; Thompson, James R.; Xu, Rui-Ming; Zhang, Zhiguo; Mer, Georges (Mayo); (Chinese Aca. Sci.)

    2011-11-02

    The histone chaperone Vps75 presents the remarkable property of stimulating the Rtt109-dependent acetylation of several histone H3 lysine residues within (H3-H4){sub 2} tetramers. To investigate this activation mechanism, we determined x-ray structures of full-length Vps75 in complex with full-length Rtt109 in two crystal forms. Both structures show similar asymmetric assemblies of a Vps75 dimer bound to an Rtt109 monomer. In the Vps75-Rtt109 complexes, the catalytic site of Rtt109 is confined to an enclosed space that can accommodate the N-terminal tail of histone H3 in (H3-H4){sub 2}. Investigation of Vps75-Rtt109-(H3-H4)2 and Vps75-(H3-H4)2 complexes by NMR spectroscopy-probed hydrogen/deuterium exchange suggests that Vps75 guides histone H3 in the catalytic enclosure. These findings clarify the basis for the enhanced acetylation of histone H3 tail residues by Vps75-Rtt109.

  8. KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing Genomic Loss in Small Cell Lung Cancer.

    Science.gov (United States)

    SimĂł-Riudalbas, Laia; PĂ©rez-Salvia, Montserrat; Setien, Fernando; Villanueva, Alberto; Moutinho, Catia; MartĂ­nez-CardĂșs, Anna; Moran, Sebastian; Berdasco, Maria; Gomez, Antonio; Vidal, Enrique; Soler, Marta; Heyn, Holger; Vaquero, Alejandro; de la Torre, Carolina; BarcelĂł-Batllori, Silvia; Vidal, August; Roz, Luca; Pastorino, Ugo; Szakszon, Katalin; Borck, Guntram; Moura, Conceição S; Carneiro, FĂĄtima; Zondervan, Ilse; Savola, Suvi; Iwakawa, Reika; Kohno, Takashi; Yokota, Jun; Esteller, Manel

    2015-09-15

    Recent efforts to sequence human cancer genomes have highlighted that point mutations in genes involved in the epigenetic setting occur in tumor cells. Small cell lung cancer (SCLC) is an aggressive tumor with poor prognosis, where little is known about the genetic events related to its development. Herein, we have identified the presence of homozygous deletions of the candidate histone acetyltransferase KAT6B, and the loss of the corresponding transcript, in SCLC cell lines and primary tumors. Furthermore, we show, in vitro and in vivo, that the depletion of KAT6B expression enhances cancer growth, while its restoration induces tumor suppressor-like features. Most importantly, we demonstrate that KAT6B exerts its tumor-inhibitory role through a newly defined type of histone H3 Lys23 acetyltransferase activity. ©2015 American Association for Cancer Research.

  9. The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells.

    Science.gov (United States)

    McConnell, Kristopher H; Dixon, Michael; Calvi, Brian R

    2012-10-01

    DNA replication origin activity changes during development. Chromatin modifications are known to influence the genomic location of origins and the time during S phase that they initiate replication in different cells. However, how chromatin regulates origins in concert with cell differentiation remains poorly understood. Here, we use developmental gene amplification in Drosophila ovarian follicle cells as a model to investigate how chromatin modifiers regulate origins in a developmental context. We find that the histone acetyltransferase (HAT) Chameau (Chm) binds to amplicon origins and is partially required for their function. Depletion of Chm had relatively mild effects on origins during gene amplification and genomic replication compared with previous knockdown of its ortholog HBO1 in human cells, which has severe effects on origin function. We show that another HAT, CBP (Nejire), also binds amplicon origins and is partially required for amplification. Knockdown of Chm and CBP together had a more severe effect on nucleosome acetylation and amplicon origin activity than knockdown of either HAT alone, suggesting that these HATs collaborate in origin regulation. In addition to their local function at the origin, we show that Chm and CBP also globally regulate the developmental transition of follicle cells into the amplification stages of oogenesis. Our results reveal a complexity of origin epigenetic regulation by multiple HATs during development and suggest that chromatin modifiers are a nexus that integrates differentiation and DNA replication programs.

  10. Inhibition of PCAF Histone Acetyltransferase, Cytotoxicity and Cell Permeability of 2-Acylamino-1-(3- or 4-Carboxy-phenylbenzamides

    Directory of Open Access Journals (Sweden)

    Eunsook Ma

    2012-11-01

    Full Text Available Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenylbenzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 ÎŒM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B assay against seven human cancer cell lines: HT-29 (colon, HCT-116 (colon, MDA-231 (breast, A549 (lung, Hep3B (hepatoma, HeLa (cervical and Caki (kidney and one normal cell line (HSF. Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC50: 29.17 ÎŒM, human lung cancer (A549, IC50: 32.09 ÎŒM cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC50: 35.49 ÎŒM and HCT 116, IC50: 27.56 ÎŒM, human lung cancer (A549, IC50: 30.69 ÎŒM, and human cervical cancer (HeLa, IC50: 34.41 ÎŒM cell lines. The apparent permeability coefficient (Papp, cm/s values of two compounds (16 and 17 were evaluated as 68.21 and 71.48 × 10−6 cm/s by Caco-2 cell permeability assay.

  11. Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome

    Science.gov (United States)

    Steunou, Anne-Lise; Cramet, Myriam; Rossetto, Dorine; Aristizabal, Maria J.; Lacoste, Nicolas; Drouin, Simon; CÎté, Valérie; Paquet, Eric; Utley, Rhea T.; Krogan, Nevan; Robert, François; Kobor, Michael S.

    2016-01-01

    Recognition of histone marks by reader modules is thought to be at the heart of epigenetic mechanisms. These protein domains are considered to function by targeting regulators to chromosomal loci carrying specific histone modifications. This is important for proper gene regulation as well as propagation of epigenetic information. The NuA4 acetyltransferase complex contains two of these reader modules, an H3K4me3-specific plant homeodomain (PHD) within the Yng2 subunit and an H3K36me2/3-specific chromodomain in the Eaf3 subunit. While each domain showed a close functional interaction with the respective histone mark that it recognizes, at the biochemical level, genetic level (as assessed with epistatic miniarray profile screens), and phenotypic level, cells with the combined loss of both readers showed greatly enhanced phenotypes. Chromatin immunoprecipitation coupled with next-generation sequencing experiments demonstrated that the Yng2 PHD specifically directs H4 acetylation near the transcription start site of highly expressed genes, while Eaf3 is important downstream on the body of the genes. Strikingly, the recruitment of the NuA4 complex to these loci was not significantly affected. Furthermore, RNA polymerase II occupancy was decreased only under conditions where both PHD and chromodomains were lost, generally in the second half of the gene coding regions. Altogether, these results argue that methylated histone reader modules in NuA4 are not responsible for its recruitment to the promoter or coding regions but, rather, are required to orient its acetyltransferase catalytic site to the methylated histone 3-bearing nucleosomes in the surrounding chromatin, cooperating to allow proper transition from transcription initiation to elongation. PMID:27550811

  12. Phosphorylation of p300 by ATM controls the stability of NBS1

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Eun Ryoung [Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); Choi, Jae Duk [Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); School of Biological Sciences, Seoul National University, Seoul 151 (Korea, Republic of); Jeong, Gajin [School of Biological Sciences, Seoul National University, Seoul 151 (Korea, Republic of); Lee, Jong-Soo, E-mail: jsjlee@mail.ajou.ac.kr [Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 443-749 (Korea, Republic of)

    2010-07-09

    Acetyltransferase, p300 is a transcriptional cofactor of signal-responsive transcriptional regulation. The surveillance kinase ataxia-telangiectasia mutated (ATM) plays a central role in regulation of a wide range of cellular DNA damage responses. Here, we investigated whether and how ATM mediates phosphorylation of p300 in response to DNA damage and how p300 phosphorylation is functionally linked to DNA damage. ATM-phosphorylated p300 in vitro and in vivo, in response to DNA damage. Phosphorylation of p300 proteins was observed upon {gamma}-irradiation in ATM{sup +} cells but not ATM{sup -} cells. Importantly, expression of nonphosphorylatable serine to alanine form of p300 (S106A) destabilized both p300 and NBS1 proteins, after DNA damage. These data demonstrate that ATM transduces a DNA damage signal to p300, and that ATM-dependent phosphorylation of p300 is required for stabilization of NBS1 proteins in response to DNA damage.

  13. Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice

    Science.gov (United States)

    Bricambert, Julien; Miranda, Jonatan; Benhamed, Fadila; Girard, Jean; Postic, Catherine; Dentin, Renaud

    2010-01-01

    Obesity and type 2 diabetes are associated with increased lipogenesis in the liver. This results in fat accumulation in hepatocytes, a condition known as hepatic steatosis, which is a form of nonalcoholic fatty liver disease (NAFLD), the most common cause of liver dysfunction in the United States. Carbohydrate-responsive element–binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, has emerged as a major player in the development of hepatic steatosis in mice. However, the molecular mechanisms enhancing its transcriptional activity remain largely unknown. In this study, we have identified the histone acetyltransferase (HAT) coactivator p300 and serine/threonine kinase salt-inducible kinase 2 (SIK2) as key upstream regulators of ChREBP activity. In cultured mouse hepatocytes, we showed that glucose-activated p300 acetylated ChREBP on Lys672 and increased its transcriptional activity by enhancing its recruitment to its target gene promoters. SIK2 inhibited p300 HAT activity by direct phosphorylation on Ser89, which in turn decreased ChREBP-mediated lipogenesis in hepatocytes and mice overexpressing SIK2. Moreover, both liver-specific SIK2 knockdown and p300 overexpression resulted in hepatic steatosis, insulin resistance, and inflammation, phenotypes reversed by SIK2/p300 co-overexpression. Finally, in mouse models of type 2 diabetes and obesity, low SIK2 activity was associated with increased p300 HAT activity, ChREBP hyperacetylation, and hepatic steatosis. Our findings suggest that inhibition of hepatic p300 activity may be beneficial for treating hepatic steatosis in obesity and type 2 diabetes and identify SIK2 activators and specific p300 inhibitors as potential targets for pharmaceutical intervention. PMID:21084751

  14. The chromodomain-containing histone acetyltransferase TIP60 acts as a code reader, recognizing the epigenetic codes for initiating transcription.

    Science.gov (United States)

    Kim, Chul-Hong; Kim, Jung-Woong; Jang, Sang-Min; An, Joo-Hee; Seo, Sang-Beom; Choi, Kyung-Hee

    2015-01-01

    TIP60 can act as a transcriptional activator or a repressor depending on the cellular context. However, little is known about the role of the chromodomain in the functional regulation of TIP60. In this study, we found that TIP60 interacted with H3K4me3 in response to TNF-α signaling. TIP60 bound to H3K4me3 at the promoters of the NF-ÎșB target genes IL6 and IL8. Unlike the wild-type protein, a TIP60 chromodomain mutant did not localize to chromatin regions. Because TIP60 binds to histones with specific modifications and transcriptional regulators, we used a histone peptide assay to identify histone codes recognized by TIP60. TIP60 preferentially interacted with methylated or acetylated histone H3 and H4 peptides. Phosphorylation near a lysine residue significantly reduced the affinity of TIP60 for the modified histone peptides. Our findings suggest that TIP60 acts as a functional link between the histone code and transcriptional regulators.

  15. The Histone Acetyltransferase Gcn5 Regulates ncRNA-ICR1 and FLO11 Expression during Pseudohyphal Development in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Long-Chi Wang

    2015-01-01

    Full Text Available Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5 in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT. In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development.

  16. The Histone Acetyltransferase Gcn5 Regulates ncRNA-ICR1 and FLO11 Expression during Pseudohyphal Development in Saccharomyces cerevisiae.

    Science.gov (United States)

    Wang, Long-Chi; Montalvo-Munoz, Fernando; Tsai, Yuan-Chan; Liang, Chung-Yi; Chang, Chun-Chuan; Lo, Wan-Sheng

    2015-01-01

    Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5) in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT). In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development.

  17. P 300 EVENT RELATED POTENTIAL IN DEPRESSION

    OpenAIRE

    Singh, R; Shukla, R.; Dalal, P. K.; Sinha, P.K.; Trivedi, J.K.

    2000-01-01

    P300 component of the event related potential (ERP) provides one neurophysiological index of cognitive dysfunction in depression. Forty subjects fulfilling DSM-III criteria for depression were compared to 40 age and sex matched normal controls. The P300 was recorded using the auditory odd-ball paradigm. Depressives had a significantly prolonged P300 latency and reduced P300 amplitude as compared to the controls. The P300 latency showed a significant positive correlation with age of the patien...

  18. Genetic interaction between mutations in c-Myb and the KIX domains of CBP and p300 affects multiple blood cell lineages and influences both gene activation and repression.

    Directory of Open Access Journals (Sweden)

    Lawryn H Kasper

    Full Text Available Adult blood cell production or definitive hematopoiesis requires the transcription factor c-Myb. The closely related KAT3 histone acetyltransferases CBP (CREBBP and p300 (EP300 bind c-Myb through their KIX domains and mice homozygous for a p300 KIX domain mutation exhibit multiple blood defects. Perplexingly, mice homozygous for the same KIX domain mutation in CBP have normal blood. Here we test the hypothesis that the CBP KIX domain contributes subordinately to hematopoiesis via a genetic interaction with c-Myb. We assessed hematopoiesis in mice bearing compound mutations of c-Myb and/or the KIX domains of CBP and p300, and measured the effect of KIX domain mutations on c-Myb-dependent gene expression. We found that in the context of a p300 KIX mutation, the CBP KIX domain mutation affects platelets, B cells, T cells, and red cells. Gene interaction (epistasis analysis provides mechanistic evidence that blood defects in KIX mutant mice are consistent with reduced c-Myb and KIX interaction. Lastly, we demonstrated that the CBP and p300 KIX domains contribute to both c-Myb-dependent gene activation and repression. Together these results suggest that the KIX domains of CBP, and especially p300, are principal mediators of c-Myb-dependent gene activation and repression that is required for definitive hematopoiesis.

  19. Genetic Interaction between Mutations in c-Myb and the KIX Domains of CBP and p300 Affects Multiple Blood Cell Lineages and Influences Both Gene Activation and Repression

    Science.gov (United States)

    Kasper, Lawryn H.; Fukuyama, Tomofusa; Lerach, Stephanie; Chang, Yunchao; Xu, Wu; Wu, Song; Boyd, Kelli L.; Brindle, Paul K.

    2013-01-01

    Adult blood cell production or definitive hematopoiesis requires the transcription factor c-Myb. The closely related KAT3 histone acetyltransferases CBP (CREBBP) and p300 (EP300) bind c-Myb through their KIX domains and mice homozygous for a p300 KIX domain mutation exhibit multiple blood defects. Perplexingly, mice homozygous for the same KIX domain mutation in CBP have normal blood. Here we test the hypothesis that the CBP KIX domain contributes subordinately to hematopoiesis via a genetic interaction with c-Myb. We assessed hematopoiesis in mice bearing compound mutations of c-Myb and/or the KIX domains of CBP and p300, and measured the effect of KIX domain mutations on c-Myb-dependent gene expression. We found that in the context of a p300 KIX mutation, the CBP KIX domain mutation affects platelets, B cells, T cells, and red cells. Gene interaction (epistasis) analysis provides mechanistic evidence that blood defects in KIX mutant mice are consistent with reduced c-Myb and KIX interaction. Lastly, we demonstrated that the CBP and p300 KIX domains contribute to both c-Myb-dependent gene activation and repression. Together these results suggest that the KIX domains of CBP, and especially p300, are principal mediators of c-Myb-dependent gene activation and repression that is required for definitive hematopoiesis. PMID:24340053

  20. The Histone Acetyltransferase GCN5 Expression Is Elevated and Regulated by c-Myc and E2F1 Transcription Factors in Human Colon Cancer

    Science.gov (United States)

    Yin, Yan-Wei; Jin, Hong-Jian; Zhao, Wenjing; Gao, Beixue; Fang, Jiangao; Wei, Junmin; Zhang, Donna D.; Zhang, Jianing; Fang, Deyu

    2017-01-01

    The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy. PMID:26637399

  1. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    Directory of Open Access Journals (Sweden)

    Xiang Yuan

    2017-11-01

    Full Text Available Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC. We further define the molecular circuits that govern these processes by showing that SET modulated DOCK7/RAC1 and cofilin signaling events. Moreover, a detailed analysis of the spatial distribution of RAC1 and cofilin allowed us to decipher the synergistical contributions of the two in coordinating the advancing dynamics by measuring architectures, polarities, and cytoskeletal organizations of the lamellipodia leading edges. In further investigations in vivo, we identified their unique role at multiple levels of the invasive cascade for SET cell and indicate the necessity for their functional balance to enable efficient invasion as well. Additionally, SET epigenetically repressed miR-30c expression by deacetylating histones H2B and H4 on its promoter, which was functionally important for the biological effects of SET in our cell-context. Finally, we corroborated our findings in vivo by evaluating the clinical relevance of SET signaling in the metastatic burden in mice and a large series of patients with ESCC at diagnosis, observing it's significance in predicting metastasis formation. Our findings uncovered a novel signaling network initiated by SET that epigenetically modulated ESCC properties and suggest that targeting the regulatory axis might be a promising strategy to inhibit migration and metastasis.

  2. P300 and Probability in Children.

    Science.gov (United States)

    Ladish, Christine; Polich, John

    1989-01-01

    Investigated the relationship between P300 or P3 event-related brain potential and cognitive development by assessing contributions of short-term memory to changes in component amplitude and latency in 5- to 14-year-old children. Results suggested that cognitive development is indexed by decreases in P300 latency. (SAK)

  3. Alexithymia and the brain potential P300

    NARCIS (Netherlands)

    Bermond, B.; Righart, R.; Ridderinkhof, K.R.; Moormann, P.P.

    2008-01-01

    Background: The P300 is an event-related potential occurring at about 300 ms post-stimulus. The P300 covaries in amplitude with the perceived significance of the stimulus as well as with its emotional valence. Alexithymia refers to severe reductions in the cognitive as well as affective components

  4. Enhancer of Acetyltransferase Chameau (EAChm) Is a Novel Transcriptional Co-Activator

    OpenAIRE

    Takeya Nakagawa; Tsuyoshi Ikehara; Masamichi Doiguchi; Yuko Imamura; Miki Higashi; Mitsuhiro Yoneda; Takashi Ito

    2015-01-01

    Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT) plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm) famil...

  5. Reduced Histone H3 Acetylation in CD4+ T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults

    Directory of Open Access Journals (Sweden)

    Xi-yu Liu

    2015-01-01

    Full Text Available Aims. Latent autoimmune diabetes in adults (LADA is the result of gene-environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4+ T lymphocytes from LADA patients. Methods. Blood CD4+ T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP and histone deacetylases (HDAC1, HDAC2, and HDAC7 was measured by real-time polymerase chain reaction (RT-PCR. Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients’ CD4+ T lymphocytes (P<0.05. Global level of H4 acetylation was not statistically different. Among LADA, CD4+ T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated. Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4+ T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications.

  6. P300 Latency and Memory Span Development.

    Science.gov (United States)

    Howard, Lawrence; Polich, John

    1985-01-01

    Digit span and latency from P300 component of event-related brain potential--a measure of stimulus evaluation time--were obtained from children and adults. Increases in digit span were associated with decreases in peak latency for children but not adults, suggesting that immediate memory development is tightly coupled with decreases in speed of


  7. In vitro targeting reveals intrinsic histone tail specificity of the Sin3/histone deacetylase and N-CoR/SMRT corepressor complexes.

    NARCIS (Netherlands)

    Vermeulen, M.; Carrozza, MJ; Lasonder, E.; Workman, JL; Logie, C.; Stunnenberg, H.G.

    2004-01-01

    The histone code is among others established via differential acetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). To unambiguously determine the histone tail specificity of HDAC-containing complexes, we have established an in vitro system consisting of

  8. IkappaB kinase alpha-mediated derepression of SMRT potentiates acetylation of RelA/p65 by p300.

    Science.gov (United States)

    Hoberg, Jamie E; Popko, Anita E; Ramsey, Catherine S; Mayo, Marty W

    2006-01-01

    Over the last several years, significant progress has been made in identifying chromatin-regulated events that govern NF-kappaB transcription. Using either laminin attachment or tumor necrosis factor alpha as a physiological stimulus of NF-kappaB activation, we demonstrate that IkappaB kinase alpha (IKKalpha) is recruited to chromatin in distinct phases. In the initial phase, IKKalpha is responsible for derepressing the silencing mediator for retinoic acid and thyroid hormone receptor (SMRT)-histone deacetylase 3 (HDAC3) corepressor complex from the p50 homodimer. However, in the latter phase, chromatin-bound IKKalpha coordinates the simultaneous phosphorylation of RelA/p65(S536) and SMRT(S2410) as detected by chromatin immunoprecipitation (ChIP) assays. Although phosphorylated SMRT remains bound to the active p50-RelA/p65 heterodimer of NF-kappaB, derepression of SMRT is evidenced by the loss of chromatin-associated HDAC3 activity. ChIP and re-ChIP analysis demonstrates that phosphorylation of RelA/p65(S536) and SMRT(S2410) occurs prior to acetylation of RelA/p65 at K310. Moreover, IKKalpha-induced phosphorylation of RelA/p65(S536) displaces corepressor activity, allowing p300-mediated acetylation of RelA/p65. Introduction of nonphosphorylatable mutants of RelA/p65 and SMRT proteins or the inhibition of IKK activity results in active repression of NF-kappaB promoters by tethering the SMRT-HDAC3 complex. Similar to phosphorylation within the Rel homology domain of RelA/p65, which governs an exchange of HDAC1 for CBP/p300 acetyltransferases, we demonstrate that phosphorylation within the transactivation domain of RelA/p65(S536) displaces SMRT-HDAC3 repressor activity, allowing p300 to acetylate RelA/p65.

  9. Empathy, Motivation, and P300 BCI performance

    Directory of Open Access Journals (Sweden)

    Sonja C Kleih

    2013-10-01

    Full Text Available Motivation moderately influences Brain-Computer Interface (BCI performance in healthy subjects when monetary reward is used to manipulate extrinsic motivation. However, the motivation to use a BCI of severely paralyzed patients, who are potentially in need for BCI, could mainly be internal and thus, an intrinsic motivator may be more powerful. Also healthy subjects who participate in BCI studies could be intrinsically motivated as they may wish to contribute to research and thus extrinsic motivation by monetary reward would be less important than the content of the study. In this respect, motivation could be defined as motivation-to-help. The aim of this study was to investigate, whether subjects with high motivation for helping and who are highly empathic would perform better with a BCI controlled by event-related potentials (P300-BCI. We included N=20 healthy young participants naĂŻve to BCI and grouped them according to their motivation for participating in a BCI study in a low and highly motivated group. Motivation was further manipulated with interesting or boring presentations about BCI and the possibility to help patients. Motivation for helping did neither influence BCI performance nor the P300 amplitude. Post-hoc, subjects were re-grouped according to their ability for perspective taking. We found significantly higher P300 amplitudes on parietal electrodes in participants with a low ability for perspective taking and therefore, lower empathy, as compared to participants with higher empathy. The lack of an effect of motivation on BCI performance contradicts previous findings and thus, requires further investigation. We speculate that subjects with higher empathy were less able to focus attention on the BCI task. Good perspective takers with regards to patients in potential need of BCI, may be more emotionally involved and therefore, less able to allocate attention on the BCI task at hand.

  10. The MYST Domain Acetyltransferase Chameau Functions in Epigenetic Mechanisms of Transcriptional Repression

    National Research Council Canada - National Science Library

    Grienenberger, Aurélie; Miotto, Benoit; Sagnier, Thierry; Cavalli, Giacomo; Schramke, Vera; Geli, Vincent; Mariol, Marie-Christine; Berenger, Hélene; Graba, Yacine; Pradel, Jacques

    2002-01-01

    .... While modification by histone acetyltransferase (HAT) is usually linked to transcriptional activation, we provide here evidence for HAT function in several types of epigenetic repression. Chameau (Chm...

  11. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    Science.gov (United States)

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  12. Cognitive and biological determinants of P300: An integrative review.

    NARCIS (Netherlands)

    Kok, A.; Polich, J.

    1995-01-01

    Describes and evaluates the P300 component's biological determinants in normal Ss by using the concept of arousal as an explanatory mechanism. First, the methodological and theoretical background of the P300 is sketched, with the issues surrounding its neurophysiological origins and functional

  13. Promoter-bound p300 complexes facilitate post-mitotic transmission of transcriptional memory.

    Science.gov (United States)

    Wong, Madeline M; Byun, Jung S; Sacta, Maria; Jin, Qihuang; Baek, SongJoon; Gardner, Kevin

    2014-01-01

    A central hallmark of epigenetic inheritance is the parental transmission of changes in patterns of gene expression to progeny without modification of DNA sequence. Although, the trans-generational conveyance of this molecular memory has been traditionally linked to covalent modification of histone and/or DNA, recent studies suggest a role for proteins that persist or remain bound within chromatin to "bookmark" specific loci for enhanced or potentiated responses in daughter cells immediately following cell division. In this report we describe a role for p300 in enabling gene bookmarking by pre-initiation complexes (PICs) containing RNA polymerase II (pol II), Mediator and TBP. Once formed these complexes require p300 to enable reacquisition of protein complex assemblies, chromatin modifications and long range chromatin interactions that facilitate post-mitotic transmission of transcriptional memory of prior environmental stimuli.

  14. Promoter-bound p300 complexes facilitate post-mitotic transmission of transcriptional memory.

    Directory of Open Access Journals (Sweden)

    Madeline M Wong

    Full Text Available A central hallmark of epigenetic inheritance is the parental transmission of changes in patterns of gene expression to progeny without modification of DNA sequence. Although, the trans-generational conveyance of this molecular memory has been traditionally linked to covalent modification of histone and/or DNA, recent studies suggest a role for proteins that persist or remain bound within chromatin to "bookmark" specific loci for enhanced or potentiated responses in daughter cells immediately following cell division. In this report we describe a role for p300 in enabling gene bookmarking by pre-initiation complexes (PICs containing RNA polymerase II (pol II, Mediator and TBP. Once formed these complexes require p300 to enable reacquisition of protein complex assemblies, chromatin modifications and long range chromatin interactions that facilitate post-mitotic transmission of transcriptional memory of prior environmental stimuli.

  15. The Apoptotic Effects of the P300 Activator on Breast Cancer and Lung Fibroblast Cell Lines

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Salahshoor

    2013-10-01

    Full Text Available Background: P300 is an enzyme that acetylates histones during stress. It alsoacetylates several non-histone proteins, including P53 which is the most important tumorsuppressor gene. P53 plays an important role in the apoptosis of tumor cells. Hereby,this study describes the potency of cholera toxin B subunit as a P300 activator to induceapoptosis in a breast cancer cell line (MCF-7 and a lung fibroblast cell line (MRC-5as a non-tumorigenic control sample. Methods: MCF-7 and MRC-5 were cultured in RPMI-1640 and treated with orwithout cholera toxin B subunit at the concentration of 85.43 ÎŒmol/L, based on the half-maximal inhibitory concentration index at different times (24, 48 and 72 h. Thepercentage of apoptotic cells was measured by flow cytometry. Real-time quantitativeRT-PCR was performed to estimate the mRNA expression of P300 in MCF-7 and MRC-5 with cholera toxin B subunit at different times. We used the ELISA and Bradford proteintechniques to detect levels of total and acetylated P53 protein generated in MCF-7 andMRC-5. Results: Our findings indicated that the cholera toxin B subunit effectively andsignificantly induced more apoptosis in MCF-7 compared to MRC-5. We showed thatexpression of P300 up-regulated by increasing the time of the cholera toxin B subunittreatment in MCF-7 but not in MRC-5. In addition, the acetylated and total P53protein levels increased more in MCF-7 cells than in MRC-5 cells.Conclusion: Cholera toxin B subunit induced significant cell death in MCF-7, butit could be well tolerated in MRC-5. Therefore, cholera toxin B subunit can besuggested as an anti-cancer agent.

  16. P300 brain computer interface: current challenges and emerging trends

    Directory of Open Access Journals (Sweden)

    Reza eFazel-Rezai

    2012-07-01

    Full Text Available A brain-computer interface (BCI enables communication without movement based on brain signals measured with electroencephalography (EEG. BCIs usually rely on one of three types of signals: the P300 and other components of the event-related potential (ERP, steady state visual evoked potential (SSVEP, or event related desynchronization (ERD. Although P300 BCIs were introduced over twenty years ago, the past few years have seen a strong increase in P300 BCI research. This closed-loop BCI approach relies on the P300 and other components of the event-related potential (ERP, based on an oddball paradigm presented to the subject. In this paper, we overview the current status of P300 BCI technology, and then discuss new directions: paradigms for eliciting P300s; signal processing methods; applications; and hybrid BCIs. We conclude that P300 BCIs are quite promising, as several emerging directions have not yet been fully explored and could lead to improvements in bit rate, reliability, usability, and flexibility.

  17. P300 brain computer interface: current challenges and emerging trends

    Science.gov (United States)

    Fazel-Rezai, Reza; Allison, Brendan Z.; Guger, Christoph; Sellers, Eric W.; Kleih, Sonja C.; KĂŒbler, Andrea

    2012-01-01

    A brain-computer interface (BCI) enables communication without movement based on brain signals measured with electroencephalography (EEG). BCIs usually rely on one of three types of signals: the P300 and other components of the event-related potential (ERP), steady state visual evoked potential (SSVEP), or event related desynchronization (ERD). Although P300 BCIs were introduced over twenty years ago, the past few years have seen a strong increase in P300 BCI research. This closed-loop BCI approach relies on the P300 and other components of the ERP, based on an oddball paradigm presented to the subject. In this paper, we overview the current status of P300 BCI technology, and then discuss new directions: paradigms for eliciting P300s; signal processing methods; applications; and hybrid BCIs. We conclude that P300 BCIs are quite promising, as several emerging directions have not yet been fully explored and could lead to improvements in bit rate, reliability, usability, and flexibility. PMID:22822397

  18. P300 event-related potentials in children with dyslexia.

    Science.gov (United States)

    Papagiannopoulou, Eleni A; Lagopoulos, Jim

    2017-04-01

    To elucidate the timing and the nature of neural disturbances in dyslexia and to further understand the topographical distribution of these, we examined entire brain regions employing the non-invasive auditory oddball P300 paradigm in children with dyslexia and neurotypical controls. Our findings revealed abnormalities for the dyslexia group in (i) P300 latency, globally, but greatest in frontal brain regions and (ii) decreased P300 amplitude confined to the central brain regions (Fig. 1). These findings reflect abnormalities associated with a diminished capacity to process mental workload as well as delayed processing of this information in children with dyslexia. Furthermore, the topographical distribution of these findings suggests a distinct spatial distribution for the observed P300 abnormalities. This information may be useful in future therapeutic or brain stimulation intervention trials.

  19. P300 brain potential among workers exposed to organic solvents

    Directory of Open Access Journals (Sweden)

    Bente E. Moen

    2009-10-01

    Full Text Available  SUMMARYThe P300 component of the auditory event-related brain potential was examined in a group of 11workers exposed to low levels of organic solvents in a paint factory and 11 unexposed controls beforeand after 3 weeks of summer vacation. The P300 latency time was found to be prolonged among theexposed workers compared to the reference group before the summer vacation, and to be significantlylonger before the vacation than after in the exposed group.The P300 component was also examined in a group of 85 seamen from chemical tankers, experiencingpeak exposures to organic solvents. They were compared to a reference group of unexposedseamen. Comparing these two groups, no difference was found in the P300 latency time. No relationshipbetween the P300 latency time and exposure was found in a multiple regression analysis, includingthe variables age, alcohol consumption, smoking and cerebral concussions.The study indicates the occurrence of an acute biological effect in the nervous system related toorganic solvent exposure, expressed by prolonged P300 latency time. This was found at very lowexposure levels and should be studied further.

  20. Vitamin A deficiency impairs spatial learning and memory: the mechanism of abnormal CBP-dependent histone acetylation regulated by retinoic acid receptor alpha.

    Science.gov (United States)

    Hou, Nali; Ren, Lan; Gong, Min; Bi, Yang; Gu, Yan; Dong, Zhifang; Liu, Youxue; Chen, Jie; Li, Tingyu

    2015-04-01

    Vitamin A (VA) is an essential micronutrient. Numerous studies have confirmed that VA deficiency (VAD) leads to a decline in learning and memory function. Our previous studies have demonstrated that retinoic acid nuclear receptor α (RARα) in the hippocampus plays a crucial role in learning and memory, but the exact mechanism for this process is unclear. Epigenetic modifications, particularly histone acetylation, are involved in nervous system development, learning and memory function, and the pathogenesis of neurodegenerative diseases. Histone acetyltransferases (HATs), such as CREB-binding protein (CBP), E1A-binding protein p300 (p300), and p300/CBP-associated factor (PCAF), are critical for regulating memory function. The current study uses RARα and CBP as examples to study the connections between the RA signaling pathway and histone acetylation modification and to reveal the epigenetic mechanism in VAD-induced learning and memory impairment. This study examined the expression of RARα, HATs, acetylated histone H3/H4, and memory-related genes (Zif268, cFos, FosB), as well as the interaction of RARα and CBP in the hippocampus of 8-week-old rats. Additionally, the changes shown in vivo were further assessed in primary cultured neurons with the inhibition or overexpression of RARα. We found significantly lower levels of histone acetylation in the VAD rats. Furthermore, this downregulation, which impairs learning and memory, is induced by the dysregulation of CBP-dependent histone acetylation that is mediated by RARα. This work provides a solid theoretical foundation and experimental basis for the importance of ensuring sufficient nutritional VA during pregnancy and early life to prevent impairments of learning and memory in adulthood.

  1. Enhancer of Acetyltransferase Chameau (EAChm Is a Novel Transcriptional Co-Activator.

    Directory of Open Access Journals (Sweden)

    Takeya Nakagawa

    Full Text Available Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm family. EAChm is a negatively charged acidic protein retaining aspartate and glutamate. Furthermore, we identified that Chameau and EAChm stimulate transcription in vitro together with purified general transcription factors. In addition, RNA-seq analysis of Chameu KD and EAChm KD S2 cells suggest that Chameau and EAChm regulate transcription of common genes in vivo. Our results suggest that EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity.

  2. Enhancer of Acetyltransferase Chameau (EAChm) Is a Novel Transcriptional Co-Activator.

    Science.gov (United States)

    Nakagawa, Takeya; Ikehara, Tsuyoshi; Doiguchi, Masamichi; Imamura, Yuko; Higashi, Miki; Yoneda, Mitsuhiro; Ito, Takashi

    2015-01-01

    Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT) plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm) family. EAChm is a negatively charged acidic protein retaining aspartate and glutamate. Furthermore, we identified that Chameau and EAChm stimulate transcription in vitro together with purified general transcription factors. In addition, RNA-seq analysis of Chameu KD and EAChm KD S2 cells suggest that Chameau and EAChm regulate transcription of common genes in vivo. Our results suggest that EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity.

  3. LatĂȘncia do potencial evocado auditivo P300 em idosos P300 auditory evoked potential latency in elderly

    Directory of Open Access Journals (Sweden)

    Maria José Santos Cóser

    2010-06-01

    Full Text Available DistĂșrbios auditivos corticais no idoso podem ser avaliados pelo P300. A falta de valores contemporĂąneos de referĂȘncia da latĂȘncia do P300 em idosos saudĂĄveis motivou este estudo. OBJETIVO: Estimar o efeito da idade sobre a latĂȘncia do P300 em um grupo de idosos. MATERIAL E MÉTODO: Foram estudados 62 idosos, com limiares tonais atĂ© 40 dBNA nas frequĂȘncias de 1000 e 2000 Hz, divididos em grupos de acordo com a idade (60-64, 65-69 e 70-74 anos. Foram avaliados pela pesquisa da latĂȘncia do P300 em resposta ao estĂ­mulo raro de 2000 Hz e ao frequente de 1000 Hz, ambos na intensidade de 80 dBNA. FORMA DE ESTUDO: ClĂ­nico, corte transversal observacional, individual comparado, prospectivo. RESULTADOS: A latĂȘncia no Grupo 60 foi 337,26 ms (DP 11,31, no Grupo 65 foi 351,86 ms (DP 29,05 e no Grupo 70 foi 370,19ms (DP 23,40. A regressĂŁo linear dos valores de latĂȘncia do P300 mostrou um aumento de 2,85 ms por ano de idade. A anĂĄlise estatĂ­stica mostrou que os resultados obtidos foram significativos. CONCLUSÃO: A latĂȘncia do P300 aumenta com a idade em uma taxa de 2,85 ms por ano entre a idade de 60 e 74 anos.Auditory cortical disorders in the elderly can be assessed by the P300. The lack of contemporary reference values of P300 latency in healthy elderly motivated this study. AIM: To estimate the effect of age on P300 latency in a group of elderly. METHODS: We studied 62 elderly patients with pure tone thresholds up to 40 dB HL at the frequencies of 1000 and 2000 Hz, divided into groups according to age (60-64, 65-69 and 70-74 years. Were assessed by the P300 latency in response to the rare stimulus of 2000 Hz and 1000 Hz frequencies, both in the intensity of 80 dB HL. STUDY DESIGN: clinical, cross-sectional observational individual compared prospective. RESULTS: The latency in Group 60 was 337.26 ms (SD 11.31 in Group 65 was 351.86 ms (SD 29.05 and in Group 70 it was 370.19 ms (SD 23.40. The linear regression of the values of P300 latency

  4. Beta-HPV 5 and 8 E6 promote p300 degradation by blocking AKT/p300 association.

    Directory of Open Access Journals (Sweden)

    Heather L Howie

    2011-08-01

    Full Text Available The E6 oncoprotein from high-risk genus alpha human papillomaviruses (α-HPVs, such as HPV 16, has been well characterized with respect to the host-cell proteins it interacts with and corresponding signaling pathways that are disrupted due to these interactions. Less is known regarding the interacting partners of E6 from the genus beta papillomaviruses (ÎČ-HPVs; however, it is generally thought that ÎČ-HPV E6 proteins do not interact with many of the proteins known to bind to α-HPV E6. Here we identify p300 as a protein that interacts directly with E6 from both α- and ÎČ-HPV types. Importantly, this association appears much stronger with ÎČ-HPV types 5 and 8-E6 than with α-HPV type 16-E6 or ÎČ-HPV type 38-E6. We demonstrate that the enhanced association between 5/8-E6 and p300 leads to p300 degradation in a proteasomal-dependent but E6AP-independent manner. Rather, 5/8-E6 inhibit the association of AKT with p300, an event necessary to ensure p300 stability within the cell. Finally, we demonstrate that the decreased p300 protein levels concomitantly affect downstream signaling events, such as the expression of differentiation markers K1, K10 and Involucrin. Together, these results demonstrate a unique way in which ÎČ-HPV E6 proteins are able to affect host-cell signaling in a manner distinct from that of the α-HPVs.

  5. P300 Event-Related Potentials in Children with Dyslexia

    Science.gov (United States)

    Papagiannopoulou, Eleni A.; Lagopoulos, Jim

    2017-01-01

    To elucidate the timing and the nature of neural disturbances in dyslexia and to further understand the topographical distribution of these, we examined entire brain regions employing the non-invasive auditory oddball P300 paradigm in children with dyslexia and neurotypical controls. Our findings revealed abnormalities for the dyslexia group in


  6. Cooperation of p300 and PCAF in the control of microRNA 200c/141 transcription and epithelial characteristics.

    Directory of Open Access Journals (Sweden)

    Yoshiaki Mizuguchi

    Full Text Available Epithelial to mesenchymal transition (EMT not only occurs during embryonic development and in response to injury, but is an important element in cancer progression. EMT and its reverse process, mesenchymal to epithelial transition (MET is controlled by a network of transcriptional regulators and can be influenced by posttranscriptional and posttranslational modifications. EMT/MET involves many effectors that can activate and repress these transitions, often yielding a spectrum of cell phenotypes. Recent studies have shown that the miR-200 family and the transcriptional suppressor ZEB1 are important contributors to EMT. Our previous data showed that forced expression of SPRR2a was a powerful inducer of EMT and supports the findings by others that SPRR gene members are highly upregulated during epithelial remodeling in a variety of organs. Here, using SPRR2a cells, we characterize the role of acetyltransferases on the microRNA-200c/141 promoter and their effect on the epithelial/mesenchymal status of the cells. We show that the deacetylase inhibitor TSA as well as P300 and PCAF can cause a shift towards epithelial characteristics in HUCCT-1-SPRR2a cells. We demonstrate that both P300 and PCAF act as cofactors for ZEB1, forming a P300/PCAF/ZEB1 complex on the miR200c/141 promoter. This binding results in lysine acetylation of ZEB1 and a release of ZEB1 suppression on miR-200c/141 transcription. Furthermore, disruption of P300 and PCAF interactions dramatically down regulates miR-200c/141 promoter activity, indicating a PCAF/P300 cooperative function in regulating the transcriptional suppressor/activator role of ZEB1. These data demonstrate a novel mechanism of miRNA regulation in mediating cell phenotype.

  7. Does the 'P300' speller depend on eye gaze?

    Science.gov (United States)

    Brunner, P.; Joshi, S.; Briskin, S.; Wolpaw, J. R.; Bischof, H.; Schalk, G.

    2010-10-01

    Many people affected by debilitating neuromuscular disorders such as amyotrophic lateral sclerosis, brainstem stroke or spinal cord injury are impaired in their ability to, or are even unable to, communicate. A brain-computer interface (BCI) uses brain signals, rather than muscles, to re-establish communication with the outside world. One particular BCI approach is the so-called 'P300 matrix speller' that was first described by Farwell and Donchin (1988 Electroencephalogr. Clin. Neurophysiol. 70 510-23). It has been widely assumed that this method does not depend on the ability to focus on the desired character, because it was thought that it relies primarily on the P300-evoked potential and minimally, if at all, on other EEG features such as the visual-evoked potential (VEP). This issue is highly relevant for the clinical application of this BCI method, because eye movements may be impaired or lost in the relevant user population. This study investigated the extent to which the performance in a 'P300' speller BCI depends on eye gaze. We evaluated the performance of 17 healthy subjects using a 'P300' matrix speller under two conditions. Under one condition ('letter'), the subjects focused their eye gaze on the intended letter, while under the second condition ('center'), the subjects focused their eye gaze on a fixation cross that was located in the center of the matrix. The results show that the performance of the 'P300' matrix speller in normal subjects depends in considerable measure on gaze direction. They thereby disprove a widespread assumption in BCI research, and suggest that this BCI might function more effectively for people who retain some eye-movement control. The applicability of these findings to people with severe neuromuscular disabilities (particularly in eye-movements) remains to be determined.

  8. Histone Chaperone Jun Dimerization Protein 2 (JDP2: Role in Cellular Senescence and Aging

    Directory of Open Access Journals (Sweden)

    Yu-Chang Huang

    2010-10-01

    Full Text Available Transcription factor Jun dimerization protein 2 (JDP2 binds directly to histones and DNA, and inhibits p300-mediated acetylation of core histones and reconstituted nucleosomes that contain JDP2-recognition DNA sequences. The region of JDP2 that encompasses its histone-binding domain and DNA-binding region is essential to inhibit histone acetylation by histone acetyltransferases. Moreover, assays of nucleosome assembly in vitro demonstrate that JDP2 also has histone-chaperone activity. The mutation of the region responsible for inhibition of histone acetyltransferase activity within JDP2 eliminates repression of transcription from the c-jun promoter by JDP2, as well as JDP2-mediated inhibition of retinoic-acid-induced differentiation. Thus JDP2 plays a key role as a repressor of cell differentiation by regulating the expression of genes with an activator protein 1 (AP-1 site via inhibition of histone acetylation and/or assembly and disassembly of nucleosomes. Senescent cells show a series of alterations, including flatten and enlarged morphology, increase in nonspecific acidic ÎČ-galactosidase activity, chromatin condensation, and changes in gene expression patterns. The onset and maintenance of senescence are regulated by two tumor suppressors, p53 and retinoblastoma proteins. The expression of p53 and retinoblastoma proteins is regulated by two distinct proteins, p16Ink4a and Arf, respectively, which are encoded by cdkn2a. JDP2 inhibits recruitment of the polycomb repressive complexes 1 and 2 (PRC-1 and PRC-2 to the promoter of the gene that encodes p16Ink4a and inhibits the methylation of lysine 27 of histone H3 (H3K27. The PRCs associate with the p16Ink4a/Arf locus in young proliferating cells and dissociate from it in senescent cells. Therefore, it seems that chromatin-remodeling factors that regulate association and dissociation of PRCs, and are controlled by JDP2, might play an important role in the senescence program. The molecular

  9. P300 correlates with learning & memory abilities and fluid intelligence

    OpenAIRE

    Amin, Hafeez Ullah; Malik, Aamir Saeed; Kamel, Nidal; Chooi, Weng-Tink; Hussain, Muhammad

    2015-01-01

    Background Educational psychology research has linked fluid intelligence with learning and memory abilities and neuroimaging studies have specifically associated fluid intelligence with event related potentials (ERPs). The objective of this study is to find the relationship of ERPs with learning and memory recall and predict the memory recall score using P300 (P3) component. Method A sample of thirty-four healthy subjects between twenty and thirty years of age was selected to perform three ta...

  10. P300 Detection Based on EEG Shape Features.

    Science.gov (United States)

    Alvarado-Gonzålez, Montserrat; Garduño, Edgar; Bribiesca, Ernesto; Yåñez-Suårez, Oscar; Medina-Bañuelos, Verónica

    2016-01-01

    We present a novel approach to describe a P300 by a shape-feature vector, which offers several advantages over the feature vector used by the BCI2000 system. Additionally, we present a calibration algorithm that reduces the dimensionality of the shape-feature vector, the number of trials, and the electrodes needed by a Brain Computer Interface to accurately detect P300s; we also define a method to find a template that best represents, for a given electrode, the subject's P300 based on his/her own acquired signals. Our experiments with 21 subjects showed that the SWLDA's performance using our shape-feature vector was 93%, that is, 10% higher than the one obtained with BCI2000-feature's vector. The shape-feature vector is 34-dimensional for every electrode; however, it is possible to significantly reduce its dimensionality while keeping a high sensitivity. The validation of the calibration algorithm showed an averaged area under the ROC (AUROC) curve of 0.88. Also, most of the subjects needed less than 15 trials to have an AUROC superior to 0.8. Finally, we found that the electrode C4 also leads to better classification.

  11. Post-Training Intrahippocampal Inhibition of Class I Histone Deacetylases Enhances Long-Term Object-Location Memory

    Science.gov (United States)

    Hawk, Joshua D.; Florian, Cedrick; Abel, Ted

    2011-01-01

    Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance


  12. Using the detectability index to predict P300 speller performance

    Science.gov (United States)

    Mainsah, B. O.; Collins, L. M.; Throckmorton, C. S.

    2016-12-01

    Objective. The P300 speller is a popular brain-computer interface (BCI) system that has been investigated as a potential communication alternative for individuals with severe neuromuscular limitations. To achieve acceptable accuracy levels for communication, the system requires repeated data measurements in a given signal condition to enhance the signal-to-noise ratio of elicited brain responses. These elicited brain responses, which are used as control signals, are embedded in noisy electroencephalography (EEG) data. The discriminability between target and non-target EEG responses defines a user’s performance with the system. A previous P300 speller model has been proposed to estimate system accuracy given a certain amount of data collection. However, the approach was limited to a static stopping algorithm, i.e. averaging over a fixed number of measurements, and the row-column paradigm. A generalized method that is also applicable to dynamic stopping (DS) algorithms and other stimulus paradigms is desirable. Approach. We developed a new probabilistic model-based approach to predicting BCI performance, where performance functions can be derived analytically or via Monte Carlo methods. Within this framework, we introduce a new model for the P300 speller with the Bayesian DS algorithm, by simplifying a multi-hypothesis to a binary hypothesis problem using the likelihood ratio test. Under a normality assumption, the performance functions for the Bayesian algorithm can be parameterized with the detectability index, a measure which quantifies the discriminability between target and non-target EEG responses. Main results. Simulations with synthetic and empirical data provided initial verification of the proposed method of estimating performance with Bayesian DS using the detectability index. Analysis of results from previous online studies validated the proposed method. Significance. The proposed method could serve as a useful tool to initially assess BCI performance

  13. Effects of Carbocysteine and Beclomethasone on Histone Acetylation/Deacetylation Processes in Cigarette Smoke Exposed Bronchial Epithelial Cells.

    Science.gov (United States)

    Pace, Elisabetta; Di Vincenzo, Serena; Ferraro, Maria; Siena, Liboria; Chiappara, Giuseppina; Dino, Paola; Vitulo, Patrizio; Bertani, Alessandro; Saibene, Federico; Lanata, Luigi; Gjomarkaj, Mark

    2017-10-01

    Histone deacetylase expression/activity may control inflammation, cell senescence, and responses to corticosteroids. Cigarette smoke exposure, increasing oxidative stress, may negatively affect deacetylase expression/activity. The effects of cigarette smoke extracts (CSE), carbocysteine, and beclomethasone dipropionate on chromatin remodeling processes in human bronchial epithelial cells are largely unknown. The present study was aimed to assess the effects of cigarette smoke, carbocysteine, and beclomethasone dipropionate on histone deacetylase 3 (HDAC3) expression/activity, N-CoR (nuclear receptor corepressor) expression, histone acetyltransferases (HAT) (p300/CBP) expression, p-CREB and IL-1 m-RNA expression, neutrophil chemotaxis. Increased p-CREB expression was observed in the bronchial epithelium of smokers. CSE increased p-CREB expression and decreased HDAC3 expression and activity and N-CoR m-RNA and protein expression. At the same time, CSE increased the expression of the HAT, p300/CBP. All these events increased acetylation processes within the cells and were associated to increased IL-1 m-RNA expression and neutrophil chemotaxis. The incubation of CSE exposed cells with carbocysteine and beclomethasone counteracted the effects of cigarette smoke on HDAC3 and N-CoR but not on p300/CBP. The increased deacetylation processes due to carbocysteine and beclomethasone dipropionate incubation is associated to reduced p-CREB, IL-1 m-RNA expression, neutrophil chemotaxis. These findings suggest a new role of combination therapy with carbocysteine and beclomethasone dipropionate in restoring deacetylation processes compromised by cigarette smoke exposure. J. Cell. Physiol. 232: 2851-2859, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Auditory P300 event-related potential in tobacco smokers.

    Science.gov (United States)

    Guney, Figen; Genc, Bulent Oguz; Kutlu, Ruhusen; Ilhan, Bilge Cetin

    2009-10-01

    The aim of this study was to elucidate the chronic effects of tobacco smoking on the P300, a neurophysiological index of cognitive function. Prospective study participants were recruited from a family medicine polyclinic. We selected 32 right-handed smokers who had smoked more than 15 cigarettes per day, by inhalation, for more than 2 years. The control population consisted of 32 right-handed, age-matched healthy individuals who had never smoked. Event-related potentials (ERPs) were recorded with the auditory "oddball" two-tone discrimination task. The data from the central (Cz) and frontal (Fz) electrodes were analyzed. The P300 and N1 amplitudes at Fz were lower in the study population compared to the control group. The early component of ERP, the measure of mental speed (N1) latency at Fz was prolonged in the study group compared to the controls, possibly because early cognitive processes such as sensory input or initial encoding of sensory information were delayed in this group. For those who smoke, a decreased N1 amplitude might indicate delayed information processing and possibly short-term memory disturbance. Thus, chronic tobacco smoking may produce prefrontal cognitive dysfunction.

  15. Stacked Autoencoders for the P300 Component Detection

    Directory of Open Access Journals (Sweden)

    Lukáơ Vaƙeka

    2017-05-01

    Full Text Available Novel neural network training methods (commonly referred to as deep learning have emerged in recent years. Using a combination of unsupervised pre-training and subsequent fine-tuning, deep neural networks have become one of the most reliable classification methods. Since deep neural networks are especially powerful for high-dimensional and non-linear feature vectors, electroencephalography (EEG and event-related potentials (ERPs are one of the promising applications. Furthermore, to the authors' best knowledge, there are very few papers that study deep neural networks for EEG/ERP data. The aim of the experiments subsequently presented was to verify if deep learning-based models can also perform well for single trial P300 classification with possible application to P300-based brain-computer interfaces. The P300 data used were recorded in the EEG/ERP laboratory at the Department of Computer Science and Engineering, University of West Bohemia, and are publicly available. Stacked autoencoders (SAEs were implemented and compared with some of the currently most reliable state-of-the-art methods, such as LDA and multi-layer perceptron (MLP. The parameters of stacked autoencoders were optimized empirically. The layers were inserted one by one and at the end, the last layer was replaced by a supervised softmax classifier. Subsequently, fine-tuning using backpropagation was performed. The architecture of the neural network was 209-130-100-50-20-2. The classifiers were trained on a dataset merged from four subjects and subsequently tested on different 11 subjects without further training. The trained SAE achieved 69.2% accuracy that was higher (p < 0.01 than the accuracy of MLP (64.9% and LDA (65.9%. The recall of 58.8% was slightly higher when compared with MLP (56.2% and LDA (58.4%. Therefore, SAEs could be preferable to other state-of-the-art classifiers for high-dimensional event-related potential feature vectors.

  16. Plant Responses to Abiotic Stress Regulated by Histone Deacetylases

    Directory of Open Access Journals (Sweden)

    Ming Luo

    2017-12-01

    Full Text Available In eukaryotic cells, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are modulated by histone acetyltransferases and histone deacetylases (HDACs. Recent studies indicate that HDACs play essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance regarding the plant HDACs and their functions in the regulation of abiotic stress responses. The role of HDACs in autophagy was also discussed.

  17. P300, probability, and introverted/extroverted personality types.

    Science.gov (United States)

    Cahill, J M; Polich, J

    1992-05-01

    Extreme introverted and extroverted subject groups (n = 24 each) containing equal numbers of male and females were assessed with the P300 (P3) component of the event-related potential (ERP). A two-tone auditory discrimination task in which the probability of the target stimulus varied systematically in different conditions (.20, .40, .60, .80) was used to elicit the ERPs. The P3 amplitude demonstrated a significant interaction between personality type, probability, and subject gender and was generally smaller for introverts than for extroverts. Female subjects tended to have larger overall P3 components than male subjects. P3 latency was not affected by the personality variable. The results support previous findings for ERP differences between introverts and extroverts and suggest that personality type differentially influences target stimulus probability effects. The findings are discussed in terms of individual differences in cortical activity on P3 amplitude and personality measures.

  18. Mdm2 RING mutation enhances p53 transcriptional activity and p53-p300 interaction.

    Directory of Open Access Journals (Sweden)

    Hilary V Clegg

    Full Text Available The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation. Aside from its ubiquitin ligase function, Mdm2 has been believed to be capable of suppressing p53's transcriptional activity by binding with and masking the transactivation domain of p53. The ability of Mdm2 to restrain p53 activity by binding alone, without ubiquitination, was challenged by a 2007 study using a knockin mouse harboring a single cysteine-to-alanine point mutation (C462A in Mdm2's RING domain. Mouse embryonic fibroblasts with this mutation, which abrogates Mdm2's E3 ubiquitin ligase activity without affecting its ability to bind with p53, were unable to suppress p53 activity. In this study, we utilized the Mdm2(C462A mouse model to characterize in further detail the role of Mdm2's RING domain in the control of p53. Here, we show in vivo that the Mdm2(C462A protein not only fails to suppress p53, but compared to the complete absence of Mdm2, Mdm2(C462A actually enhances p53 transcriptional activity toward p53 target genes p21/CDKN1A, MDM2, BAX, NOXA, and 14-3-3σ. In addition, we found that Mdm2(C462A facilitates the interaction between p53 and the acetyltransferase CBP/p300, and it fails to heterodimerize with its homolog and sister regulator of p53, Mdmx, suggesting that a fully intact RING domain is required for Mdm2's inhibition of the p300-p53 interaction and for its interaction with Mdmx. These findings help us to better understand the complex regulation of the Mdm2-p53 pathway and have important implications for chemotherapeutic agents targeting Mdm2, as they suggest that inhibition of Mdm2's E3 ubiquitin ligase activity may be sufficient for increasing p53 activity in vivo, without the need to block Mdm2-p53 binding.

  19. PSG gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins.

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    Soledad A Camolotto

    Full Text Available BACKGROUND: Lysine acetylation is an important post-translational modification that plays a central role in eukaryotic transcriptional activation by modifying chromatin and transcription-related factors. Human pregnancy-specific glycoproteins (PSG are the major secreted placental proteins expressed by the syncytiotrophoblast at the end of pregnancy and represent early markers of cytotrophoblast differentiation. Low PSG levels are associated with complicated pregnancies, thus highlighting the importance of studying the mechanisms that control their expression. Despite several transcription factors having been implicated as key regulators of PSG gene family expression; the role of protein acetylation has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Here, we explored the role of acetylation on PSG gene expression in the human placental-derived JEG-3 cell line. Pharmacological inhibition of histone deacetylases (HDACs up-regulated PSG protein and mRNA expression levels, and augmented the amount of acetylated histone H3 associated with PSG 5'regulatory regions. Moreover, PSG5 promoter activation mediated by Sp1 and KLF6, via the core promoter element motif (CPE, -147/-140, was markedly enhanced in the presence of the HDAC inhibitor trichostatin A (TSA. This effect correlated with an increase in Sp1 acetylation and KLF6 nuclear localization as revealed by immunoprecipitation and subcellular fractionation assays. The co-activators PCAF, p300, and CBP enhanced Sp1-dependent PSG5 promoter activation through their histone acetylase (HAT function. Instead, p300 and CBP acetyltransferase domain was dispensable for sustaining co-activation of PSG5 promoter by KLF6. CONCLUSIONS/SIGNIFICANCE: Results are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6 following an augmented Sp1 acetylation and KLF6 nuclear localization.

  20. Histone H3 lysine 4 methyltransferase KMT2D.

    Science.gov (United States)

    Froimchuk, Eugene; Jang, Younghoon; Ge, Kai

    2017-09-05

    Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and MLL2 in humans and Mll4 in mice, belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein over 5500 amino acids in size and is partially functionally redundant with KMT2C. KMT2D is widely expressed in adult tissues and is essential for early embryonic development. The C-terminal SET domain is responsible for its H3K4 methyltransferase activity and is necessary for maintaining KMT2D protein stability in cells. KMT2D associates with WRAD (WDR5, RbBP5, ASH2L, and DPY30), NCOA6, PTIP, PA1, and H3K27 demethylase UTX in one protein complex. It acts as a scaffold protein within the complex and is responsible for maintaining the stability of UTX. KMT2D is a major mammalian H3K4 mono-methyltransferase and co-localizes with lineage determining transcription factors on transcriptional enhancers. It is required for the binding of histone H3K27 acetyltransferases CBP and p300 on enhancers, enhancer activation and cell-type specific gene expression during differentiation. KMT2D plays critical roles in regulating development, differentiation, metabolism, and tumor suppression. It is frequently mutated in developmental diseases, such as Kabuki syndrome and congenital heart disease, and various forms of cancer. Further understanding of the mechanism through which KMT2D regulates gene expression will reveal why KMT2D mutations are so harmful and may help generate novel therapeutic approaches. Published by Elsevier B.V.

  1. Relationship between lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation.

    Science.gov (United States)

    HernĂĄndez-Ledesma, Blanca; Hsieh, Chia-Chien; de Lumen, Ben O

    2011-07-01

    Dysfunction of histone acetyltransferases (HATs) or histone deacetylases (HDACs) involved in histones acetylation has been associated with cancer. Inhibitors of these enzymes are becoming potential targets for new therapies. This study reports by Western-Blot analysis, that peptide lunasin is mainly an in vitro inhibitor of histone H4 acetylation by P300/cAMP-response element-binding protein (CBP)-associated factor (PCAF), with IC₅₀ values dependent on the lysine position sensitive to be acetylated (0.83 ÎŒM (H4-Lys 8), 1.27 ÎŒM (H4-Lys 12) and 0.40 ÎŒM (H4-Lys 5, 8, 12, 16)). Lunasin is also capable of inhibiting H3 acetylation (IC₅₀ of 5.91 ÎŒM (H3-Lys 9) and 7.81 ÎŒM (H3-Lys 9, 14)). Studies on structure-activity relationship establish that lunasin's sequence are essential for inhibiting H4 acetylation whereas poly-D sequence is the main active sequence responsible for H3 acetylation inhibition. Lunasin also inhibits H3 and H4 acetylation and cell proliferation (IC₅₀ of 181 ÎŒM) in breast cancer MDA-MB-231 cells. Moreover, this peptide decreases expression of cyclins and cyclin dependent kinases-4 and -6, implicated in cell cycle pathways. Results from this study demonstrates lunasin's role as modulator of histone acetylation and protein expression that might contribute on its chemopreventive properties against breast cancer. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. P300-based brain computer interface experimental setup.

    Science.gov (United States)

    Arboleda, Carolina; Garcia, Eliana; Posada, Alejandro; Torres, Robinson

    2009-01-01

    A Brain-Computer interface (BCI) is a communication system that enables the generation of a control signal from brain signals such as sensorymotor rhythms and evoked potentials; therefore, it constitutes a novel communication option for people with severe motor disabilities (such as Amyotrophic Lateral Sclerosis patients). This paper presents the development of a P300-based BCI. This prototype uses a homemade six-channel electroencephalograph for the acquisition of the signals, and a visual stimulation matrix; since this matrix contains letters of the alphabet as well as images associated to them, it permits word-writing and the elaboration of messages with the images. To process the signals the software BCI2000 and MATLAB 7.0 were used. The latter was used to program three linear translation algorithms (Stepwise Linear Discriminant Analysis, Lineal Discriminant Analysis and Least Squares) to convert the brain signals into communication signals. These algorithms had a classification accuracy of 90.73 %, 95.75 % and 89.45 % respectively, when using raw data; and of 90.78%, 49.48 % and 53.9 %, when data was previously common-average filtered. The experimental setup was tested in ten healthy volunteers; 5 of them got a 100% success, 1 a 90% success, 2 an around 70% success and 2 a 50% success, in the online free-spelling tests.

  3. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes.

    Science.gov (United States)

    Pasini, Diego; Malatesta, Martina; Jung, Hye Ryung; Walfridsson, Julian; Willer, Anton; Olsson, Linda; Skotte, Julie; Wutz, Anton; Porse, Bo; Jensen, Ole NĂžrregaard; Helin, Kristian

    2010-08-01

    Polycomb group (PcG) proteins are transcriptional repressors, which regulate proliferation and cell fate decisions during development, and their deregulated expression is a frequent event in human tumours. The Polycomb repressive complex 2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is believed that this activity mediates transcriptional repression. Despite the recent progress in understanding PcG function, the molecular mechanisms by which the PcG proteins repress transcription, as well as the mechanisms that lead to the activation of PcG target genes are poorly understood. To gain insight into these mechanisms, we have determined the global changes in histone modifications in embryonic stem (ES) cells lacking the PcG protein Suz12 that is essential for PRC2 activity. We show that loss of PRC2 activity results in a global increase in H3K27 acetylation. The methylation to acetylation switch correlates with the transcriptional activation of PcG target genes, both during ES cell differentiation and in MLL-AF9-transduced hematopoietic stem cells. Moreover, we provide evidence that the acetylation of H3K27 is catalyzed by the acetyltransferases p300 and CBP. Based on these data, we propose that the PcG proteins in part repress transcription by preventing the binding of acetyltransferases to PcG target genes.

  4. Inhibition of the HIF1α-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II)

    Science.gov (United States)

    Jayatunga, Madura K. P.; Thompson, Sam; McKee, Tawnya C.; Chan, Mun Chiang; Reece, Kelie M.; Hardy, Adam P.; Sekirnik, Rok; Seden, Peter T.; Cook, Kristina M.; McMahon, James B.; Figg, William D.; Schofield, Christopher J.; Hamilton, Andrew D.

    2014-01-01

    Protein-protein interactions between the hypoxia inducible transcription factor (HIF) and the transcriptional coactivators p300/CBP are potential cancer targets due to their role in the hypoxic response. A natural product based screen led to the identification of indandione and benzoquinone derivatives that reduce the tight interaction between a HIF-1α fragment and the CH1 domain of p300. The indandione derivatives were shown to fragment to give ninhydrin, which was identified as the active species. Both the naphthoquinones and ninhydrin were observed to induce Zn(II) ejection from p300 and the catalytic domain of the histone demethylase KDM4A. Together with previous reports on the effects of reated compounds on HIF-1α and other systems, the results suggest that care should be taken in interpreting biological results obtained with highly electrophilic/ thiol modifying compounds. PMID:25023609

  5. The NoGo P300 ‘anteriorization’ effect and response inhibition

    OpenAIRE

    Salisbury, Dean F.; Griggs, Carlye B.; Shenton, Martha Elizabeth; McCarley, Robert William

    2004-01-01

    Objective: The P300 event-related potential shows anterior P300 increases on NoGo tasks (target stimulus = withhold response) relative to Go tasks (target stimulus = commit response). This `NoGo anteriorization' has been hypothesized to reflect response inhibition. However, silent-count tasks show similar P300 anteriorization. The P300 anteriorization on silent-count tasks relative to Go tasks cannot reflect inhibition-related processes, and questions the degree to which anteriorization obser...

  6. High glucose induced alteration of SIRTs in endothelial cells causes rapid aging in a p300 and FOXO regulated pathway.

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    Rokhsana Mortuza

    Full Text Available In diabetes, some of the cellular changes are similar to aging. We hypothesized that hyperglycemia accelerates aging-like changes in the endothelial cells (ECs and tissues leading to structural and functional damage. We investigated glucose-induced aging in 3 types of ECs using senescence associated ÎČ-gal (SA ÎČ-gal staining and cell morphology. Alterations of sirtuins (SIRTs and their downstream mediator FOXO and oxidative stress were investigated. Relationship of such alteration with histone acetylase (HAT p300 was examined. Similar examinations were performed in tissues of diabetic animals. ECs in high glucose (HG showed evidence of early senescence as demonstrated by increased SA ÎČ-gal positivity and reduced replicative capacities. These alterations were pronounced in microvascular ECs. They developed an irregular and hypertrophic phenotype. Such changes were associated with decreased SIRT (1-7 mRNA expressions. We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others' expression. Furthermore, HG caused reduction in FOXO1's DNA binding ability and antioxidant target gene expressions. Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes. Diabetic animals showed increased cellular senescence in renal glomerulus and retinal blood vessels along with reduced SIRT1 mRNA expressions in these tissues. Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway.

  7. P300 event-related potential in euthymic patients with bipolar disorder.

    Science.gov (United States)

    Lahera, G; Pedrera, A; Cabañes, L; Fernandez-Lorente, J; Simal, P; Montes, J M; Saiz-Ruiz, J

    2009-02-01

    Auditory P300 event-related potential (ERP) and performance on Sustained Attention were evaluated in 24 euthymic bipolar patients and 38 healthy volunteers. There were no significant differences between groups, and performance in sustained attention had no significant influence in the P300 responses. P300 response might be driven by the presence of mood symptoms.

  8. P300 correlates with learning & memory abilities and fluid intelligence.

    Science.gov (United States)

    Amin, Hafeez Ullah; Malik, Aamir Saeed; Kamel, Nidal; Chooi, Weng-Tink; Hussain, Muhammad

    2015-09-23

    Educational psychology research has linked fluid intelligence with learning and memory abilities and neuroimaging studies have specifically associated fluid intelligence with event related potentials (ERPs). The objective of this study is to find the relationship of ERPs with learning and memory recall and predict the memory recall score using P300 (P3) component. A sample of thirty-four healthy subjects between twenty and thirty years of age was selected to perform three tasks: (1) Raven's Advanced Progressive Matrices (RAPM) test to assess fluid intelligence; (2) learning and memory task to assess learning ability and memory recall; and (3) the visual oddball task to assess brain-evoked potentials. These subjects were divided into High Ability (HA) and Low Ability (LA) groups based on their RAPM scores. A multiple regression analysis was used to predict the learning & memory recall and fluid intelligence using P3 amplitude and latency. Behavioral results demonstrated that the HA group learned and recalled 10.89 % more information than did the LA group. ERP results clearly showed that the P3 amplitude of the HA group was relatively larger than that observed in the LA group for both the central and parietal regions of the cerebrum; particularly during the 300-400 ms time window. In addition, a shorter latency for the P3 component was observed at Pz site for the HA group compared to the LA group. These findings agree with previous educational psychology and neuroimaging studies which reported an association between ERPs and fluid intelligence as well as learning performance. These results also suggest that the P3 component is associated with individual differences in learning and memory recall and further indicate that P3 amplitude might be used as a supporting factor in standard psychometric tests to assess an individual's learning & memory recall ability; particularly in educational institutions to aid in the predictability of academic skills.

  9. CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: regulation by BET.

    Science.gov (United States)

    Clifford, Rachel L; Patel, Jamie K; John, Alison E; Tatler, Amanda L; Mazengarb, Lisa; Brightling, Christopher E; Knox, Alan J

    2015-05-01

    Asthma is characterized by airway inflammation and remodeling and CXCL8 is a CXC chemokine that drives steroid-resistant neutrophilic airway inflammation. We have shown that airway smooth muscle (ASM) cells isolated from asthmatic individuals secrete more CXCL8 than cells from nonasthmatic individuals. Here we investigated chromatin modifications at the CXCL8 promoter in ASM cells from nonasthmatic and asthmatic donors to further understand how CXCL8 is dysregulated in asthma. ASM cells from asthmatic donors had increased histone H3 acetylation, specifically histone H3K18 acetylation, and increased binding of histone acetyltransferase p300 compared with nonasthmatic donors but no differences in CXCL8 DNA methylation. The acetylation reader proteins Brd3 and Brd4 were bound to the CXCL8 promoter and Brd inhibitors inhibited CXCL8 secretion from ASM cells by disrupting Brd4 and RNA polymerase II binding to the CXCL8 promoter. Our results show a novel dysregulation of CXCL8 transcriptional regulation in asthma characterized by a promoter complex that is abnormal in ASM cells isolated from asthmatic donors and can be modulated by Brd inhibitors. Brd inhibitors may provide a new therapeutic strategy for steroid-resistant inflammation. Copyright © 2015 the American Physiological Society.

  10. The Event-related Potential P300 in Patients with Migraine.

    Science.gov (United States)

    Titlic, Marina; Mise, Nikolina Ivica; Pintaric, Irena; Rogosic, Veljko; Vanjaka-Rogosic, Lucija; Mihalj, Mario; Jurinovic, Pavao; Katic, Ana Curkovic; Andjelinovic, Maja

    2015-12-01

    Recording of event-related potentials by using oddball paradigm of auditory P300 has yielded conflicting results in migraine. The aim of this study was to demonstrate that migraine patients have reduced P300 amplitude and prolonged P300 latency, suggesting alterations of the cognitive-evaluative component. We recruited 29 migraine patients (24 females; median age 40 years) and 29 healthy age- and gender-matched participants. Participants were subjected to the same testing procedures of auditory P300 by discrimination the target auditory stimulus from the frequent stimulus, and analyzing P300 target/frequent stimulus amplitudes, and P300 target/frequent stimulus latencies. Patients with migraine don't have prolonged P300 target stimulus latency, but have a longer P300 frequent stimulus latency for 17.5ms. Out of 29 participants with migraine 8 had pathological P300 target stimulus amplitude, and 19 had pathological P300 frequent stimulus amplitude. People with migraine have altered the P300 which indicates the presence of cognitive dysfunction in these patients and importance of early diagnosis and intervention to preventing any deterioration in cognitive functions.

  11. Combined frontal and parietal P300 amplitudes indicate compensated cognitive processing across the lifespan

    Science.gov (United States)

    van Dinteren, Rik; Arns, Martijn; Jongsma, Marijtje L. A.; Kessels, Roy P. C.

    2014-01-01

    In the present study the frontal and parietal P300, elicited in an auditory oddball paradigm were investigated in a large sample of healthy participants (N = 1572), aged 6–87. According to the concepts of the compensation-related utilization of neural circuits hypothesis (CRUNCH) it was hypothesized that the developmental trajectories of the frontal P300 would reach a maximum in amplitude at an older age than the amplitude of the parietal P300 amplitude. In addition, the amplitude of the frontal P300 was expected to increase with aging in adulthood in contrast to a decline in amplitude of the parietal P300 amplitude. Using curve-fitting methods, a comparison was made between the developmental trajectories of the amplitudes of the frontal and parietal P300. It was found that the developmental trajectories of frontal and parietal P300 amplitudes differed significantly across the lifespan. During adulthood, the amplitude of the parietal P300 declines with age, whereas both the frontal P300 amplitude and behavioral performance remain unaffected. A lifespan trajectory of combined frontal and parietal P300 amplitudes was found to closely resemble the lifespan trajectory of behavioral performance. Our results can be understood within the concepts of CRUNCH. That is, to compensate for declining neural resources, older participants recruit additional neural resources of prefrontal origin and consequently preserve a stable behavioral performance. Though, a direct relation between amplitude of the frontal P300 and compensatory mechanisms cannot yet be claimed. PMID:25386141

  12. Combined frontal and parietal P300 amplitudes indicate compensated cognitive processing across the lifespan

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    Rik evan Dinteren

    2014-10-01

    Full Text Available In the present study the frontal and parietal P300, elicited in an auditory oddball paradigm were investigated in a large sample of healthy participants (N=1,572, aged 6-87. According to the concepts of the compensation-related utilization of neural circuits hypothesis (CRUNCH it was hypothesized that the developmental trajectories of the frontal P300 would reach a maximum in amplitude at an older age than the amplitude of the parietal P300 amplitude. In addition, the amplitude of the frontal P300 was expected to increase with aging in adulthood in contrast to a decline in amplitude of the parietal P300 amplitude. Using curve-fitting methods, a comparison was made between the developmental trajectories of the amplitudes of the frontal and parietal P300. It was found that the developmental trajectories of frontal and parietal P300 amplitudes differed significantly across the lifespan. During adulthood, the amplitude of the parietal P300 declines with age, whereas both the frontal P300 amplitude and behavioral performance remain unaffected. A lifespan trajectory of combined frontal and parietal P300 amplitudes was found to closely resemble the lifespan trajectory of behavioral performance. Our results can be understood within the concepts of CRUNCH. That is, to compensate for declining neural resources, older participants recruit additional neural resources of prefrontal origin and consequently preserve a stable behavioral performance. Though, a direct relation between amplitude of the frontal P300 and compensatory mechanisms cannot yet be claimed.

  13. Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells.

    LENUS (Irish Health Repository)

    Duncan, Henry F

    2012-03-01

    Histone deacetylase inhibitors (HDACis) alter the homeostatic balance between 2 groups of cellular enzymes, histone deacetylases (HDACs) and histone acetyltransferases (HATs), increasing transcription and influencing cell behavior. This study investigated the potential of 2 HDACis, valproic acid (VPA) and trichostatin A (TSA), to promote reparative processes in pulp cells as assayed by viability, cell cycle, and mineralization analyses.

  14. Expanding the Reader Landscape of Histone Acylation.

    Science.gov (United States)

    Khan, Abid; Bridgers, Joseph B; Strahl, Brian D

    2017-04-04

    In this issue of Structure,Klein et al. (2017) expand our understanding of what reader domains bind to by showing that MORF, a double PHD domain containing lysine acetyltransferase, is a preferential reader of histone lysine acylation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dopaminergic mechanisms of target detection - P300 event related potential and striatal dopamine.

    Science.gov (United States)

    Pogarell, Oliver; Padberg, Frank; Karch, Susanne; Segmiller, Felix; Juckel, Georg; Mulert, Christoph; Hegerl, Ulrich; Tatsch, Klaus; Koch, Walter

    2011-12-30

    The P300 is a cortically generated event related potential (ERP) widely used in neurophysiological research since it is related to cognitive functions and central information processing. Intracerebral recordings and functional neuroimaging studies have demonstrated that this potential is generated by various brain regions including frontal, temporal and parietal cortices. Regarding the neurochemical background, clinical and genetic investigations suggest that dopaminergic neurons could be involved in the generation of the P300. However, there is no direct evidence in vivo that P300 amplitudes and latencies are related to dopaminergic parameters. The aim of this study was to further elucidate dopaminergic aspects of the P300 ERP by combining neurophysiological and nuclear medicine assessments in vivo. Patients with a major depressive episode underwent both P300 recordings and dynamic [ÂčÂČÂłI] IBZM SPECT for the evaluation of striatal dopamine D₂/D₃-receptor availability. There were statistically significant positive correlations of the striatal dopamine D₂/D₃-receptor status with P300 amplitudes and significant negative correlations with P300 latencies. Using this combined approach, the study presents direct evidence in vivo that the central dopaminergic system might play an important role in the generation of the P300 and that central dopaminergic activity could be involved in the modulation of P300 parameters. This association might be of relevance for the interpretation of P300 studies in psychiatric disorders. 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Neuronal correlates of a virtual-reality-based passive sensory P300 network.

    Science.gov (United States)

    Chen, Chun-Chuan; Syue, Kai-Syun; Li, Kai-Chiun; Yeh, Shih-Ching

    2014-01-01

    P300, a positive event-related potential (ERP) evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person's intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM) for ERP and a novel virtual reality (VR)-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients' analytic results with this study. For example, the task

  17. Neuronal correlates of a virtual-reality-based passive sensory P300 network.

    Directory of Open Access Journals (Sweden)

    Chun-Chuan Chen

    Full Text Available P300, a positive event-related potential (ERP evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person's intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM for ERP and a novel virtual reality (VR-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients' analytic results with this study. For example

  18. Neuronal Correlates of a Virtual-Reality-Based Passive Sensory P300 Network

    Science.gov (United States)

    Chen, Chun-Chuan; Syue, Kai-Syun; Li, Kai-Chiun; Yeh, Shih-Ching

    2014-01-01

    P300, a positive event-related potential (ERP) evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person’s intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM) for ERP and a novel virtual reality (VR)-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients’ analytic results with this study. For example, the task

  19. Histone Acetylation in Fungal Pathogens of Plants

    Directory of Open Access Journals (Sweden)

    Junhyun Jeon

    2014-03-01

    Full Text Available Acetylation of histone lysine residues occurs in different organisms ranging from yeast to plants and mammals for the regulation of diverse cellular processes. With the identification of enzymes that create or reverse this modification, our understanding on histone acetylation has expanded at an amazing pace during the last two decades. In fungal pathogens of plants, however, the importance of such modification has only just begun to be appreciated in the recent years and there is a dearth of information on how histone acetylation is implicated in fungal pathogenesis. This review covers the current status of research related to histone acetylation in plant pathogenic fungi and considers relevant findings in the interaction between fungal pathogens and host plants. We first describe the families of histone acetyltransferases and deacetylases. Then we provide the cases where histone acetylation was investigated in the context of fungal pathogenesis. Finally, future directions and perspectives in epigenetics of fungal pathogenesis are discussed.

  20. SĂ­ndrome da apneia obstrutiva do sono e o potencial auditivo P300 Obstructive sleep apnea and P300 evoked auditory potential

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Martins

    2011-12-01

    Full Text Available A SĂ­ndrome da Apneia Obstrutiva do Sono (SAOS diminui as capacidades da atenção, memĂłria e concentração, fatores relacionados com a cognição. A anĂĄlise dos parĂąmetros do P300 auditivo permitiria inferir disfunção cognitiva. OBJETIVO: Comparar os dados da polissonografia e do P300 auditivo em adultos, roncopatas primĂĄrios com portadores de SAOS. CASUÍSTICA E MÉTODO: Estudo prospectivo em roncopatas primĂĄrios (N=12 e em portadores de SAOS (N=54, submetidos Ă  polissonografia definidos pelo Ă­ndice de apneia e hipopneia (IAH. As variĂĄveis da polissonografia e as do P300 foram comparadas, pelos testes "T" de Student, exato de Fisher, regressĂŁo logĂ­stica e anĂĄlise de correlação com nĂ­vel de significĂąncia de 5%. RESULTADOS: O IAH apresentou correlação inversa com a oximetria em ambos os grupos. A prevalĂȘncia do P300 foi menor no G.SAOS (teste exato de Fisher, p=0,027. A idade dos pacientes nĂŁo influenciou a prevalĂȘncia do P300 (anĂĄlise de regressĂŁo; p=0,232. A amplitude do P300 foi menor do G.SAOS (teste "T" de Student; p=0,003 a latĂȘncia do P300 foi semelhante em ambos os grupos (teste "T" de Student; p=0,89. CONCLUSÃO: A redução da amplitude do P300 nos portadores de SAOS sugere disfunção cognitiva induzida por diminuição da memĂłria auditiva.The obstructive sleep apnea syndrome (OSAS reduces attention span, memory and concentration capacities, all associated with cognition. The analysis of the auditory P300 parameters could help infer cognitive dysfunction. OBJECTIVE: To compare the data from polysomnography and the auditory P300 in adults, primary snorers with OSAS patients. MATERIALS AND METHODS: Prospective study with primary snorers (N=12 and in OSAS patients (N=54, submitted to polysomnography, defined by the apnea-hypopnea index (AHI. The polysomnography and P300 variables were compared by the t-Student test, the Exact Fisher's Test, logistic regression and analysis of correlation with a significance

  1. [Histone variants and histone exchange].

    Science.gov (United States)

    Wu, Nan; Gui, Jian-Fang

    2006-04-01

    Histones, as the basic components of nucleosome, are essential to chromatin structure and function. To adapt to various states of chromatin, corresponding histone variants are incorporated in nucleosome, and certain modifications also occur on the variants' tails. These variants change the conformation and stability of nucleosome to facilitate transcriptional activation or deactivation, DNA repairing, heterochromatin formation, and others. During histone exchange, chromatin remodeling complex facilitates histone variant deposition into nucleosome, and different variants have diverse deposition pathways. Recently, research on histone variants is not only a new hotspot in epigenetics, but also a new annotation of "histone code". In addition, histone exchange reveals new changing mechanism of DNA-histone interaction.

  2. P300 development across the lifespan: A systematic review and meta-analysis

    OpenAIRE

    Rik van Dinteren; Martijn Arns; Marijtje L. A. Jongsma; Roy P C Kessels

    2014-01-01

    BACKGROUND: The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm, and has been associated with cognitive information processing (e.g. memory, attention, executive function). This paper reviews the development of the auditory P300 across the lifespan. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review and meta-analysis on the P300 was performed including 75 studies (n = 2...

  3. The Event-related Potential P300 in Patients with Migraine

    OpenAIRE

    Titlic, Marina; Mise, Nikolina Ivica; Pintaric, Irena; Rogosic, Veljko; Vanjaka-Rogosic, Lucija; Mihalj, Mario; Jurinovic, Pavao; Katic, Ana Curkovic;; Andjelinovic, Maja

    2015-01-01

    Objective: Recording of event-related potentials by using oddball paradigm of auditory P300 has yielded conflicting results in migraine. The aim of this study was to demonstrate that migraine patients have reduced P300 amplitude and prolonged P300 latency, suggesting alterations of the cognitive-evaluative component. Methods: We recruited 29 migraine patients (24 females; median age 40 years) and 29 healthy age- and gender-matched participants. Participants were subjected to the same testing ...

  4. Connecting the P300 to the diagnosis and prognosis of unconscious patients.

    Science.gov (United States)

    Li, Ran; Song, Wei-Qun; Du, Ju-Bao; Huo, Su; Shan, Gui-Xiang

    2015-03-01

    The residual consciousness of unconscious patients can be detected by studying the P300, a wave among event-related potentials. Previous studies have applied tones, the subject's name and other names as stimuli. However, the results were not satisfactory. In this study, we changed the constituent order of subjects' two-character names to create derived names. The subject's derived names, together with tones and their own names, were used as auditory stimuli in event-related potential experiments. Healthy controls and unconscious patients were included in this study and made to listen to these auditory stimuli. In the two paradigms, a sine tone followed by the subject's own name and the subject's derived name followed by the subject's own name were used as standard and deviant stimuli, respectively. The results showed that all healthy controls had the P300 using both paradigms, and that the P300 in the second paradigm had a longer latency and two peaks. All minimally conscious state patients had the P300 in the first paradigm and the majority of them had the P300 in the second paradigm. Most vegetative state patients had no P300. Patients who showed the P300 in the two paradigms had more residual consciousness, and patients with the two-peak P300 had a higher probability of awakening within a short time. Our experimental findings suggest that the P300 event-related potential could reflect the conscious state of unconscious patients.

  5. ABR and auditory P300 findings inchildren with ADHD Achados em ABR e P300 auditivo em crianças com TDAH

    Directory of Open Access Journals (Sweden)

    Eliane Schochat

    2002-09-01

    Full Text Available Auditory processing disorders (APD, also referred as central auditory processing disorders (CAPD and attention deficit hyperactivity disorders (ADHD have become popular diagnostic entities for school age children. It has been demonstrated a high incidence of comorbid ADHD with communication disorders and auditory processing disorder. The aim of this study was to investigate ABR and P300 auditory evoked potentials in children with ADHD, in a double-blind study. Twenty-one children, ages between 7 and 10 years, with a primary diagnosis of ADHD, participated in this experiment. Results showed that all children had normal ABR with normal latency for wave V. Results also showed that among 42 ears combined 52.38% did not have P300. For the medicated subjects we observed that among 28 ears, 42.85% did not have P300 and for the non-medicated 71.43% (N = 14 ears did not have P300. Our results suggest that the medicated subjects had more presence of P300 (57.15% than the non-medicated group (28.57%, though the absence of these potentials were high among the group - 52.38%.AlteraçÔes do processamento auditivo, tambĂ©m chamadas alteraçÔes no processamento auditivo central e o transtorno do deficit de atenção/ hiperatividade (TDAH, tornaram-se entidades populares nos diagnĂłsticos de crianças escolares. Uma grande incidĂȘncia de TDAH em comorbidade com alteraçÔes na comunicação e com o processamento auditivo central tem sido demonstrada. O objetivo deste estudo foi investigar potenciais evocados auditivos, ABR e P300, em crianças com TDAH, em um estudo duplo cego. Vinte e uma crianças, idades entre 7 e 10 anos, com diagnostico primĂĄrio de TDAH, participaram deste experimento. Os resultados mostraram que todas as crianças tinham ABR com latĂȘncia normal para a onda V e que, entre 42 orelhas, 52,38% nĂŁo tinham P300. Para os sujeitos medicados observou-se que entre 28 orelhas, 42,85% nĂŁo tinham P300 e para os nĂŁo medicados 71,43% (N = 14

  6. Musical rhythms and their influence on P300 velocity in young females Ritmos musicais diferentes: influĂȘncia da velocidade no P300 em jovens mulheres

    Directory of Open Access Journals (Sweden)

    Cintia Ishii de SĂĄ

    2011-04-01

    Full Text Available Exposure to music may be useful in the P300 retest and avoid habituation. AIM: To verify the influence of the exposure to different kinds of music in P300 in young females. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: Forty-five women aged from 20 to 36 years were evaluated. P300 was studied before and after musical stimulation with different rhythms. Brazilian songs, international songs, and classical music melodies were selected. Each song had its velocity altered and was named as fast and slow. Subjects were divided into 2 groups exposed to music: one group was exposed to the fast version and the other to the slow version. The control group not exposed to music and was evaluated within the same time period of the others. RESULT: There were statistically significant differences when comparing P300 amplitude in the first and third stimulation with the comparison group. CONCLUSION: In the same subject, several sequential registrations of P300 caused habituation, which was not seen during exposure to music before P300 recording. Exposure to music at preset different velocities did not affect the P300 in young females.Exposição musical pode auxiliar na reavaliação do P300 e evitar habituação. OBJETIVO: Verificar influĂȘncia Ă  exposição a diferentes tipos de mĂșsica e velocidades no P300 em mulheres. FORMA DO ESTUDO: ClĂ­nico prospectivo. MATERIAIS E MÉTODOS: Participaram 45 mulheres, entre 20 e 36 anos. Estudamos o P300 antes e apĂłs estimulação musical. Selecionamos uma melodia brasileira, melodia nĂŁo brasileira e melodia clĂĄssica. A mesma mĂșsica teve sua velocidade alterada para rĂĄpida e lenta. A amostra foi constituĂ­da por dois grupos com exposição Ă  mĂșsica: um grupo foi exposto aos trĂȘs tipos de mĂșsica com velocidade lenta e o outro grupo exposto Ă s mesmas mĂșsicas com velocidade rĂĄpida. E, um grupo comparação cujas medidas foram feitas sem exposição musical respeitando-se apenas os intervalos de tempo

  7. Contribution of auditory P300 test to the diagnosis of mild cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Yilmaz, Fikriye TĂŒter; Özkaynak, SehĂŒr Siber; Barçin, Ebru

    2017-12-01

    Abnormalities in auditory P300 test have been observed in patients with Parkinson's disease (PD). We aimed to investigate whether or not additional electrophysiological tests assist in making the clinical diagnosis of mild cognitive impairment in Parkinson's disease (PD-MCI), and we evaluated P300 changes in patients with non-demented PD and analyzed the correlation between the cognitive features and P300 changes. Twenty patients with PD who had been diagnosed with mild cognitive impairment (PD-MCI group) according to the Movement Disorder Society (MDS) 2012 PD-MCI level II criteria, 21 patients with PD without cognitive impairment (PD-Normal group), and 20 control subjects (control group) who were neurologically normal were examined by the standard auditory oddball paradigm. The N100, P200, N200, and P300 latencies and N100-P200, P200-N200, and N200-P300 amplitudes were measured and analyzed. P300 latencies recorded from Fz, Cz, and Pz and N200 latency recorded from Fz were significantly longer in the PD-MCI group than in the PD-Normal and the control group (respectively p P300 amplitude recorded from Fz was significantly lower in PD-MCI group than those in the other groups (p = 0.038). While P300 was obtained in all patients in the PD-Normal and the control group, it was lost in 35% of PD-MCI patients. The results show that P300 provides a diagnostic tool for detecting PDMCI. We suggest that P300 prolongation and loss of P300 potential could be used as supportive parameter in the diagnosis of PD-MCI.

  8. Post-training intrahippocampal inhibition of class I histone deacetylases enhances long-term object-location memory

    OpenAIRE

    Hawk, Joshua D.; Florian, CĂ©drick; Abel, Ted

    2011-01-01

    Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance long-term memory have focused on the fear-conditioning task using broad-spectrum HDAC inhibitors. We have found that post-training intrahippocampal a...

  9. The adaptor protein ARA55 and the nuclear kinase HIPK1 assist c-Myb in recruiting p300 to chromatin.

    Science.gov (United States)

    Bengtsen, Mads; SĂžrensen, Linda; Aabel, Linn; Ledsaak, Marit; Matre, Vilborg; Gabrielsen, Odd Stokke

    2017-07-01

    LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs, have been shown to play diverse roles in several cellular processes. A common theme is that they mediate important protein-protein interactions that are key to their function. Androgen receptor-associated protein 55 (ARA55) belongs to this family of bridging proteins containing four C-terminal LIM domains. It has a dual role with functions both at focal adhesions and in the nucleus, apparently shuttling between the two compartments. In the present work, we have expanded our understanding of its nuclear functions by showing that it interacts with three nuclear regulators not previously linked to ARA55. We first identified ARA55 as a novel interaction partner of the nuclear kinase HIPK1 and found that ARA55, like HIPK1, also interacts with the transcription factor c-Myb. In search of a function for these associations, we observed that the coactivator p300 not only binds to c-Myb, but to ARA55 as well. When combined, c-Myb, p300, HIPK1 and ARA55 caused strong synergistic activation of a chromatinized reporter gene. In parallel, all partners, including p300, were efficiently recruited to chromatin at the c-Myb-bound promoter. Consistent with this cooperation, we found that c-Myb and ARA55 share a common set of target genes in an osteosarcoma cellular context. We propose that ARA55 and HIPK1 assist c-Myb in recruiting the coactivator and acetyltransferase p300 to chromatin. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Minipig negative slow wave demonstrates target/nontarget differences in P300 paradigm

    DEFF Research Database (Denmark)

    Arnfred, Sidse Marie; Lind, Nanna Marie; Moustgaard, Anette Caroline

    2003-01-01

    The negative slow wave (NSW) is a late component of the event-related potential (ERP) in man modulated like the P300 by the stimulus, the task, and the response demand. Aiming at the development of a minipig model of schizophrenia, we investigated scalp ERPs in an auditory P300 paradigm in six...

  11. Convolutional neural networks for P300 detection with application to brain-computer interfaces.

    Science.gov (United States)

    Cecotti, Hubert; GrÀser, Axel

    2011-03-01

    A Brain-Computer Interface (BCI) is a specific type of human-computer interface that enables the direct communication between human and computers by analyzing brain measurements. Oddball paradigms are used in BCI to generate event-related potentials (ERPs), like the P300 wave, on targets selected by the user. A P300 speller is based on this principle, where the detection of P300 waves allows the user to write characters. The P300 speller is composed of two classification problems. The first classification is to detect the presence of a P300 in the electroencephalogram (EEG). The second one corresponds to the combination of different P300 responses for determining the right character to spell. A new method for the detection of P300 waves is presented. This model is based on a convolutional neural network (CNN). The topology of the network is adapted to the detection of P300 waves in the time domain. Seven classifiers based on the CNN are proposed: four single classifiers with different features set and three multiclassifiers. These models are tested and compared on the Data set II of the third BCI competition. The best result is obtained with a multiclassifier solution with a recognition rate of 95.5 percent, without channel selection before the classification. The proposed approach provides also a new way for analyzing brain activities due to the receptive field of the CNN models.

  12. P300 after head injury : Pseudodelay caused by reduced P3A amplitude

    NARCIS (Netherlands)

    Elting, JW; van der Naalt, J; van Weerden, TW; De Keyser, J; Maurits, NM

    2005-01-01

    Objective: We compared conventional P300 analysis with source analysis in normal subjects and head-injury patients. Based on earlier findings of improved P300 component identification and reduced P3B latency variability with source analysis in normal subjects, our aim was to investigate whether

  13. P300 after head injury: pseudodelay caused by reduced P3A amplitude.

    Science.gov (United States)

    Elting, Jan-Willem; van der Naalt, Joukje; van Weerden, Tiemen W; De Keyser, Jacques; Maurits, Natasha M

    2005-11-01

    We compared conventional P300 analysis with source analysis in normal subjects and head-injury patients. Based on earlier findings of improved P300 component identification and reduced P3B latency variability with source analysis in normal subjects, our aim was to investigate whether source analysis could improve the distinction between these groups. In total, 21 healthy control subjects and 21 patients with mild to moderate head injury were included in this study. A standard auditory 2-tone oddball paradigm was used. Latencies and amplitudes obtained with conventional P300 analysis were compared with source analysis results. With conventional analysis, head-injury patients had delayed P300 latencies and reduced P300 amplitudes in comparison to controls, while source analysis showed no latency differences for both P3A and P3B components. Instead, source analysis indicated absence of P3A components in 43% of patients. The P300 delay in head-injury patients, observed with conventional analysis, is a pseudodelay caused by decreased P3A amplitudes. Consequently, the unaffected P3B component with its later latency determines conventional P300 latency in these patients. Conventional P300 latency cannot be used to conclude that there was delayed early stimulus processing in head-injury patients.

  14. P300 analysis techniques in cognitive impairment after brain injury : Comparison with neuropsychological and imaging data

    NARCIS (Netherlands)

    Elting, Jan Willem; Maurits, Natasha; van Weerden, Tom; Spikman, Joke; De Keyser, Jacques; van der Naalt, Joukje

    2008-01-01

    Primary objective: To compare P300 source analysis with conventional analysis in patients with cognitive impairment after brain injury. Methods and procedures: P300 results were compared with neuropsychological test data and imaging data in 21 healthy control subjects and 33 patients with brain

  15. Coupled particle filtering : A new approach for P300-based analysis of mental fatigue

    NARCIS (Netherlands)

    Jarchi, Delaram; Sanei, Saeid; Mohseni, Hamid R.; Lorist, Monicque M.

    A new method for investigating mental fatigue based on P300 variability is presented here. In this approach a new coupled particle filtering for tracking variability of P300 subcomponents, i.e., P3a and P3b, across trials is developed. The latency, amplitude, and width of each subcomponent, as the

  16. P300 component identification using source analysis techniques : Reduced latency variability

    NARCIS (Netherlands)

    Elting, JW; van Weerden, TW; van der Naalt, J; De Keyser, JHA; Maurits, NM

    P300 latency variability in normal subjects is a complicating factor in clinical event-related potential studies because it limits diagnostic applicability. The current study was conducted to determine whether identification of P300 (P3A and P3B) components using source analysis techniques can

  17. Mental Ability, P300, and Mismatch Negativity: Analysis of Frequency and Duration Discrimination

    Science.gov (United States)

    Troche, Stefan J.; Houlihan, Michael E.; Stelmack, Robert M.; Rammsayer, Thomas H.

    2009-01-01

    Individual differences in mental ability (MA) were examined with event-related potentials (ERP). In addition to using an auditory frequency discrimination task, a duration discrimination task was used to elicit P300 and mismatch negativity (MMN) components of the ERP. Frequency and duration P300 latencies explained 9% and 10% of variance of MAB


  18. An Asynchronous P300 BCI With SSVEP-Based Control State Detection

    DEFF Research Database (Denmark)

    Panicker, Rajesh C.; Puthusserypady, Sadasivan; Sun, Ying

    2011-01-01

    In this paper, an asynchronous brain–computer interface (BCI) system combining the P300 and steady-state visually evoked potentials (SSVEPs) paradigms is proposed. The information transfer is accomplished using P300 event-related potential paradigm and the control state (CS) detection is achieved...

  19. P300 component of event-related potentials in persons with asperger disorder.

    Science.gov (United States)

    Iwanami, Akira; Okajima, Yuka; Ota, Haruhisa; Tani, Masayuki; Yamada, Takashi; Yamagata, Bun; Hashimoto, Ryuichiro; Kanai, Chieko; Takashio, Osamu; Inamoto, Atsuko; Ono, Taisei; Takayama, Yukiko; Kato, Nobumasa

    2014-10-01

    In the present study, we investigated auditory event-related potentials in adults with Asperger disorder and normal controls using an auditory oddball task and a novelty oddball task. Task performance and the latencies of P300 evoked by both target and novel stimuli in the two tasks did not differ between the two groups. Analysis of variance revealed that there was a significant interaction effect between group and electrode site on the mean amplitude of the P300 evoked by novel stimuli, which indicated that there was an altered distribution of the P300 in persons with Asperger disorder. In contrast, there was no significant interaction effect on the mean P300 amplitude elicited by target stimuli. Considering that P300 comprises two main subcomponents, frontal-central-dominant P3a and parietal-dominant P3b, our results suggested that persons with Asperger disorder have enhanced amplitude of P3a, which indicated activated prefrontal function in this task.

  20. [Diagnostic P300 threshold based on the analysis of receiver operating characteristic curve].

    Science.gov (United States)

    Qiu, Yao-qin; Tang, Yun-xiang; He, Jia

    2013-11-05

    To explore the diagnostic application of receiver operating characteristic (ROC) curve of P300 amplitude and latency in schizophrenia. ROC curve of P300 amplitude and latency was plotted from 91 first episode schizophrenia (FES) and 141 normal controls (NC). Youden's index and distance were calculated in ROC curve to determine the optimal cutoff point of P300 amplitude and latency for schizophrenic diagnosis. Then the subjects were layered by gender and age for improved diagnostic accuracy. The area under ROC curve for P300 amplitude for predicting schizophrenia was 0.746 (P 40 years (28.80%) patients. P300 amplitude has certain values in schizophrenic diagnosis. Gender and age stratification may enhance the diagnostic efficiency of ROC curve in the diagnosis of frequent schizophrenia.

  1. Effects of mental workload and fatigue on the P300, alpha and theta band power during operation of an ERP (P300) brain-computer interface.

    Science.gov (United States)

    KĂ€thner, Ivo; Wriessnegger, Selina C; MĂŒller-Putz, Gernot R; KĂŒbler, Andrea; Halder, Sebastian

    2014-10-01

    The study aimed at revealing electrophysiological indicators of mental workload and fatigue during prolonged usage of a P300 brain-computer interface (BCI). Mental workload was experimentally manipulated with dichotic listening tasks. Medium and high workload conditions alternated. Behavioral measures confirmed that the manipulation of mental workload was successful. Reduced P300 amplitude was found for the high workload condition. Along with lower performance and an increase in the subjective level of fatigue, an increase of power in the alpha band was found for the last as compared to the first run of both conditions. The study confirms that a combination of signals derived from the time and frequency domain of the electroencephalogram is promising for the online detection of workload and fatigue. It also demonstrates that satisfactory accuracies can be achieved by healthy participants with the P300 speller, despite constant distraction and when pursuing the task for a long time. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. A new hybrid BCI paradigm based on P300 and SSVEP.

    Science.gov (United States)

    Wang, Minjue; Daly, Ian; Allison, Brendan Z; Jin, Jing; Zhang, Yu; Chen, Lanlan; Wang, Xingyu

    2015-04-15

    P300 and steady-state visual evoked potential (SSVEP) approaches have been widely used for brain-computer interface (BCI) systems. However, neither of these approaches can work for all subjects. Some groups have reported that a hybrid BCI that combines two or more approaches might provide BCI functionality to more users. Hybrid P300/SSVEP BCIs have only recently been developed and validated, and very few avenues to improve performance have been explored. The present study compares an established hybrid P300/SSVEP BCIs paradigm to a new paradigm in which shape changing, instead of color changing, is adopted for P300 evocation to decrease the degradation on SSVEP strength. The result shows that the new hybrid paradigm presented in this paper yields much better performance than the normal hybrid paradigm. A performance increase of nearly 20% in SSVEP classification is achieved using the new hybrid paradigm in comparison with the normal hybrid paradigm. All the paradigms except the normal hybrid paradigm used in this paper obtain 100% accuracy in P300 classification. The new hybrid P300/SSVEP BCIs paradigm in which shape changing, instead of color changing, could obtain as high classification accuracy of SSVEP as the traditional SSVEP paradigm and could obtain as high classification accuracy of P300 as the traditional P300 paradigm. P300 did not interfere with the SSVEP response using the new hybrid paradigm presented in this paper, which was superior to the normal hybrid P300/SSVEP paradigm. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. P300 Development across the Lifespan: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    van Dinteren, Rik; Arns, Martijn; Jongsma, Marijtje L. A.; Kessels, Roy P. C.

    2014-01-01

    Background The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm, and has been associated with cognitive information processing (e.g. memory, attention, executive function). This paper reviews the development of the auditory P300 across the lifespan. Methodology/Principal Findings A systematic review and meta-analysis on the P300 was performed including 75 studies (n = 2,811). Scopus was searched for studies using healthy subjects and that reported means of P300 latency and amplitude measured at Pz and mean age. These findings were validated in an independent, existing cross-sectional dataset including 1,572 participants from ages 6–87. Curve-fitting procedures were applied to obtain a model of P300 development across the lifespan. In both studies logarithmic Gaussian models fitted the latency and amplitude data best. The P300 latency and amplitude follow a maturational path from childhood to adolescence, resulting in a period that marks a plateau, after which degenerative effects begin. We were able to determine ages that mark a maximum (in P300 amplitude) or trough (in P300 latency) segregating maturational from degenerative stages. We found these points of deflection occurred at different ages. Conclusions/Significance It is hypothesized that latency and amplitude index different aspects of brain maturation. The P300 latency possibly indexes neural speed or brain efficiency. The P300 amplitude might index neural power or cognitive resources, which increase with maturation. PMID:24551055

  4. P300 development across the lifespan: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rik van Dinteren

    Full Text Available BACKGROUND: The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm, and has been associated with cognitive information processing (e.g. memory, attention, executive function. This paper reviews the development of the auditory P300 across the lifespan. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review and meta-analysis on the P300 was performed including 75 studies (n = 2,811. Scopus was searched for studies using healthy subjects and that reported means of P300 latency and amplitude measured at Pz and mean age. These findings were validated in an independent, existing cross-sectional dataset including 1,572 participants from ages 6-87. Curve-fitting procedures were applied to obtain a model of P300 development across the lifespan. In both studies logarithmic Gaussian models fitted the latency and amplitude data best. The P300 latency and amplitude follow a maturational path from childhood to adolescence, resulting in a period that marks a plateau, after which degenerative effects begin. We were able to determine ages that mark a maximum (in P300 amplitude or trough (in P300 latency segregating maturational from degenerative stages. We found these points of deflection occurred at different ages. CONCLUSIONS/SIGNIFICANCE: It is hypothesized that latency and amplitude index different aspects of brain maturation. The P300 latency possibly indexes neural speed or brain efficiency. The P300 amplitude might index neural power or cognitive resources, which increase with maturation.

  5. A covert attention P300-based brain-computer interface: Geospell.

    Science.gov (United States)

    Aloise, Fabio; AricĂČ, Pietro; Schettini, Francesca; Riccio, Angela; Salinari, Serenella; Mattia, Donatella; Babiloni, Fabio; Cincotti, Febo

    2012-01-01

    The Farwell and Donchin P300 speller interface is one of the most widely used brain-computer interface (BCI) paradigms for writing text. Recent studies have shown that the recognition accuracy of the P300 speller decreases significantly when eye movement is impaired. This report introduces the GeoSpell interface (Geometric Speller), which implements a stimulation framework for a P300-based BCI that has been optimised for operation in covert visual attention. We compared the Geospell with the P300 speller interface under overt attention conditions with regard to effectiveness, efficiency and user satisfaction. Ten healthy subjects participated in the study. The performance of the GeoSpell interface in covert attention was comparable with that of the P300 speller in overt attention. As expected, the effectiveness of the spelling decreased with the new interface in covert attention. The NASA task load index (TLX) for workload assessment did not differ significantly between the two modalities. This study introduces and evaluates a gaze-independent, P300-based brain-computer interface, the efficacy and user satisfaction of which were comparable with those off the classical P300 speller. Despite a decrease in effectiveness due to the use of covert attention, the performance of the GeoSpell far exceeded the threshold of accuracy with regard to effective spelling.

  6. Causality in the association between P300 and alpha event-related desynchronization.

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    Weiwei Peng

    Full Text Available Recent findings indicated that both P300 and alpha event-related desynchronization (α-ERD were associated, and similarly involved in cognitive brain functioning, e.g., attention allocation and memory updating. However, an explicit causal influence between the neural generators of P300 and α-ERD has not yet been investigated. In the present study, using an oddball task paradigm, we assessed the task effect (target vs. non-target on P300 and α-ERD elicited by stimuli of four sensory modalities, i.e., audition, vision, somatosensory, and pain, estimated their respective neural generators, and investigated the information flow among their neural generators using time-varying effective connectivity in the target condition. Across sensory modalities, the scalp topographies of P300 and α-ERD were similar and respectively maximal at parietal and occipital regions in the target condition. Source analysis revealed that P300 and α-ERD were mainly generated from posterior cingulate cortex and occipital lobe respectively. As revealed by time-varying effective connectivity, the cortical information was consistently flowed from α-ERD sources to P300 sources in the target condition for all four sensory modalities. All these findings showed that P300 in the target condition is modulated by the changes of α-ERD, which would be useful to explore neural mechanism of cognitive information processing in the human brain.

  7. Use of a Green Familiar Faces Paradigm Improves P300-Speller Brain-Computer Interface Performance.

    Science.gov (United States)

    Li, Qi; Liu, Shuai; Li, Jian; Bai, Ou

    2015-01-01

    A recent study showed improved performance of the P300-speller when the flashing row or column was overlaid with translucent pictures of familiar faces (FF spelling paradigm). However, the performance of the P300-speller is not yet satisfactory due to its low classification accuracy and information transfer rate. To investigate whether P300-speller performance is further improved when the chromatic property and the FF spelling paradigm are combined. We proposed a new spelling paradigm in which the flashing row or column is overlaid with translucent green pictures of familiar faces (GFF spelling paradigm). We analyzed the ERP waveforms elicited by the FF and proposed GFF spelling paradigms and compared P300-speller performance between the two paradigms. Significant differences in the amplitudes of four ERP components (N170, VPP, P300, and P600f) were observed between both spelling paradigms. Compared to the FF spelling paradigm, the GFF spelling paradigm elicited ERP waveforms of higher amplitudes and resulted in improved P300-speller performance. Combining the chromatic property (green color) and the FF spelling paradigm led to better classification accuracy and an increased information transfer rate. These findings demonstrate a promising new approach for improving the performance of the P300-speller.

  8. [The possibility of a multiresolution wavelet analysis for detecting the P300 event related potential].

    Science.gov (United States)

    Aldea, Roxana; Lazăr, Anca Mihaela

    2012-01-01

    The main objective is to high-light the P300 potential on certain electroencephalographic signals. P300 occurs at a relatively well defined time in relation to a stimulus and it represents a signal with a specified band frequency. The electroencephalographic (EEG) was recorded with 4 wet electrodes by means of g.MOBIlab+ module, a g.tec acquisition system. The multiresolution wavelet transform was chosen to extract the P300 potential from the EEG signal because it provides information on both time and frequency domains. The multiresolution wavelet transform decomposes the signal in sub-bands and it helps to highlight the P300 potential. The spectrum of the P300 potential is around 3Hz. For the multiresolution wavelet decomposition this corresponds to coefficients of approximation of order 4 according to 0 to 60 Hz band of the original EEG signal. The representation of these coefficients emphasizes a better detection of P300 potential then in the original signal. It is shown to be a more appropriate method than the direct analysis of the signal because it works with lower dimensional signals. This method of detection of the P300 potential can be used successfully in the implementation of a Brain Computer Interface (BCI).

  9. A P300 event related potential technique for assessment of sexually oriented interest.

    Science.gov (United States)

    Vardi, Yoram; Volos, Michal; Sprecher, Elliot; Granovsky, Yelena; Gruenwald, Ilan; Yarnitsky, David

    2006-12-01

    Despite all of the modern, sophisticated tests that exist for diagnosing and assessing male and female sexual disorders, to our knowledge there is no objective psychophysiological test to evaluate sexual arousal and interest. We provide preliminary data showing a decrease in auditory P300 wave amplitude during exposure to sexually explicit video clips and a significant correlation between the auditory P300 amplitude decrease and self-reported scores of sexual arousal and interest in the clips. A total of 30 healthy subjects were exposed to several blocks of auditory stimuli administered using an oddball paradigm. Baseline auditory P300 amplitudes were obtained and auditory stimuli were then delivered while viewing visual clips with 3 types of content, including sport, scenery and sex. Auditory P300 amplitude significantly decreased during viewing clips of all contents. Viewing sexual content clips caused a maximal decrease in P300 amplitude (p P300 amplitude decrease was significantly related to the sexual interest score (r = 0.37, p = 0.042) but not to interest in clips of nonsexual content. The change in auditory P300 amplitude during exposure to visual stimuli with sexual context seems to be an objective measure of subject sexual interest. This method might be applied to assess therapeutic intervention and as a diagnostic tool for assessing disorders of impaired libido or psychogenic sexual dysfunction.

  10. p300 and C/EBPÎČ-regulated IKKÎČ expression are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells.

    Science.gov (United States)

    Huang, Zheng-Wei; Lien, Gi-Shih; Lin, Chien-Huang; Jiang, Chun-Ping; Chen, Bing-Chang

    2017-07-01

    Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8 (CXCL8) play critical roles in lung inflammation. Our previous study showed that c-Src-dependent IÎșB kinase (IKK)/IÎșBα/nuclear factor (NF)-ÎșB and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding protein ÎČ (C/EBPÎČ) activation are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. In this study, we aimed to investigate the roles of p300 and C/EBPÎČ-reliant IKKÎČ expression in thrombin-induced IL-8/CXCL8 expression. Thrombin-induced increases in IL-8/CXCL8-luciferase activity and IL-8/CXCL8 release were inhibited by p300 small interfering (siRNA). Thrombin-caused histone H3 acetylation was attenuated by p300 siRNA. Stimulation of cells with thrombin for 12h resulted in increases in IKKÎČ expression and phosphorylation in human lung epithelial cells. However, thrombin did not affect p65 expression. Moreover, 12h of thrombin stimulation produced increases in IKKÎČ expression and phosphorylation, and IÎșBα phosphorylation, which were inhibited by C/EBPÎČ siRNA. Finally, treatment of cells with thrombin caused increases in p300 and C/EBPÎČ complex formation, p65 and C/EBPÎČ complex formation, and recruitment of p300, p65, and C/EBPÎČ to the IL-8/CXCL8 promoter. These results imply that p300-dependent histone H3 acetylation and C/EBPÎČ-regulated IKKÎČ expression contribute to thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Results of this study will help clarify C/EBPÎČ signaling pathways involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Connecting the P300 to the diagnosis and prognosis of unconscious patients

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    Ran Li

    2015-01-01

    Full Text Available The residual consciousness of unconscious patients can be detected by studying the P300, a wave among event-related potentials. Previous studies have applied tones, the subjectâ€Čs name and other names as stimuli. However, the results were not satisfactory. In this study, we changed the constituent order of subjectsâ€Čtwo-character names to create derived names. The subjectâ€Čs derived names, together with tones and their own names, were used as auditory stimuli in event-related potential experiments. Healthy controls and unconscious patients were included in this study and made to listen to these auditory stimuli. In the two paradigms, a sine tone followed by the subjectâ€Čs own name and the subjectâ€Čs derived name followed by the subjectâ€Čs own name were used as standard and deviant stimuli, respectively. The results showed that all healthy controls had the P300 using both paradigms, and that the P300 in the second paradigm had a longer latency and two peaks. All minimally conscious state patients had the P300 in the first paradigm and the majority of them had the P300 in the second paradigm. Most vegetative state patients had no P300. Patients who showed the P300 in the two paradigms had more residual consciousness, and patients with the two-peak P300 had a higher probability of awakening within a short time. Our experimental findings suggest that the P300 event-related potential could reflect the conscious state of unconscious patients.

  12. Multifactorial determinants of target and novelty-evoked P300 amplitudes in children of addicted parents.

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    Anja S Euser

    Full Text Available BACKGROUND: Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD] uniquely contributed to P300 amplitude variation above and beyond these other variables. METHODS: Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80 and normal-risk controls (NR;n=100 while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. RESULTS: HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. CONCLUSION: Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents.

  13. Multifactorial Determinants of Target and Novelty-Evoked P300 Amplitudes in Children of Addicted Parents

    Science.gov (United States)

    Euser, Anja S.; Evans, Brittany E.; Greaves-Lord, Kirstin; van de Wetering, Ben J. M.; Huizink, Anja C.; Franken, Ingmar H. A.

    2013-01-01

    Background Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD]) uniquely contributed to P300 amplitude variation above and beyond these other variables. Methods Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80) and normal-risk controls (NR;n=100) while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. Results HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. Conclusion Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents. PMID:24244616

  14. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

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    Hong SU

    2013-03-01

    Full Text Available Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3 and Ac-H4 in human renal mesangial cell (HMCs as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, high glucose group (HG, 25mmol/L D-glucose×2d, memory groups (M1, M2, M3, 25mmol/L D-glucose×2days + 5.5mmol/L D-glucose×3d, 6d or 9d, persisting normal glucose group (NG, 5.5mmol/L D-glucose×9d. ② Advanced glycation end products memory model: normal glucose group (NG, 5.5mmol/ L D-glucose×2d, NG+AGEs group (AGEs, 5.5mmol/L D-glucose+250”g/ml AGEs×2d; AGEs memory group (AGEs-M, 5.5mmol/L D-glucose + 250”g/ml AGEs×2d + 5.5mmol/L D-glucose×3d; BSA control group (NG+BSA, 5.5mmol/L D-glucose + 250”g/ml BSA×2d. ⑱ H2O2 was used to simulate oxidative stress memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, NG+H2O2 group (H2O2, 5.5mmol/L D-glucose +100”mol/L H2O2×30min; H2O2 memory group [(5.5mmol/ L D-glucose + 100”mol/L H2O2×30min + 5.5mmol/L D-glucose×3d]; normal glucose control group (NG3, 5.5mmol/L D-glucose×3d. ④ Transfection with PKCÎČ2 memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d; high glucose group (HG, 25mmol/L D-glucose×2d; memory group (M, 25mmol/L D-glucose×2d + 5.5mmol/L D-glucose×3d; Ad5-null memory group (HN, 25mmol/L D-glucose + Ad5-null×2d + 5.5mmol/L D-glucose×3d; PKCÎČ2 memory group (PO, 25mmol/L D-glucose + Ad5-PKCÎČ2×2d + 5.5mmol/L D-glucose×3d; inhibitor of PKCÎČ2 memory group (PI, 25mmol/L D-glucose×2d + 10”mol/L CGP53353 + 5.5mmol/L D-glucose×3d. The expression of intracellular reactive oxygen species (ROS was detected by fluorescence microscope and fluorescence microplate reader. The expression levels of p300, Ac-H3, Ac-H4 and PKCÎČ2 proteins were

  15. Tapas K Kundu Small molecule modulators of Epigenetic ...

    Indian Academy of Sciences (India)

    Histone acetyltransferase inhibitors. Lysyl CoA (p300). H3 CoA20. (PCAF). Anacardic acid. (p300/PCAF). Garcinol. (p300/PCAF). Curcumin (p300/CBP) γ- butyrolactones (CBP/GCN5). Isothiazolones (p300/PCAF). LTK14 (p300). Lau and Kundu et al., Mol Cell, 2000. Lau and Kundu et al., Mol Cell, 2000. Balasubramanyam ...

  16. Attention and P300-based BCI performance in people with amyotrophic lateral sclerosis

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    Angela eRiccio

    2013-11-01

    Full Text Available The purpose of this study was to investigate the support of attentional and memory processes in controlling a P300-based brain-computer interface (BCI in people suffering from amyotrophic lateral sclerosis (ALS. Eight people with ALS performed two behavioural tasks: i a rapid serial visual presentation (RSVP task, screening the temporal filtering capacity and the speed of the update of the attentive filter, and ii a change detection task, screening the memory capacity and the spatial filtering capacity. The participants were also asked to perform a P300-based BCI spelling task. By using correlation and regression analyses, we found that only the temporal filtering capacity in the RSVP task was a predictor of both the P300-based BCI accuracy and of the amplitude of the P300 elicited performing the BCI task. We concluded that the ability to keep the attentional filter active during the selection of a target influences performance in BCI control.

  17. Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes.

    Science.gov (United States)

    Byun, Jung S; Wong, Madeline M; Cui, Wenwu; Idelman, Gila; Li, Quentin; De Siervi, Adriana; Bilke, Sven; Haggerty, Cynthia M; Player, Audrey; Wang, Yong Hong; Thirman, Michael J; Kaberlein, Joseph J; Petrovas, Constantinos; Koup, Richard A; Longo, Dan; Ozato, Keiko; Gardner, Kevin

    2009-11-17

    Profiling the dynamic interaction of p300 with proximal promoters of human T cells identified a class of genes that rapidly coassemble p300 and RNA polymerase II (pol II) following mitogen stimulation. Several of these p300 targets are immediate early genes, including FOS, implicating a prominent role for p300 in the control of primary genetic responses. The recruitment of p300 and pol II rapidly transitions to the assembly of several elongation factors, including the positive transcriptional elongation factor (P-TEFb), the bromodomain-containing protein (BRD4), and the elongin-like eleven nineteen lysine-rich leukemia protein (ELL). However, transcription at many of these rapidly induced genes is transient, wherein swift departure of P-TEFb, BRD4, and ELL coincides with termination of transcriptional elongation. Unexpectedly, both p300 and pol II remain accumulated or "bookmarked" at the proximal promoter long after transcription has terminated, demarking a clear mechanistic separation between the recruitment and elongation phases of transcription in vivo. The bookmarked pol II is depleted of both serine-2 and serine-5 phosphorylation of its C-terminal domain and remains proximally positioned at the promoter for hours. Surprisingly, these p300/pol II bookmarked genes can be readily reactivated, and elongation factors can be reassembled by subsequent addition of nonmitogenic agents that, alone, have minimal effects on transcription in the absence of prior preconditioning by mitogen stimulation. These findings suggest that p300 is likely to play an important role in biological processes in which transcriptional bookmarking or preconditioning influences cellular growth and development through the dynamic priming of genes for response to rechallenge by secondary stimuli.

  18. Cerebral lesions and event-related potential P300 using positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Yasujiro; Okamoto, Kazuma; Tanaka, Makoto; Kondoh, Susumu; Hirai, Shunsaku (Gunma Univ., Maebashi (Japan). School of Medicine)

    1993-06-01

    To determine what lesions are involved in prolonging event-related potential P300 latency, regional cerebral blood flow (rCBF) and metabolism were investigated by positron emission tomography (PET) in a total of 40 patients with neurologic diseases (12 with chronic cerebrovascular disorder, 9 with spino-cerebellar degeneration, 4 with Alzheimer's type dementia, 4 with amyotrophic lateral sclerosis, and 11 with miscellaneous diseases). There was inverse correlation between rCBF and P300 latency in terms of any of the whole, left, and right hemispheres: P300 latency was associated with decreased rCBF. This was more noticeable in the cerebral cortex than white matter and in the right than left hemisphere, although there was no significant difference between them. In none of the regions, however, was there significant correlation between cerebral oxygen consumption and P300 latency. When the right and left frontal, temporal, parietal and occipital cortexes, thalamus, putamen, and caudatum were examined as regions of interest, there was significantly inverse correlation between rCBF and P300 latency in all regions except for the occipital cortex. This was more noticeable on the right than the left side, although no significant difference was observed. Cerebral oxygen consumption in these lesions did not correlate with P300 latency. In the study on bilateral rCBF difference, decreased rCBF confined to the right parietal lobe, bilateral thalamus and bilateral temporal lobes was found to be associated with a significantly prolonged P300 latency. Thus, rCBF in these regions seemed to be particularly responsible for P300 latency. (N.K.).

  19. P300 component of the auditory event-related potentials and dyslexia.

    Science.gov (United States)

    Ortiz Alonso, T; Navarro, M; Vila Abad, E

    1990-01-01

    Ten normal children (mean age = 9 years) and 12 dyslexic children (mean age = 8.1 years) were compared for latency, amplitude and topographic distribution of both parameters of P300. We found a significant increase in P300 latency in the dyslexic group. Noteworthy is the increase in amplitude in the central parietal area in the control group. These facts and their incidence are discussed in the present study.

  20. Effects of low-frequency repetitive transcranial magnetic stimulation on event-related potential P300

    Science.gov (United States)

    Torii, Tetsuya; Sato, Aya; Iwahashi, Masakuni; Iramina, Keiji

    2012-04-01

    The present study analyzed the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity. P300 latency of event-related potential (ERP) was used to evaluate the effects of low-frequency and short-term rTMS by stimulating the supramarginal gyrus (SMG), which is considered to be the related area of P300 origin. In addition, the prolonged stimulation effects on P300 latency were analyzed after applying rTMS. A figure-eight coil was used to stimulate left-right SMG, and intensity of magnetic stimulation was 80% of motor threshold. A total of 100 magnetic pulses were applied for rTMS. The effects of stimulus frequency at 0.5 or 1 Hz were determined. Following rTMS, an odd-ball task was performed and P300 latency of ERP was measured. The odd-ball task was performed at 5, 10, and 15 min post-rTMS. ERP was measured prior to magnetic stimulation as a control. Electroencephalograph (EEG) was measured at Fz, Cz, and Pz that were indicated by the international 10-20 electrode system. Results demonstrated that different effects on P300 latency occurred between 0.5-1 Hz rTMS. With 1 Hz low-frequency magnetic stimulation to the left SMG, P300 latency decreased. Compared to the control, the latency time difference was approximately 15 ms at Cz. This decrease continued for approximately 10 min post-rTMS. In contrast, 0.5 Hz rTMS resulted in delayed P300 latency. Compared to the control, the latency time difference was approximately 20 ms at Fz, and this delayed effect continued for approximately 15 min post-rTMS. Results demonstrated that P300 latency varied according to rTMS frequency. Furthermore, the duration of the effect was not similar for stimulus frequency of low-frequency rTMS.

  1. Mismatch Negativity But Not P300 Is Associated With Functional Disability in Schizophrenia.

    Science.gov (United States)

    Hamilton, Holly K; Perez, Veronica B; Ford, Judith M; Roach, Brian J; Jaeger, Judith; Mathalon, Daniel H

    2017-08-03

    Mismatch negativity (MMN) and P300 event-related potential (ERP) reductions in schizophrenia (SZ) reflect preattentive and attention-mediated auditory processing deficits, respectively. Although both have been linked to cognitive deficits in SZ, their relative contributions to real-world functioning are unclear. We sought to determine the functional significance of disrupted auditory processing in SZ by examining MMN and P300 in typically disabled low-functioning patients and in patients with high levels of independent role functioning. MMN to auditory deviants and P300 to infrequent auditory target and nontarget novel stimuli were assessed in 20 high-functioning SZ patients (HF-SZ), 17 low-functioning patients (LF-SZ), and 35 healthy comparison (HC) subjects. There was a group effect on MMN and P300 amplitudes across stimulus types. MMN was significantly diminished in LF-SZ compared to HF-SZ and HC, and HF-SZ demonstrated comparable MMN to HC. In contrast, P300 was significantly reduced in both LF-SZ and HF-SZ compared to HC. Logistic regression suggested independent sensitivity of MMN to functioning in SZ over and above P300 measures. Neither MMN nor P300 were associated with positive or negative symptom severity. Results replicate MMN and P300 abnormalities in SZ, and also suggest that the neural mechanisms associated with the preattentive detection of auditory deviance are most compromised in patients with functional disability. MMN may index pathophysiological processes that are critical for optimal functioning in SZ. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2017.

  2. Coherence in P300 as a predictor for the recovery from disorders of consciousness.

    Science.gov (United States)

    Zhang, Ye; Li, Ran; Du, Jubao; Huo, Su; Hao, Jianhui; Song, Weiqun

    2017-07-13

    Accurate and reliable prognostic judgments for disorders of consciousness (DOCs) can provide useful information for clinicians in the establishment of appropriate care plan, and may affect end-of-life decisions of caregivers. But until now no certain or standardized prognostic indicator has been constructed to predict the probability of awareness recovery. This study aims to assess higher-order cortical information processing in DOCs by event-related potential (ERP) and determine the value of P300 to predict the long-term prognosis. Two locked-in (LIS) patients and eighteen DOCs were evaluated with a hierarchical cognitive assessment by ERP. We used subject's own name (SON) as a deviant stimulus, 1000Hz tone and subject's derived name (SDN) as a standard stimulus in two paradigms respectively. P300 elicited by SON was used to assess the information processing. The patients' clinical outcomes were followed up at 2, 6 and 12 months after ERP recordings. The results showed that a P300 component was observed in both paradigms in two LIS patients. All of MCS and four out of nine UWS/VS showed an intact P300 in either paradigm. All of the five patients with P300 in both paradigms were finally awake after 12 months, while none of the eight patients without P300 regained consciousness. A highly significant relationship between P300 and subsequent recovery was found. The results provide evidence that P300 in the hierarchical bedside neurophysiologic oddball procedure can accurately characterize the level of cognitive preservation, and may serve as an alternative tool to predict the likelihood of recovery of DOCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [The P300 based brain-computer interface: effect of stimulus position in a stimulus train].

    Science.gov (United States)

    Ganin, I P; Shishkin, S L; Kochetova, A G; Kaplan, A Ia

    2012-01-01

    The P300 brain-computer interface (BCI) is currently the most efficient BCI. This interface is based on detection of the P300 wave of the brain potentials evoked when a symbol related to the intended input is highlighted. To increase operation speed of the P300 BCI, reduction of the number of stimuli repetitions is needed. This reduction leads to increase of the relative contribution to the input symbol detection from the reaction to the first target stimulus. It is known that the event-related potentials (ERP) to the first stimulus presentations can be different from the ERP to stimuli presented latter. In particular, the amplitude of responses to the first stimulus presentations is often increased, which is beneficial for their recognition by the BCI. However, this effect was not studied within the BCI framework. The current study examined the ERP obtained from healthy participants (n = 14) in the standard P300 BCI paradigm using 10 trials, as well as in the modified P300 BCI with stimuli presented on moving objects in triple-trial (n = 6) and single-trial (n = 6) stimulation modes. Increased ERP amplitude was observed in response to the first target stimuli in both conditions, as well as in the single-trial mode comparing to triple-trial. We discuss the prospects of using the specific features of the ERP to first stimuli and the single-trial ERP for optimizing the high-speed modes in the P300 BCIs.

  4. Moving Away From Error-Related Potentials to Achieve Spelling Correction in P300 Spellers.

    Science.gov (United States)

    Mainsah, Boyla O; Morton, Kenneth D; Collins, Leslie M; Sellers, Eric W; Throckmorton, Chandra S

    2015-09-01

    P300 spellers can provide a means of communication for individuals with severe neuromuscular limitations. However, its use as an effective communication tool is reliant on high P300 classification accuracies ( > 70%) to account for error revisions. Error-related potentials (ErrP), which are changes in EEG potentials when a person is aware of or perceives erroneous behavior or feedback, have been proposed as inputs to drive corrective mechanisms that veto erroneous actions by BCI systems. The goal of this study is to demonstrate that training an additional ErrP classifier for a P300 speller is not necessary, as we hypothesize that error information is encoded in the P300 classifier responses used for character selection. We perform offline simulations of P300 spelling to compare ErrP and non-ErrP based corrective algorithms. A simple dictionary correction based on string matching and word frequency significantly improved accuracy (35-185%), in contrast to an ErrP-based method that flagged, deleted and replaced erroneous characters (-47-0%) . Providing additional information about the likelihood of characters to a dictionary-based correction further improves accuracy. Our Bayesian dictionary-based correction algorithm that utilizes P300 classifier confidences performed comparably (44-416%) to an oracle ErrP dictionary-based method that assumed perfect ErrP classification (43-433%).

  5. "Cognitive" visual acuity estimation based on the event-related potential P300 component.

    Science.gov (United States)

    Heinrich, Sven P; Marhöfer, David; Bach, Michael

    2010-09-01

    An objective assessment of sensory and sensuo-cognitive function, based on physiological signals rather than on the behavioral response of a patient, is often advisable, albeit challenging. Evoked potentials are frequently used as an objective measure, but usually fail to detect defects beyond primary sensory areas, including those of psychogenic origin. Here we assess whether the event-related P300 component may be used to measure "cognitive" visual acuity. A visual oddball paradigm was used to elicit P300 responses in subjects with normal or artificially blurred vision. Probe stimuli consisted of infrequently presented gratings with spatial frequencies in the range of 2.2-16.2 cycles per degree, which could be either target or non-target stimuli depending on their orientation. Frequent stimuli were homogeneously grey fields. Without blur, rare stimuli of all spatial frequencies produced reliable P300 responses. Blur abolished the P300 to fine gratings consistently in 10 of 11 subjects. The drop in P300 amplitude was steep, rather than gradual, between visible and invisible gratings. The P300 is sensitive to identify the resolution threshold and thus may serve as a tool for estimating acuity in cases of visual impairments. The study presents a tool for the objective assessment of acuity in cases of higher-level visual impairments. The concept can most likely be extended to other sensory modalities. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. P300 event related potential application to cognitive status assessment of the patients with subclinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dejanović M.

    2015-01-01

    Full Text Available Disturbances of thyroid function are often accompanied by cognitive and affective disorders. Assessment of cognitive status in the patients with subclinical hypothyroidism represents a possibility for early diagnostics of cognitive impairment and timely introduction of necessary pharmacotherapy treatment. The aim of this study was to quantify whether there are P3 event related potential (ERP deviations as electrophysiological markers of cognitive activity in patients with subclinical hypothyroidism. P300 potentials were examined in thirty patients with subclinical hypothyroidism and in 30 healthy subjects of the control group. P300 was recorded using the classic auditory oddball paradigm, with 20% of target and 80% of non-target stimuli. The results analysis showed a significantly longer latency P300 and reduced amplitude P300 in subjects with subclinical hypothyroidism compared to euthyroid subjects. There is also a statistically significant negative correlation between the results of a mini mental state examination and the P300 latency at Fz electrode (r= -0.47, p <0.01 and Cz electrode (r= -0.43, p =0.017. P300 ERP is important in the evaluation of patients with subclinical hypothyroidism, due to the sensitivity in the detection cognitive disorders.

  7. Reduced NGF serum levels and abnormal P300 event-related potential in first episode schizophrenia.

    Science.gov (United States)

    Xiong, Peng; Zeng, Yong; Zhu, Zuxin; Tan, Deyong; Xu, Fei; Lu, Jin; Wan, Jing; Ma, Mingxing

    2010-06-01

    Nerve growth factor (NGF) plays a crucial role in central nervous system neuron plasticity. Low levels of serum NGF in schizophrenic patients suggest that the neurotrophin contributes to the pathogenesis of the disease. NGF is also thought to alter characteristics of event-related brain potential (ERP) components. The auditory-evoked P300 ERP component, considered an index of brain activity, has reduced amplitude in acute and chronic schizophrenia. This study evaluated the relationship among serum NGF levels, P300 characteristics, and Positive and Negative Symptom Scale (PANSS) scores in first episode, neuroleptic naive schizophrenic patients (N=30) and healthy controls (N=28). Serum NGF was measured by ELISA and P300 elicited using auditory oddball paradigm. Compared to control subjects, schizophrenic patients had significantly reduced serum NGF (pP300 amplitudes at Fz (p=0.003). Additionally, there was a positive correlation between serum NGF serum and P300 amplitude at Fz. No correlation was found between serum NGF or P300 characteristics and PANSS scores. These results suggest that the effects of NGF in schizophrenia are related not only to regulation of neurodevelopment, but also to the electrophysiological characteristics of nerve growth factor. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Event related potential (ERP) P300 after 6 months residence at 4115 meter.

    Science.gov (United States)

    Thakur, Lalan; Ray, Koushik; Anand, J P; Panjwani, Usha

    2011-07-01

    The P300 wave is an event related potential (ERP) elicited by infrequent, task-relevant stimuli and appeared at about 300 ms, represents higher cognitive function of information processing, working memory or stimulus categorization. Hypobaric hypoxia deteriorates the cognitive function during the short term stay (days to few weeks) at high altitude. The present study was carried out to evaluate the P300 responses during long duration stay (1 month and 6 months) at high altitude (HA, 4115 m) in a sample of Indian lowlanders. The study was carried out on 18 healthy male volunteers at sea level (SL). The volunteers were stage inducted to 4115 m altitude in the Eastern Himalayas. The P300 was recorded after 1 and 6 months of their stay at HA. The latencies of peaks N100, P200 and N200 waves did not show any significant changes after 1 and 6 months of stay at HA as compared to SL. The P300 latency was significantly delayed after 1 month and further delayed after 6 month of residence at 4115 m. The P200 and P300 amplitudes did not show any changes. The increase in P300 latency indicated that long duration of stay at high altitude slows the stimulus evaluation processes. The observations suggest that hypoxia causes slowing of the signal processing at HA. The magnitude of the effects of hypobaric hypoxia may be dependent upon the duration of residence at high altitude.

  9. P300 Amplitude in Alzheimer's Disease: A Meta-Analysis and Meta-Regression.

    Science.gov (United States)

    Hedges, Dawson; Janis, Rebecca; Mickelson, Stephen; Keith, Cierra; Bennett, David; Brown, Bruce L

    2016-01-01

    Alzheimer's disease accounts for 60% of all dementia. Numerous biomarkers have been developed that can help in making an early diagnosis. The P300 is an event-related potential that may be abnormal in Alzheimer's disease. Given the possible association between P300 amplitude and Alzheimer's disease and the need for biomarkers in early Alzheimer's disease, the main purpose of this meta-analysis and meta-regression was to characterize P300 amplitude in probable Alzheimer's disease compared to healthy controls. Using online search engines, we identified peer-reviewed articles containing amplitude measures for the P300 in response to a visual or auditory oddball stimulus in subjects with Alzheimer's disease and in a healthy control group and pooled effect sizes for differences in P300 amplitude between Alzheimer's disease and control groups to obtain summary effect sizes. We also used meta-regression to determine whether age, sex, educational attainment, or dementia severity affected the association between P300 amplitude and Alzheimer's disease. Twenty articles containing a total of 646 subjects met inclusion and exclusion criteria. The overall effect size from all electrode locations was 1.079 (95% confidence interval=0.745-1.412, PP300 amplitude is smaller in subjects with Alzheimer's disease than in healthy controls. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  10. PIAS1 binds p300 and behaves as a coactivator or corepressor of the transcription factor c-Myb dependent on SUMO-status.

    Science.gov (United States)

    Ledsaak, Marit; Bengtsen, Mads; MolvĂŠrsmyr, Ann-Kristin; Fuglerud, Bettina Maria; Matre, Vilborg; Eskeland, Ragnhild; Gabrielsen, Odd Stokke

    2016-05-01

    The PIAS proteins (Protein Inhibitor of Activated STATs) constitute a family of multifunctional nuclear proteins operating as SUMO E3 ligases and being involved in a multitude of interactions. They participate in a range of biological processes, also beyond their well-established role in the immune system and cytokine signalling. They act both as transcriptional corepressors and coactivators depending on the context. In the present work, we investigated mechanisms by which PIAS1 causes activation or repression of c-Myb dependent target genes. Analysis of global expression data shows that c-Myb and PIAS1 knockdowns affect a subset of common targets, but with a dual outcome consistent with a role of PIAS1 as either a corepressor or coactivator. Our mechanistic studies show that PIAS1 engages in a novel interaction with the acetyltransferase and coactivator p300. Interaction and ChIP analysis suggest a bridging function where PIAS1 enhances p300 recruitment to c-Myb-bound sites through interaction with both proteins. In addition, the E3 activity of PIAS1 enhances further its coactivation. Remarkably, the SUMO status of c-Myb had a decisive role, indicating a SUMO-dependent switch in the way PIAS1 affects c-Myb, either as a coactivator or corepressor. Removal of the two major SUMO-conjugation sites in c-Myb (2KR mutant), which enhances its activity significantly, turned PIAS1 into a corepressor. Also, p300 was less efficiently recruited to chromatin by c-Myb-2KR. We propose that PIAS1 acts as a "protein inhibitor of activated c-Myb" in the absence of SUMOylation while, in its presence, PIAS behaves as a "protein activator of repressed c-Myb". Copyright © 2016 Elsevier B.V. All rights reserved.

  11. A Role for Histone Deacetylases in the Cellular and Behavioral Mechanisms Underlying Learning and Memory

    Science.gov (United States)

    Mahgoub, Melissa; Monteggia, Lisa M.

    2014-01-01

    Histone deacetylases (HDACs) are a family of chromatin remodeling enzymes that restrict access of transcription factors to the DNA, thereby repressing gene expression. In contrast, histone acetyltransferases (HATs) relax the chromatin structure allowing for an active chromatin state and promoting gene transcription. Accumulating data have


  12. The MYST domain acetyltransferase Chameau functions in epigenetic mechanisms of transcriptional repression.

    Science.gov (United States)

    Grienenberger, Aurélie; Miotto, Benoit; Sagnier, Thierry; Cavalli, Giacomo; Schramke, Vera; Geli, Vincent; Mariol, Marie Christine; Berenger, Hélene; Graba, Yacine; Pradel, Jacques

    2002-04-30

    Reversible acetylation of histone tails plays an important role in chromatin remodelling and regulation of gene activity. While modification by histone acetyltransferase (HAT) is usually linked to transcriptional activation, we provide here evidence for HAT function in several types of epigenetic repression. Chameau (Chm), a new Drosophila member of the MYST HAT family, dominantly suppresses position effect variegation (PEV), is required for the maintenance of Hox gene silencing by Polycomb group (PcG) proteins, and can partially substitute for the MYST Sas2 HAT in yeast telomeric position effect (TPE). Finally, we provide in vivo evidence that the acetyltransferase activity of Chm is required in these processes, since a variant protein mutated in the catalytic domain no longer rescues PEV modification, telomeric silencing of SAS2-deficient yeast cells, nor lethality of chm mutant flies. These findings emphasize the role of an acetyltransferase in gene silencing, which supports, according to the histone code hypothesis, that transcription at a particular locus is determined by a precise combination of histone tail modifications rather than by overall acetylation levels.

  13. Impact of spatial filters during sensor selection in a visual P300 brain-computer interface.

    Science.gov (United States)

    Rivet, B; Cecotti, H; Maby, E; Mattout, J

    2012-01-01

    A challenge in designing a Brain-Computer Interface (BCI) is the choice of the channels, e.g. the most relevant sensors. Although a setup with many sensors can be more efficient for the detection of Event-Related Potential (ERP) like the P300, it is relevant to consider only a low number of sensors for a commercial or clinical BCI application. Indeed, a reduced number of sensors can naturally increase the user comfort by reducing the time required for the installation of the EEG (electroencephalogram) cap and can decrease the price of the device. In this study, the influence of spatial filtering during the process of sensor selection is addressed. Two of them maximize the Signal to Signal-plus-Noise Ratio (SSNR) for the different sensor subsets while the third one maximizes the differences between the averaged P300 waveform and the non P300 waveform. We show that the locations of the most relevant sensors subsets for the detection of the P300 are highly dependent on the use of spatial filtering. Applied on data from 20 healthy subjects, this study proves that subsets obtained where sensors are suppressed in relation to their individual SSNR are less efficient than when sensors are suppressed in relation to their contribution once the different selected sensors are combined for enhancing the signal. In other words, it highlights the difference between estimating the P300 projection on the scalp and evaluating the more efficient sensor subsets for a P300-BCI. Finally, this study explores the issue of channel commonality across subjects. The results support the conclusion that spatial filters during the sensor selection procedure allow selecting better sensors for a visual P300 Brain-Computer Interface.

  14. A general population twin study of conduct problems and the auditory P300 waveform.

    Science.gov (United States)

    Bertoletti, Eleonora; Michelini, Giorgia; Moruzzi, Sara; Ferrer, Giuseppina; Ferini-Strambi, Luigi; Stazi, Maria Antonietta; Ogliari, Anna; Battaglia, Marco

    2014-01-01

    Reduced amplitude of the P300 event-related potential has been consistently associated with a variety of externalising problems, including conduct disorder. The few available genetically-informative studies of these relationships, however, were conducted among adolescents/adults (i.e., at an age when conduct disorder has typically already become manifest). Among 200 general population twins with a mean age of 9 years (range 6-14 years), we studied the relationship between the P300 waveform elicited by an auditory oddball task and the DSM-oriented conduct problems scale of the Child Behavior Checklist 6-18. Conduct problems scores were negatively and significantly correlated (r = -0.19, p = 0.01) with P300 amplitude; correlations between P300 amplitude and the other DSM-oriented Child Behavior Checklist scales were non-significant, except for oppositional defiant problems (p = 0.01). We found moderate heritability estimates for both P300 amplitude (0.58, CI:0.37;0.73) and conduct problems (0.52, CI:0.25;0.70). Bivariate twin analyses indicated that the covariation between these two phenotypes can be explained by additive genetic factors only, with a genetic correlation of -0.33. An association between reduced P300 amplitude and conduct problems can be substantiated already in childhood, at an age that precedes the most typical onset of conduct disorder. This relationship appears to be genetic in nature. Reduced P300 amplitude can represent a valuable marker for conduct problems, and can contribute to the early identification of children at high-risk for conduct disorder.

  15. Coherent activity in bilateral parieto-occipital cortices during P300-BCI operation

    Directory of Open Access Journals (Sweden)

    Kouji eTakano

    2014-05-01

    Full Text Available The visual P300 brain computer interface (BCI, a popular system for EEG-based BCI, uses the P300 event-related potential to select an icon arranged in a flicker matrix. In earlier studies, we used green/blue luminance and chromatic changes in the P300 BCI system and reported that this luminance and chromatic flicker matrix was associated with better performance and greater subject comfort compared with the conventional white/gray luminance flicker matrix. To highlight areas involved in improved P300-BCI performance, we used simultaneous EEG-fMRI recordings and showed enhanced activities in bilateral and right lateralized parieto-occipital areas. Here, to capture coherent activities of the areas during P300-BCI, we collected whole-head 306-channel MEG data. When comparing functional connectivity between the right and left parieto-occipital channels, significantly greater functional connectivity in the alpha band was observed under the green/blue flicker matrix condition than under the white/gray flicker matrix condition. Current sources were estimated with a narrow-band adaptive spatial filter, and mean imaginary coherence (MIC was computed in the alpha band. Significantly greater coherence was observed in the right posterior parietal cortex under the green/blue than under the white/gray condition. Reanalysis of previous EEG-based P300-BCI data showed significant correlations between the power of the coherence of the bilateral parieto-occipital cortices and their performance accuracy. These results suggest that coherent activity in the bilateral parieto-occipital cortices plays a significant role in effectively driving the P300-BCI.

  16. Analysis of neural sources of p300 event-related potential in normal and schizophrenic participants.

    Science.gov (United States)

    Sabeti, Malihe; Moradi, Ehsan; Katebi, Serajeddin

    2011-01-01

    The P300 event-related potential (ERP) is associated with attention and memory operations of the brain. P300 is changed in many cognitive disorders such as dementia, Alzheimer, schizophrenia, and major depression disorder. Therefore, investigation on basis of this component can help to improve our understanding of pathophysiology of such disorders and fundamentals of memory and attention mechanism. In this study, electroencephalography (EEG) signals of 20 schizophrenic patients and 20 age-matched normal subjects are analyzed. The oddball paradigm has been used to record the P300, where two stimuli including target and standard are presented with different probabilities in a random order. Data analysis is carried out using conventional averaging techniques as well as P300 source localization with low-resolution brain electromagnetic tomography (LORETA). The results show that the P300 components stem from a wide cerebral cortex network and defining a small definite cortical zone as its generator is impossible. In normal group, cingulate gyrus, one of the essential components of working memory circuit that was reported by Papez, is found to be the most activated area and it can be in line with the hypothesis that at least a part of the P300 is elicited by working-memory circuit. In schizophrenic group, frontal lobe is the most activated area that was responsible for P300 sources. Our results show that the cingulate gyrus is not activated in comparison with normal group, which is in line with previous results that dysfunction of the anterior cingulate cortex plays a prominent role in the schizophrenia disorder.

  17. Heart rate and P300: Integrating peripheral and central indices of cognitive processing.

    Science.gov (United States)

    Guerra, Pedro Maria; SĂĄnchez-Adam, Alicia; Miccoli, Laura; Polich, John; Vila, Jaime

    2016-02-01

    To assess the integration of peripheral (heart rate, HR) and central (event-related potential, P300) measures of cognition, the present study varied inter-stimulus presentation time (ISI) and employed comparable data reduction methods for the HR and ERP data. Young adults (n=33) performed an auditory oddball count task in which the ISI was varied (short vs. long, to maximize target detection for both measures) and task condition (single stimulus, short-ISI oddball, long-ISI oddball, to assay stimulus presentation condition between HR and P300). The off-line cardiotachometer method parallels signal averaging and was applied to HR data reduction. The main goal was to characterize target vs. standard processing in each measurement type using appropriate recording approaches with respect to differentiating the two stimuli in each task (target vs. silence, target vs. standard short-ISI, target vs. standard long-ISI). Results demonstrated reliable differences between target/standard stimuli for both the biphasic HR (deceleration/acceleration) signal and for P300 amplitude production, with larger amplitudes for target than standard. The short and long ISIs yielded no reliable initial HR deceleration differences, but the late acceleration was observed for the long-ISI condition only. Correlational analysis between HR and P300 measures indicated that people with smaller HR deceleration had larger P300 amplitude suggesting that the larger target/standard differences for HR deceleration and P300 amplitude, observed at an experimental level, are reversed at an individual level. The contributions of simultaneously recording HR and P300 to characterize cognition and theoretical implications are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Documenting, modelling and exploiting P300 amplitude changes due to variable target delays in Donchin's speller

    Science.gov (United States)

    Citi, Luca; Poli, Riccardo; Cinel, Caterina

    2010-10-01

    The P300 is an endogenous event-related potential (ERP) that is naturally elicited by rare and significant external stimuli. P300s are used increasingly frequently in brain-computer interfaces (BCIs) because the users of ERP-based BCIs need no special training. However, P300 waves are hard to detect and, therefore, multiple target stimulus presentations are needed before an interface can make a reliable decision. While significant improvements have been made in the detection of P300s, no particular attention has been paid to the variability in shape and timing of P300 waves in BCIs. In this paper we start filling this gap by documenting, modelling and exploiting a modulation in the amplitude of P300s related to the number of non-targets preceding a target in a Donchin speller. The basic idea in our approach is to use an appropriately weighted average of the responses produced by a classifier during multiple stimulus presentations, instead of the traditional plain average. This makes it possible to weigh more heavily events that are likely to be more informative, thereby increasing the accuracy of classification. The optimal weights are determined through a mathematical model that precisely estimates the accuracy of our speller as well as the expected performance improvement w.r.t. the traditional approach. Tests with two independent datasets show that our approach provides a marked statistically significant improvement in accuracy over the top-performing algorithm presented in the literature to date. The method and the theoretical models we propose are general and can easily be used in other P300-based BCIs with minimal changes.

  19. Localizing P300 generators in high-density event- related potential with fMRI.

    Science.gov (United States)

    Li, Yuezhi; Wang, Li-Qun; Hu, Yong

    2009-03-01

    To assess the effects of stimulus context on the P300 component, an eight-orientation Landolt ring task was introduced. As the stimulus context of this task differs from the traditional two-stimulus oddball paradigm, the purpose here was to apply EEG/fMRI integration to investigate the localization and activities of the P300 generators involved with this task. Ten healthy subjects performed the visual P300 task while fMRI and 64-channel ERP data were acquired. The voltage topographical maps of the P300 component were calculated and analyzed for the main activation foci. Furthermore, constraints from fMRI were used to identify the source activities of visual P300 ERP. Analysis of the hemodynamic response to the visual target stimuli revealed a distributed network of neural sources in the bilateral parietal lobules, middle and inferior frontal gyrus, precentral and postcentral cortex, and anterior cingulate gyrus. The analysis particularly showed preponderant activations of the bilateral superior parietal lobules. In this target detection design, two distinct P300 peaks were observed in the dipole waveforms, the bilateral prefrontal and the right inferior parietal dipole waveforms displayed the higher peak at short latency, while the four parietal, the anterior cingulate, and the temporal dipole waveforms had the higher peak at long latency. Compared with the classical oddball paradigm, the amplitude decreased in this study, which might be related to its particular stimulus context. The source technique was utilized to yield a realistic 11-dipole model and distinguish the anatomical generators of early and late components of the P300 response.

  20. Objective measurement of visual resolution using the P300 to self-facial images.

    Science.gov (United States)

    Marhöfer, David J; Bach, Michael; Heinrich, Sven P

    2015-10-01

    To assess visual acuity objectively "beyond V1", the P300 event-related potential is a promising candidate and closely associated with conscious perception. However, the P300 can be willfully modulated, a disadvantage for objective visual acuity estimation. Faces are very salient stimuli and difficult to ignore. Here, we present a P300-type paradigm to assess visual acuity with faces. Gray-scale portraits of the respective subject served as oddball stimuli (probability 1/7), scrambled versions of these as the standard stimuli (probability 6/7). Furthermore, stimuli were spatially high-pass filtered (at 0, 2.2, 4.2 and 8.3 cpd), making them recognizable only with sufficient acuity. Acuity was systematically reduced by dioptric blur, chosen individually to render faces unrecognizable when high-passed at ≄ 4.2 cpd. EEG was recorded from 11 subjects at 32 scalp positions and re-referenced to the average of TP9 and TP10. One of the rare face variants was designated as target, for which a button had to be pressed. The event-related potential was dominated by the P300 at 300-800 ms. All subjects had a significant (P P300 for 0- to 8.3-cpd filtering. When vision was blurred, the fraction of significant P300 responses to 8.3-cpd filtered faces dropped to 18%, but stayed at 100% for 4.2 cpd. Another component, the vertex positive potential (VPP) at 170 ms, was undetectable in most participants with blur and all levels of filtering, even when the images were recognizable. The study demonstrates the feasibility of a face-based P300 approach to objectively assess visual acuity. The sensitivity to stimulus degradation was comparable to that of a grating-based approach as previously reported. An unexpected finding was the differing behavior of the P300 and the VPP. The VPP was quite sensitive to high-pass filtering, while the P300 sustained stronger filtering, although for its generation, the faces must also be discriminated from scrambled faces.

  1. A hybrid BCI system combining P300 and SSVEP and its application to wheelchair control.

    Science.gov (United States)

    Li, Yuanqing; Pan, Jiahui; Wang, Fei; Yu, Zhuliang

    2013-11-01

    In this paper, a hybrid brain-computer interface (BCI) system combining P300 and steady-state visual evoked potential (SSVEP) is proposed to improve the performance of asynchronous control. The four groups of flickering buttons were set in the graphical user interface. Each group contained one large button in the center and eight small buttons around it, all of which flashed at a fixed frequency (e.g., 7.5 Hz) to evoke SSVEP. At the same time, the four large buttons of the four groups were intensified through shape and color changes in a random order to produce P300 potential. During the control state, the user focused on a desired group of buttons (target buttons) to evoke P300 potential and SSVEP, simultaneously. Discrimination between the control and idle states was based on the detection of both P300 and SSVEP on the same group of buttons. As an application, this method was used to produce a "go/stop" command in real-time wheelchair control. Several experiments were conducted, and data analysis results showed that combining P300 potential and SSVEP significantly improved the performance of the BCI system in terms of detection accuracy and response time.

  2. Cognitive deterioration and changes of P300 during total sleep deprivation.

    Science.gov (United States)

    Lee, Heon-Jeong; Kim, Leen; Suh, Kwang-Yoon

    2003-10-01

    The study was conducted to evaluate the cognitive deteriorations induced by sleep deprivation with the computerized neurocognitive tests and the P300 event-related potential. Thirty healthy college students (22 men, eight women) participated in the present study. Subjects remained awake for 38 h under continuous surveillance. In the morning and the evening of the two study days, the computerized neurocognitive tests and the P300 were performed. In vigilance test and reaction unit test, there were significant cognitive impairments during sleep deprivation. However, in the cognitrone test there was significant functional improvement, which might be due to the practice effect. The P300 latency was significantly prolonged and the amplitudes decreased during sleep deprivation. The cognitive impairment during 38 h of sleep deprivation was mainly in terms of vigilance and reaction time. In contrast, higher complex cognitive function such as fine perceptual analyses, visual discrimination and working memory might be not affected by 38 h of total sleep deprivation. The changes of P300 were significantly correlated with the results of vigilance and reaction unit tests but not with the cognitrone test. Taken together, these results suggest that the P300 changes that occur during sleep deprivation are a reflection of the decrement in vigilance, which prolongs reaction time.

  3. P300 and Neuropsychological assessment in Mild Cognitive Impairment and Alzheimer Dementia

    Directory of Open Access Journals (Sweden)

    Mario eParra

    2012-12-01

    Full Text Available Only a small proportion of individuals with Mild Cognitive Impairment (MCI will convert to dementia. Methods currently available to identify risk for conversion do not combine enough sensitivity and specificity, which is even more problematic in low-educated populations. Current guidelines suggest the use of combined markers for dementia to enhance the prediction accuracy of assessment methods. The present study adhered to this proposal and investigated the sensitivity and specificity of the electrophysiological component P300 and standard neuropsychological tests to assess patients with Alzheimer’s disease (AD and MCI recruited from a low-income country. The neuropsychological battery comprised tests of memory, attention, language, praxis and executive functions. The P300 was recorded using a classical visual odd-ball paradigm. Three variables were found to achieve sensitivity and specificity values above 80% (Immediate and Delayed recall of word list – CERAD – and the latency of P300 for both MCI and AD. When they entered the model together (i.e., combined approach the sensitivity for MCI increased to 96% and the specificity remained high (80%. Our preliminary findings suggest that the combined use of sensitive neuropsychological tasks and the analysis of the P300 may offer a very useful method for the preclinical assessment of AD, particularly in populations with low socioeconomic and educational levels. Our results provide a platform and justification to employ more resources to convert P300 and related parameters into a biological marker for AD.

  4. Psychophysiological correlates in male to female transsexuals studied with a P300 investigation.

    Science.gov (United States)

    Papageorgiou, C; Papageorgaki, P; Tolis, G; Rabavilas, A D; Christodoulou, G N

    2003-04-01

    Transsexualism is thought to be related to cortical processes reflecting a complex mosaic of biological, psychological and social/cultural information. Since the P300 component of event-related potentials is considered as an index of attentional processes, the present study focuses on auditory P300 elicited during a short memory test in male to female (MF) transsexuals, compared with that in healthy controls. The P300 component was evaluated during the anticipatory period of a short memory test in 13 MF transsexuals who had a gender reassignment operation, at least 3 years previously (mean time 17-6 years, range 3-31 years) and 26 healthy subjects (11 males and 15 females) matched for age and educational level. MF transsexuals exhibited significant reduction of P300 amplitude in the left frontal and temporoparietal areas in comparison to the control group. Furthermore, the group of transsexuals showed a significant delay of P300 latency in comparison to the controls, at the central frontal region. These findings point to significant psychophysiological alterations of distributed cortical circuits in MF transsexuals. These alterations may be critically related to the biological substrate of MF transsexualism.

  5. A P300 brain-computer interface based on a modification of the mismatch negativity paradigm.

    Science.gov (United States)

    Jin, Jing; Sellers, Eric W; Zhou, Sijie; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

    2015-05-01

    The P300-based brain-computer interface (BCI) is an extension of the oddball paradigm, and can facilitate communication for people with severe neuromuscular disorders. It has been shown that, in addition to the P300, other event-related potential (ERP) components have been shown to contribute to successful operation of the P300 BCI. Incorporating these components into the classification algorithm can improve the classification accuracy and information transfer rate (ITR). In this paper, a single character presentation paradigm was compared to a presentation paradigm that is based on the visual mismatch negativity. The mismatch negativity paradigm showed significantly higher classification accuracy and ITRs than a single character presentation paradigm. In addition, the mismatch paradigm elicited larger N200 and N400 components than the single character paradigm. The components elicited by the presentation method were consistent with what would be expected from a mismatch paradigm and a typical P300 was also observed. The results show that increasing the signal-to-noise ratio by increasing the amplitude of ERP components can significantly improve BCI speed and accuracy. The mismatch presentation paradigm may be considered a viable option to the traditional P300 BCI paradigm.

  6. [The P300-based brain-computer interface: presentation of the complex "flash + movement" stimuli].

    Science.gov (United States)

    Ganin, I P; Kaplan, A Ia

    2014-01-01

    The P300 based brain-computer interface requires the detection of P300 wave of brain event-related potentials. Most of its users learn the BCI control in several minutes and after the short classifier training they can type a text on the computer screen or assemble an image of separate fragments in simple BCI-based video games. Nevertheless, insufficient attractiveness for users and conservative stimuli organization in this BCI may restrict its integration into real information processes control. At the same time initial movement of object (motion-onset stimuli) may be an independent factor that induces P300 wave. In current work we checked the hypothesis that complex "flash + movement" stimuli together with drastic and compact stimuli organization on the computer screen may be much more attractive for user while operating in P300 BCI. In 20 subjects research we showed the effectiveness of our interface. Both accuracy and P300 amplitude were higher for flashing stimuli and complex "flash + movement" stimuli compared to motion-onset stimuli. N200 amplitude was maximal for flashing stimuli, while for "flash + movement" stimuli and motion-onset stimuli it was only a half of it. Similar BCI with complex stimuli may be embedded into compact control systems requiring high level of user attention under impact of negative external effects obstructing the BCI control.

  7. Cognitive impairment in Chinese IIDDs revealed by MoCA and P300.

    Science.gov (United States)

    Zeng, Qiuming; Dong, Xiaohua; Ruan, Chunyun; Hu, Bo; Zhou, Binting; Xue, Yuanyuan; Liu, Yu; Yang, Huan

    2017-08-01

    To investigate the value of MoCA and auditory P300 as a cognitive assessment tool in chinese idiopathic inflammatory-demyelinating diseases (IIDDs), eighty three consecutive patients with IIDDs and thirteen sex- and age-matched healthy controls were recruited in the study. MMSE, MoCA and auditory P300 potential were administrated to each participant. The percentage of cognitive impairment in IIDDs patients was 24.1% by using MMSE, while the percentage was 81.9% by using MoCA. The majority of IIDDs participants had MMSE scores in the normal range. In contrast, few IIDDs participants scored in the normal range on the MoCA. Age, EDSS and depression correlated negatively with the total score of MoCA and MMSE. Years of education correlated positively with MoCA and MMSE. ADEM patients scored lower on all MoCA subtests. Prolonged latency P300 which negatively correlated with MoCA and reduced P300 amplitude which positively correlated with MoCA were detected in IIDDs patients. Thus MoCA is superior to the MMSE as a cognitive impairment scan tool and P300 is useful for detecting cogntive deficiency in chinese IIDDs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The effect of duration of multiple sclerosis and expanded disability status scale on P300

    Directory of Open Access Journals (Sweden)

    Parisa Rasoulifard

    2013-05-01

    Full Text Available Background and Aim: Multiple sclerosis (MS is characterized with inflammation, demyelization and gliosis. It may be relapsing, remitting, or progressive. Cognitive impairment is relatively prevalent in patients wit h multiple sclerosis and as duration of disease is longer as cognition impairment is more. To understand the cognitive impairment, event related potential can be considered as a valuable tool. This study aimed to investigate the influence of duration of disease and expanded disability status scale (EDSS on the amplitude and latency of the event related potentials of P300 in patients with multiple sclerosis. Methods: In this cross-sectional and non-intervention study, 21 patients with multiple sclerosis with mean age of 27.8 with SD 7.1 years (between 18 to 50 years were enrolled. The patients were selected randomly. The correlation of P300 event-related potential and oddball paradigm was assessed, using two 1000 and 2000 Hz tone burst stimulus. Results: There was a significant correlation between the latency of P300 wave and duration of disease and expanded disability status scale (p 0.50. The correlation of amplitude of P300 and duration of disease and expanded disability status scale was not significant (p>0.05. Conclusion: Significant correlation between the latency of P300 and the duration of multiple sclerosis and expanded disability status scale can be a sign of central nervous system changes. Besides, there is a relation between physical disability and cognitive impairments.

  9. P300 ERP Component Depends on Both Spatial Frequency and Contrast

    Directory of Open Access Journals (Sweden)

    Li-Ting Tsai

    2011-05-01

    Full Text Available Contrast perception depends on not only the early visual responses, but also top-down modulations. We measured how does P300, a well-documented event-related potential (ERP index for top-down influence, change with both spatial frequency and contrast. ERP were acquired from 10 participants, aged 18–50 years, when they were performing a visual oddball task. The target was a Gabor patch whose spatial frequency was either 4 or 8 cy/degree and contrasts 90% or 30%. The probability of target presence in a trial was 30%. All target stimuli produced a reliable P300 component. At the low spatial frequency, the amplitude of P300 was larger and the latency was shorter for the low contrast patterns than for the higher contrast ones for all electrodes. Such difference was not observed in high spatial frequency patterns. The latency was slightly longer for high spatial frequency patterns than the low spatial frequency ones. Our results showed an interaction between spatial frequency and contrast in P300. The characteristics of P300 at low spatial frequency correlated with task difficulty, but not at high spatial frequency. This suggests that the top-down influence on contrast perception may be spatial frequency depended.

  10. An Auditory-Tactile Visual Saccade-Independent P300 Brain-Computer Interface.

    Science.gov (United States)

    Yin, Erwei; Zeyl, Timothy; Saab, Rami; Hu, Dewen; Zhou, Zongtan; Chau, Tom

    2016-02-01

    Most P300 event-related potential (ERP)-based brain-computer interface (BCI) studies focus on gaze shift-dependent BCIs, which cannot be used by people who have lost voluntary eye movement. However, the performance of visual saccade-independent P300 BCIs is generally poor. To improve saccade-independent BCI performance, we propose a bimodal P300 BCI approach that simultaneously employs auditory and tactile stimuli. The proposed P300 BCI is a vision-independent system because no visual interaction is required of the user. Specifically, we designed a direction-congruent bimodal paradigm by randomly and simultaneously presenting auditory and tactile stimuli from the same direction. Furthermore, the channels and number of trials were tailored to each user to improve online performance. With 12 participants, the average online information transfer rate (ITR) of the bimodal approach improved by 45.43% and 51.05% over that attained, respectively, with the auditory and tactile approaches individually. Importantly, the average online ITR of the bimodal approach, including the break time between selections, reached 10.77 bits/min. These findings suggest that the proposed bimodal system holds promise as a practical visual saccade-independent P300 BCI.

  11. [Changes of the event related potential P300 following topiramate treatment in children with epilepsy].

    Science.gov (United States)

    Yang, Wen; Li, Mei

    2008-10-01

    The event related potential (ERP-P300) is useful to determine cognitive disturbances. This study examined the changes of ERP-P300 following different dosages of topiramate (TPM) treatment in children with epilepsy in order to investigate the effect of different dosages of TPM on cognitive function. Thirty cases of benign childhood epilepsy with centrotemporal spikes (BECTS) were first administered with TPM at a dosage of 2 mg/kg/d for 6 months. Afterwards they received another 6 months of TPM treatment at a dosage of 5 mg/kg/d. ERP-P300 was tested before and after different dosages of TPM treatment. There were no significant differences in the latency and amplitude of ERP-P300 before and after 6 months low dosages of TPM treatment. However, the latency was more prolonged and the amplitude was reduced in the ERP-P300 testing after 6 months high dosage of TMP treatment (Prelated to its dosage in children with epilepsy.

  12. The Performance of EEG-P300 Classification using Backpropagation Neural Networks

    Directory of Open Access Journals (Sweden)

    Arjon Turnip

    2013-12-01

    Full Text Available Electroencephalogram (EEG recordings signal provide an important function of brain-computer communication, but the accuracy of their classification is very limited in unforeseeable signal variations relating to artifacts. In this paper, we propose a classification method entailing time-series EEG-P300 signals using backpropagation neural networks to predict the qualitative properties of a subject’s mental tasks by extracting useful information from the highly multivariate non-invasive recordings of brain activity. To test the improvement in the EEG-P300 classification performance (i.e., classification accuracy and transfer rate with the proposed method, comparative experiments were conducted using Bayesian Linear Discriminant Analysis (BLDA. Finally, the result of the experiment showed that the average of the classification accuracy was 97% and the maximum improvement of the average transfer rate is 42.4%, indicating the considerable potential of the using of EEG-P300 for the continuous classification of mental tasks.

  13. Separation and Localisation of P300 Sources and Their Subcomponents Using Constrained Blind Source Separation

    Science.gov (United States)

    Spyrou, Loukianos; Jing, Min; Sanei, Saeid; Sumich, Alex

    2006-12-01

    Separation and localisation of P300 sources and their constituent subcomponents for both visual and audio stimulations is investigated in this paper. An effective constrained blind source separation (CBSS) algorithm is developed for this purpose. The algorithm is an extension of the Infomax BSS system for which a measure of distance between a carefully measured P300 and the estimated sources is used as a constraint. During separation, the proposed CBSS method attempts to extract the corresponding P300 signals. The locations of the corresponding sources are then estimated with some indeterminancy in the results. It can be seen that the locations of the sources change for a schizophrenic patient. The experimental results verify the statistical significance of the method and its potential application in the diagnosis and monitoring of schizophrenia.

  14. P300 in obsessive-compulsive disorder: source localization and the effects of treatment.

    Science.gov (United States)

    Andreou, Christina; Leicht, Gregor; Popescu, Vlad; Pogarell, Oliver; Mavrogiorgou, Paraskevi; Rujescu, Dan; Giegling, Ina; Zaudig, Michael; Juckel, Georg; Hegerl, Ulrich; Mulert, Christoph

    2013-12-01

    Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Brain fingerprinting classification concealed information test detects US Navy military medical information with P300

    Directory of Open Access Journals (Sweden)

    Lawrence A. Farwell

    2014-12-01

    Full Text Available A classification concealed information test (CIT used the brain fingerprinting method of applying P300 event-related potential (ERP in detecting information that is 1 acquired in real life and 2 unique to US Navy experts in military medicine. Military medicine experts and non-experts were asked to push buttons in response to 3 types of text stimuli. Targets contain known information relevant to military medicine, are identified to subjects as relevant, and require pushing one button. Subjects are told to push another button to all other stimuli. Probes contain concealed information relevant to military medicine, and are not identified to subjects. Irrelevants contain equally plausible, but incorrect/irrelevant information. Error rate was 0%. Median and mean statistical confidences for individual determinations were 99.9% with no indeterminates (results lacking sufficiently high statistical confidence to be classified. We compared error rate and statistical confidence for determinations of both information present and information absent produced by classification CIT (Is a probe ERP more similar to a target or to an irrelevant ERP? versus comparison CIT (Does a probe produce a larger ERP than an irrelevant? using P300 plus the late negative component (LNP; together, P300-MERMER. Comparison CIT produced a significantly higher error rate (20% and lower statistical confidences -- mean 67%; information-absent mean was 28.9%, less than chance (50%. We compared analysis using P300 alone with the P300 + LNP. P300 alone produced the same 0% error rate but significantly lower statistical confidences. These findings add to the evidence that the brain fingerprinting methods as described here provide sufficient conditions to produce less than 1% error rate and greater than 95% median statistical confidence in a CIT on information obtained in the course of real life that is characteristic of individuals with specific training, expertise, or organizational

  16. Fusion of P300 and eye-tracker data for spelling using BCI2000

    Science.gov (United States)

    Kalika, Dmitry; Collins, Leslie; Caves, Kevin; Throckmorton, Chandra

    2017-10-01

    Objective. Various augmentative and alternative communication (AAC) devices have been developed in order to aid communication for individuals with communication disorders. Recently, there has been interest in combining EEG data and eye-gaze data with the goal of developing a hybrid (or ‘fused’) BCI (hBCI) AAC system. This work explores the effectiveness of a speller that fuses data from an eye-tracker and the P300 speller in order to create a hybrid P300 speller. Approach. This hybrid speller collects both eye-tracking and EEG data in parallel, and the user spells characters on the screen in the same way that they would if they were only using the P300 speller. Online and offline experiments were performed. The online experiments measured the performance of the speller for sixteen non-disabled participants, while the offline simulations were used to assess the robustness of the hybrid system. Main results. Online results showed that for fifteen non-disabled participants, using eye-gaze in a Bayesian framework with EEG data from the P300 speller improved accuracy (0.0163+/- 2.72 , 0.085+/- 0.111 , 0.080+/- 0.106 for estimated, medium and high variance configurations) and reduced the average number of flashes required to spell a character compared to the standard P300 speller that relies solely on EEG data (-53.27+/- 25.87 , -36.15+/- 19.3 , -18.85+/- 12.43 for estimated, medium and high variance configurations). Offline simulations indicate that the system provides more robust performance than a standalone eye gaze system. Significance. The results of this work on non-disabled participants shows the potential efficacy of hybrid P300 and eye-tracker speller. Further validation on the amyotrophic lateral sceloris population is needed to assess the benefit of this hybrid system.

  17. [Quantitative EEG and event-related potentials (P300) in partial epilepsy].

    Science.gov (United States)

    Wang, Zhongjin; Wang, Shuang; Ding, Meiping

    2013-05-01

    Quantitative EEG and event-related potential P300 were used to evaluate impairment of cerebral function in patient with partial epilepsy. W value was calculated (power of EEG ÎŽ and Ξ rhythm divided by power of α and ÎČ rhythm ) for the extent of focal cortical dysfunction. The W values in left partial epilepsy group, right partial epilepsy group and control group during interictal period compared. The latency, amplitude and reaction time of P300 potential change were observed in each groups. The W values in F(8), T(4) and T(6) regions in patients with left partial epilepsy (P P300 was 54. 76%, the latency, amplitude and reaction team were significantly different to the control group. The abnormal rate of P300 in left and right partial epilepsy groups were 77. 78% and 37.50%, respectively, and the former is significantly higher than the latter. The amplitudes of P300 in C(z) and P(z) of left partial epilepsy were significantly lower than those of right partial epilepsy and control group (P P300 in C(z) and P(z) of all partial epilepsy were significantly longer than those of control group (P < 0.05), however, no difference was found between left and right partial epilepsy. In partial epilepsy the cortical dysfunction occurs ipsilaterally to the epileptogenic zone, and extent of cortical dysfunction is positively correlated with duration of disease course. Cerebral dysfunction in left partial epilepsy is more severe than that in right partial epilepsy.

  18. Effect of transcranial magnetic stimulation on P300 of event-related potential.

    Science.gov (United States)

    Iwahashi, M; Katayama, Y; Ueno, S; Iramina, K

    2009-01-01

    When the odd stimulation is presented, the positive component of electroencephalograph is induced at around 300 ms after the odd stimulation. This positive component is called P300. Many studies suggest that P300 may result from the summation of activity from multiple generators located in widespread cortical and subcortical areas. However, there is still no conclusive indication of the sources of P300. In this paper, we focus on the left supramaginal gyrus as one of the sources of P300. We investigated the temporal aspect of this area using TMS (transcranial magnetic stimulation). We investigated the relationship between the latency of the P300 and an effect of TMS when the left supramarginal gyrus was stimulated by TMS. In our previous study, we reported a method of removing stimulus artifact during TMS with Sample-and-Hold circuit and electroencephalogram (EEG) activity evoked by TMS could be measured successfully. In addition to this method, independent component analysis (ICA) was also applied to recorded EEG data in order to remove the stimulus artifact by off-line analysis. By using these methods, short latency (P300 was delayed around 50 ms. Difference of the peak latency between the control measurement and the case of TMS applying at 150 ms was not significant. However, the differences of the peak latency of the control measurement and the peak latency of the measurement in the cases of TMS applying at 200 ms and 250 ms was significant (p<0.05). We considered that this delay was due to inhibiting to recognize the target stimulation.

  19. Brain fingerprinting classification concealed information test detects US Navy military medical information with P300

    Science.gov (United States)

    Farwell, Lawrence A.; Richardson, Drew C.; Richardson, Graham M.; Furedy, John J.

    2014-01-01

    A classification concealed information test (CIT) used the “brain fingerprinting” method of applying P300 event-related potential (ERP) in detecting information that is (1) acquired in real life and (2) unique to US Navy experts in military medicine. Military medicine experts and non-experts were asked to push buttons in response to three types of text stimuli. Targets contain known information relevant to military medicine, are identified to subjects as relevant, and require pushing one button. Subjects are told to push another button to all other stimuli. Probes contain concealed information relevant to military medicine, and are not identified to subjects. Irrelevants contain equally plausible, but incorrect/irrelevant information. Error rate was 0%. Median and mean statistical confidences for individual determinations were 99.9% with no indeterminates (results lacking sufficiently high statistical confidence to be classified). We compared error rate and statistical confidence for determinations of both information present and information absent produced by classification CIT (Is a probe ERP more similar to a target or to an irrelevant ERP?) vs. comparison CIT (Does a probe produce a larger ERP than an irrelevant?) using P300 plus the late negative component (LNP; together, P300-MERMER). Comparison CIT produced a significantly higher error rate (20%) and lower statistical confidences: mean 67%; information-absent mean was 28.9%, less than chance (50%). We compared analysis using P300 alone with the P300 + LNP. P300 alone produced the same 0% error rate but significantly lower statistical confidences. These findings add to the evidence that the brain fingerprinting methods as described here provide sufficient conditions to produce less than 1% error rate and greater than 95% median statistical confidence in a CIT on information obtained in the course of real life that is characteristic of individuals with specific training, expertise, or organizational

  20. [P300 potential in chldren with psychogenic nonepileptic events and tension headache].

    Science.gov (United States)

    Steczkowska, MaƂgorzata; Stolarska-WeryƄska, Urszula; Fiederer, Krystyna; KaciƄski, Marek

    2016-01-01

    Psychotherapy is being used as the primary treatment in nonepileptic psychogenic seizures and tension headaches in children. Children's intelectual functioning is related to certain endogenous neurophysiological parameters. The goal of this study was to establish whether the endogenous potential P300 is different in children with nonepileptic psychogenic events and with tension headaches, and whether it changes under the influence of the cognitive-behavioral psychotherapy. The study included a group of 47 children: 20 with nonepileptic psychogenic seizures (18 girls and 2 boys), aged 11.09-17.11 years, and 27 children with tension headache (25 girls and 2 boys), aged 10.11-17.11 years. The P300 potential was induced using an auditory stimulus. The reaction time, the amount of mistakes and the percentage of attention focus was measured in all children. All children attended 8-10 psychotherapy sessions. The P300 potential was registered before and after the course of therapy, and additionally in both cycles also after a 3 minutes hyperventilation. Medium P300 parameters were closer to normal in the group of children with tension headaches rather than in the group with nonepileptic seizures. The shorter was the reaction time in the first measurement, the higher the attention score and the shorter the reaction time in the second measurement - this was visible in the results of children with nonepileptic seizures, in contrast to children with tension headaches. The use of hyperventilation caused a noticeable extension of the reaction time in the P300 measurement, with other components unchanged (mistake count and percentage of attention focus). The endogenous potential P300 does vary, although on a statistically insignificant level, in groups of children with tension headaches and nonepileptic seizures.

  1. Spatial Filter Feature Extraction Methods for P300 BCI Speller: A Comparison

    DEFF Research Database (Denmark)

    Chiou, Eleni; Puthusserypady, Sadasivan

    2017-01-01

    Brain Computer Interface (BCI) systems enable subjects affected by neuromuscular disorders to interact with the outside world. A P300 speller uses Event Related Potential (ERP) components, generated in the brain in the presence of a target stimulus, to extract information about the user’s intent...... classifiers, namely the Support Vector Machine (SVM) and Fisher’s Linear Discriminant Analysis (FLDA). In addition, it is shown that the incorporation of some prior knowledge regarding the location of P300 elicitation on the scalp can reduce the computational load while maintaining or even improving...

  2. Histone modifications affect differential regulation of TGFÎČ- induced NADPH oxidase 4 (NOX4) by wild-type and mutant p53

    Science.gov (United States)

    Boudreau, Howard E.; Ma, Wei Feng; Korzeniowska, Agnieszka; Park, Jonathan J.; Bhagwat, Medha A.; Leto, Thomas L.

    2017-01-01

    Previously, we showed wild-type (WT) and mutant (mut) p53 differentially regulate reactive oxygen species (ROS) generation by NADPH oxidase-4 (NOX4): p53-WT suppresses TGFÎČ-induced NOX4, ROS and cell migration, whereas tumor-associated mut-p53 proteins enhance NOX4 expression and cell migration. Here, we extended our findings on the effects of p53 on NOX4 in several tumors and examined the basis of NOX4 transcriptional regulation by p53 and SMAD3. Statistical analysis of expression data from primary tumors available from The Cancer Genome Atlas (TCGA) detected correlations between mut-p53 and increased NOX4 expression. Furthermore, by altering p53 levels in cell culture models we showed several common tumor-associated mutant forms support TGFÎČ/SMAD3-dependent NOX4 expression. Deletion analysis revealed two critical SMAD3 binding elements (SBE) required for mut-p53-dependent NOX4 induction, whereas p53-WT caused dose-dependent suppression of NOX4 transcription. ChIP analysis revealed SMAD3 and p53-WT or mut-p53 associate with SBEs and p53 response elements in a TGFÎČ-dependent manner. Interestingly, the repressive effects of p53-WT on NOX4 were relieved by mutation of its transactivation domain or histone deacetylase (HDAC) inhibitor treatment. Overexpression of p300, a transcriptional co-regulator and histone acetyltransferase (HAT), enhanced p53-mediated NOX4 induction, whereas HAT-inactive p300 reduced NOX4 expression. Mut-p53 augmented TGFÎČ-stimulated histone acetylation within the NOX4 promoter. Finally, wound assays demonstrated NOX4 and p300 promote TGFÎČ/mut-p53-mediated cell migration. Our studies provide new insight into TGFÎČ/SMAD3 and mut-p53-mediated NOX4 induction involving epigenetic control of NOX4 in tumor cell migration, suggesting NOX4 is a potential therapeutic target to combat tumor progression and metastasis. PMID:28574838

  3. Effects of ZNF804A on auditory P300 response in schizophrenia.

    LENUS (Irish Health Repository)

    O'Donoghue, T

    2014-01-01

    The common variant rs1344706 within the zinc-finger protein gene ZNF804A has been strongly implicated in schizophrenia (SZ) susceptibility by a series of recent genetic association studies. Although associated with a pattern of altered neural connectivity, evidence that increased risk is mediated by an effect on cognitive deficits associated with the disorder has been equivocal. This study investigated whether the same ZNF804A risk allele was associated with variation in the P300 auditory-evoked response, a cognitively relevant putative endophenotype for SZ. We compared P300 responses in carriers and noncarriers of the ZNF804A risk allele genotype groups in Irish patients and controls (n=97). P300 response was observed to vary according to genotype in this sample, such that risk allele carriers showed relatively higher P300 response compared with noncarriers. This finding accords with behavioural data reported by our group and others. It is also consistent with the idea that ZNF804A may have an impact on cortical efficiency, reflected in the higher levels of activations required to achieve comparable behavioural accuracy on the task used.

  4. Individual differences in P300 amplitude: a genetic study in adolescent twins

    NARCIS (Netherlands)

    van Beijsterveldt, C.E.M.; Molenaar, P.C.M.; de Geus, E.J.C.; Boomsma, D.I.

    1998-01-01

    Using quantitative genetic research designs, we decomposed phenotypic variance in P300 parameters into genetic and environmental components. The twin method was used to carry out this decomposition. Event related potentials (ERPs) were measured during a visual oddball paradigm in a sample of 213

  5. Individual differences in P300 amplitude: A genetic study in adolescent twins.

    NARCIS (Netherlands)

    van Beijsterveld, C.E.M.; Molenaar, P.C.M.; de Geus, E.J.C.; Boomsma, D.I.

    1998-01-01

    Using quantitative genetic research designs, we decomposed phenotypic variance in P300 parameters into genetic and environmental components. The twin method was used to carry out this decomposition. Event related potentials (ERPs) were measured during a visual oddball paradigm in a sample of 213

  6. Multifactorial Determinants of Target and Novelty-Evoked p300 Amplitudes in Children of Addicted Parents

    NARCIS (Netherlands)

    Euser, A.S.; Evans, B.E.; Greaves-Lord, K.; van de Wetering, B.J.M.; Huizink, A.C.; Franken, I.H.A.

    2013-01-01

    Background: Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events,

  7. P300 WAVE CONFIRMATION IN PATIENTS WITH PARKINSON’S DISEASE

    Directory of Open Access Journals (Sweden)

    Marko PiĆĄljar

    2001-11-01

    Full Text Available Background. Mild to moderate cognitive dysfunction is a frequent complaint of patients with Parkinson’s disease, though the clinical picture of dementia is rarely reported.Methods. The development of cognitive deficits seams to be associated with hypokinesia and rigidy rather than tremor. In our study, auditory ERP were used to confirm cognitive alterations in two groups of non-demented patients with idiopathic Parkinson’s disease. Mini mental test was performed to exclude clinical picture of dementia. Patients were classified according to the Hoehen-Yahr and Webster scale. The Beck depression score in Parkinson’s patient was assessed.Auditory event related potentials were recorded using the »oddball« paradigm. The waves N100, P200, N200 and P300 were recorded and their latencies and amplitudes measured.Results and conclusions. The P300 latencies in both patients group were significantly longer (p < 0.05, than in the control group. P300 latency was longer in non tremor group. There were no significant statistical differences in latencies between the both groups. All patients had normal N100 latency. Significant decline of P300 amplitude was found only in non-tremor group (p < 0.001.

  8. Word-level language modeling for P300 spellers based on discriminative graphical models

    Science.gov (United States)

    Delgado Saa, Jaime F.; de Pesters, Adriana; McFarland, Dennis; Çetin, MĂŒjdat

    2015-04-01

    Objective. In this work we propose a probabilistic graphical model framework that uses language priors at the level of words as a mechanism to increase the performance of P300-based spellers. Approach. This paper is concerned with brain-computer interfaces based on P300 spellers. Motivated by P300 spelling scenarios involving communication based on a limited vocabulary, we propose a probabilistic graphical model framework and an associated classification algorithm that uses learned statistical models of language at the level of words. Exploiting such high-level contextual information helps reduce the error rate of the speller. Main results. Our experimental results demonstrate that the proposed approach offers several advantages over existing methods. Most importantly, it increases the classification accuracy while reducing the number of times the letters need to be flashed, increasing the communication rate of the system. Significance. The proposed approach models all the variables in the P300 speller in a unified framework and has the capability to correct errors in previous letters in a word, given the data for the current one. The structure of the model we propose allows the use of efficient inference algorithms, which in turn makes it possible to use this approach in real-time applications.

  9. Emotional Arousal at Memory Encoding Enhanced P300 in the Concealed Information Test

    Directory of Open Access Journals (Sweden)

    Akemi Osugi

    2018-01-01

    Full Text Available Previous studies have reported that the concealed information test (CIT is a reliable and powerful method for detecting information. However, the external validity of the CIT studies has not been fully proven. In particular, few studies have examined the effects of emotional arousal at memory encoding on physiological responses in the CIT. The present study investigated the influence on the CIT of the magnitude of emotional arousal at memory encoding of a mock crime, using the P300 component of the event-related brain potential (ERP. In accord with the assumptions of excitation-transfer theory, we presented emotionally arousing pictures before a mock crime. Participants were randomly assigned to either a high emotional arousal group (n = 10 or a low emotional arousal group (n = 11, viewing pictures expected to arouse emotion at a high or low level, respectively. Subsequently, all participants enacted the same mock crime, in which they were instructed to stab a pillow with a sharp-edged tool (e.g., a kitchen knife or ice pick as if harassing a mannequin lying on a bed. After the antecedent emotional experience, the P300-based CIT was conducted. Participants in the high arousal group showed significantly greater P300 amplitudes in response to a probe stimulus compared with the low arousal group. No differences were found between the groups in response to irrelevant stimuli. These results support the notion that emotional arousal influences the P300 in the CIT paradigm.

  10. With long intervals, inter-stimulus interval is the critical determinant of P300 amplitude

    NARCIS (Netherlands)

    Sambeth, A.; Maes, J.H.R.; Brankack, J.

    2004-01-01

    Previous research, using short inter-stimulus intervals (1-4 s), suggests that the P300 of the human event-related potential during oddball and single-stimulus tasks is mainly affected by target-to-target interval (TTI). The present study tested the validity of this claim at longer intervals in a

  11. Activation of Basal Gluconeogenesis by Coactivator p300 Maintains Hepatic Glycogen Storage

    Science.gov (United States)

    Cao, Jia; Meng, Shumei; Ma, Anlin; Radovick, Sally; Wondisford, Fredric E.

    2013-01-01

    Because hepatic glycogenolysis maintains euglycemia during early fasting, proper hepatic glycogen synthesis in the fed/postprandial states is critical. It has been known for decades that gluconeogenesis is essential for hepatic glycogen synthesis; however, the molecular mechanism remains unknown. In this report, we show that depletion of hepatic p300 reduces glycogen synthesis, decreases hepatic glycogen storage, and leads to relative hypoglycemia. We previously reported that insulin suppressed gluconeogenesis by phosphorylating cAMP response element binding protein-binding protein (CBP) at S436 and disassembling the cAMP response element-binding protein-CBP complex. However, p300, which is closely related to CBP, lacks the corresponding S436 phosphorylation site found on CBP. In a phosphorylation-competent p300G422S knock-in mouse model, we found that mutant mice exhibited reduced hepatic glycogen content and produced significantly less glycogen in a tracer incorporation assay in the postprandial state. Our study demonstrates the important and unique role of p300 in glycogen synthesis through maintaining basal gluconeogenesis. PMID:23770612

  12. Sleep inertia and autonomic effects on post-nap P300 event-related potential.

    Science.gov (United States)

    Takahashi, M; Arito, H

    1998-10-01

    The objective of this study was to examine the relationship between post-nap measures of alertness and performance and non-rapid eye movement (NREM) sleep and parasympathetic activity during brief naps. Thirty healthy subjects were randomly assigned to no-nap, 15-min, and 45-min nap conditions after normal home sleep at prior night. Each nap was taken after lunch and monitored by electroencephalogram (EEG), electromyogram, electrooculogram, and electrocardiogram (ECG). Deep NREM sleep was quantified by EEG delta power density and the parasympathetic activity was quantified by the ECG high-frequency (HF) component of R-R interval variability during the 15- and 45-min naps. The P300 event-related potential, subjective sleepiness, and performance on a 90-min English transcription task were measured 30 min and 3 hr after the naps and tested for their association with the EEG and ECG measures. A positive correlation was obtained between EEG delta power density during the naps and P300 latency 30 min after the naps (r = 0.476, p sleep inertia prolongs the P300 latency immediately after the naps, and that the parasympathetic predominance during the naps may improve subsequent alertness as assessed by the shortened P300 latency 3 hr after the naps.

  13. Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

    Science.gov (United States)

    Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

    2007-01-01

    The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with


  14. Comparison of Auditory Event-Related Potential P300 in Sighted and Early Blind Individuals

    Directory of Open Access Journals (Sweden)

    Fatemeh Heidari

    2010-06-01

    Full Text Available Background and Aim: Following an early visual deprivation, the neural network involved in processing auditory spatial information undergoes a profound reorganization. In order to investigate this process, event-related potentials provide accurate information about time course neural activation as well as perception and cognitive processes. In this study, the latency and amplitude of auditory P300 were compared in sighted and early blind individuals in age range of 18-25 years old.Methods: In this cross-sectional study, auditory P300 potential was measured in conventional oddball paradigm by using two tone burst stimuli (1000 and 2000 Hz on 40 sighted subjects and 19 early blind subjects with mean age 20.94 years old.Results: The mean latency of P300 in early blind subjects was significantly smaller than sighted subjects (p=0.00.( There was no significant difference in amplitude between two groups (p>0.05.Conclusion: Reduced latency of P300 in early blind subjects in comparison to sighted subjects probably indicates the rate of automatic processing and information categorization is faster in early blind subjects because of sensory compensation. It seems that neural plasticity increases the rate of auditory processing and attention in early blind subjects.

  15. Late auditory event-related evoked potential (P300) in Down's syndrome patients.

    Science.gov (United States)

    César, Carla Patrícia Hernandez Alves Ribeiro; Caovilla, Heloisa Helena; Munhoz, Mårio Sérgio Lei; Ganança, Maurício Malavasi

    2010-01-01

    Down syndrome is caused by a trisomy of chromosome 21 and is associated with central auditory processing deficit, learning disability and, probably, early-onset Alzheimer's disease. To evaluate the latencies and amplitudes of evoked late auditory potential related to P300 events and their changes in young adults with Down's syndrome. Prospective case study. P300 test latency and amplitudes were evaluated in 17 individuals with Down's syndrome and 34 healthy individuals. RESULTS The P300 latency (N1, P2, N2 and P3) was longer and the N2-P3 amplitude was lower in individuals with Down syndrome when compared to those in the control group. In young adults with Down syndrome, N1, P2, N2 and P3 latencies of late auditory evoked potential related to P300 events were prolonged, and N2 - P3 amplitudes were significantly reduced, suggesting integration impairment between the auditory association area and cortical and subcortical areas of the central nervous system.

  16. Mental Ability and the Effect of Pattern Violation Discrimination on P300 and Mismatch Negativity

    Science.gov (United States)

    Sculthorpe, Lauren D.; Stelmack, Robert M.; Campbell, Kenneth B.

    2009-01-01

    The relation between mental ability and the ability to detect auditory pattern violations was examined using event-related potential measures, specifically P300 and mismatch negativity (MMN). Thirty female volunteers were presented with a two tone alternating pattern containing infrequent repetition violations in passive (ignore) then active


  17. Genetic Correlation Between the P300 Event-Related Brain Potential and the EEG Power Spectrum

    NARCIS (Netherlands)

    Anokhin, A.P.; van Baal, G.C.M.; van Beijsterveldt, C.E.M.; de Geus, E.J.C.; Grant, J.; Boomsma, D.I.

    2001-01-01

    Previous studies have demonstrated moderate heritability of the P300 component of event-related brain potentials (ERPs) and high heritability of background electroencephalogram (EEG) power spectrum. However, it is unclear whether EEG and ERPs are influenced by common or independent genetic factors.

  18. The interrelationship between movement and cognition: Ξ rhythm and the P300 event-related potential.

    Science.gov (United States)

    Shin, Jonghan

    2011-07-01

    The relationship among brain electrophysiological activity, motor activity, and cognition has been a matter of great interest. For example, it has been discussed whether hippocampal theta rhythm reflects motor activity or cognitive activity, whereas it is widely accepted that the P300 event-related potential (ERP) reflects cognitive processes such as updating working memory. Here, we investigated the interrelationships among motor activity, hippocampal theta rhythm, and hippocampal P300 ERP using electrophysiological and behavioral data recorded from rats performing an auditory discrimination task (i.e., the auditory oddball paradigm) in a chamber with and without a running-wheel. We found that the hippocampal theta rhythm generated during locomotion codes information about self-motion, and event-related increases in hippocampal theta rhythm observed when rats performed the auditory discrimination cognitive task reflect a change in motor behavior after learning the cognitive task. Interestingly, the hippocampal P300 ERP occurred coincidently with increases in the power and frequency of hippocampal theta rhythm. In addition, we found that changes in theta rhythm observed during spontaneous wheel running without performing a cognitive task as well as when performing the cognitive task are associated with changes in delta- and gamma-band EEG activities. These major findings are discussed with respect to current hypotheses regarding P300 ERP and theta-, delta-, and gamma-band EEG activities in brain functions. Copyright © 2010 Wiley-Liss, Inc.

  19. Prediction of Auditory and Visual P300 Brain-Computer Interface Aptitude

    Science.gov (United States)

    Halder, Sebastian; Hammer, Eva Maria; Kleih, Sonja Claudia; Bogdan, Martin; Rosenstiel, Wolfgang; Birbaumer, Niels; KĂŒbler, Andrea

    2013-01-01

    Objective Brain-computer interfaces (BCIs) provide a non-muscular communication channel for patients with late-stage motoneuron disease (e.g., amyotrophic lateral sclerosis (ALS)) or otherwise motor impaired people and are also used for motor rehabilitation in chronic stroke. Differences in the ability to use a BCI vary from person to person and from session to session. A reliable predictor of aptitude would allow for the selection of suitable BCI paradigms. For this reason, we investigated whether P300 BCI aptitude could be predicted from a short experiment with a standard auditory oddball. Methods Forty healthy participants performed an electroencephalography (EEG) based visual and auditory P300-BCI spelling task in a single session. In addition, prior to each session an auditory oddball was presented. Features extracted from the auditory oddball were analyzed with respect to predictive power for BCI aptitude. Results Correlation between auditory oddball response and P300 BCI accuracy revealed a strong relationship between accuracy and N2 amplitude and the amplitude of a late ERP component between 400 and 600 ms. Interestingly, the P3 amplitude of the auditory oddball response was not correlated with accuracy. Conclusions Event-related potentials recorded during a standard auditory oddball session moderately predict aptitude in an audiory and highly in a visual P300 BCI. The predictor will allow for faster paradigm selection. Significance Our method will reduce strain on patients because unsuccessful training may be avoided, provided the results can be generalized to the patient population. PMID:23457444

  20. Dissociable Mechanisms Supporting Awareness: The P300 and Gamma in a Linguistic Attentional Blink Task

    Science.gov (United States)

    Karns, Christina M.; Neville, Helen

    2012-01-01

    As demonstrated by the attentional blink (AB) phenomenon, awareness for attended stimuli is governed by sharp capacity limits. We used a linguistic AB task to investigate the neural mechanisms that underlie failures of awareness, examining both event-related potentials and oscillatory brain activity to correctly reported and missed second targets (T2s) presented after a correctly reported first target (T1) in a rapid visual stream of distractors. Correctly reported targets occurring at a short lag (250 ms) after T1—within the classic AB period—elicited enhanced late gamma activity relative to incorrectly reported targets but showed no P300 modulation relative to missed targets. In contrast, correctly reported targets presented at a long lag (830 ms)—outside the classic AB period—elicited a greater P300 component but did not significantly modulate oscillatory activity. This double dissociation suggests that there are multiple neural mechanisms supporting awareness that may operate in parallel. Either the P300 or the gamma can index impairment in the cascade of processing leading to a target's entry into awareness. We conclude that the P300 and gamma activity reflect functionally distinct neural mechanisms, each of which plays an independent role in awareness. PMID:22166765

  1. Adaptation in P300 braincomputer interfaces: A two-classifier cotraining approach

    DEFF Research Database (Denmark)

    Panicker, Rajesh C.; Sun, Ying; Puthusserypady, Sadasivan

    2010-01-01

    A cotraining-based approach is introduced for constructing high-performance classifiers for P300-based braincomputer interfaces (BCIs), which were trained from very little data. It uses two classifiers: Fishers linear discriminant analysis and Bayesian linear discriminant analysis progressively...

  2. Prediction of auditory and visual p300 brain-computer interface aptitude.

    Directory of Open Access Journals (Sweden)

    Sebastian Halder

    Full Text Available OBJECTIVE: Brain-computer interfaces (BCIs provide a non-muscular communication channel for patients with late-stage motoneuron disease (e.g., amyotrophic lateral sclerosis (ALS or otherwise motor impaired people and are also used for motor rehabilitation in chronic stroke. Differences in the ability to use a BCI vary from person to person and from session to session. A reliable predictor of aptitude would allow for the selection of suitable BCI paradigms. For this reason, we investigated whether P300 BCI aptitude could be predicted from a short experiment with a standard auditory oddball. METHODS: Forty healthy participants performed an electroencephalography (EEG based visual and auditory P300-BCI spelling task in a single session. In addition, prior to each session an auditory oddball was presented. Features extracted from the auditory oddball were analyzed with respect to predictive power for BCI aptitude. RESULTS: Correlation between auditory oddball response and P300 BCI accuracy revealed a strong relationship between accuracy and N2 amplitude and the amplitude of a late ERP component between 400 and 600 ms. Interestingly, the P3 amplitude of the auditory oddball response was not correlated with accuracy. CONCLUSIONS: Event-related potentials recorded during a standard auditory oddball session moderately predict aptitude in an audiory and highly in a visual P300 BCI. The predictor will allow for faster paradigm selection. SIGNIFICANCE: Our method will reduce strain on patients because unsuccessful training may be avoided, provided the results can be generalized to the patient population.

  3. Comparative Study of SSVEP- and P300-Based Models for the Telepresence Control of Humanoid Robots

    Science.gov (United States)

    Li, Mengfan

    2015-01-01

    In this paper, we evaluate the control performance of SSVEP (steady-state visual evoked potential)- and P300-based models using Cerebot—a mind-controlled humanoid robot platform. Seven subjects with diverse experience participated in experiments concerning the open-loop and closed-loop control of a humanoid robot via brain signals. The visual stimuli of both the SSVEP- and P300- based models were implemented on a LCD computer monitor with a refresh frequency of 60 Hz. Considering the operation safety, we set the classification accuracy of a model over 90.0% as the most important mandatory for the telepresence control of the humanoid robot. The open-loop experiments demonstrated that the SSVEP model with at most four stimulus targets achieved the average accurate rate about 90%, whereas the P300 model with the six or more stimulus targets under five repetitions per trial was able to achieve the accurate rates over 90.0%. Therefore, the four SSVEP stimuli were used to control four types of robot behavior; while the six P300 stimuli were chosen to control six types of robot behavior. Both of the 4-class SSVEP and 6-class P300 models achieved the average success rates of 90.3% and 91.3%, the average response times of 3.65 s and 6.6 s, and the average information transfer rates (ITR) of 24.7 bits/min 18.8 bits/min, respectively. The closed-loop experiments addressed the telepresence control of the robot; the objective was to cause the robot to walk along a white lane marked in an office environment using live video feedback. Comparative studies reveal that the SSVEP model yielded faster response to the subject’s mental activity with less reliance on channel selection, whereas the P300 model was found to be suitable for more classifiable targets and required less training. To conclude, we discuss the existing SSVEP and P300 models for the control of humanoid robots, including the models proposed in this paper. PMID:26562524

  4. Comparative Study of SSVEP- and P300-Based Models for the Telepresence Control of Humanoid Robots.

    Science.gov (United States)

    Zhao, Jing; Li, Wei; Li, Mengfan

    2015-01-01

    In this paper, we evaluate the control performance of SSVEP (steady-state visual evoked potential)- and P300-based models using Cerebot-a mind-controlled humanoid robot platform. Seven subjects with diverse experience participated in experiments concerning the open-loop and closed-loop control of a humanoid robot via brain signals. The visual stimuli of both the SSVEP- and P300- based models were implemented on a LCD computer monitor with a refresh frequency of 60 Hz. Considering the operation safety, we set the classification accuracy of a model over 90.0% as the most important mandatory for the telepresence control of the humanoid robot. The open-loop experiments demonstrated that the SSVEP model with at most four stimulus targets achieved the average accurate rate about 90%, whereas the P300 model with the six or more stimulus targets under five repetitions per trial was able to achieve the accurate rates over 90.0%. Therefore, the four SSVEP stimuli were used to control four types of robot behavior; while the six P300 stimuli were chosen to control six types of robot behavior. Both of the 4-class SSVEP and 6-class P300 models achieved the average success rates of 90.3% and 91.3%, the average response times of 3.65 s and 6.6 s, and the average information transfer rates (ITR) of 24.7 bits/min 18.8 bits/min, respectively. The closed-loop experiments addressed the telepresence control of the robot; the objective was to cause the robot to walk along a white lane marked in an office environment using live video feedback. Comparative studies reveal that the SSVEP model yielded faster response to the subject's mental activity with less reliance on channel selection, whereas the P300 model was found to be suitable for more classifiable targets and required less training. To conclude, we discuss the existing SSVEP and P300 models for the control of humanoid robots, including the models proposed in this paper.

  5. Contralateral Noise Stimulation Delays P300 Latency in School-Aged Children.

    Directory of Open Access Journals (Sweden)

    Thalita Ubiali

    Full Text Available The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing.P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation.P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values.Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition.

  6. Contralateral Noise Stimulation Delays P300 Latency in School-Aged Children.

    Science.gov (United States)

    Ubiali, Thalita; Sanfins, Milaine Dominici; Borges, Leticia Reis; Colella-Santos, Maria Francisca

    2016-01-01

    The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing. P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation. P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values. Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition.

  7. the variability in P300 cognitive evoked potential amplitude in the auditory oddball paradigm

    Directory of Open Access Journals (Sweden)

    BiĆĄevac B.

    2015-01-01

    Full Text Available One of the best-studied responses of cognitive evoked potentials is a so-called 'P300', the late positive wave complex that occurs about 300-500 ms after the stimulus. It is obtained when the subject's attention is focused on a signal that is rare, especially if the signal has a motivational or emotional meaning. In the study of P300 potential, we followed the variations of potential amplitude and latency, so the objective was to examine whether there is a difference in Fz and Cz amplitudes of auditory induced cognitive evoked P300 potential depending on the performance of oddball tasks, both in male and female subjects. The study included 60 subjects (30 female respondents and 30 male respondents. P300 potential is induced by the auditory 'oddball' paradigm with 80% of non-target and 20% of target stimuli that are presented to the patient through headphones. The target tones are high tones of 2000 Hz. The standard, 1000 Hz tones the respondent should ignore but when he hears the target tones the respondent should press the button on the special handle. The value of Fz and Cz amplitudes both in male and female subjects obtained in the classical 'oddball' paradigm when the subject reacted to the signal by pressing the key with the dominant (right arm were statistically significantly lower (p>0,05 than the values of Fz and Cz amplitudes obtained when the key was pressed by the non-dominant hand. Based on this experiment it can be concluded that both in male and female subjects the performance of oddball tasks does not affect the amplitude of P300 cognitive evoked potentials.

  8. An event-related analysis of P300 by simultaneous EEG/fMRI

    Science.gov (United States)

    Wang, Li-qun; Wang, Mingshi; Mizuhara, Hiroaki

    2006-09-01

    In this study, P300 that induced by visual stimuli was examined with simultaneous EEG/fMRI. For the purpose of combine the best temporary resolution with the best special resolution together to estimate the brain function, event-related analysis contributed to this methodological trial. A 64 channel MRT-compatible MR EEG amplifier (BrainAmp: made of Brain Production GmbH, Gennany) was used in the measurement simultaneously with fMRI scanning. The reference channel is between Fz, Cz and Pz. Sampling rate of raw EEG was 5 kHz, and the MRT noise reduction was performed. EEG recording synchronized with MRI scan by our original stimulus system, and an oddball paradigm (four-oriented Landolt Ring presentation) was performed in the official manner. After P300 segmentation, the timing of P300 was exported to event-related analysis of fMRI data with SPM99 software. In single subject study, the significant activations appear in the left superior frontal, Broca's area and on both sides of the parietal lobule when P300 occurred. It is suggest that P300 may be an integration carried out by top-down signal from frontal to the parietal lobule, which regulates an Attention-Logical Judgment process. Compared with other current methods, the event related analysis by simultaneous EEG/IMRI is excellent in the point that can describe the cognitive process with reality unifying further temporary and spatial information. It is expected that examination and demonstration of the obtained result will supply with the promotion of this powerful methods.

  9. A novel hybrid auditory BCI paradigm combining ASSR and P300.

    Science.gov (United States)

    Kaongoen, Netiwit; Jo, Sungho

    2017-03-01

    Brain-computer interface (BCI) is a technology that provides an alternative way of communication by translating brain activities into digital commands. Due to the incapability of using the vision-dependent BCI for patients who have visual impairment, auditory stimuli have been used to substitute the conventional visual stimuli. This paper introduces a hybrid auditory BCI that utilizes and combines auditory steady state response (ASSR) and spatial-auditory P300 BCI to improve the performance for the auditory BCI system. The system works by simultaneously presenting auditory stimuli with different pitches and amplitude modulation (AM) frequencies to the user with beep sounds occurring randomly between all sound sources. Attention to different auditory stimuli yields different ASSR and beep sounds trigger the P300 response when they occur in the target channel, thus the system can utilize both features for classification. The proposed ASSR/P300-hybrid auditory BCI system achieves 85.33% accuracy with 9.11 bits/min information transfer rate (ITR) in binary classification problem. The proposed system outperformed the P300 BCI system (74.58% accuracy with 4.18 bits/min ITR) and the ASSR BCI system (66.68% accuracy with 2.01 bits/min ITR) in binary-class problem. The system is completely vision-independent. This work demonstrates that combining ASSR and P300 BCI into a hybrid system could result in a better performance and could help in the development of the future auditory BCI. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Caracterização da normalidade do P300 em adultos jovens Standard characterization of P300 in young adults

    Directory of Open Access Journals (Sweden)

    CĂ­ntia Santos Silva Machado

    2009-01-01

    Full Text Available OBJETIVO: Comparar com a literatura os valores de latĂȘncia e amplitude de P300 em adultos jovens brasileiros saudĂĄveis a fim de estabelecer um padrĂŁo normativo para futuros estudos, e verificar se os valores encontrados na amostra possuem correlação com o sexo, situação proposta na metodologia do exame e fases do ciclo menstrual. MÉTODOS: A amostra constou de 22 indivĂ­duos saudĂĄveis, sem queixa de desatenção, sem problemas neurolĂłgicos e auditivos, de 18 a 30 anos de idade. Todos os indivĂ­duos foram submetidos Ă  avaliação audiolĂłgica bĂĄsica a fim de excluir aqueles com perda de audição. As respostas do P300 foram obtidas com equipamento AMPLAID MK22, de dois canais e em ambiente silencioso. RESULTADOS: Os resultados de latĂȘncia encontrados na amostra, depois de comparados Ă  literatura, enquadraram-se melhor nos intervalos de latĂȘncia entre 220 e 380 ms. Somente os valores de amplitude foram influenciados pelas variĂĄveis sexo e fase do ciclo menstrual. CONCLUSÃO: Os valores de latĂȘncia da amostra nĂŁo sofreram influĂȘncia da variĂĄvel sexo, ciclo menstrual e situação, e aproximaram-se com mais fidedignidade aos valores de intervalos de latĂȘncia entre 220 e 380 ms. Contudo, os intervalos para a amplitude sofreram influĂȘncia das variĂĄveis sexo e ciclo menstrual, mas nĂŁo se enquadraram adequadamente aos valores de intervalo encontrados na literatura.PURPOSE: To compare the values of latency and amplitude of P300 of healthy Brazilian young adults with the data available on the literature, in order to establish a normative standard for future studies. In addition, the aim was also to verify if the values found in the sample were correlated to gender, situation proposed in the methodology of the examination, and phase of menstrual cycle. METHODS: The sample consisted of 22 healthy individuals, without any attention complaints, neurological or auditory disorders, and with ages ranging from 18 to 30 years. All subjects

  11. The pattern flash elicited P300-complex (PF-P300): dynamics of its topographic scalp distribution in different states of visual attention.

    Science.gov (United States)

    Taghavy, A; KĂŒgler, C F; Lösslein, H

    1988-04-01

    PF-P300 has been recorded from 13 healthy male subjects (21-35 years) in two different conditions of visual attention (transient versus sustained attention) at 16 electrode locations (10/20-system) against linked mastoids. The PFP300 complexes were measured and mapped. Thus, we obtained the following: (1) N250 did not show any significant differences between both conditions. (2) PF-P300, however, showed significantly different (p less than or equal to .05) maps between both conditions, especially bilateral frontal and left occipital with the measured PFP300a-amplitudes being higher (p less than or equal to .01) under sustained attention. The PFP300a-latencies did not show such differences. (3) N400 showed similar (p less than or equal to .001) differences in its mean peak distribution, but its latencies were shorter (p less than or equal to .01 resp. .0001) at all recording sites (except Fz, Pz) in condition (2). (4) Further evaluation of the PFP300-complex under sustained attention by means of increment mapping and multichannel potential measurements showed that PFP300 first rises at Fz, Pz, then spreads over the left occipital region and culminates bilateral frontal and parieto-occipital. Interestingly, the latencies of N250 and PFP300a were shorter at O1 (p less than or equal to .01) than at O2. With the help of electrical brain mapping it is possible to study the dynamics of both the PFP300 scalp distribution between two distinct mental states and within one mental state.

  12. Autoacetylation of the MYST lysine acetyltransferase MOF protein.

    Science.gov (United States)

    Yang, Chao; Wu, Jiang; Sinha, Sarmistha H; Neveu, John M; Zheng, Yujun George

    2012-10-12

    The MYST family of histone acetyltransferases (HATs) plays critical roles in diverse cellular processes, such as the epigenetic regulation of gene expression. Lysine autoacetylation of the MYST HATs has recently received considerable attention. Nonetheless, the mechanism and function of the autoacetylation process are not well defined. To better understand the biochemical mechanism of MYST autoacetylation and the impact of autoacetylation on the cognate histone acetylation, we carried out detailed analyses of males-absent-on-the-first (MOF), a key member of the MYST family. A number of mutant MOF proteins were produced with point mutations at several key residues near the active site of the enzyme. Autoradiography and immunoblotting data showed that mutation of these residues affects the autoacetylation activity and HAT activity of MOF by various degrees demonstrating that MOF activity is highly sensitive to the chemical changes in those residues. We produced MOF protein in the deacetylated form by using a nonspecific lysine deacetylase. Interestingly, both the autoacetylation activity and the histone acetylation activity of the deacetylated MOF were found to be very close to that of wild-type MOF, suggesting that autoacetylation of MOF only marginally modulates the enzymatic activity. Also, we found that the autoacetylation rates of MOF and deacetylated MOF were much slower than the cognate substrate acetylation. Thus, autoacetylation does not seem to contribute to the intrinsic enzymatic activity in a significant manner. These data provide new insights into the mechanism and function of MYST HAT autoacetylation.

  13. Autoacetylation of the MYST Lysine Acetyltransferase MOF Protein*

    Science.gov (United States)

    Yang, Chao; Wu, Jiang; Sinha, Sarmistha H.; Neveu, John M.; Zheng, Yujun George

    2012-01-01

    The MYST family of histone acetyltransferases (HATs) plays critical roles in diverse cellular processes, such as the epigenetic regulation of gene expression. Lysine autoacetylation of the MYST HATs has recently received considerable attention. Nonetheless, the mechanism and function of the autoacetylation process are not well defined. To better understand the biochemical mechanism of MYST autoacetylation and the impact of autoacetylation on the cognate histone acetylation, we carried out detailed analyses of males-absent-on-the-first (MOF), a key member of the MYST family. A number of mutant MOF proteins were produced with point mutations at several key residues near the active site of the enzyme. Autoradiography and immunoblotting data showed that mutation of these residues affects the autoacetylation activity and HAT activity of MOF by various degrees demonstrating that MOF activity is highly sensitive to the chemical changes in those residues. We produced MOF protein in the deacetylated form by using a nonspecific lysine deacetylase. Interestingly, both the autoacetylation activity and the histone acetylation activity of the deacetylated MOF were found to be very close to that of wild-type MOF, suggesting that autoacetylation of MOF only marginally modulates the enzymatic activity. Also, we found that the autoacetylation rates of MOF and deacetylated MOF were much slower than the cognate substrate acetylation. Thus, autoacetylation does not seem to contribute to the intrinsic enzymatic activity in a significant manner. These data provide new insights into the mechanism and function of MYST HAT autoacetylation. PMID:22918831

  14. The visual P3a in schizophrenia and bipolar disorder: effects of target and distractor stimuli on the P300.

    Science.gov (United States)

    Bestelmeyer, Patricia E G

    2012-05-15

    Amplitude reduction of the P300 event-related potential has long been suggested as a marker for schizophrenia. However, recent research has shown that this reduction in the P300 amplitude is not specific to schizophrenia as it can also be observed in related illnesses such as bipolar disorder. Due to this lack of specificity the P300 elicited using traditional oddball paradigms may be a less valuable endophenotypic marker. The current study employed a cognitively demanding three-stimulus oddball paradigm to elicit the P300 to visual target and distracting stimuli. Patients with schizophrenia showed amplitude reductions of P300 components to targets, distractors and frequent stimuli. The P300 in patients with bipolar disorder was not significantly different from either group. The pattern of results may further the understanding of the nature of the impairment in schizophrenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Towards a truly mobile auditory brain-computer interface: exploring the P300 to take away.

    Science.gov (United States)

    De Vos, Maarten; Gandras, Katharina; Debener, Stefan

    2014-01-01

    In a previous study we presented a low-cost, small, and wireless 14-channel EEG system suitable for field recordings (Debener et al., 2012, psychophysiology). In the present follow-up study we investigated whether a single-trial P300 response can be reliably measured with this system, while subjects freely walk outdoors. Twenty healthy participants performed a three-class auditory oddball task, which included rare target and non-target distractor stimuli presented with equal probabilities of 16%. Data were recorded in a seated (control condition) and in a walking condition, both of which were realized outdoors. A significantly larger P300 event-related potential amplitude was evident for targets compared to distractors (pbrain-computer interface (BCI) study. This leads us to conclude that a truly mobile auditory BCI system is feasible. © 2013.

  16. When mental fatigue maybe characterized by Event Related Potential (P300) during virtual wheelchair navigation.

    Science.gov (United States)

    Lamti, Hachem A; Gorce, Philippe; Ben Khelifa, Mohamed Moncef; Alimi, Adel M

    2016-12-01

    The goal of this study is to investigate the influence of mental fatigue on the event related potential P300 features (maximum pick, minimum amplitude, latency and period) during virtual wheelchair navigation. For this purpose, an experimental environment was set up based on customizable environmental parameters (luminosity, number of obstacles and obstacles velocities). A correlation study between P300 and fatigue ratings was conducted. Finally, the best correlated features supplied three classification algorithms which are MLP (Multi Layer Perceptron), Linear Discriminate Analysis and Support Vector Machine. The results showed that the maximum feature over visual and temporal regions as well as period feature over frontal, fronto-central and visual regions were correlated with mental fatigue levels. In the other hand, minimum amplitude and latency features didn't show any correlation. Among classification techniques, MLP showed the best performance although the differences between classification techniques are minimal. Those findings can help us in order to design suitable mental fatigue based wheelchair control.

  17. Updating P300: an integrative theory of P3a and P3b.

    Science.gov (United States)

    Polich, John

    2007-10-01

    The empirical and theoretical development of the P300 event-related brain potential (ERP) is reviewed by considering factors that contribute to its amplitude, latency, and general characteristics. The neuropsychological origins of the P3a and P3b subcomponents are detailed, and how target/standard discrimination difficulty modulates scalp topography is discussed. The neural loci of P3a and P3b generation are outlined, and a cognitive model is proffered: P3a originates from stimulus-driven frontal attention mechanisms during task processing, whereas P3b originates from temporal-parietal activity associated with attention and appears related to subsequent memory processing. Neurotransmitter actions associating P3a to frontal/dopaminergic and P3b to parietal/norepinephrine pathways are highlighted. Neuroinhibition is suggested as an overarching theoretical mechanism for P300, which is elicited when stimulus detection engages memory operations.

  18. A P300-based BCI system for controlling computer cursor movement.

    Science.gov (United States)

    Kanoh, S; Miyamoto, K; Yoshinobu, T

    2011-01-01

    A P300-based BCI (brain-computer interface) system for controlling the movement of the cursor displayed on the computer screen was proposed and evaluated. On the LCD computer screen, the cursor was displayed with the surrounded eight small circles, each of which was blinked sequentially in a random order. Five healthy subjects were requested to gaze at one of the circles placed in the preferred direction. The P300 activities elicited by the random blink of the target circle were detected by pattern classifier and they were used to move the cursor to the same direction as the target circle. It was shown that all of the subjects could control the movement of the cursor to their preferred direction by moving their gaze point in a short distance. This system can be applied to the voluntary control of the movement of the computer cursor, and the navigation of robot or video camera, without using users' extremities.

  19. Mock crime application of the Complex Trial Protocol (CTP) P300-based concealed information test.

    Science.gov (United States)

    Winograd, Michael R; Rosenfeld, J Peter

    2011-02-01

    The Complex Trial Protocol (CTP), was shown to be an improvement over the previous "three stimulus" P300-based concealed information tests (CITs). Not only was it highly accurate with autobiographical information but was also resistant to the use of countermeasures (CMs). The current study applied the CTP to the detection of incidentally acquired information in a mock crime scenario. In previous "three stimulus" mock crime studies utilizing P300-based CITs, participants memorized a guilty knowledge item(s). Special care was taken in the current study to ensure that participants' knowledge of the guilty item in the mock crime was obtained only during the commission of the act in order to bolster ecological validity. Overall, 92% of all participants in guilty, innocent, and countermeasure conditions were correctly classified. CM use was again indexed by reaction times (RTs). Copyright © 2010 Society for Psychophysiological Research.

  20. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2016-01-01

    Full Text Available Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days, or combined with acupuncture at Shenting (DU24, Tianzhu (BL10, Sishencong (Extra, Yintang (Extra, Renzhong (DU26, Neiguan (PC6, Shenmen (HT7, Fengchi (GB20, Wangu (GB12 and Baihui (DU20 (once a day for 56 days. Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  1. Brain-computer interface using P300 and virtual reality: A gaming approach for treating ADHD

    DEFF Research Database (Denmark)

    Rohani, Darius Adam; SĂžrensen, Helge Bjarup Dissing; Puthusserypady, Sadasivan

    2014-01-01

    and template-based features to detect these P300 responses. In an experimental setup using five subjects, an average error below 30% was achieved. To make it more challenging the BCI system has been embedded inside an immersive 3D virtual reality (VR) classroom with simulated distractions, which was created...... by combining a low-cost infrared camera and an “off-axis perspective projection” algorithm. This system is intended for kids by operating with four electrodes, as well as a non-intrusive VR setting. With the promising results, and considering the simplicity of the scheme, we hope to encourage future studies......This paper presents a novel brain-computer interface (BCI) system aiming at the rehabilitation of attention-deficit/hyperactive disorder in children. It uses the P300 potential in a series of feedback games to improve the subjects' attention. We applied a support vector machine (SVM) using temporal...

  2. Influence of sex on P300: an event-related potential electrophysiological study.

    Science.gov (United States)

    Bourisly, Ali K; Pothen, Annie

    2016-02-10

    The primary objective of this study was to further characterize the role of sex, if any, in event-related potentials (ERPs). More specifically, we aimed to investigate sex sensitivity with respect to the P300 ERP. Each female and male study participant underwent an oddball paradigm electroencephalography ERP session. ERP data were subjected to preprocessing and postprocessing, as well as statistical analysis. The results of the study showed that men had larger P300 amplitudes on average for both low-probability and high-probability stimuli compared with women (PP300 latencies on average than did women (PP300 ERP, which may be because of men eliciting higher response inhibition compared with women.

  3. The Single-trial Analysis of P300 and the Difference Threshold of Modulated Vibration

    Science.gov (United States)

    Ohira, Reiko; Uchida, Masahumi; Nozawa, Akio; Ide, Hideto

    This study reports the estimation of different-threshold (DT) when humans recognize various modulated vibrations using their tactile sensor. The modulated vibration consists of two frequency components. A psychological or the event related potential (ERP) measurement was used to estimate DT. ERP appears in an electro-encephalogram (EEG) when a human recognizes the information emitted by an external stimulus, and this study detects P300, which is a component of ERP. This paper proposes a single-trial analysis that uses the T-test, which deviates from the conventional method for detecting P300 called the averaged EEG method. Finally, the proposed method estimates DT. As a result, the effectiveness of the proposed method is assured by estimating DTs on five subjects.

  4. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential.

    Science.gov (United States)

    Liu, Qiang; Wang, Xiu-Juan; Zhang, Zhe-Cheng; Xue, Rong; Li, Ping; Li, Bo

    2016-03-01

    Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days), or combined with acupuncture at Shenting (DU24), Tianzhu (BL10), Sishencong (Extra), Yintang (Extra), Renzhong (DU26), Neiguan (PC6), Shenmen (HT7), Fengchi (GB20), Wangu (GB12) and Baihui (DU20) (once a day for 56 days). Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  5. Fast stimulus sequences improve the efficiency of event-related potential P300 recordings.

    Science.gov (United States)

    Mell, Dominik; Bach, Michael; Heinrich, Sven P

    2008-09-30

    The P300 is an easily recorded component of the event-related potential (ERP). Yet, it is desirable to reduce the recording duration, for instance in patient examinations. A limiting factor is the time between stimuli that is necessary for the ERP to return to baseline. We explored whether this time could be reduced, despite an overlap of responses to successive stimuli, by presenting visual stimuli at a fast rate of 4.7 s(-1)using a standard oddball paradigm. Rare stimuli occurred at a probability of 14%. The P300 was isolated by subtracting the responses to the frequent stimuli from those to the rare stimuli, thereby eliminating the influence of response overlap. We compared the efficiency of fast stimulation to that of conventionally slow stimulation by assessing the signal-to-noise ratio of the P300 amplitude. Two presentation durations of individual stimuli, namely 53 ms and 93 ms, were tested. Not unexpectedly, P300 amplitudes were smaller for the fast sequence. However, the signal-to-noise ratio improved significantly by more than 50% due to the larger number of trials within a given time interval. When targeting a given signal-to-noise ratio, fast stimulation allows for a reduction in recording time of around 35%. Median peak times were 16-56 ms shorter for the fast stimulus sequence. Topography was comparable for fast and slow stimulation, suggesting a similar functional composition of the respective responses. Fast stimulation may thus be used to replace less efficient slow stimulation schemes in clinical diagnosis and for certain experimental questions.

  6. P300 event-related potential in abstinent methamphetamine-dependent patients.

    Science.gov (United States)

    Haifeng, Jiang; Wenxu, Zhuang; Hong, Cheng; Chuanwei, Li; Jiang, Du; Haiming, Sun; Zhikang, Chen; Din, Xu; Jijun, Wang; Min, Zhao

    2015-10-01

    Substance use and abuse are characterized by biases in the attentional processing of substance-related stimuli. There are no event related potential (ERP)-based studies of attentional bias for substance-related cues among methamphetamine (MA) dependent patients. The study aimed to measure changes in P300 event-related potentials elicited by MA-related words in MA-dependent individuals at baseline and after 3 and 6 months of abstinence, examining the relationship of ERP changes to craving. 26 MA-dependent patients (14 male) newly enrolled in two compulsory treatment centers in China and 29 healthy controls (15 male) were included in this study. At baseline (2-3 weeks in treatment) and after 3 and 6 months of abstinence from MA use, we obtained ERP data during a Stroop color-matching task using MA-related and neutral words. Self-reported craving was measured by a Visual Analog Scale (VAS). Increased P300 amplitudes elicited by MA-related words were observed over left-anterior electrode sites. Abnormal P300 amplitudes declined to the normal levels of healthy controls at the end of 3 months of abstinence, and the decrease was maintained up to the end of 6 months of abstinence. The behavioral data did not show similar changes. The positive relationship between the changes of VAS scores for MA craving and the changes of P300 amplitudes over left anterior electrode sites elicited by MA-related words within the first 3 months was significant. These findings highlight the potential use of ERP as an objective index to track changes in subjective MA craving among abstinent MA-dependent patients. Copyright © 2015. Published by Elsevier Inc.

  7. Decomposing P300 into correlates of genetic risk and current symptoms in schizophrenia: An inter-trial variability analysis.

    Science.gov (United States)

    Kim, Minah; Lee, Tak Hyung; Kim, Ji-Hun; Hong, Hanwoom; Lee, Tae Young; Lee, Youngjo; Salisbury, Dean F; Kwon, Jun Soo

    2017-04-08

    The P300 event-related potential (ERP) component, which reflects cognitive processing, is a candidate biomarker for schizophrenia. However, the role of P300 in the pathophysiology of schizophrenia remains unclear because averaged P300 amplitudes reflect both genetic predisposition and current clinical status. Thus, we sought to identify which aspects of P300 are associated with genetic risk versus symptomatic status via an inter-trial variability analysis. Auditory P300, clinical symptoms, and neurocognitive function assessments were obtained from forty-five patients with schizophrenia, thirty-two subjects at genetic high risk (GHR), thirty-two subjects at clinical high risk (CHR), and fifty-two healthy control (HC) participants. Both conventional averaging and inter-trial variability analyses were conducted for P300, and results were compared across groups using analysis of variance (ANOVA). Pearson's correlation was utilized to determine associations among inter-trial variability for P300, current symptoms and neurocognitive status. Average P300 amplitude was reduced in the GHR, CHR, and schizophrenia groups compared with that in the HC group. P300 inter-trial variability was elevated in the CHR and schizophrenia groups but relatively normal in the GHR and HC groups. Furthermore, P300 inter-trial variability was significantly related to negative symptom severity and neurocognitive performance results in schizophrenia patients. These results suggest that P300 amplitude is an endophenotype for schizophrenia and that greater inter-trial variability of P300 is associated with more severe negative and cognitive symptoms in schizophrenia patients. Copyright © 2016. Published by Elsevier B.V.

  8. Targeting an efficient target-to-target interval for P300 speller brain–computer interfaces

    Science.gov (United States)

    Sellers, Eric W.; Wang, Xingyu

    2013-01-01

    Longer target-to-target intervals (TTI) produce greater P300 event-related potential amplitude, which can increase brain–computer interface (BCI) classification accuracy and decrease the number of flashes needed for accurate character classification. However, longer TTIs requires more time for each trial, which will decrease the information transfer rate of BCI. In this paper, a P300 BCI using a 7 × 12 matrix explored new flash patterns (16-, 18- and 21-flash pattern) with different TTIs to assess the effects of TTI on P300 BCI performance. The new flash patterns were designed to minimize TTI, decrease repetition blindness, and examine the temporal relationship between each flash of a given stimulus by placing a minimum of one (16-flash pattern), two (18-flash pattern), or three (21-flash pattern) non-target flashes between each target flashes. Online results showed that the 16-flash pattern yielded the lowest classification accuracy among the three patterns. The results also showed that the 18-flash pattern provides a significantly higher information transfer rate (ITR) than the 21-flash pattern; both patterns provide high ITR and high accuracy for all subjects. PMID:22350331

  9. Cognitive Evoked Potential Measurement, P300, in a group of healthy Colombian individuals

    Directory of Open Access Journals (Sweden)

    Natalia Gutiérrez Giraldo

    2013-05-01

    Full Text Available Cognitive evoked potentials are electrophysiological measurements of cognitive functions. Cognitivepotential P300 is specifically related to attention processes. Objetive: the aim of this studywas to establish reference values for latency and amplitude of P300 wave in the Colombian population and determine their variability with age, gender and education of the subjects. Methods:we studied 122 healthy subjects between 6 and 80 years, are practical potential measurementmethodology as odd-ball, in leads Cz and Pz. Results: we were able to establish reference valuesfor different age groups, and statistical significance was found with which the latency of P300wave increases with the age of individuals, and instead thereof the amplitude tends to decrease.Similarly to correlate latency and amplitude was shown an inverse relationship between them.Conclusions: no differences were found for latency and wave amplitude, gender-related or schoolsubjects as well as no difference was found when measuring the Pz derivation obtained comparedwith the wave in lead Cz.

  10. P300 as an auxiliary method in clinical practice: A review of literature

    Directory of Open Access Journals (Sweden)

    Marina Titlic

    2016-12-01

    Full Text Available Cognitive functions can be assessed and followed up over a period of time with cognitive evoked potentials (CEP P300. In this context, brainstem auditory evoked potentials (BAEP are most commonly used, but visual evoked potentials (VEP are utilized as well. The research in this area has demonstrated that these techniques could be used as a supplemental method in diagnostics of numerous diseases such as Alzheimer's disease, mild cognitive impairment, vascular dementia, epilepsy, craniocerebral trauma, Parkinson's disease, multiple sclerosis, and other degenerative diseases. In addition, P300 can also be used as an auxiliary method in the diagnostics of mental disorders conditions such as schizophrenia, panic disorders, narcotic drug addiction, nicotinism, alcoholism, etc. The method assists in monitoring the course of diseases leading to encephalopathy, such as liver and kidney damage and grave anaemia. The advantages of P300 testing are easy application, non-invasiveness, and an unlimited number of potential applications. Moreover, the results obtained with this method are measurable and can be compared.

  11. Object Extraction in Cluttered Environments via a P300-Based IFCE

    Directory of Open Access Journals (Sweden)

    Xiaoqian Mao

    2017-01-01

    Full Text Available One of the fundamental issues for robot navigation is to extract an object of interest from an image. The biggest challenges for extracting objects of interest are how to use a machine to model the objects in which a human is interested and extract them quickly and reliably under varying illumination conditions. This article develops a novel method for segmenting an object of interest in a cluttered environment by combining a P300-based brain computer interface (BCI and an improved fuzzy color extractor (IFCE. The induced P300 potential identifies the corresponding region of interest and obtains the target of interest for the IFCE. The classification results not only represent the human mind but also deliver the associated seed pixel and fuzzy parameters to extract the specific objects in which the human is interested. Then, the IFCE is used to extract the corresponding objects. The results show that the IFCE delivers better performance than the BP network or the traditional FCE. The use of a P300-based IFCE provides a reliable solution for assisting a computer in identifying an object of interest within images taken under varying illumination intensities.

  12. Autistic Traits Affect P300 Response to Unexpected Events, regardless of Mental State Inferences

    Directory of Open Access Journals (Sweden)

    Mitsuhiko Ishikawa

    2017-01-01

    Full Text Available Limited use of contextual information has been suggested as a way of understanding cognition in people with autism spectrum disorder (ASD. However, it has also been argued that individuals with ASD may have difficulties inferring others’ mental states. Here, we examined how individuals with different levels of autistic traits respond to contextual deviations by measuring event-related potentials that reflect context usage. The Autism Spectrum Quotient (AQ was used to quantify autistic-like traits in 28 university students, and 19 participants were defined as Low or High AQ groups. To additionally examine inferences about mental state, two belief conditions (with or without false belief were included. Participants read short stories in which the final sentence included either an expected or an unexpected word and rated the word’s degree of deviation from expectation. P300 waveform analysis revealed that unexpected words were associated with larger P300 waveforms for the Low AQ group, but smaller P300 responses in the High AQ group. Additionally, AQ social skill subscores were positively correlated with evaluation times in the Unexpected condition, whether a character’s belief was false or not. This suggests that autistic traits can affect responses to unexpected events, possibly because of decreased availability of context information.

  13. Evaluation of psychoacoustic tests and P300 event-related potentials in elderly patients with hyperhomocysteinemia.

    Science.gov (United States)

    Díaz-Leines, Sergio; Peñaloza-López, Yolanda R; Serrano-Miranda, Tirzo A; Flores-Ávalos, Blanca; Vidal-Ixta, Martha T; Jiménez-Herrera, Blanca

    2013-01-01

    Hyperhomocysteinemia as a risk factor for hearing impairment, neuronal damage and cognitive impairment in elderly patients is controversial and is limited by the small number of studies. The aim of this work was determine if elderly patients detected with hyperhomocysteinemia have an increased risk of developing abnormalities in the central auditory processes as compared with a group of patients with appropriate homocysteine levels, and to define the behaviour of psychoacoustic tests and long latency potentials (P300) in these patients. This was a cross-sectional, comparative and analytical study. We formed a group of patients with hyperhomocysteinemia and a control group with normal levels of homocysteine. All patients underwent audiometry, tympanometry and a selection of psychoacoustic tests (dichotic digits, low-pass filtered words, speech in noise and masking level difference), auditory evoked brainstem potentials and P300. Patients with hyperhomocysteinemia had higher values in the test of masking level difference than did the control group (P=.049) and more protracted latency in P300 (P=.000). Hyperhomocysteinemia is a factor that alters the central auditory functions. Alterations in psychoacoustic tests and disturbances in electrophysiological tests suggest that the central portion of the auditory pathway is affected in patients with hyperhomocysteinemia. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  14. The Human Factors and Ergonomics of P300-Based Brain-Computer Interfaces.

    Science.gov (United States)

    Powers, J Clark; Bieliaieva, Kateryna; Wu, Shuohao; Nam, Chang S

    2015-08-10

    Individuals with severe neuromuscular impairments face many challenges in communication and manipulation of the environment. Brain-computer interfaces (BCIs) show promise in presenting real-world applications that can provide such individuals with the means to interact with the world using only brain waves. Although there has been a growing body of research in recent years, much relates only to technology, and not to technology in use-i.e., real-world assistive technology employed by users. This review examined the literature to highlight studies that implicate the human factors and ergonomics (HFE) of P300-based BCIs. We assessed 21 studies on three topics to speak directly to improving the HFE of these systems: (1) alternative signal evocation methods within the oddball paradigm; (2) environmental interventions to improve user performance and satisfaction within the constraints of current BCI systems; and (3) measures and methods of measuring user acceptance. We found that HFE is central to the performance of P300-based BCI systems, although researchers do not often make explicit this connection. Incorporation of measures of user acceptance and rigorous usability evaluations, increased engagement of disabled users as test participants, and greater realism in testing will help progress the advancement of P300-based BCI systems in assistive applications.

  15. The Human Factors and Ergonomics of P300-Based Brain-Computer Interfaces

    Directory of Open Access Journals (Sweden)

    J. Clark Powers

    2015-08-01

    Full Text Available Individuals with severe neuromuscular impairments face many challenges in communication and manipulation of the environment. Brain-computer interfaces (BCIs show promise in presenting real-world applications that can provide such individuals with the means to interact with the world using only brain waves. Although there has been a growing body of research in recent years, much relates only to technology, and not to technology in use—i.e., real-world assistive technology employed by users. This review examined the literature to highlight studies that implicate the human factors and ergonomics (HFE of P300-based BCIs. We assessed 21 studies on three topics to speak directly to improving the HFE of these systems: (1 alternative signal evocation methods within the oddball paradigm; (2 environmental interventions to improve user performance and satisfaction within the constraints of current BCI systems; and (3 measures and methods of measuring user acceptance. We found that HFE is central to the performance of P300-based BCI systems, although researchers do not often make explicit this connection. Incorporation of measures of user acceptance and rigorous usability evaluations, increased engagement of disabled users as test participants, and greater realism in testing will help progress the advancement of P300-based BCI systems in assistive applications.

  16. The Influence of Negative Emotion on the Simon Effect as Reflected by P300

    Directory of Open Access Journals (Sweden)

    Qingguo Ma

    2013-01-01

    Full Text Available The Simon effect refers to the phenomenon that reaction time (RT is faster when stimulus and response location are congruent than when they are not. This study used the priming-target paradigm to explore the influence of induced negative emotion on the Simon effect with event-related potential techniques (ERPs. The priming stimuli were composed of two kinds of pictures, the negative and neutral pictures, selected from the International Affective Picture System (IAPS. The target stimuli included chessboards of two color types. One was red and black the other one was green and black. Each chessboard was presented on the left or the right of the screen. The participants were asked to press the response keys according to the colors of the chessboards. It was called the congruent condition if the chessboard and the response key were on the same side, otherwise incongruent condition. In this study, the emotion-priming Simon effect was found in terms of RT and P300. Negative emotion compared with neutral emotion significantly enhanced the Simon effect in the cognitive process, reflected by a larger difference of P300 latency between the incongruent and congruent trials. The results suggest that the induced negative emotion influenced the Simon effect at the late stage of the cognitive process, and the P300 latency could be considered as the reference measure. These findings may be beneficial to researches in psychology and industrial engineering in the future.

  17. Synchronised vestibular signals increase the P300 event-related potential elicited by auditory oddballs.

    Science.gov (United States)

    Schmidt-Kassow, Maren; Wilkinson, David; Denby, Emma; Ferguson, Heather

    2016-10-01

    The perception of beat within an auditory rhythm can be facilitated when accompanied by synchronised movements. Electrophysiological investigation shows that this facilitatory effect is associated with a larger P300 amplitude. It has remained unclear, however, which movement-related processes drive this P300 effect. To investigate whether vestibular signals play a role, we administered alternating, sub-sensory (mean=.3mA) galvanic current to the vestibular nerves of participants while they counted the number of oddballs presented in a stream of tones played at a rate of 1Hz. Consistent with a vestibular effect, the P300 elicited by the oddballs was increased during stimulation relative to a sham condition, but only when the frequency of the alternating current matched that at which the tones were played. This finding supports the general idea that the vestibular system is involved in audio-motor synchronisation and is the first to show by electrophysiological means that it influences cognitive processes involved in beat perception. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Acetyl-CoA carboxylase regulates global histone acetylation.

    Science.gov (United States)

    Galdieri, Luciano; Vancura, Ales

    2012-07-06

    Histone acetylation depends on intermediary metabolism for supplying acetyl-CoA in the nucleocytosolic compartment. However, because nucleocytosolic acetyl-CoA is also used for de novo synthesis of fatty acids, histone acetylation and synthesis of fatty acids compete for the same acetyl-CoA pool. The first and rate-limiting reaction in de novo synthesis of fatty acids is carboxylation of acetyl-CoA to form malonyl-CoA, catalyzed by acetyl-CoA carboxylase. In yeast Saccharomyces cerevisiae, acetyl-CoA carboxylase is encoded by the ACC1 gene. In this study, we show that attenuated expression of ACC1 results in increased acetylation of bulk histones, globally increased acetylation of chromatin histones, and altered transcriptional regulation. Together, our data indicate that Acc1p activity regulates the availability of acetyl-CoA for histone acetyltransferases, thus representing a link between intermediary metabolism and epigenetic mechanisms of transcriptional regulation.

  19. Social value orientation modulates the FRN and P300 in the chicken game.

    Science.gov (United States)

    Wang, Yiwen; Kuhlman, D Michael; Roberts, Kathryn; Yuan, Bo; Zhang, Zhen; Zhang, Wei; Simons, Robert F

    2017-07-01

    Social dilemmas pervade daily life, business, and politics. The manners in which these dilemmas are resolved depend in part on the personal characteristics of those involved. One such characteristic is Social Value Orientation (SVO), a trait-like predisposition to maximize cooperative (Pro-Social) or non-cooperative (Pro-Self) outcomes in social relationships. The present study investigated the role of SVO in modulating neural responses to outcomes in a type of social dilemma known as the Chicken Game. The Chicken Game models real-world situations involving two parties independently making a decision between cooperation and aggression. The EEG of Pro-Socials and Pro-Selfs was recorded while playing Chicken with a computer Opponent. Two ERP components were extracted: Feedback-Related Negativity (FRN) and the P300. Despite no behavioral differences in decision (i.e., cooperation, aggression), FRN results indicate that Pro-Socials experienced unreciprocated cooperation as the least desired outcome. Further, P300 results show a main effect for the Opponent's choice, such that the Opponent's cooperation was more salient than aggression. Additionally, an interaction between the Participant's and Opponent's choice showed that the effect for the Opponent's choice only occurred when the Participant chose cooperation. None of the results for P300 were moderated by SVO. For both ERP components, Pro-Selfs showed no differential responding to Chicken outcomes. In addition, FRN magnitude on trial n predicted choice on trial n+1 for Pro-Socials, but not for Pro-Selfs. P300 magnitude on trial n showed no relationship to choice on trial n+1. Results indicate that individual differences in SVO modulate FRN responses to Chicken outcomes, and that these neural reactions may have utility in predicting subsequent behaviors. For P300, there is no evidence of SVO modulation. Our general pattern of FRN responsiveness in Pro-Socials, but not in Pro-Selfs, is related to similar findings in f

  20. P300 component identification in auditory oddball and novel paradigms using source analysis techniques : Reduced latency variability in the elderly

    NARCIS (Netherlands)

    Maurits, N.; Elting, J.W.; Jager, D.K.R.B.; van der Hoeven, J.H; Brouwer, W.H.

    P300 latency variability in normal subjects limits its diagnostic applicability as a test for cognitive function. One of the causes of variation is the overlap in P300 (P3A and P3B) components resulting in inaccurate latency determination. Recently, we have shown that identification of P3A and P3B

  1. Inferior detection of information from collaborative versus individual crimes based on a P300 Concealed Information Test.

    Science.gov (United States)

    Lu, Yang; Rosenfeld, J Peter; Deng, Xiaohong; Zhang, Erhu; Zheng, Huihui; Yan, Gejun; Ouyang, Dan; Hayat, Saba Z

    2017-10-30

    The present study used a P300-based Concealed Information Test (CIT) to detect individual and collaborative crimes and to explore whether or not the P300 index is effective in identifying collaborative crime members. Participants were divided into two groups to either steal a ring alone (individual group) or collaboratively with another companion participant (collaborative group) before taking the Complex Trial Protocol test that is regarded as an accurate version of the P300-based CIT. The ERP results revealed that both groups showed significantly larger P300s to probe (the ring) than to all irrelevant stimuli (other jewelery), but the P300 amplitude difference of probe stimulus versus irrelevant stimuli in the collaborative group was significantly less than that in the individual group. For the individual diagnosis, using P300 index, the detection rate was significantly inferior for collaborative crime than individual crime, probably related to weakness of collaborative encoding. The ROC curve comparisons showed the individual guilty was effectively discriminated from the simulated-innocent (AUC = .84) and from the collaborative guilty (AUC = .83), but the collaborative guilty was not discriminable from the simulated-innocent (AUC = .66). These findings suggest that collaborative encoding of crime-related information impacts the efficiency of the P300 index, and that the P300-based CIT is not applicable when used to identify collaborative crime perpetrators. © 2017 Society for Psychophysiological Research.

  2. Using brain potentials to understand prism adaptation: the error-related negativity and the P300

    Science.gov (United States)

    MacLean, Stephane J.; Hassall, Cameron D.; Ishigami, Yoko; Krigolson, Olav E.; Eskes, Gail A.

    2015-01-01

    Prism adaptation (PA) is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN)—a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuomotor responding is shifted to the opposite direction of that initially induced by the prisms. This visuomotor aftereffect has been used to study visuomotor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided) space. In order to optimize PA's use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs) were recorded at the termination of each reach (screen-touch), then binned according to accuracy (hit vs. miss) and phase of exposure block (early, middle, late). Results show that two ERP components were evoked by screen-touch: an error-related negativity (ERN), and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN. PMID:26124715

  3. Rapid communication with a P300 matrix speller using electrocorticographic signals (ECoG

    Directory of Open Access Journals (Sweden)

    Peter eBrunner

    2011-02-01

    Full Text Available A brain-computer interface (BCI can provide a non-muscular communication channel to severely disabled people. One particular realization of a BCI is the P300 matrix speller that was originally described by Farwell and Donchin in 1988. This speller uses event-related potentials (ERPs that include the P300 ERP. All previous online studies of the P300 matrix speller used scalp-recorded electroencephalography (EEG and were limited in their communication performance to only a few characters per minute.In our study, we investigated the feasibility of using electrocorticographic (ECoG signals for online operation of the matrix speller, and determined associated spelling rates. We used the matrix speller that is implemented in the BCI2000 system. This speller used ECoG signals that were recorded from frontal, parietal, and occipital areas in one subject. This subject spelled a total of 444 characters in online experiments.The results showed that the subject sustained a rate of 17 characters per minute (i.e., 69 bits/min, and achieved a peak rate of 22 characters per minute (i.e., 113 bits/min. Detailed analysis of the results suggests that ERPs over visual areas (i.e., VEPs contribute significantly to the performance of the matrix speller BCI system. Our results also point to potential reasons for the apparent advantages in spelling performance of ECoG compared to EEG. Thus, with additional verification in more subjects, these results may further extend the communication options for people with serious neuromuscular disabilities.

  4. Conformational Flexibility and Subunit Arrangement of the Modular Yeast Spt-Ada-Gcn5 Acetyltransferase Complex*

    Science.gov (United States)

    Setiaputra, Dheva; Ross, James D.; Lu, Shan; Cheng, Derrick T.; Dong, Meng-Qiu; Yip, Calvin K.

    2015-01-01

    The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex is a highly conserved, 19-subunit histone acetyltransferase complex that activates transcription through acetylation and deubiquitination of nucleosomal histones in Saccharomyces cerevisiae. Because SAGA has been shown to display conformational variability, we applied gradient fixation to stabilize purified SAGA and systematically analyzed this flexibility using single-particle EM. Our two- and three-dimensional studies show that SAGA adopts three major conformations, and mutations of specific subunits affect the distribution among these. We also located the four functional modules of SAGA using electron microscopy-based labeling and transcriptional activator binding analyses and show that the acetyltransferase module is localized in the most mobile region of the complex. We further comprehensively mapped the subunit interconnectivity of SAGA using cross-linking mass spectrometry, revealing that the Spt and Taf subunits form the structural core of the complex. These results provide the necessary restraints for us to generate a model of the spatial arrangement of all SAGA subunits. According to this model, the chromatin-binding domains of SAGA are all clustered in one face of the complex that is highly flexible. Our results relate information of overall SAGA structure with detailed subunit level interactions, improving our understanding of its architecture and flexibility. PMID:25713136

  5. Conformational flexibility and subunit arrangement of the modular yeast Spt-Ada-Gcn5 acetyltransferase complex.

    Science.gov (United States)

    Setiaputra, Dheva; Ross, James D; Lu, Shan; Cheng, Derrick T; Dong, Meng-Qiu; Yip, Calvin K

    2015-04-17

    The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex is a highly conserved, 19-subunit histone acetyltransferase complex that activates transcription through acetylation and deubiquitination of nucleosomal histones in Saccharomyces cerevisiae. Because SAGA has been shown to display conformational variability, we applied gradient fixation to stabilize purified SAGA and systematically analyzed this flexibility using single-particle EM. Our two- and three-dimensional studies show that SAGA adopts three major conformations, and mutations of specific subunits affect the distribution among these. We also located the four functional modules of SAGA using electron microscopy-based labeling and transcriptional activator binding analyses and show that the acetyltransferase module is localized in the most mobile region of the complex. We further comprehensively mapped the subunit interconnectivity of SAGA using cross-linking mass spectrometry, revealing that the Spt and Taf subunits form the structural core of the complex. These results provide the necessary restraints for us to generate a model of the spatial arrangement of all SAGA subunits. According to this model, the chromatin-binding domains of SAGA are all clustered in one face of the complex that is highly flexible. Our results relate information of overall SAGA structure with detailed subunit level interactions, improving our understanding of its architecture and flexibility. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Effects of transcranial magnetic stimulation on the cognitive event-related potential p300: a literature review.

    Science.gov (United States)

    RĂȘgo, Samuel R M; Marcolin, Marco A; May, Geoffrey; Gjini, Klevest

    2012-10-01

    The objective of this study was to perform a systematic review regarding the effects of transcranial magnetic stimulation (TMS) on the cognitive event-related potential P300. A search was performed of the PubMed database, using the keywords "transcranial magnetic stimulation" and "P300." Eight articles were selected and, after analysis of references, one additional article was added to the list. We found the comparison among studies to be difficult, as the information regarding the effects of TMS on P300 is both scarce and heterogeneous with respect to the parameters used in TMS stimulation and the elicitation of P300. However, 7 of 9 studies found positive results. New studies need to be carried out in order to understand the contribution of these variables and others to the alteration in the latency and amplitude of the P300 wave.

  7. Bootstrapping the P300 in diagnostic psychophysiology: How many iterations are needed?

    Science.gov (United States)

    Rosenfeld, J Peter; Ward, Anne; Meijer, Ewout H; Yukhnenko, Denis

    2017-03-01

    In psychophysiological research, bootstrapping procedures are often used to classify individual participants. How many iterations are required for a reliable bootstrap test is not universally agreed upon. To investigate the number of iterations needed for a stable bootstrap estimate, we reanalyzed P300 data collected in concealed information test paradigms. We also distinguished between the bootstrap and permutations approaches. We compared results in several studies using 100 versus 1,000 versus 10,000 iterations in the bootstrap, and we concluded that 100 iterations were adequate as results from all three iteration numbers correlated highly. © 2016 Society for Psychophysiological Research.

  8. [Research of controlling of smart home system based on P300 brain-computer interface].

    Science.gov (United States)

    Wang, Jinjia; Yang, Chengjie

    2014-08-01

    Using electroencephalogram (EEG) signal to control external devices has always been the research focus in the field of brain-computer interface (BCI). This is especially significant for those disabilities who have lost capacity of movements. In this paper, the P300-based BCI and the microcontroller-based wireless radio frequency (RF) technology are utilized to design a smart home control system, which can be used to control household appliances, lighting system, and security devices directly. Experiment results showed that the system was simple, reliable and easy to be populirised.

  9. Demonstration of Early Cognitive Impairment in Parkinson’s Disease with Visual P300 Responses

    Science.gov (United States)

    ÖZMÜƞ, GĂŒlin; YERLÄ°KAYA, Deniz; GÖKÇEOĞLU, Arife; EMEK SAVAƞ, Derya Durusu; ÇAKMUR, Raif; DÖNMEZ ÇOLAKOĞLU, Beril; YENER, Görsev G.

    2017-01-01

    Introduction Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Cognitive changes in PD are less observable than motor symptoms; thus, research on cognitive processes, which are known to be impaired from the early stages of PD, is minimal. The purpose of this study is to research the brain dynamics of cognitively normal PD patients and healthy elderly controls using event-related potentials (ERPs) and to evaluate their relationships with neuropsychological tests. Methods Eighteen cognitively normal PD patients and 18 age-, gender-, and education-matched healthy controls were included in the study. Detailed neuropsychological tests were applied to all participants. Electroencephalography (EEG) was performed according to the international 10–20 system, and a classical visual oddball paradigm was used in the experiments. ERP responses in the 0.5 to 25 Hz frequency range were examined. P300 amplitude and latency values were measured from the F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, and O2 electrode sites. In addition, the correlations between P300 responses and neuropsychological test scores were analyzed. Results Significant differences were found between the P300 amplitudes of cognitively normal PD patients and healthy elderly controls [F(1,31)=9.265; p=0.005]. P300 amplitudes were significantly lower for PD patients at the F3, FZ, Cz, C4, Pz, and P4 electrode sites than for healthy elderly controls. Moderate correlations were found between Stroop test score and P4 amplitude, digit span forward and C3 and Pz amplitude, and digit span backward and O1 amplitude. Conclusion The major finding of this study was the detection of cognitive changes by electrophysiological methods in PD patients who were indicated to be cognitively normal by neuropsychological tests. These finding suggests that cognitive changes in PD patients, which are not yet reflected in neuropsychological tests, may be detected by

  10. Fully automated high-throughput chromatin immunoprecipitation for ChIP-seq: identifying ChIP-quality p300 monoclonal antibodies.

    Science.gov (United States)

    Gasper, William C; Marinov, Georgi K; Pauli-Behn, Florencia; Scott, Max T; Newberry, Kimberly; DeSalvo, Gilberto; Ou, Susan; Myers, Richard M; Vielmetter, Jost; Wold, Barbara J

    2014-06-12

    Chromatin immunoprecipitation coupled with DNA sequencing (ChIP-seq) is the major contemporary method for mapping in vivo protein-DNA interactions in the genome. It identifies sites of transcription factor, cofactor and RNA polymerase occupancy, as well as the distribution of histone marks. Consortia such as the ENCyclopedia Of DNA Elements (ENCODE) have produced large datasets using manual protocols. However, future measurements of hundreds of additional factors in many cell types and physiological states call for higher throughput and consistency afforded by automation. Such automation advances, when provided by multiuser facilities, could also improve the quality and efficiency of individual small-scale projects. The immunoprecipitation process has become rate-limiting, and is a source of substantial variability when performed manually. Here we report a fully automated robotic ChIP (R-ChIP) pipeline that allows up to 96 reactions. A second bottleneck is the dearth of renewable ChIP-validated immune reagents, which do not yet exist for most mammalian transcription factors. We used R-ChIP to screen new mouse monoclonal antibodies raised against p300, a histone acetylase, well-known as a marker of active enhancers, for which ChIP-competent monoclonal reagents have been lacking. We identified, validated for ChIP-seq, and made publicly available a monoclonal reagent called ENCITp300-1.

  11. Predictive spelling with a P300-based brain-computer interface: Increasing the rate of communication

    Science.gov (United States)

    Ryan, D.B.; Frye, G.E.; Townsend, G.; Berry, D.R.; Mesa-G, S.; Gates, N.A.; Sellers, E.W.

    2010-01-01

    This study compared a conventional P300 speller brain-computer interface (BCI) to one used in conjunction with a predictive spelling program. Performance differences in accuracy, bit rate, selections per minute, and output characters per minute (OCM) were examined. An 8×9 matrix of letters, numbers, and other keyboard commands was used. Participants (n = 24) were required to correctly complete the same 58 character sentence (i.e., correcting for errors) using the predictive speller (PS) and the non-predictive speller (NS), counterbalanced. The PS produced significantly higher OCMs than the NS. Time to complete the task in the PS condition was 12min 43sec as compared to 20min 20sec in the NS condition. Despite the marked improvement in overall output, accuracy was significantly higher in the NS paradigm. P300 amplitudes were significantly larger in the NS than in the PS paradigm; which is attributed to increased workload and task demands. These results demonstrate the potential efficacy of predictive spelling in the context of BCI. PMID:21278858

  12. An Asynchronous P300-Based Brain-Computer Interface Web Browser for Severely Disabled People.

    Science.gov (United States)

    Martinez-Cagigal, Victor; Gomez-Pilar, Javier; Alvarez, Daniel; Hornero, Roberto

    2017-08-01

    This paper presents an electroencephalographic (EEG) P300-based brain-computer interface (BCI) Internet browser. The system uses the "odd-ball" row-col paradigm for generating the P300 evoked potentials on the scalp of the user, which are immediately processed and translated into web browser commands. There were previous approaches for controlling a BCI web browser. However, to the best of our knowledge, none of them was focused on an assistive context, failing to test their applications with a suitable number of end users. In addition, all of them were synchronous applications, where it was necessary to introduce a "read-mode" command in order to avoid a continuous command selection. Thus, the aim of this study is twofold: 1) to test our web browser with a population of multiple sclerosis (MS) patients in order to assess the usefulness of our proposal to meet their daily communication needs; and 2) to overcome the aforementioned limitation by adding a threshold that discerns between control and non-control states, allowing the user to calmly read the web page without undesirable selections. The browser was tested with sixteen MS patients and five healthy volunteers. Both quantitative and qualitative metrics were obtained. MS participants reached an average accuracy of 84.14%, whereas 95.75% was achieved by control subjects. Results show that MS patients can successfully control the BCI web browser, improving their personal autonomy.

  13. Affective Stimuli for an Auditory P300 Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Akinari Onishi

    2017-09-01

    Full Text Available Gaze-independent brain computer interfaces (BCIs are a potential communication tool for persons with paralysis. This study applies affective auditory stimuli to investigate their effects using a P300 BCI. Fifteen able-bodied participants operated the P300 BCI, with positive and negative affective sounds (PA: a meowing cat sound, NA: a screaming cat sound. Permuted stimuli of the positive and negative affective sounds (permuted-PA, permuted-NA were also used for comparison. Electroencephalography data was collected, and offline classification accuracies were compared. We used a visual analog scale (VAS to measure positive and negative affective feelings in the participants. The mean classification accuracies were 84.7% for PA and 67.3% for permuted-PA, while the VAS scores were 58.5 for PA and −12.1 for permuted-PA. The positive affective stimulus showed significantly higher accuracy and VAS scores than the negative affective stimulus. In contrast, mean classification accuracies were 77.3% for NA and 76.0% for permuted-NA, while the VAS scores were −50.0 for NA and −39.2 for permuted NA, which are not significantly different. We determined that a positive affective stimulus with accompanying positive affective feelings significantly improved BCI accuracy. Additionally, an ALS patient achieved 90% online classification accuracy. These results suggest that affective stimuli may be useful for preparing a practical auditory BCI system for patients with disabilities.

  14. 7 mg nicotine patch fails to enhance P300 neural indices of cognitive control among nonsmokers.

    Science.gov (United States)

    Evans, David E; Jentink, Kade G; Sutton, Steven K; Van Rensburg, Kate Janse; Drobes, David J

    2014-11-01

    Nicotine administration facilitates and nicotine deprivation reduces cognitive control in smokers. Importantly, nicotine effects on cognition may reinforce smoking behavior, especially among individuals who have cognitive deficits. The target P300 (P3b) and distracter P300 (P3a) are well-validated electrocortical markers of attention- and memory-related cognitive control processes. Nicotine deprivation has been shown to reduce P3b/P3a amplitudes. The current study sought to examine the direct effects of nicotine on P3b/P3a amplitudes among nonsmokers. It was hypothesized that nicotine would increase P3b and P3a amplitudes, and that individuals lower on trait cognitive control would show greater nicotine-induced increases. 78 nonsmokers attended two separate experimental sessions, during which they performed the P3b/P3a evoking 3-stimulus oddball task following nicotine (7-mg) or placebo patch administration. Nicotine did not enhance P3b or P3a amplitudes, nor did trait cognitive control moderate the influence of nicotine on these indices. Nicotine-induced changes in P3 amplitudes may be limited to nicotine deprivation and/or nonsmokers may be fundamentally different with respect to the influence of nicotine on P3b/P3a indices of cognitive control. Directions for future research that may further examine the effects of nicotine on P3b/P3a independent of withdrawal reversal are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. P300 Source Localization Contrasts in Body-Focused Repetitive Behaviors and Tic Disorders

    Directory of Open Access Journals (Sweden)

    GeneviÚve Sauvé

    2017-07-01

    Full Text Available Tic disorders (TD and body-focused repetitive behaviors (BFRB have similar phenotypes that can be challenging to distinguish in clinical settings. Both disorders show high rates of comorbid psychiatric conditions, dysfunctional basal ganglia activity, atypical cortical functioning in the prefrontal and motor cortical regions, and cognitive deficits. Clinicians frequently confound the two disorders and it is important to find reliable objective methods to discriminate TD and BFRB. Neuropsychological tests and event-related potential (ERP studies have yielded inconsistent results regarding a possible context updating deficit in TD and BFRB patients. However, most previous studies did not control for the presence of comorbid psychiatric condition and medication status, which might have confounded the findings reported to date. Hence, we aimed to investigate the psychophysiology of working memory using ERP in carefully screened TD and BFRB patients excluding those with psychiatric comorbidity and those taking psychoactive medication. The current study compared 12 TD patients, 12 BRFB patients, and 15 healthy control participants using a motor oddball task (button press. The P300 component was analyzed as an index of working memory functioning. Results showed that BFRB patients had decreased P300 oddball effect amplitudes over the right hemisphere compared to the TD and control groups. Clinical groups presented different scalp distributions compared to controls, which could represent a potential endophenotype candidate of BFRB and TD.

  16. Social status level and dimension interactively influence person evaluations indexed by P300s.

    Science.gov (United States)

    Gyurovski, Ivo; Kubota, Jennifer; Cardenas-Iniguez, Carlos; Cloutier, Jasmin

    2017-05-15

    Functional neuroimaging research suggests that status-based evaluations may not solely depend on the level of social status but also on the conferred status dimension. However, no reports to date have studied how status level and dimension shape early person evaluations. To explore early status-based person evaluations, event-related brain potential data were collected from 29 participants while they indicated the status level and dimension of faces that had been previously trained to be associated with one of four status types: high moral, low moral, high financial, or low financial. Analysis of the P300 amplitude (previously implicated in social evaluation) revealed an interaction of status level and status dimension such that enhanced P300 amplitudes were observed in response to targets of high financial and low moral status relative to targets of low financial and high moral status. Implications of these findings are discussed in the context of our current understanding of status-based evaluation and, more broadly, of the processes by which person knowledge may shape person perception and evaluation.

  17. Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb/p300 interaction.

    Science.gov (United States)

    Uttarkar, Sagar; DassĂ©, Emilie; Coulibaly, Anna; Steinmann, Simone; Jakobs, Anke; Schomburg, Caroline; Trentmann, Amke; Jose, Joachim; Schlenke, Peter; Berdel, Wolfgang E; Schmidt, Thomas J; MĂŒller-Tidow, Carsten; Frampton, Jon; Klempnauer, Karl-Heinz

    2016-03-03

    The transcription factor Myb plays a key role in the hematopoietic system and has been implicated in the development of leukemia and other human cancers. Inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. However, because of a lack of suitable inhibitors, the feasibility of therapeutic approaches based on Myb inhibition has not been explored. We have identified the triterpenoid Celastrol as a potent low-molecular-weight inhibitor of the interaction of Myb with its cooperation partner p300. We demonstrate that Celastrol suppresses the proliferative potential of acute myeloid leukemia (AML) cells while not affecting normal hematopoietic progenitor cells. Furthermore, Celastrol prolongs the survival of mice in a model of an aggressive AML. Overall, our work demonstrates the therapeutic potential of a small molecule inhibitor of the Myb/p300 interaction for the treatment of AML and provides a starting point for the further development of Myb-inhibitory compounds for the treatment of leukemia and, possibly, other tumors driven by deregulated Myb. © 2016 by The American Society of Hematology.

  18. Magnetic stimulation at acupoints relieves mental fatigue: An Event Related Potential (P300) study.

    Science.gov (United States)

    Yang, Shuo; Qiao, Yanyun; Wang, Lei; Hao, Pengru

    2017-07-20

    Mental fatigue caused by continuous cognitive tasks represents one of the most worrying modern health problems. Event Related Potential (ERP) P300 is thought to be associated with cognitive function. This study aimed at characterizing the neural activity correlated with the attentional processes and exploring a novelty method which combine the magnetic stimulation and acupoint to relieve mental fatigue caused by continuous cognitive tasks. P300 (P3a and P3b) were extracted at three points: when subjects felt relaxed, at the point of mental fatigue, and after the subjects were stimulated at acupoints. The amplitudes and latencies of P3a and P3b were analyzed statistically. Among the four features (P3a amplitude, P3a latency, P3b amplitude, and P3b latency), only P3b amplitude was found to have a significant difference between the resting state and the mental fatigue state. And P3b amplitude significantly increased after magnetic stimulation at the acupoints. Subjects experiencing mental fatigue demonstrated a significant decrease in P3b amplitude in the parietal region, suggesting attenuation of resource allocation for selective attention. P3b amplitude significantly increased after magnetic stimulation at acupoints indicating that this strategy can be used to improve selective attention and relieve mental fatigue.

  19. New stimulation pattern design to improve P300-based matrix speller performance at high flash rate

    Science.gov (United States)

    Polprasert, Chantri; Kukieattikool, Pratana; Demeechai, Tanee; Ritcey, James A.; Siwamogsatham, Siwaruk

    2013-06-01

    Objective. We propose a new stimulation pattern design for the P300-based matrix speller aimed at increasing the minimum target-to-target interval (TTI). Approach. Inspired by the simplicity and strong performance of the conventional row-column (RC) stimulation, the proposed stimulation is obtained by modifying the RC stimulation through alternating row and column flashes which are selected based on the proposed design rules. The second flash of the double-flash components is then delayed for a number of flashing instants to increase the minimum TTI. The trade-off inherited in this approach is the reduced randomness within the stimulation pattern. Main results. We test the proposed stimulation pattern and compare its performance in terms of selection accuracy, raw and practical bit rates with the conventional RC flashing paradigm over several flash rates. By increasing the minimum TTI within the stimulation sequence, the proposed stimulation has more event-related potentials that can be identified compared to that of the conventional RC stimulations, as the flash rate increases. This leads to significant performance improvement in terms of the letter selection accuracy, the raw and practical bit rates over the conventional RC stimulation. Significance. These studies demonstrate that significant performance improvement over the RC stimulation is obtained without additional testing or training samples to compensate for low P300 amplitude at high flash rate. We show that our proposed stimulation is more robust to reduced signal strength due to the increased flash rate than the RC stimulation.

  20. Time-Shift Correlation Algorithm for P300 Event Related Potential Brain-Computer Interface Implementation.

    Science.gov (United States)

    Liu, Ju-Chi; Chou, Hung-Chyun; Chen, Chien-Hsiu; Lin, Yi-Tseng; Kuo, Chung-Hsien

    2016-01-01

    A high efficient time-shift correlation algorithm was proposed to deal with the peak time uncertainty of P300 evoked potential for a P300-based brain-computer interface (BCI). The time-shift correlation series data were collected as the input nodes of an artificial neural network (ANN), and the classification of four LED visual stimuli was selected as the output node. Two operating modes, including fast-recognition mode (FM) and accuracy-recognition mode (AM), were realized. The proposed BCI system was implemented on an embedded system for commanding an adult-size humanoid robot to evaluate the performance from investigating the ground truth trajectories of the humanoid robot. When the humanoid robot walked in a spacious area, the FM was used to control the robot with a higher information transfer rate (ITR). When the robot walked in a crowded area, the AM was used for high accuracy of recognition to reduce the risk of collision. The experimental results showed that, in 100 trials, the accuracy rate of FM was 87.8% and the average ITR was 52.73 bits/min. In addition, the accuracy rate was improved to 92% for the AM, and the average ITR decreased to 31.27 bits/min. due to strict recognition constraints.

  1. P300 Source Localization Contrasts in Body-Focused Repetitive Behaviors and Tic Disorders

    Science.gov (United States)

    SauvĂ©, GeneviĂšve; O’Connor, Kieron P.; Blanchet, Pierre J.

    2017-01-01

    Tic disorders (TD) and body-focused repetitive behaviors (BFRB) have similar phenotypes that can be challenging to distinguish in clinical settings. Both disorders show high rates of comorbid psychiatric conditions, dysfunctional basal ganglia activity, atypical cortical functioning in the prefrontal and motor cortical regions, and cognitive deficits. Clinicians frequently confound the two disorders and it is important to find reliable objective methods to discriminate TD and BFRB. Neuropsychological tests and event-related potential (ERP) studies have yielded inconsistent results regarding a possible context updating deficit in TD and BFRB patients. However, most previous studies did not control for the presence of comorbid psychiatric condition and medication status, which might have confounded the findings reported to date. Hence, we aimed to investigate the psychophysiology of working memory using ERP in carefully screened TD and BFRB patients excluding those with psychiatric comorbidity and those taking psychoactive medication. The current study compared 12 TD patients, 12 BRFB patients, and 15 healthy control participants using a motor oddball task (button press). The P300 component was analyzed as an index of working memory functioning. Results showed that BFRB patients had decreased P300 oddball effect amplitudes over the right hemisphere compared to the TD and control groups. Clinical groups presented different scalp distributions compared to controls, which could represent a potential endophenotype candidate of BFRB and TD. PMID:28671557

  2. Time-Shift Correlation Algorithm for P300 Event Related Potential Brain-Computer Interface Implementation

    Directory of Open Access Journals (Sweden)

    Ju-Chi Liu

    2016-01-01

    Full Text Available A high efficient time-shift correlation algorithm was proposed to deal with the peak time uncertainty of P300 evoked potential for a P300-based brain-computer interface (BCI. The time-shift correlation series data were collected as the input nodes of an artificial neural network (ANN, and the classification of four LED visual stimuli was selected as the output node. Two operating modes, including fast-recognition mode (FM and accuracy-recognition mode (AM, were realized. The proposed BCI system was implemented on an embedded system for commanding an adult-size humanoid robot to evaluate the performance from investigating the ground truth trajectories of the humanoid robot. When the humanoid robot walked in a spacious area, the FM was used to control the robot with a higher information transfer rate (ITR. When the robot walked in a crowded area, the AM was used for high accuracy of recognition to reduce the risk of collision. The experimental results showed that, in 100 trials, the accuracy rate of FM was 87.8% and the average ITR was 52.73 bits/min. In addition, the accuracy rate was improved to 92% for the AM, and the average ITR decreased to 31.27 bits/min. due to strict recognition constraints.

  3. Tyrosine ameliorates heat induced delay in event related potential P300 and contingent negative variation.

    Science.gov (United States)

    Kishore, Krishna; Ray, Koushik; Anand, J P; Thakur, Lalan; Kumar, Sanjeev; Panjwani, Usha

    2013-12-01

    The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the reduction of cognitive decline during heat exposure (HE) using event-related potential P300, and contingent negative variation (CNV) was evaluated. Ten healthy males, age 20-30years participated in the study. Volunteers received placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45°C+30% RH). P300 latency was significantly increased (p<0.01) during exposure with placebo, which was reduced significantly (p<0.01) after tyrosine supplementation. There was an increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in M100 amplitude (p<0.01) during HE with placebo, which returns to near normal level with the tyrosine administration. A significantly higher plasma norepinephrine (p<0.05), dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure. HE increases the brain catecholamine activity thereby reduces the plasma norepinephrine and dopamine level leading to a reduction in cognitive performances. Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. A robust sensor-selection method for P300 brain-computer interfaces

    Science.gov (United States)

    Cecotti, H.; Rivet, B.; Congedo, M.; Jutten, C.; Bertrand, O.; Maby, E.; Mattout, J.

    2011-02-01

    A brain-computer interface (BCI) is a specific type of human-computer interface that enables direct communication between human and computer through decoding of brain activity. As such, event-related potentials like the P300 can be obtained with an oddball paradigm whose targets are selected by the user. This paper deals with methods to reduce the needed set of EEG sensors in the P300 speller application. A reduced number of sensors yields more comfort for the user, decreases installation time duration, may substantially reduce the financial cost of the BCI setup and may reduce the power consumption for wireless EEG caps. Our new approach to select relevant sensors is based on backward elimination using a cost function based on the signal to signal-plus-noise ratio, after some spatial filtering. We show that this cost function selects sensors' subsets that provide a better accuracy in the speller recognition rate during the test sessions than selected subsets based on classification accuracy. We validate our selection strategy on data from 20 healthy subjects.

  5. High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Yun

    2011-01-01

    Full Text Available Abstract Background It has been suggested that p300 participates in the regulation of a wide range of cell biological processes and mutation of p300 has been identified in certain types of human cancers. However, the expression dynamics of p300 in hepatocellular carcinoma (HCC and its clinical/prognostic significance are unclear. Methods In this study, the methods of reverse transcription-polymerase chain reaction (RT-PCR, Western blotting and immunohistochemistry (IHC were utilized to investigate protein/mRNA expression of p300 in HCCs. Receiver operating characteristic (ROC curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. Results Up-regulated expression of p300 mRNA and protein was observed in the majority of HCCs by RT-PCR and Western blotting, when compared with their adjacent non-malignant liver tissues. According to the ROC curves, the cutoff score for p300 high expression was defined when more than 60% of the tumor cells were positively stained. High expression of p300 was examined in 60/123 (48.8% of HCCs and in 8/123 (6.5% of adjacent non-malignant liver tissues. High expression of p300 was correlated with higher AFP level, larger tumor size, multiplicity, poorer differentiation and later stage (P P = 0.001. In different subsets of HCC patients, p300 expression was also a prognostic indicator in patients with stage II (P = 0.007 and stage III (P = 0.011. Importantly, p300 expression was evaluated as an independent prognostic factor in multivariate analysis (P = 0.021. Consequently, a new clinicopathologic prognostic model with three poor prognostic factors (p300 expression, AFP level and vascular invasion was constructed. The model could significantly stratify risk (low, intermediate and high for overall survival (P Conclusions Our findings provide a basis for the concept that high expression of p300 in HCC may be important in the acquisition of

  6. EEG correlates of P300-based brain-computer interface (BCI) performance in people with amyotrophic lateral sclerosis

    Science.gov (United States)

    Mak, Joseph N.; McFarland, Dennis J.; Vaughan, Theresa M.; McCane, Lynn M.; Tsui, Phillippa Z.; Zeitlin, Debra J.; Sellers, Eric W.; Wolpaw, Jonathan R.

    2012-04-01

    The purpose of this study was to identify electroencephalography (EEG) features that correlate with P300-based brain-computer interface (P300 BCI) performance in people with amyotrophic lateral sclerosis (ALS). Twenty people with ALS used a P300 BCI spelling application in copy-spelling mode. Three types of EEG features were found to be good predictors of P300 BCI performance: (1) the root-mean-square amplitude and (2) the negative peak amplitude of the event-related potential to target stimuli (target ERP) at Fz, Cz, P3, Pz, and P4; and (3) EEG theta frequency (4.5-8 Hz) power at Fz, Cz, P3, Pz, P4, PO7, PO8 and Oz. A statistical prediction model that used a subset of these features accounted for >60% of the variance in copy-spelling performance (p < 0.001, mean R2 = 0.6175). The correlations reflected between-subject, rather than within-subject, effects. The results enhance understanding of performance differences among P300 BCI users. The predictors found in this study might help in: (1) identifying suitable candidates for long-term P300 BCI operation; (2) assessing performance online. Further work on within-subject effects needs to be done to establish whether P300 BCI user performance could be improved by optimizing one or more of these EEG features.

  7. Effects of etizolam and ethyl loflazepate on the P300 event-related potential in healthy subjects.

    Science.gov (United States)

    Fukami, Goro; Hashimoto, Tasuku; Shirayama, Yukihiko; Hasegawa, Tadashi; Watanabe, Hiroyuki; Fujisaki, Mihisa; Hashimoto, Kenji; Iyo, Masaomi

    2010-11-03

    Benzodiazepines carry the risk of inducing cognitive impairments, which may go unnoticed while profoundly disturbing social activity. Furthermore, these impairments are partly associated with the elimination half-life (EH) of the substance from the body. The object of the present study was to examine the effects of etizolam and ethyl loflazepate, with EHs of 6 h and 122 h, respectively, on information processing in healthy subjects. Healthy people were administered etizolam and ethyl loflazepate acutely and subchronically (14 days). The auditory P300 event-related potential and the neuropsychological batteries described below were employed to assess the effects of drugs on cognition. The P300 event-related potential was recorded before and after drug treatments. The digit symbol test, trail making test, digit span test and verbal paired associates test were administered to examine mental slowing and memory functioning. Acute administration of drugs caused prolongation in P300 latency and reduction in P300 amplitude. Etizolam caused a statistically significant prolongation in P300 latency compared to ethyl loflazepate. Furthermore, subchronic administration of etizolam, but not ethyl loflazepate, still caused a weak prolongation in P300 latency. In contrast, neuropsychological tests showed no difference. The results indicate that acute administration of ethyl loflazepate induces less effect on P300 latency than etizolam.

  8. P300 Event-Related Potentials Differentiate Better Performing Individuals With Traumatic Brain Injury: A Preliminary Study of Semantic Processing.

    Science.gov (United States)

    Davis, Tara M; Hill, Benjamin D; Evans, Kelli J; Tiffin, Shelby; Stanley, Nicholas; Fields, Kelly; Russ, Katherine; Bindele, Huybrechts Frazier; Gordon-Hickey, Susan

    To measure the effect of traumatic brain injury on the cognitive processing of words, as measured by the P300, in a semantic categorization task. Eight adults with a history of moderate to severe traumatic brain injury and 8 age- and gender-matched controls. A pilot study measuring cognitive event-related potentials in response to word pairs that were either in same or different semantic categories. The P300 (P3b) component of the auditory event-related potential and neuropsychological assessment. Two patterns of P300 amplitude related to brain injury were observed. Participants with poorer performance on neuropsychological tests exhibited reduced P300 amplitude as compared to controls but showed the typical P300 parietal scalp distribution. In contrast, better performing participants demonstrated robust P300 amplitude but a substantially altered scalp distribution, characterized by the recruitment of anterior brain regions in addition to parietal activation. The recruitment of frontal areas after traumatic brain injury may represent compensatory neural mechanisms utilized to successfully maximize task performance. The P300 in a semantic processing paradigm may be a sensitive marker of neural plasticity that could be used to improve functional outcomes in cognitive remediation paradigms.

  9. P300 amplitude and response speed relate to preserved cognitive function in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Sundgren, Mathias; Nikulin, Vadim V; Maurex, Liselotte; Wahlin, Åke; Piehl, Fredrik; Brismar, Tom

    2015-04-01

    To explore if cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) is associated with abnormal neural function and if there is evidence of neural compensatory mechanisms. Seventy-two RRMS patients and 89 healthy control subjects were included in a cross-sectional study. Event-related brain potential (P300) and response time (RT) were recorded with visual and auditory choice reaction tasks. Cognitive function was evaluated with an 18 item test battery. Patients had a decrease in cognitive function (pP300 amplitude frontally. P300 amplitude was normal in other brain areas and RT was normal. P300 latency was normal except for an increase in auditory latency occipitally. Cognitive performance correlated positively with parietal P300 amplitude in patients but not in controls. Cognition had stronger correlation (negative) with RT in patients than in controls. Patients with low P300 amplitude and long RT were more often cognitively impaired. This indicates that general factors such as signal amplitude and speed are limiting for cognitive function in RRMS patients. The increase in frontal P300 amplitude may be a compensatory effect. Our findings suggest that high amplitude and fast speed may be protective against cognitive impairment. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. A feed-forward repression mechanism anchors the Sin3/histone deacetylase and N-CoR/SMRT corepressors on chromatin

    NARCIS (Netherlands)

    Vermeulen, M.; Walter, W.; Guezennec, X.S. le; Kim, J.; Edayathumangalam, R.S.; Lasonder, E.; Luger, K.; Roeder, R.G.; Logie, C.; Berger, S.L.; Stunnenberg, H.G.

    2006-01-01

    Transcription in eukaryotes is governed in part by histone acetyltransferase (HAT)- and histone deacetylase (HDAC)-containing complexes that are recruited via activators and repressors, respectively. Here, we show that the Sin3/HDAC and N-CoR/SMRT corepressor complexes repress transcription from

  11. The P300 event-related potential and smoking--a population-based case-control study.

    Science.gov (United States)

    Mobascher, A; Brinkmeyer, J; Warbrick, T; Wels, C; Wagner, M; GrĂŒnder, G; Spreckelmeyer, K N; Wienker, T; Diaz Lacava, A; Dahmen, N; Böttcher, M; Thuerauf, N; Clepce, M; Kiefer, F; De Millas, W; Gallinat, J; Winterer, G

    2010-08-01

    A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers. The main purpose of the present study was to provide an in-depth description of smoking-related behavioral, biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters. In this case-control study N=1318 participants (smokers and never-smoking controls) were investigated at 6 German academic institutions. Study participants were randomly selected from the general population. Subjects with mental disorders including alcoholism and drug abuse were excluded. The main outcome measure was the P300 global field power (GFP). We found a lower P300 GFP in current smokers compared to never-smoking controls. Furthermore a correlation between measures of smoking severity and P300 GFP reduction was found. Non-addicted smokers exhibited normal P300 ERP measures. This study provides further evidence that the P300 ERP is reduced in current smokers even in the absence of potentially confounding psychiatric comorbidity. Thus, P300 amplitude reduction clearly is part of the electrophysiological phenotype of smokers. Our results provide the phenotypical groundwork for future multidimensional analyses of genotype-phenotype relationships in the field of smoking and nicotine dependence. Copyright 2010 Elsevier B.V. All rights reserved.

  12. A multi-resolution approach to localize neural sources of P300 event-related brain potential.

    Science.gov (United States)

    Sabeti, M; Katebi, S D; Rastgar, K; Azimifar, Z

    2016-09-01

    P300 is probably the most well-known component of event-related brain potentials (ERPs). Using an oddball paradigm, a P300 component can be identified, that is, elicited by the target stimuli recognition. Since P300 is associated with attention and memory operations of the brain, investigation of this component can improve our understanding of these mechanisms. The present study is aimed at identifying the P300 generators in 30 healthy subjects aged 18-30 years using time-reduction region-suppression linearly constrained minimum variance (TR-LCMV) beamformer. In our study, TR-LCMV beamformer with multi-resolution approach is proposed, coarse-resolution space to find the approximated coherent source locations, fine-resolution space to estimate covariance matrix for dimension reduction of determined regions, and normal-resolution space to localize the P300 generators in the brain. Our results over simulated and real data showed that this approach is a suitable tool to the analysis of ERP fields with localizing superior and inferior frontal lobe, middle temporal gyrus, parietal lobe, and cingulate gyrus as the most prominent sources of P300. The result of P300 localization was finally compared with the other localization methods and it is demonstrated that enhanced performance is achieved. Our results showed that the P300 originates from a widespread neuronal network in the brain and not from a specific region. Our finding over simulated and real data demonstrated the ability of the TR-LCMV algorithm for P300 source localization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. High-resolution genome-wide mapping of histone modifications.

    Science.gov (United States)

    Roh, Tae-young; Ngau, Wing Chi; Cui, Kairong; Landsman, David; Zhao, Keji

    2004-08-01

    The expression patterns of eukaryotic genomes are controlled by their chromatin structure, consisting of nucleosome subunits in which DNA of approximately 146 bp is wrapped around a core of 8 histone molecules. Post-translational histone modifications play an essential role in modifying chromatin structure. Here we apply a combination of SAGE and chromatin immunoprecipitation (ChIP) protocols to determine the distribution of hyperacetylated histones H3 and H4 in the Saccharomyces cerevisiae genome. We call this approach genome-wide mapping technique (GMAT). Using GMAT, we find that the highest acetylation levels are detected in the 5' end of a gene's coding region, but not in the promoter. Furthermore, we show that the histone acetyltransferase, GCN5p, regulates H3 acetylation in the promoter and 5' end of the coding regions. These findings indicate that GMAT should find valuable applications in mapping target sites of chromatin-modifying enzymes.

  14. A Fuzzy Integral Ensemble Method in Visual P300 Brain-Computer Interface.

    Science.gov (United States)

    Cavrini, Francesco; Bianchi, Luigi; Quitadamo, Lucia Rita; Saggio, Giovanni

    2016-01-01

    We evaluate the possibility of application of combination of classifiers using fuzzy measures and integrals to Brain-Computer Interface (BCI) based on electroencephalography. In particular, we present an ensemble method that can be applied to a variety of systems and evaluate it in the context of a visual P300-based BCI. Offline analysis of data relative to 5 subjects lets us argue that the proposed classification strategy is suitable for BCI. Indeed, the achieved performance is significantly greater than the average of the base classifiers and, broadly speaking, similar to that of the best one. Thus the proposed methodology allows realizing systems that can be used by different subjects without the need for a preliminary configuration phase in which the best classifier for each user has to be identified. Moreover, the ensemble is often capable of detecting uncertain situations and turning them from misclassifications into abstentions, thereby improving the level of safety in BCI for environmental or device control.

  15. An improved P300 pattern in BCI to catch user’s attention

    Science.gov (United States)

    Jin, Jing; Zhang, Hanhan; Daly, Ian; Wang, Xingyu; Cichocki, Andrzej

    2017-06-01

    Objective. Brain-computer interfaces (BCIs) can help patients who have lost control over most muscles but are still conscious and able to communicate or interact with the environment. One of the most popular types of BCI is the P300-based BCI. With this BCI, users are asked to count the number of appearances of target stimuli in an experiment. To date, the majority of visual P300-based BCI systems developed have used the same character or picture as the target for every stimulus presentation, which can bore users. Consequently, users attention may decrease or be negatively affected by adjacent stimuli. Approach. In this study, a new stimulus is presented to increase user concentration. Honeycomb-shaped figures with 1-3 red dots were used as stimuli. The number and the positions of the red dots in the honeycomb-shaped figure were randomly changed during BCI control. The user was asked to count the number of the dots presented in each flash instead of the number of times they flashed. To assess the performance of this new stimulus, another honeycomb-shaped stimulus, without red dots, was used as a control condition. Main results. The results showed that the honeycomb-shaped stimuli with red dots obtained significantly higher classification accuracies and information transfer rates (p  <  0.05) compared to the honeycomb-shaped stimulus without red dots. Significance. The results indicate that this proposed method can be a promising approach to improve the performance of the BCI system and can be an efficient method in daily application.

  16. An Efficient Framework for EEG Analysis with Application to Hybrid Brain Computer Interfaces Based on Motor Imagery and P300.

    Science.gov (United States)

    Long, Jinyi; Wang, Jue; Yu, Tianyou

    2017-01-01

    The hybrid brain computer interface (BCI) based on motor imagery (MI) and P300 has been a preferred strategy aiming to improve the detection performance through combining the features of each. However, current methods used for combining these two modalities optimize them separately, which does not result in optimal performance. Here, we present an efficient framework to optimize them together by concatenating the features of MI and P300 in a block diagonal form. Then a linear classifier under a dual spectral norm regularizer is applied to the combined features. Under this framework, the hybrid features of MI and P300 can be learned, selected, and combined together directly. Experimental results on the data set of hybrid BCI based on MI and P300 are provided to illustrate competitive performance of the proposed method against other conventional methods. This provides an evidence that the method used here contributes to the discrimination performance of the brain state in hybrid BCI.

  17. An Efficient Framework for EEG Analysis with Application to Hybrid Brain Computer Interfaces Based on Motor Imagery and P300

    Directory of Open Access Journals (Sweden)

    Jinyi Long

    2017-01-01

    Full Text Available The hybrid brain computer interface (BCI based on motor imagery (MI and P300 has been a preferred strategy aiming to improve the detection performance through combining the features of each. However, current methods used for combining these two modalities optimize them separately, which does not result in optimal performance. Here, we present an efficient framework to optimize them together by concatenating the features of MI and P300 in a block diagonal form. Then a linear classifier under a dual spectral norm regularizer is applied to the combined features. Under this framework, the hybrid features of MI and P300 can be learned, selected, and combined together directly. Experimental results on the data set of hybrid BCI based on MI and P300 are provided to illustrate competitive performance of the proposed method against other conventional methods. This provides an evidence that the method used here contributes to the discrimination performance of the brain state in hybrid BCI.

  18. The value of P300 event related potentials in the assessment of cognitive function in subclinical hypothyroidism.

    Science.gov (United States)

    Dejanović, Mirjana; Ivetić, Vesna; Nestorović, Vojkan; Milanović, Zvezdan; Erić, Mirela

    2017-03-01

    Mild hypothyroidism (thyroid stimulating hormone [TSH] less than 10 mIU/L) induces reversible cognitive dysfunction, which can be evaluated by event related potentials (ERP). So far, only little is known about the impact of subclinical hypothyroidism on ERP as electrophysiological markers of cognitive activity. The aim of this study was to follow-up P300 latencies and amplitudes in patients with subclinical hypothyroidism and to evaluate the influence of thyroxine treatment which led to the normalization of TSH level in serum. We recorded the P300 wave using an auditory oddball paradigm in 60 patients (mean age 51.1±6.2 years, range 40-62 years), with subclinical hypothyroidism (normal mean value of FT4, with elevated TSH levels) at baseline, after 3 months, after 6 months and in 30 healthy control subjects. 30 patients treated six months with L-thyroxine until the normalization of TSH and 30 patients received placebo. The P300 latencies in patients with subclinical hypothyroidism were significantly longer, and the P300 amplitudes were significantly smaller than those of the control group. In the thyroxine treated patients P300 latency continuously decreased over the observation period with a significant difference after 6 months compared to baseline (Phypothyroidism. The P300 latency stands out as a marker for cognitive function recovery during treatment with thyroxine.

  19. Incorporation of Inter-Subject Information to Improve the Accuracy of Subject-Specific P300 Classifiers.

    Science.gov (United States)

    Xu, Minpeng; Liu, Jing; Chen, Long; Qi, Hongzhi; He, Feng; Zhou, Peng; Wan, Baikun; Ming, Dong

    2016-05-01

    Although the inter-subject information has been demonstrated to be effective for a rapid calibration of the P300-based brain-computer interface (BCI), it has never been comprehensively tested to find if the incorporation of heterogeneous data could enhance the accuracy. This study aims to improve the subject-specific P300 classifier by adding other subject's data. A classifier calibration strategy, weighted ensemble learning generic information (WELGI), was developed, in which elementary classifiers were constructed by using both the intra- and inter-subject information and then integrated into a strong classifier with a weight assessment. 55 subjects were recruited to spell 20 characters offline using the conventional P300-based BCI, i.e. the P300-speller. Four different metrics, the P300 accuracy and precision, the round accuracy, and the character accuracy, were performed for a comprehensive investigation. The results revealed that the classifier constructed on the training dataset in combination with adding other subject's data was significantly superior to that without the inter-subject information. Therefore, the WELGI is an effective classifier calibration strategy which uses the inter-subject information to improve the accuracy of subject-specific P300 classifiers, and could also be applied to other BCI paradigms.

  20. Influence of P300 latency jitter on event related potential-based brain-computer interface performance

    Science.gov (United States)

    AricĂČ, P.; Aloise, F.; Schettini, F.; Salinari, S.; Mattia, D.; Cincotti, F.

    2014-06-01

    Objective. Several ERP-based brain-computer interfaces (BCIs) that can be controlled even without eye movements (covert attention) have been recently proposed. However, when compared to similar systems based on overt attention, they displayed significantly lower accuracy. In the current interpretation, this is ascribed to the absence of the contribution of short-latency visual evoked potentials (VEPs) in the tasks performed in the covert attention modality. This study aims to investigate if this decrement (i) is fully explained by the lack of VEP contribution to the classification accuracy; (ii) correlates with lower temporal stability of the single-trial P300 potentials elicited in the covert attention modality. Approach. We evaluated the latency jitter of P300 evoked potentials in three BCI interfaces exploiting either overt or covert attention modalities in 20 healthy subjects. The effect of attention modality on the P300 jitter, and the relative contribution of VEPs and P300 jitter to the classification accuracy have been analyzed. Main results. The P300 jitter is higher when the BCI is controlled in covert attention. Classification accuracy negatively correlates with jitter. Even disregarding short-latency VEPs, overt-attention BCI yields better accuracy than covert. When the latency jitter is compensated offline, the difference between accuracies is not significant. Significance. The lower temporal stability of the P300 evoked potential generated during the tasks performed in covert attention modality should be regarded as the main contributing explanation of lower accuracy of covert-attention ERP-based BCIs.

  1. Developmental Endophenotypes: Indexing Genetic Risk for Substance Abuse with the P300 Brain Event-Related Potential.

    Science.gov (United States)

    Iacono, William G; Malone, Stephen M

    2011-12-01

    Although substance use disorders are heritable, their complexity has made identifying genes underlying their development challenging. Endophenotypes, biologically informed quantitative measures that index genetic risk for a disorder, are being recognized for their potential to assist the search for disorder relevant genes. After outlining criteria for an endophenotype that includes developmental considerations, we review how the brain P300 response serves as an index of genetic risk for substance abuse and related externalizing disorders. The P300 response is highly heritable and associated broadly with characteristics of externalizing disorder, including childhood disruptive disorders, antisociality, and precocious expression of deviant behavior. This association appears to be mediated by shared genetic influences. Prospective studies confirm that reduced P300 amplitude present in youth prior to significant exposure to addictive substances is associated with the subsequent development of substance use disorders. Despite pronounced change in mean level over the course of development, P300 amplitude shows strong rank order stability with repeated assessment through young adulthood. In addition, P300 developmental trajectories based on multiple assessments show very high heritability and may be especially informative as measures of genetic risk. Collectively, these findings provide strong support that P300 amplitude and its change through development reflect genetic vulnerability to substance abuse and related externalizing psychopathology.

  2. Correlação do potencial evocado P300 com aspectos cognitivos e depressivos do envelhecimento Correlation of the P300 evoked potential in depressive and cognitive aspects of aging

    Directory of Open Access Journals (Sweden)

    Elisiane Crestani de Miranda

    2012-10-01

    Full Text Available O P300 Ă© um potencial evocado auditivo de longa latĂȘncia dependente das habilidades cognitivas. Acredita-se que alteraçÔes cognitivas decorrentes ou nĂŁo por sintomas depressivos possam interferir no P300. OBJETIVO: Verificar a influĂȘncia do envelhecimento, dos aspectos cognitivos e depressivos na latĂȘncia do P300 em idosos. MÉTODO: Estudo clĂ­nico e experimental com 60 idosos com perda auditiva neurossensorial de grau leve a moderadamente grave, sendo 20 do sexo masculino e 40 feminino e idade mĂ©dia de 71,1 anos. Os participantes realizaram o potencial evocado auditivo de longa latĂȘncia, no qual foi estudada a latĂȘncia do P300 (milissegundos. Os aspectos cognitivos foram avaliados por meio do Miniexame do Estado Mental (MEEM e Escala de Avaliação da Doença de Alzheimer (ADAS-Cog. Na avaliação da sintomatologia depressiva, foi aplicada a Escala de DepressĂŁo GeriĂĄtrica (EDG-15. RESULTADOS: Observou-se uma correlação positiva significante entre a LatĂȘncia e Idade (p = 0,031. Entretanto, nĂŁo houve diferença significante entre a latĂȘncia do P300 e as categorias do ADAS-Cog (p = 0,584, MEEM (p = 0,199 e EDG (p = 0,541. CONCLUSÃO:O avanço da idade ocasionou um aumento da latĂȘncia do P300, porĂ©m, o desempenho cognitivo e a presença de sintomatologia depressiva nĂŁo influenciaram os resultados do P300 nesta população de idosos.The P300 is a long-latency auditory evoked potential highly dependent on cognitive skills. It is believed that cognitive changes caused or not by depressive symptoms may interfere with the P300. AIM: To investigate the influence of aging, cognitive and depression aspects of the P300 latency in elderly people. METHODS: Clinical and experimental study with 60 elderly patients with sensorineural hearing loss of mild to moderately severe level, 20 males and 40 females, average age of 71.1. Participants were submitted to the long latency auditory evoked potential, in which the P300 latency (milliseconds

  3. [Effect of mental fatigue induced by repeated continuous calculation tasks on event-related brain potential (P300)].

    Science.gov (United States)

    Okamura, Noritaka

    2007-09-01

    It is well known that the amplitude and latency of P300 in event-related brain potentials (ERPs) evoked by performing the oddball paradigm reflect the extent of individuals' selective attention. The purpose of this study was to examine whether P300 is a reliable measure for evaluating mental fatigue. In addition to the measurement of auditory ERPs derived from Fz, Cz and Pz, the concentrations of lactic acid, cortisol in plasma and the reaction time of the oddball paradigm, which are believed to reflect fatigue, were measured. In an attempt to cause mental fatigue, 12 healthy college students (8 males, 4 females; 19.5 +/- 0.5 yr; mean +/- S.D.) were forced to perform a continuous addition task using the Uchida-Kreperin test paper for about 2 h. Before the task, the latencies of P300 in Fz, Cz and Pz were 295.6 +/- 8.7 msec, 298.8 +/- 8.5 msec and 297.5 +/- 7.2 msec (mean +/- S.D.), respectively, and after the task they were 312.6 +/- 11.2 msec, 314.6 +/- 10.1 msec and 315.8 +/- 8.7 msec, respectively. A significant difference in the latency before and after the task was detected (pP300 was prolonged in all recording positions, Fz, Cz and Pz. In a control experiment where the continuous addition task was not loaded, a significant change of the latency was not detected. The amplitude of P300 didn't change significantly in all recording positions after the task. In the control experiment, the amplitude of P300 did not change significantly. On the other hand, the changes in the concentrations of lactic acid and cortisol and the reaction time were not induced by the continuous addition task. The prolongation of the latency of P300 would originate from a decline in brain function. In this study, a prolongation of the latency of P300 after the task was detected in all subjects. It is well known that the value of P300 changes with modification of the recording condition, therefore a recording of P300 under the same conditions is required for qualitative evaluation.

  4. Rapid P300 brain-computer interface communication with a head-mounted display

    Directory of Open Access Journals (Sweden)

    Ivo eKĂ€thner

    2015-06-01

    Full Text Available Visual ERP (P300 based brain-computer interfaces (BCIs allow for fast and reliable spelling and are intended as a muscle-independent communication channel for people with severe paralysis. However, they require the presentation of visual stimuli in the field of view of the user. A head mounted display could allow convenient presentation of visual stimuli in situations, where mounting a conventional monitor might be difficult or not feasible (e.g. at a patient’s bedside. To explore if similar accuracies can be achieved with a virtual reality (VR headset compared to a conventional flat screen monitor, we conducted an experiment with 18 healthy participants. We also evaluated it with a person in the locked-in state (LIS to verify that usage of the headset is possible for a severely paralyzed person. Healthy participants performed online spelling with three different display methods. In one condition a 5x5 letter matrix was presented on a conventional 22 inch TFT monitor. Two configurations of the VR headset were tested. In the first (glasses A, the same 5x5 matrix filled the field of view of the user. In the second (glasses B, single letters of the matrix filled the field of view of the user. The participant in the LIS tested the VR headset on 3 different occasions (glasses A condition only. For healthy participants, average online spelling accuracies were 94% (15.5 bits/min using three flash sequences for spelling with the monitor and glasses A and 96% (16.2 bits/min with glasses B. In one session, the participant in the LIS reached an online spelling accuracy of 100% (10 bits/min using the glasses A condition. We also demonstrated that spelling with one flash sequence is possible with the VR headset for healthy users (mean: 32.1 bits/min, maximum reached by one user: 71.89 bits/min at 100% accuracy. We conclude that the VR headset allows for rapid P300 BCI communication in healthy users and may be a suitable display option for severely

  5. Histone deacetylases in memory and cognition.

    Science.gov (United States)

    Penney, Jay; Tsai, Li-Huei

    2014-12-09

    Over the past 30 years, lysine acetylation of histone and nonhistone proteins has become established as a key modulator of gene expression regulating numerous aspects of cell biology. Neuronal growth and plasticity are no exception; roles for lysine acetylation and deacetylation in brain function and dysfunction continue to be uncovered. Transcriptional programs coupling synaptic activity to changes in gene expression are critical to the plasticity mechanisms underlying higher brain functions. These transcriptional programs can be modulated by changes in histone acetylation, and in many cases, transcription factors and histone-modifying enzymes are recruited together to plasticity-associated genes. Lysine acetylation, catalyzed by lysine acetyltransferases (KATs), generally promotes cognitive performance, whereas the opposing process, catalyzed by histone lysine deacetylases (HDACs), appears to negatively regulate cognition in multiple brain regions. Consistently, mutation or deregulation of different KATs or HDACs contributes to neurological dysfunction and neurodegeneration. HDAC inhibitors have shown promise as a treatment to combat the cognitive decline associated with aging and neurodegenerative disease, as well as to ameliorate the symptoms of depression and posttraumatic stress disorder, among others. In this review, we discuss the evidence for the roles of HDACs in cognitive function as well as in neurological disorders and disease. In particular, we focus on HDAC2, which plays a central role in coupling lysine acetylation to synaptic plasticity and mediates many of the effects of HDAC inhibition in cognition and disease. Copyright © 2014, American Association for the Advancement of Science.

  6. Source imaging of P300 auditory evoked potentials and clinical correlations in patients with posttraumatic stress disorder.

    Science.gov (United States)

    Bae, Kyung-Yeol; Kim, Do-Won; Im, Chang-Hwan; Lee, Seung-Hwan

    2011-12-01

    Posttraumatic stress disorder (PTSD) is associated with abnormal information processing. The P300 component of event-related potentials (ERPs) is known to be a useful marker of information processing. The purposes of this study were to determine the P300 current source density in PTSD patients, and its relationship with symptom severity. ERPs were recorded in 30 PTSD patients and 33 healthy controls while participants were performing the auditory oddball task. We compared P300 current source density data--obtained by standardized low-resolution brain electromagnetic tomography (sLORETA)--between the two groups. The correlation between P300 current source density and clinical symptoms (as evaluated using the Korean version of the Structured Interview for PTSD--K-SIPS and Davidson Trauma Scale--K-DTS) was conducted. In PTSD patients, the current source density of P300 is significantly reduced in the inferior frontal gyrus, precentral gyrus, insula, and anterior cingulate compared to healthy controls. Total K-DTS scores were correlated with the P300 current source density in the posterior cingulate gyrus. The K-SIP B items (re-experiencing) and K-SIB D items (increased arousal) were positively correlated with P300 current source densities in several brain regions located in the frontal, parietal, and temporal lobe (psource densities in the superior and middle frontal gyri in the frontal lobes (psource densities reflected the pathophysiology of PTSD patients. PTSD symptoms were related to different neural activities, depending on their symptom characteristics. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Association between hippocampal volume and P300 event related potential in psychosis: support for the Kraepelinian divide.

    Science.gov (United States)

    Dutt, Anirban; Ganguly, Taposhri; Shaikh, Madiha; Walshe, Muriel; Schulze, Katja; Marshall, Nicolette; Constante, Miguel; McDonald, Colm; Murray, Robin M; Allin, Matthew P G; Bramon, Elvira

    2012-01-16

    Abnormalities of the P300 event related potential (ERP) and of hippocampal structure are observed in individuals with psychotic disorders and their unaffected relatives. The understanding and clinical management of psychotic disorders are largely based on the descriptive Kraepelinian distinction between 'dementia praecox' and 'manic depressive psychosis', and not dependant on any well demarcated biological underpinnings. The hippocampus is postulated to be one of the main P300 generators, yet it remains unknown whether hippocampal volume decrements are associated with P300 deficits in psychosis, and whether any association is shared across non-affective and affective psychotic disorders. 228 subjects from the Maudsley Family Psychosis Study comprising 55 patients with non-affective psychosis, 23 patients with psychotic bipolar disorder, 98 unaffected relatives, and 52 unrelated controls contributed structural MRI and ERP data. To study the relationship between hippocampal volume and P300 ERP, a seemingly unrelated regression methodology was used, accounting for whole brain volumes, clinical groups, age and gender in the analysis. An association between left hippocampal volume and P300 latency in the combined sample comprising non-affective and affective psychotic patients, their relatives and controls was observed. There was an inverse relationship between brain structure and function in that prolongation of P300 latencies was associated with smaller left hippocampal volumes. On subdividing the sample based on Kraepelinian dichotomy, this association remained significant only for the non-affective psychosis group, comprising patients and their unaffected relatives. Based on our findings, P300 latency, a measure of the speed of neural transmission, appears to be related to the size of the left hippocampus in schizophrenia, but not in psychotic bipolar disorder. It seems that underlying neuro-biological characteristics could help in unravelling the traditional

  8. Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions

    Science.gov (United States)

    Stephens, David S [Stone Mountain, GA; Gudlavalleti, Seshu K [Kensington, MD; Tzeng, Yih-Ling [Atlanta, GA; Datta, Anup K [San Diego, CA; Carlson, Russell W [Athens, GA

    2011-02-08

    Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

  9. Channel selection based on phase measurement in P300-based brain-computer interface.

    Directory of Open Access Journals (Sweden)

    Minpeng Xu

    Full Text Available Most EEG-based brain-computer interface (BCI paradigms include specific electrode positions. As the structures and activities of the brain vary with each individual, contributing channels should be chosen based on original records of BCIs. Phase measurement is an important approach in EEG analyses, but seldom used for channel selections. In this paper, the phase locking and concentrating value-based recursive feature elimination approach (PLCV-RFE is proposed to produce robust-EEG channel selections in a P300 speller. The PLCV-RFE, deriving from the phase resetting mechanism, measures the phase relation between EEGs and ranks channels by the recursive strategy. Data recorded from 32 electrodes on 9 subjects are used to evaluate the proposed method. The results show that the PLCV-RFE substantially reduces channel sets and improves recognition accuracies significantly. Moreover, compared with other state-of-the-art feature selection methods (SSNRSF and SVM-RFE, the PLCV-RFE achieves better performance. Thus the phase measurement is available in the channel selection of BCI and it may be an evidence to indirectly support that phase resetting is at least one reason for ERP generations.

  10. The portable P300 dialing system based on tablet and Emotiv Epoc headset.

    Science.gov (United States)

    Tong Jijun; Zhang Peng; Xiao Ran; Ding Lei

    2015-08-01

    A Brain-computer interface (BCI) is a novel communication system that translates brain signals into a control signal. Now with the appearance of the commercial EEG headsets and mobile smart platforms (tablet, smartphone), it is possible to develop the mobile BCI system, which can greatly improve the life quality of patients suffering from motor disease, such as amyotrophic lateral scleroses (ALS), multiple sclerosis, cerebral palsy and head trauma. This study adopted a 14-channel Emotiv EPOC headset and Microsoft surface pro 3 to realize a dialing system, which was represented by 4×3 matrices of alphanumeric characters. The performance of the online portable dialing system based on P300 is satisfying. The average classification accuracy reaches 88.75±10.57% in lab and 73.75±16.94% in metro, while the information transfer rate (ITR) reaches 7.17±1.80 and 5.05±2.17 bits/min respectively. This means the commercial EEG headset and tablet has good prospect in developing real time BCI system in realistic environments.

  11. A p300 and SIRT1 Regulated Acetylation Switch of C/EBPα Controls Mitochondrial Function

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    Mohamad A. Zaini

    2018-01-01

    Full Text Available Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα. Protein lysine acetylation is a key post-translational modification (PTM that integrates cellular metabolic cues with other physiological processes. Here, we show that C/EBPα is acetylated by the lysine acetyl transferase (KAT p300 and deacetylated by the lysine deacetylase (KDAC sirtuin1 (SIRT1. SIRT1 is activated in times of energy demand by high levels of nicotinamide adenine dinucleotide (NAD+ and controls mitochondrial biogenesis and function. A hypoacetylated mutant of C/EBPα induces the transcription of mitochondrial genes and results in increased mitochondrial respiration. Our study identifies C/EBPα as a key mediator of SIRT1-controlled adaption of energy homeostasis to changes in nutrient supply.

  12. Small-Molecule Disruption of the Myb/p300 Cooperation Targets Acute Myeloid Leukemia Cells.

    Science.gov (United States)

    Uttarkar, Sagar; Piontek, Therese; Dukare, Sandeep; Schomburg, Caroline; Schlenke, Peter; Berdel, Wolfgang E; MĂŒller-Tidow, Carsten; Schmidt, Thomas J; Klempnauer, Karl-Heinz

    2016-12-01

    The transcription factor c-Myb is essential for the proliferation of hematopoietic cells and has been implicated in the development of leukemia and other human cancers. Pharmacologic inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. By using a Myb reporter cell line, we have identified plumbagin and several naphthoquinones as potent low-molecular weight Myb inhibitors. We demonstrate that these compounds inhibit c-Myb by binding to the c-Myb transactivation domain and disrupting the cooperation of c-Myb with the coactivator p300, a major driver of Myb activity. Naphthoquinone-induced inhibition of c-Myb suppresses Myb target gene expression and induces the differentiation of the myeloid leukemia cell line HL60. We demonstrate that murine and human primary acute myeloid leukemia cells are more sensitive to naphthoquinone-induced inhibition of clonogenic proliferation than normal hematopoietic progenitor cells. Overall, our work demonstrates for the first time the potential of naphthoquinones as small-molecule Myb inhibitors that may have therapeutic potential for the treatment of leukemia and other tumors driven by deregulated Myb. Mol Cancer Ther; 15(12); 2905-15. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. Incorporating advanced language models into the P300 speller using particle filtering

    Science.gov (United States)

    Speier, W.; Arnold, C. W.; Deshpande, A.; Knall, J.; Pouratian, N.

    2015-08-01

    Objective. The P300 speller is a common brain-computer interface (BCI) application designed to communicate language by detecting event related potentials in a subject’s electroencephalogram signal. Information about the structure of natural language can be valuable for BCI communication, but attempts to use this information have thus far been limited to rudimentary n-gram models. While more sophisticated language models are prevalent in natural language processing literature, current BCI analysis methods based on dynamic programming cannot handle their complexity. Approach. Sampling methods can overcome this complexity by estimating the posterior distribution without searching the entire state space of the model. In this study, we implement sequential importance resampling, a commonly used particle filtering (PF) algorithm, to integrate a probabilistic automaton language model. Main result. This method was first evaluated offline on a dataset of 15 healthy subjects, which showed significant increases in speed and accuracy when compared to standard classification methods as well as a recently published approach using a hidden Markov model (HMM). An online pilot study verified these results as the average speed and accuracy achieved using the PF method was significantly higher than that using the HMM method. Significance. These findings strongly support the integration of domain-specific knowledge into BCI classification to improve system performance.

  14. Modafinil improves event related potentials P300 and contingent negative variation after 24 h sleep deprivation.

    Science.gov (United States)

    Ray, Koushik; Chatterjee, Abhirup; Panjwani, Usha; Kumar, Sanjeev; Sahu, Surajit; Ghosh, Sayan; Thakur, Lalan; Anand, Jag Parvesh

    2012-08-21

    The efficacy of modafinil as a countermeasure in the reduction of cognitive decline following 24 h of sleep deprivation (SD) on subjective sleepiness scales, event-related potential (ERP) P300, and contingent negative variation (CNV) was evaluated. Eleven healthy males, age 25-30 years participated. The experiment was performed in five sessions on different days between 7 and 8a.m. Session 1, baseline recordings; Session 2, after one night's SD; Session 3, 48 h of recovery from SD; Session 4, after 1 week of Session 1, following one night's SD along with modafinil (400mg/day); Session 5, 48 h of recovery after SD+modafinil. Subjective sleepiness scores increased significantly after SD as compared to baseline (PP300 peak latencies of ERP following SD (PP300 peak latencies after SD (PP300 amplitudes and CNV N100, M200 peak latencies and M100, M200 amplitudes were observed. The results strongly suggest that modafinil in a dose of 400mg/day, reduces the subjective sleepiness and cognitive decline following 24 h of SD. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. P300 event-related potential as an indicator of inattentional deafness?

    Science.gov (United States)

    Giraudet, Louise; St-Louis, Marie-Eve; Scannella, Sébastien; Causse, Mickaël

    2015-01-01

    An analysis of airplane accidents reveals that pilots sometimes purely fail to react to critical auditory alerts. This inability of an auditory stimulus to reach consciousness has been coined under the term of inattentional deafness. Recent data from literature tends to show that tasks involving high cognitive load consume most of the attentional capacities, leaving little or none remaining for processing any unexpected information. In addition, there is a growing body of evidence for a shared attentional capacity between vision and hearing. In this context, the abundant information in modern cockpits is likely to produce inattentional deafness. We investigated this hypothesis by combining electroencephalographic (EEG) measurements with an ecological aviation task performed under contextual variation of the cognitive load (high or low), including an alarm detection task. Two different audio tones were played: standard tones and deviant tones. Participants were instructed to ignore standard tones and to report deviant tones using a response pad. More than 31% of the deviant tones were not detected in the high load condition. Analysis of the EEG measurements showed a drastic diminution of the auditory P300 amplitude concomitant with this behavioral effect, whereas the N100 component was not affected. We suggest that these behavioral and electrophysiological results provide new insights on explaining the trend of pilots' failure to react to critical auditory information. Relevant applications concern prevention of alarms omission, mental workload measurements and enhanced warning designs.

  16. A Fuzzy Integral Ensemble Method in Visual P300 Brain-Computer Interface

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    Francesco Cavrini

    2016-01-01

    Full Text Available We evaluate the possibility of application of combination of classifiers using fuzzy measures and integrals to Brain-Computer Interface (BCI based on electroencephalography. In particular, we present an ensemble method that can be applied to a variety of systems and evaluate it in the context of a visual P300-based BCI. Offline analysis of data relative to 5 subjects lets us argue that the proposed classification strategy is suitable for BCI. Indeed, the achieved performance is significantly greater than the average of the base classifiers and, broadly speaking, similar to that of the best one. Thus the proposed methodology allows realizing systems that can be used by different subjects without the need for a preliminary configuration phase in which the best classifier for each user has to be identified. Moreover, the ensemble is often capable of detecting uncertain situations and turning them from misclassifications into abstentions, thereby improving the level of safety in BCI for environmental or device control.

  17. Circadian course of the P300 ERP in patients with amyotrophic lateral sclerosis - implications for brain-computer interfaces (BCI).

    Science.gov (United States)

    Erlbeck, Helena; Mochty, Ursula; KĂŒbler, Andrea; Real, Ruben G L

    2017-01-07

    Accidents or neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) can lead to progressing, extensive, and complete paralysis leaving patients aware but unable to communicate (locked-in state). Brain-computer interfaces (BCI) based on electroencephalography represent an important approach to establish communication with these patients. The most common BCI for communication rely on the P300, a positive deflection arising in response to rare events. To foster broader application of BCIs for restoring lost function, also for end-users with impaired vision, we explored whether there were specific time windows during the day in which a P300 driven BCI should be preferably applied. The present study investigated the influence of time of the day and modality (visual vs. auditory) on P300 amplitude and latency. A sample of 14 patients (end-users) with ALS and 14 healthy age matched volunteers participated in the study and P300 event-related potentials (ERP) were recorded at four different times (10, 12 am, 2, & 4 pm) during the day. Results indicated no differences in P300 amplitudes or latencies between groups (ALS patients v. healthy participants) or time of measurement. In the auditory condition, latencies were shorter and amplitudes smaller as compared to the visual condition. Our findings suggest applicability of EEG/BCI sessions in patients with ALS throughout normal waking hours. Future studies using actual BCI systems are needed to generalize these findings with regard to BCI effectiveness/efficiency and other times of day.

  18. Classification effects of real and imaginary movement selective attention tasks on a P300-based brain-computer interface

    Science.gov (United States)

    Salvaris, Mathew; Sepulveda, Francisco

    2010-10-01

    Brain-computer interfaces (BCIs) rely on various electroencephalography methodologies that allow the user to convey their desired control to the machine. Common approaches include the use of event-related potentials (ERPs) such as the P300 and modulation of the beta and mu rhythms. All of these methods have their benefits and drawbacks. In this paper, three different selective attention tasks were tested in conjunction with a P300-based protocol (i.e. the standard counting of target stimuli as well as the conduction of real and imaginary movements in sync with the target stimuli). The three tasks were performed by a total of 10 participants, with the majority (7 out of 10) of the participants having never before participated in imaginary movement BCI experiments. Channels and methods used were optimized for the P300 ERP and no sensory-motor rhythms were explicitly used. The classifier used was a simple Fisher's linear discriminant. Results were encouraging, showing that on average the imaginary movement achieved a P300 versus No-P300 classification accuracy of 84.53%. In comparison, mental counting, the standard selective attention task used in previous studies, achieved 78.9% and real movement 90.3%. Furthermore, multiple trial classification results were recorded and compared, with real movement reaching 99.5% accuracy after four trials (12.8 s), imaginary movement reaching 99.5% accuracy after five trials (16 s) and counting reaching 98.2% accuracy after ten trials (32 s).

  19. Auditory P300 event-related potentials and neurocognitive functions in opioid dependent men and their brothers.

    Science.gov (United States)

    Singh, Shubh Mohan; Basu, Debasish; Kohli, Adarsh; Prabhakar, Sudesh

    2009-01-01

    Event-related-potentials (especially P300) and cognitive functioning as potential endophenotypes have not been studied in opioid dependence. We compared auditory P300 and cognitive functions in opioid-dependent men, their brothers and normal controls in an exploratory study with a view to find shared genetic factors in the development of opioid dependence. Twenty abstinent opioid-dependent males, their brothers and twenty matched controls were administered Wisconsin card sorting test (WCST), digit span test, trail making test-B, and auditory event-related potentials (P300) from an oddball task were recorded. The opioid dependent group performed the worst, the brothers group was intermediate, and the control group performed the best on tests of WCST, digit span and trail making test-B. The opioid dependent group had the smallest amplitudes and longest latencies of P300, and was followed by the brothers group who had an intermediate position and the control group who had the largest amplitudes and the shortest latencies. P300 and executive neurocognitive functions can be considered endophenotypes for the genetic study of vulnerability to opioid dependence. These are reflective of executive dysfunction and disrupted behavioral inhibition and the intermediate position of brothers suggests a common genetic substrate as a component of the etiology.

  20. Histone propionylation is a mark of active chromatin.

    Science.gov (United States)

    Kebede, Adam F; Nieborak, Anna; Shahidian, Lara Zorro; Le Gras, Stephanie; Richter, Florian; Gómez, Diana Aguilar; Baltissen, Marijke P; Meszaros, Gergo; Magliarelli, Helena de Fatima; Taudt, Aaron; Margueron, Raphael; Colomé-Tatché, Maria; Ricci, Romeo; Daujat, Sylvain; Vermeulen, Michiel; Mittler, Gerhard; Schneider, Robert

    2017-12-01

    Histones are highly covalently modified, but the functions of many of these modifications remain unknown. In particular, it is unclear how histone marks are coupled to cellular metabolism and how this coupling affects chromatin architecture. We identified histone H3 Lys14 (H3K14) as a site of propionylation and butyrylation in vivo and carried out the first systematic characterization of histone propionylation. We found that H3K14pr and H3K14bu are deposited by histone acetyltransferases, are preferentially enriched at promoters of active genes and are recognized by acylation-state-specific reader proteins. In agreement with these findings, propionyl-CoA was able to stimulate transcription in an in vitro transcription system. Notably, genome-wide H3 acylation profiles were redefined following changes to the metabolic state, and deletion of the metabolic enzyme propionyl-CoA carboxylase altered global histone propionylation levels. We propose that histone propionylation, acetylation and butyrylation may act in combination to promote high transcriptional output and to couple cellular metabolism with chromatin structure and function.

  1. PTEN Interacts with Histone H1 and Controls Chromatin Condensation

    Science.gov (United States)

    Chen, Zhu Hong; Zhu, Minglu; Yang, Jingyi; Liang, Hui; He, Jinxue; He, Shiming; Wang, Pan; Kang, Xi; McNutt, Michael A.; Yin, Yuxin; Shen, Wen H.

    2014-01-01

    SUMMARY Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development and metabolism. Here we report on the interplay of PTEN, histone H1 and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C-terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may deteriorate chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling. PMID:25199838

  2. Avaliação pelo P300 de crianças com e sem epilepsia e rendimento escolar Assessment through P300 of epileptic and non-epileptic children and school performance

    Directory of Open Access Journals (Sweden)

    JUCELEI F. VISIOLI-MELO

    2000-06-01

    Full Text Available Dificuldade de aprendizagem Ă© situação comum em crianças com epilepsia. DistĂșrbios da inteligĂȘncia tĂȘm sido associados com epilepsia. O potencial cognitivo (P300 Ă© um adjunto clĂ­nico para mensurar neurofisiologicamente o processo cognitivo. Foram estudadas 99 crianças com 10 anos a 11 anos e 11 meses. Do Grupo I, sem epilepsia, faziam parte 64 crianças, das quais 32 com bom rendimento e outras 32 com mau rendimento escolar. Do Grupo II, com epilepsia, faziam parte 35 crianças, sendo 21 com bom rendimento escolar e 15 com mau rendimento escolar. NĂŁo foi encontrada diferença significativa na latĂȘncia do P300 entre os dois grupos. Quando foram estratificados segundo o desempenho escolar, as crianças do Grupo I, com bom rendimento escolar, apresentaram latĂȘncia do P300 de 336 ms e as com mau rendimento escolar, latĂȘncia de 382 ms; as crianças do Grupo II, com bom rendimento escolar, apresentaram latĂȘncia do P300 de 363 ms e as com mau rendimento escolar, latĂȘncia de 400 ms, com diferença significativa. Essa diferença estava localizada entre as crianças nĂŁo epilĂ©pticas com bom desempenho escolar e as com mau desempenho escolar, epilĂ©pticas ou nĂŁo.Learning disability is common in epileptic children. Epilepsy has been associated with disorders of intelligence. Cognitive potential (P300 is considered to be a clinical aid in the neurophysiological measurement of the cognitive process. Ninety-nine children between the ages of 10 years and 11 years and 11 months formed our sample, with good and poor school performance. Group I, non-epileptic, had 64 children of whom 32 had good and 32 poor school performance. Group II, epileptic, had 35 children, of whom 21 had good and 15 poor school performance. No significant difference in P300 latency was found between Groups I and II. When groups were stratified based on school performance, Group I children with good school performance had P300 latency of 336 ms, while the ones with poor

  3. Event-related potentials (P300 and neuropsychological assessment in boys exhibiting Duchenne muscular dystrophy Potencial evocado cognitivo (P300 e testagem neuropsicolĂłgica em pacientes com distrofia muscular de Duchenne

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    Marcus Vinicius Della Coletta

    2007-03-01

    Full Text Available OBJECTIVE: To examine auditory cognitive evoked potentials (P300 potentials and neuropsychological dysfunction in patients with Duchenne muscular dystrophy (DMD. METHOD: P300 potentials and neuropsychological test results were obtained from 16 healthy control boys and 20 DMD patients. Full Intelligence Quotients (IQ were estimated for patients and control group. Mean age was 9.5 years in the DMD patient group, and 10 years in the control group (p>0.05. RESULTS: The mean IQ values were 64.35 in the DMD patients and 82.68 in the control group (p=0.01. Mean P300 values were 347.6 in the DMD group and 337.4 in the control group (p=0.14. There was no significant correlation between parameters in each group. CONCLUSION: DMD patients showed a poor performance as evaluated by P300 potential compared to the control group, although the difference was not statistically significant. Systematic alterations in neuropsychological test results were found, the differences paralleling those detected in IQ.OBJETIVO: Avaliar potenciais evocados cognitivos auditivos (P300 e disfunçÔes neuropsicolĂłgicas em pacientes com distrofia muscular de Duchenne (DMD. MÉTODO: Potenciais auditivos P300 e testes neuropsicolĂłgicos foram obtidos de 16 controles e 20 pacientes com DMD. Valores de quociente de inteligĂȘncia (QI foram estimados para os dois grupos. A media de idade foi de 9.5 anos no grupo DMD e 10 anos no grupo controle (p>0.05. RESULTADOS: Os valores mĂ©dios de QI foram 64.35 no grupo DMD e 82.68 no grupo controle (p=0.01. A mĂ©dia de valores de P300 foi 347.6 no grupo DMD e 337.4 no grupo controle (p=0.14. NĂŁo houve correlação significativa entre os parĂąmetros em cada grupo. CONCLUSÃO: Os pacientes com DMD mostraram um pior desempenho nas testagens de P300 quando comparados com o grupo controle, embora a diferença nĂŁo tenha apresentado diferença significativa. AlteraçÔes sistemĂĄticas foram encontradas nos testes neuropsicolĂłgicos, correspondendo Ă

  4. Potencial evocado auditivo tardio relacionado a eventos (P300 na sĂ­ndrome de Down Late auditory event-related evoked potential (P300 in Down's syndrome patients

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    Carla PatrĂ­cia Hernandez Alves Ribeiro CĂ©sar

    2010-04-01

    Full Text Available A sĂ­ndrome de Down Ă© causada pela trissomia do cromossomo 21 e estĂĄ associada com alteração do processamento auditivo, distĂșrbio de aprendizagem e, provavelmente, inĂ­cio precoce de Doença de Alzheimer. OBJETIVO: Avaliar as latĂȘncias e amplitudes do potencial evocado auditivo tardio relacionado a eventos (P300 e suas alteraçÔes em indivĂ­duos jovens adultos com sĂ­ndrome de Down. MATERIAL E MÉTODO: Estudo de caso prospectivo. LatĂȘncias e amplitudes do P300 foram avaliadas em 17 indivĂ­duos com sĂ­ndrome de Down e 34 indivĂ­duos sadios. RESULTADOS: Foram identificadas latĂȘncias do P300 (N1, P2, N2 e P3 prolongadas e amplitude N2 - P3 diminuĂ­da nos indivĂ­duos com sĂ­ndrome de Down quando comparados ao grupo controle. CONCLUSÃO: Em indivĂ­duos jovens adultos com sĂ­ndrome de Down ocorre aumento das latĂȘncias N1, P2, N2 e P3, e diminuição significativa da amplitude N2-P3 do potencial evocado auditivo tardio relacionado a eventos (P300, sugerindo prejuĂ­zo da integração da ĂĄrea de associação auditiva com as ĂĄreas corticais e subcorticais do sistema nervoso central.Down syndrome is caused by a trisomy of chromosome 21 and is associated with central auditory processing deficit, learning disability and, probably, early-onset Alzheimer's disease. AIM: to evaluate the latencies and amplitudes of evoked late auditory potential related to P300 events and their changes in young adults with Down's syndrome. MATERIALS AND METHODS: Prospective case study. P300 test latency and amplitudes were evaluated in 17 individuals with Down's syndrome and 34 healthy individuals. RESULTS The P300 latency (N1, P2, N2 and P3 was longer and the N2-P3 amplitude was lower in individuals with Down syndrome when compared to those in the control group. CONCLUSION: In young adults with Down syndrome, N1, P2, N2 and P3 latencies of late auditory evoked potential related to P300 events were prolonged, and N2 - P3 amplitudes were significantly reduced

  5. A SUMO-regulated activation function controls synergy of c-Myb through a repressor–activator switch leading to differential p300 recruitment

    Science.gov (United States)

    MolvĂŠrsmyr, Ann-Kristin; SĂŠther, Thomas; Gilfillan, Siv; Lorenzo, Petra Isabel; KvalĂžy, Heidi; Matre, Vilborg; Gabrielsen, Odd Stokke

    2010-01-01

    Synergy between transcription factors operating together on complex promoters is a key aspect of gene activation. The ability of specific factors to synergize is restricted by sumoylation (synergy control, SC). Focusing on the haematopoietic transcription factor c-Myb, we found evidence for a strong SC linked to SUMO-conjugation in its negative regulatory domain (NRD), while AMV v-Myb has escaped this control. Mechanistic studies revealed a SUMO-dependent switch in the function of NRD. When NRD is sumoylated, the activity of c-Myb is reduced. When sumoylation is abolished, NRD switches into being activating, providing the factor with a second activation function (AF). Thus, c-Myb harbours two AFs, one that is constitutively active and one in the NRD being SUMO-regulated (SRAF). This double AF augments c-Myb synergy at compound natural promoters. A similar SUMO-dependent switch was observed in the regulatory domains of Sp3 and p53. We show that the change in synergy behaviour correlates with a SUMO-dependent differential recruitment of p300 and a corresponding local change in histone H3 and H4 acetylation. We therefore propose a general model for SUMO-mediated SC, where SUMO controls synergy by determining the number and strength of AFs associated with a promoter leading to differential chromatin signatures. PMID:20385574

  6. Performance of the Emotiv Epoc headset for P300-based applications.

    Science.gov (United States)

    Duvinage, Matthieu; Castermans, Thierry; Petieau, Mathieu; Hoellinger, Thomas; Cheron, Guy; Dutoit, Thierry

    2013-06-25

    For two decades, EEG-based Brain-Computer Interface (BCI) systems have been widely studied in research labs. Now, researchers want to consider out-of-the-lab applications and make this technology available to everybody. However, medical-grade EEG recording devices are still much too expensive for end-users, especially disabled people. Therefore, several low-cost alternatives have appeared on the market. The Emotiv Epoc headset is one of them. Although some previous work showed this device could suit the customer's needs in terms of performance, no quantitative classification-based assessments compared to a medical system are available. This paper aims at statistically comparing a medical-grade system, the ANT device, and the Emotiv Epoc headset by determining their respective performances in a P300 BCI using the same electrodes. On top of that, a review of previous Emotiv studies and a discussion on practical considerations regarding both systems are proposed. Nine healthy subjects participated in this experiment during which the ANT and the Emotiv systems are used in two different conditions: sitting on a chair and walking on a treadmill at constant speed. The Emotiv headset performs significantly worse than the medical device; observed effect sizes vary from medium to large. The Emotiv headset has higher relative operational and maintenance costs than its medical-grade competitor. Although this low-cost headset is able to record EEG data in a satisfying manner, it should only be chosen for non critical applications such as games, communication systems, etc. For rehabilitation or prosthesis control, this lack of reliability may lead to serious consequences. For research purposes, the medical system should be chosen except if a lot of trials are available or when the Signal-to-Noise Ratio is high. This also suggests that the design of a specific low-cost EEG recording system for critical applications and research is still required.

  7. Methodological considerations about the use of bimodal oddball P300 in psychiatry: topography and reference effect

    Directory of Open Access Journals (Sweden)

    Elisa Schroder

    2016-09-01

    Full Text Available Event-Related Potentials (ERPs bimodal oddball task has disclosed increased sensitivity to show P300 modulations to subclinical symptoms. Even if the utility of such a procedure has still to be confirmed at a clinical level, gathering normative values of this new oddball variant may be of the greatest interest. We specifically addressed the challenge of defining the best location for the recording of P3a and P3b components and selecting the best reference to use by investigating the effect of an offline re-reference procedure on recorded bimodal P3a and P3b. Forty young and healthy subjects were submitted to a bimodal (synchronized and always congruent visual and auditory stimuli three-stimulus oddball task in which 140 frequent bimodal stimuli, 30 deviant target stimuli and 30 distractors were presented. Task consisted in clicking as soon as possible on the targets, and not paying attention to frequent stimuli and distractors. This procedure allowed us to record, for each individual, the P3a component, referring to the novelty process related to distractors processing, and the P3b component, linked to the processing of the target stimuli. Results showed that both P3a and P3b showed maximal amplitude in Pz. However, P3a displayed a more central distribution. Nose reference was also shown to give maximal amplitudes compared with average and linked mastoids references. These data were discussed in light of the necessity to develop multi-site recording guidelines to furnish sets of ERPs data comparable across laboratories.

  8. Methodological Considerations about the Use of Bimodal Oddball P300 in Psychiatry: Topography and Reference Effect.

    Science.gov (United States)

    Schröder, Elisa; Kajosch, Hendrik; Verbanck, Paul; Kornreich, Charles; Campanella, Salvatore

    2016-01-01

    Event-related potentials (ERPs) bimodal oddball task has disclosed increased sensitivity to show P300 modulations to subclinical symptoms. Even if the utility of such a procedure has still to be confirmed at a clinical level, gathering normative values of this new oddball variant may be of the greatest interest. We specifically addressed the challenge of defining the best location for the recording of P3a and P3b components and selecting the best reference to use by investigating the effect of an oïŹ„ine re-reference procedure on recorded bimodal P3a and P3b. Forty young and healthy subjects were submitted to a bimodal (synchronized and always congruent visual and auditory stimuli) three-stimulus oddball task in which 140 frequent bimodal stimuli, 30 deviant "target" stimuli and 30 distractors were presented. Task consisted in clicking as soon as possible on the targets, and not paying attention to frequent stimuli and distractors. This procedure allowed us to record, for each individual, the P3a component, referring to the novelty process related to distractors processing, and the P3b component, linked to the processing of the target stimuli. Results showed that both P3a and P3b showed maximal amplitude in Pz. However, P3a displayed a more central distribution. Nose reference was also shown to give maximal amplitudes compared with average and linked mastoids references. These data were discussed in light of the necessity to develop multi-site recording guidelines to furnish sets of ERPs data comparable across laboratories.

  9. DRD2 A1 allele and P300 abnormalities in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Blum, K. [Univ. of Texas Health Science Center, San Antonio, TX (United States)]|[PATH Foundation, Princeton, NJ (United States); Wood, R.; Sheridan, L.P.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1994-09-01

    Obesity is a heterogeneous and prevalent disorder having both inheritable and environmental components. The role of the dopamine system in P300 has been implicated. We genotyped 193 neuropsychiatrically ill patients with and without comorbid drug and alcohol/abuse/dependence and obesity for the prevalence of the A1 allele of the DRD2 gene. We found a significant linear trend ({chi}{sup 2} = 40.4, df=1, p<0.00001) where the percent prevalence of the A1 increased with increasing polysubstance abuse. Where the A1 allele was found in 44% of 40 obese subjects, the A1 allele prevalence was found in as much as 91% of 11 obese subjects with comorbid polysubstance abuse. 53 obese subjects having a mean body weight (BMI) of 34.6{+-}8.2 were mapped for brain electrical activity and compared with 15 controls with a BMI of 22.3{+-}3.0 (P<.001). The P3 amplitude was significantly different (two tailed; t=3.24, df=16.2, P = 0.005), whereas P3 latency was not significant. Preliminarily, we found a significant decreased P3 amplitude correlated with parental polysubstance abuse (p=0.4) with prolongation of P3 latency correlated with the three risk factors of parental substance abuse, chemical dependency and carbohydrate bingeing (P<0.02). Finally, in a small sample, the A1 allele was present in 25% of probands having 0 risk compared to 66% in those obese subjects with any risk. This work represents the first electrophysiological data to implicate P3 abnormalities in a subset of obesity and further confirms an association of the DRD2 gene and a electrophysiological marker previously indicated to have predictive value in vulnerability to addictive behaviors.

  10. Therapeutic effect of Cryptotanshinone on experimental rheumatoid arthritis through downregulating p300 mediated-STAT3 acetylation.

    Science.gov (United States)

    Wang, Ying; Zhou, Chun; Gao, Hui; Li, Cuixian; Li, Dong; Liu, Peiqing; Huang, Min; Shen, Xiaoyan; Liu, Liang

    2017-08-15

    The balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, plays a critical role in rheumatoid arthritis (RA). The differentiation of Th17 cells requires the activation of STAT3, which determines the balance of Th17/Treg. Here, we investigated the therapeutic effect of Cryptotanshinone (CTS) on collagen induced mouse arthritis and explored the underlying mechanisms. Arthritis was induced in DBA/1 mice with bovine collagen type II and complete Freund's adjuvant. CTS was given at 20mgkg -1 d -1 or 60mgkg -1 d -1 by gavage for 6weeks. The immuno-inflammation and joint destruction were evaluated and the balance of Th17/Treg was determined. STAT3 acetylation and phosphorylation were detected by western blotting, and the involvement of p300 was investigated by siRNA and plasmid overexpression. CTS at a dose of 60mgkg -1 d -1 ameliorated the inflammation and joint destruction in CIA mice. It improved Th17/Treg imbalance, and inhibited both acetylation and phosphorylation of STAT3. CTS reduced p300 expression and its binding to STAT3, but increased phosphorylated AMPK. Knockdown of p300 mimicked the inhibitory effect of CTS on STAT3 acetylation and phosphorylation, which could be partially rescued by overexpression of p300-WT, but not p300-dominant negative (DN) construct. Our study suggested that the anti-arthritis effects of CTS were attained through suppression of p300-mediated STAT3 acetylation. Our data suggest that CTS might be a potential immune modulator for RA treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A region-based two-step P300-based brain-computer interface for patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ikegami, Shiro; Takano, Kouji; Kondo, Kiyohiko; Saeki, Naokatsu; Kansaku, Kenji

    2014-11-01

    The P300-based brain-computer interface (BCI) is designed to help patients with motor disabilities to control their environment, and it has been used successfully in patients with amyotrophic lateral sclerosis (ALS). However, some ALS patients were unable to use the visual P300-BCI with the conventional row/column presentation. In this study, we evaluated the effect of a newly developed region-based two-step P300 speller, which has a larger flashing area than the conventional visual array. Seven ALS patients and seven age- and sex-matched able-bodied control subjects were required to input hiragana characters using our P300 BCI system. We prepared two types of input procedures, the conventional row/column (RC) speller and the two-step speller, and evaluated their online performance. The mean online accuracy of the ALS patients was 24% for the RC condition and 55% for the two-step condition. The accuracy of the control subjects was 71% and 83% for the RC and two-step condition, respectively. Accuracy in ALS patients was significantly lower than that in the control subjects, and the new visual stimuli significantly increased accuracy of ALS patients. Using the new speller, two ALS patients showed an initial accuracy sufficient for practical use (>70%). The other two ALS patients, who performed better in the first trial using the new speller, continued to experience the BCI system, and their mean accuracy increased to 92%. The two-step procedure for the visual P300 BCI system provided significantly increased accuracy for ALS patients compared with a conventional RC speller. The new region-based two-step P300 speller was effective in ALS patients, and the system may be beneficial to expand their range of activities. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Reduction of auditory event-related P300 amplitude in subjects with at-risk mental state for schizophrenia.

    Science.gov (United States)

    OzgĂŒrdal, Seza; Gudlowski, Yehonala; Witthaus, Henning; Kawohl, Wolfram; Uhl, Idun; Hauser, Marta; Gorynia, Inge; Gallinat, JĂŒrgen; Heinze, Martin; Heinz, Andreas; Juckel, Georg

    2008-10-01

    Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia in its prodromal states. As revealed by previous studies, event-related potential components such as auditory evoked P300 associated with cognitive processes, such as attention and orientation, are known to be reduced in amplitude in acute and chronic as well as in medicated and unmedicated patients. It is, however, unclear whether a P300 amplitude reduction occurs before the schizophrenic psychosis is fully manifested. We studied patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with an at-risk mental state showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as first-episode patients and chronic patients with schizophrenia and compared these groups to healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm. Groups differed significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532, p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non-medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001) compared to the healthy controls. The study revealed that there are neurophysiological changes as the reduction in P300 amplitudes begins early in schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown psychosis, and that these changes seem to have a progressive course from prodromal to chronic state of schizophrenia as assumed in this cross-sectional study.

  13. Separation of P300 event-related potential using time varying time-lag blind source separation algorithm.

    Science.gov (United States)

    Sabeti, Malihe; Boostani, Reza

    2017-07-01

    Synchronous averaging over time locked single-trial of event-related potential (ERP) is known as the simplest scheme to extract P300 component. This method assumes the P300 features are invariant through the time while they are affected by factors like brain fatigue and habitation. In this study, a new scheme is proposed termed as time-varying time-lag blind source separation (TT-BSS) which is upon the second order statistics of signal to separate P300 waveform from the background electroencephalogram (EEG) while it captures the time variation of P300 component. The time-lag parameter for all channels is determined by maximizing the correlation (similarity) between two successive trials. As the time-lag parameter is varying by time (trial to trial), an average is taken over the time-lag covariance matrices of all two consecutive trials. TT-BSS finally estimates a transform (separating matrix) by joint diagnolization of the covariance matrix of trials and the averaged covariance matrix of the time varying time-lag. To assess the proposed scheme, synthetic and real EEGs containing P300 are used. The EEG signals were collected from twenty schizophrenic and twenty age-matched normal subjects via 20 channels through the resting state and in presence of the oddball audio stimulus. Empirical achievements over the simulated and real EEGs imply on the superiority of TT-BSS in dynamic estimation of P300 characteristics compared to state-of-the-art counterparts such as constant time-lag BSS, constrained BSS and synchronous averaging. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A single high dose of escitalopram increases mismatch negativity without affecting processing negativity or P300 amplitude in healthy volunteers

    DEFF Research Database (Denmark)

    Wienberg, M; GlenthĂžj, Birte Yding; Jensen, K S

    2009-01-01

    Information processing deficits are commonly found in psychiatric illnesses, while at the biochemical level serotonin seems to play a role in nearly all psychiatric disorders. Processing negativity (PN), mismatch negativity (MMN) and P300 amplitude are electrophysiological measures of information...... processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally...

  15. Arylamine n-acetyltransferases in eukaryotic microorganisms

    Science.gov (United States)

    Microorganisms can survive highly toxic environments through numerous xenobiotic metabolizing enzymes, including arylamine N-acetyltransferases (NATs). NAT genes are present in bacteria, archaea, protists and fungi. In lower taxa of fungi, NAT genes are found in chytridiomycetes. In Dikarya, NAT gen...

  16. Histone acetyl transferase 1 is essential for mammalian development, genome stability, and the processing of newly synthesized histones H3 and H4.

    Science.gov (United States)

    Nagarajan, Prabakaran; Ge, Zhongqi; Sirbu, Bianca; Doughty, Cheryl; Agudelo Garcia, Paula A; Schlederer, Michaela; Annunziato, Anthony T; Cortez, David; Kenner, Lukas; Parthun, Mark R

    2013-06-01

    Histone acetyltransferase 1 is an evolutionarily conserved type B histone acetyltransferase that is thought to be responsible for the diacetylation of newly synthesized histone H4 on lysines 5 and 12 during chromatin assembly. To understand the function of this enzyme in a complex organism, we have constructed a conditional mouse knockout model of Hat1. Murine Hat1 is essential for viability, as homozygous deletion of Hat1 results in neonatal lethality. The lungs of embryos and pups genetically deficient in Hat1 were much less mature upon histological evaluation. The neonatal lethality is due to severe defects in lung development that result in less aeration and respiratory distress. Many of the Hat1(-/-) neonates also display significant craniofacial defects with abnormalities in the bones of the skull and jaw. Hat1(-/-) mouse embryonic fibroblasts (MEFs) are defective in cell proliferation and are sensitive to DNA damaging agents. In addition, the Hat1(-/-) MEFs display a marked increase in genome instability. Analysis of histone dynamics at sites of replication-coupled chromatin assembly demonstrates that Hat1 is not only responsible for the acetylation of newly synthesized histone H4 but is also required to maintain the acetylation of histone H3 on lysines 9, 18, and 27 during replication-coupled chromatin assembly.

  17. Histone acetyl transferase 1 is essential for mammalian development, genome stability, and the processing of newly synthesized histones H3 and H4.

    Directory of Open Access Journals (Sweden)

    Prabakaran Nagarajan

    2013-06-01

    Full Text Available Histone acetyltransferase 1 is an evolutionarily conserved type B histone acetyltransferase that is thought to be responsible for the diacetylation of newly synthesized histone H4 on lysines 5 and 12 during chromatin assembly. To understand the function of this enzyme in a complex organism, we have constructed a conditional mouse knockout model of Hat1. Murine Hat1 is essential for viability, as homozygous deletion of Hat1 results in neonatal lethality. The lungs of embryos and pups genetically deficient in Hat1 were much less mature upon histological evaluation. The neonatal lethality is due to severe defects in lung development that result in less aeration and respiratory distress. Many of the Hat1(-/- neonates also display significant craniofacial defects with abnormalities in the bones of the skull and jaw. Hat1(-/- mouse embryonic fibroblasts (MEFs are defective in cell proliferation and are sensitive to DNA damaging agents. In addition, the Hat1(-/- MEFs display a marked increase in genome instability. Analysis of histone dynamics at sites of replication-coupled chromatin assembly demonstrates that Hat1 is not only responsible for the acetylation of newly synthesized histone H4 but is also required to maintain the acetylation of histone H3 on lysines 9, 18, and 27 during replication-coupled chromatin assembly.

  18. Histone Acetyl Transferase 1 Is Essential for Mammalian Development, Genome Stability, and the Processing of Newly Synthesized Histones H3 and H4

    Science.gov (United States)

    Nagarajan, Prabakaran; Ge, Zhongqi; Sirbu, Bianca; Doughty, Cheryl; Agudelo Garcia, Paula A.; Schlederer, Michaela; Annunziato, Anthony T.; Cortez, David; Kenner, Lukas; Parthun, Mark R.

    2013-01-01

    Histone acetyltransferase 1 is an evolutionarily conserved type B histone acetyltransferase that is thought to be responsible for the diacetylation of newly synthesized histone H4 on lysines 5 and 12 during chromatin assembly. To understand the function of this enzyme in a complex organism, we have constructed a conditional mouse knockout model of Hat1. Murine Hat1 is essential for viability, as homozygous deletion of Hat1 results in neonatal lethality. The lungs of embryos and pups genetically deficient in Hat1 were much less mature upon histological evaluation. The neonatal lethality is due to severe defects in lung development that result in less aeration and respiratory distress. Many of the Hat1−/− neonates also display significant craniofacial defects with abnormalities in the bones of the skull and jaw. Hat1−/− mouse embryonic fibroblasts (MEFs) are defective in cell proliferation and are sensitive to DNA damaging agents. In addition, the Hat1−/− MEFs display a marked increase in genome instability. Analysis of histone dynamics at sites of replication-coupled chromatin assembly demonstrates that Hat1 is not only responsible for the acetylation of newly synthesized histone H4 but is also required to maintain the acetylation of histone H3 on lysines 9, 18, and 27 during replication-coupled chromatin assembly. PMID:23754951

  19. Inhibition of the PCAF histone acetyl transferase and cell proliferation by isothiazolones

    NARCIS (Netherlands)

    Dekker, Frank J.; Ghizzoni, Massimo; van der Meer, Nanette; Wisastra, Rosalina; Haisma, Hidde J.

    2009-01-01

    Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyl transferases (HATs) in the cell and have relevance for oncology. We present a systematic investigation of the inhibition of the HAT p300/CBP Associated Factor (PCAF) by isothiazolones with different substitutions.

  20. Effects of aging on P300 between late young-age and early middle-age adulthood: an electroencephalogram event-related potential study.

    Science.gov (United States)

    Bourisly, Ali K

    2016-09-28

    The aim of this study was to identify age-related changes of P300 peak amplitude and P300 latency between closely separated nonsenile age groups (late young-aged adults and early middle-aged adults) and to investigate whether or not P300 has the potential to be used as a measure of cognitive aging even among nonsenile age groups. Twenty-eight adults (25-55 years old) completed an event-related potential oddball task. The elicitation of both P300 peak amplitude and P300 latency indicated age-related changes of P300. The results of the study showed that the P300 target peak amplitude was significantly larger in late young age compared with early middle age and that P300 target latency was also significantly delayed in early middle age compared with late young age. The results of this work contribute toward research efforts on a consensus on how aging affects event-related potential and/or P300. The main conclusions are that there exist significant age-related P300 changes even between closely separated, relatively younger, and nonsenile age groups, and that P300 has the potential to be used as a measure for cognitive aging even in nonsenile adults.

  1. Mental Rotational Ability Is Correlated with Spatial but Not Verbal Working Memory Performance and P300 Amplitude in Males

    Science.gov (United States)

    Christie, Gregory J.; Cook, Charles M.; Ward, Brian J.; Tata, Matthew S.; Sutherland, Janice; Sutherland, Robert J.; Saucier, Deborah M.

    2013-01-01

    This study investigated how both sex and individual differences in a mental rotation test (MRT) influence performance on working memory (WM). To identify the neural substrate supporting these differences, brain electrical activity was measured using the event-related potential technique. No significant sex differences were observed in a test of verbal WM, however males were significantly faster than females to respond to probe stimuli in a test of spatial WM. This difference was no longer significant after controlling for differences in MRT score, suggesting that rotational ability mediates performance in the spatial memory task for both sexes. A posterior P300 was observed in both tasks as participants encoded information into memory, however the amplitude of the P300 correlated with RT in the spatial task but not in the verbal task. Individual differences in the MRT also correlated with RT and with the amplitude of the P300, but again only in the spatial task. After splitting the analysis by sex, partial correlations controlling for MRT revealed that for males, individual differences in rotational ability completely mediated the correlation between the P300 and RT in the spatial task. This mediating effect was not observed for the female participants. The results therefore suggest a relatively stronger association in males between innate mental rotational ability, spatial memory performance, and brain electrophysiological processes supporting spatial memory. PMID:23437381

  2. Parsing the late positive complex: mental chronometry and the ERP components that inhabit the neighborhood of the P300.

    Science.gov (United States)

    Dien, Joseph; Spencer, Kevin M; Donchin, Emanuel

    2004-09-01

    Falkenstein, Hohnsbein, and Hoorman (1994) suggested that common measures of P300 latency confound a "P-SR" component whose latency corresponds to stimulus evaluation time and a "P-CR" component whose latency varies with response-selection time, thus casting doubt on work in mental chronometry that relies on P300 latency. We report here a replication and extension of Falkenstein et al. (1994) using a high-density 129-electrode montage with 11 subjects. Spatiotemporal PCA was used to extract the components of the ERP. A centroid measure is also introduced for detecting waveform-timing changes beyond just peak latency. In terms of componentry, we argue that the P-SR and the P-CR, correspond to the P3a/Novelty P3 and the P300, respectively. Conceptually, we dispute the proposed distinction between stimulus evaluation and response selection. We suggest a four-stage ERP model of information processing and place the P3a and the P300 in this framework.

  3. Mental rotational ability is correlated with spatial but not verbal working memory performance and P300 amplitude in males.

    Directory of Open Access Journals (Sweden)

    Gregory J Christie

    Full Text Available This study investigated how both sex and individual differences in a mental rotation test (MRT influence performance on working memory (WM. To identify the neural substrate supporting these differences, brain electrical activity was measured using the event-related potential technique. No significant sex differences were observed in a test of verbal WM, however males were significantly faster than females to respond to probe stimuli in a test of spatial WM. This difference was no longer significant after controlling for differences in MRT score, suggesting that rotational ability mediates performance in the spatial memory task for both sexes. A posterior P300 was observed in both tasks as participants encoded information into memory, however the amplitude of the P300 correlated with RT in the spatial task but not in the verbal task. Individual differences in the MRT also correlated with RT and with the amplitude of the P300, but again only in the spatial task. After splitting the analysis by sex, partial correlations controlling for MRT revealed that for males, individual differences in rotational ability completely mediated the correlation between the P300 and RT in the spatial task. This mediating effect was not observed for the female participants. The results therefore suggest a relatively stronger association in males between innate mental rotational ability, spatial memory performance, and brain electrophysiological processes supporting spatial memory.

  4. The bimodal P300 oddball component is decreased in patients with an adjustment disorder: An event-related potentials study.

    Science.gov (United States)

    Kajosch, Hendrik; Gallhofer, Bernd; Corten, Philippe; From, LĂ©on; Verbanck, Paul; Campanella, Salvatore

    2016-10-01

    We found previously that use of a bimodal oddball design with synchronized pairs of audio-visual stimuli increased the sensitivity of the P300 wave to detect subclinical anxiety-depression in otherwise healthy subjects. Here, we wished to determine whether these P300 modulations would also be encountered when a clinical population comprised of patients with an adjustment disorder (AJD) was compared to healthy controls. Two groups, each comprised of twenty-five participants (AJD patients, and controls; N=50) had to detect deviant stimuli among frequent stimuli in an oddball task by clicking on a button. Separate blocks involving audio (A), visual (V) or bimodal congruent (AV) stimuli were used and compared. P300 amplitudes of the control group were higher than those displayed by AJD patients, but only in the bimodal AV oddball task, while unimodal (visual or auditory) oddball tasks did not reveal any significant differences. The increased sensitivity of the bimodal P300 that we observed previously in subclinical anxiety-depression was also observed in AJD patients. The impaired "bimodal congruence effect" in AJD suggests that these patients have altered integrative processes, which has potential implications for cognitive therapy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. [Evaluation of the event-related potential (ERP-P300) in patients with hepatic cirrhosis without encephalopathy].

    Science.gov (United States)

    Teodoro, Vinicius; Bragagnolo Jr, MaurĂ­cio; Lucchesi, LĂ­gia; Kondo, MĂĄrio; Tufik, SĂ©rgio

    2008-01-01

    In hepatic cirrhosis structural liver alterations occur leading to the loss of the organ functions with neuro-psychiatric consequence, as cognitive dysfunctions. One of the most effective ways of objectively evaluating cognition is to measure electrophysiological activity in the central nervous system trough event-related potentials (ERP-P300). To assess the value of the event-related potential (ERP) in order to determine cognitive disturbances in patients with liver cirrhosis and to assist in the diagnosis of minimal hepatic encephalopathy. Fifty patients with liver cirrhosis were selected, without clinical symptoms of hepatic encephalopathy and 35 healthy volunteers, matched by sex and age. The patients were submitted to clinical-neurological and laboratorial examination. The ERP-P300 was performed by the two groups to determine cognitive disturbances. The study showed significant differences between the ERP-P300 latency averages of the two groups. The ERP-P300 is simple to use and depends on controllable variables. It is also easy to reproduce and, when properly used, can be useful both to determine cognitive disturbances in patients with hepatic cirrhosis and to assist in minimal hepatic encephalopathy diagnosis.

  6. A change in the parameters of P300 evoked potentials in relation to the degree of exacerbation of pain syndrome

    Directory of Open Access Journals (Sweden)

    A P Rachin

    2012-01-01

    Full Text Available In chronic pain, the state of suprasegmental brain structures (the cortex, limbic system, truncodiencephalic structures, which form the motivational-affective and cognitive components of pain behavior, actively affects pain afferentation as well. The purpose of the study was to comparatively analyze the parameters and topographic distribution of P300 cognitive evoked potential in patients with lower back pain. Sixty patients aged 22 to 60 years were examined. The authors made their clinical and neurological examinations, collected medical history data, and assessed back pain intensity by a visual analog scale. The findings were compared with the parameters of cognitive evoked potentials (the separating of P300 to count; keystroke in the recognition of significant stimuli; elaboration of a verbal and nonverbal visual stimulation protocol, by using emotionally significant stimuli. The processes of recognition and differentiation, those of directed attention, and the rate of information processing slowed down in patients with different stages of pain syndrome. The P300 separating procedure using the emotionally significant stimuli allows one to assess the specific features of chronization of pain syndromes and the presence of pain memory in the central nervous system of such patients. The estimation of P300 parameters over time or during treatment are of particular value for the optimization and evaluation of its efficiency.

  7. Acetyl-CoA Carboxylase Regulates Global Histone Acetylation*♩

    Science.gov (United States)

    Galdieri, Luciano; Vancura, Ales

    2012-01-01

    Histone acetylation depends on intermediary metabolism for supplying acetyl-CoA in the nucleocytosolic compartment. However, because nucleocytosolic acetyl-CoA is also used for de novo synthesis of fatty acids, histone acetylation and synthesis of fatty acids compete for the same acetyl-CoA pool. The first and rate-limiting reaction in de novo synthesis of fatty acids is carboxylation of acetyl-CoA to form malonyl-CoA, catalyzed by acetyl-CoA carboxylase. In yeast Saccharomyces cerevisiae, acetyl-CoA carboxylase is encoded by the ACC1 gene. In this study, we show that attenuated expression of ACC1 results in increased acetylation of bulk histones, globally increased acetylation of chromatin histones, and altered transcriptional regulation. Together, our data indicate that Acc1p activity regulates the availability of acetyl-CoA for histone acetyltransferases, thus representing a link between intermediary metabolism and epigenetic mechanisms of transcriptional regulation. PMID:22580297

  8. Test-Retest of Long Latency Auditory Evoked Potentials (P300) with Pure Tone and Speech Stimuli.

    Science.gov (United States)

    Perez, Ana Paula; Ziliotto, Karin; Pereira, Liliane Desgualdo

    2017-04-01

    Introduction Long latency auditory evoked potentials, especially P300, have been used for clinical evaluation of mental processing. Many factors can interfere with Auditory Evoked Potential - P300 results, suggesting large intra and inter-subject variations. Objective The objective of the study was to identify the reliability of P3 components (latency and amplitude) over 4-6 weeks and the most stable auditory stimulus with the best test-retest agreement. Methods Ten normal-hearing women participated in the study. Only subjects without auditory processing problems were included. To determine the P3 components, we elicited long latency auditory evoked potential (P300) by pure tone and speech stimuli, and retested after 4-6 weeks using the same parameters. We identified P300 latency and amplitude by waveform subtraction. Results We found lower coefficient of variation values in latency than in amplitude, with less variability analysis when speech stimulus was used. There was no significant correlation in latency measures between pure tone and speech stimuli, and sessions. There was a significant intrasubject correlation between measures of latency and amplitude. Conclusion These findings show that amplitude responses are more robust for the speech stimulus when compared with its pure tone counterpart. The P300 indicated stability for latency and amplitude measures when the test-retest was applied. Reliability was higher for amplitude than for latency, with better agreement when the pure tone stimulus was used. However, further research with speech stimulus is needed to clarify how these stimuli are processed by the nervous system.

  9. Relation between language, audio-vocal psycholinguistic abilities and P300 in children having specific language impairment.

    Science.gov (United States)

    Shaheen, Elham Ahmed; Shohdy, Sahar Saad; Abd Al Raouf, Mahmoud; Mohamed El Abd, Shereen; Abd Elhamid, Asmss

    2011-09-01

    Specific language impairment is a relatively common developmental condition in which a child fails to develop language at the typical rate despite normal general intellectual abilities, adequate exposure to language, and in the absence of hearing impairments, or neurological or psychiatric disorders. There is much controversy about the extent to which the auditory processing deficits are important in the genesis specific language impairment. The objective of this paper is to assess the higher cortical functions in children with specific language impairment, through assessing neurophysiological changes in order to correlate the results with the clinical picture of the patients to choose the proper rehabilitation training program. This study was carried out on 40 children diagnosed to have specific language impairment and 20 normal children as a control group. All children were subjected to the assessment protocol applied in Kasr El-Aini hospital. They were also subjected to a language test (receptive, expressive and total language items), the audio-vocal items of Illinois test of psycholinguistic (auditory reception, auditory association, verbal expression, grammatical closure, auditory sequential memory and sound blending) as well as audiological assessment that included peripheral audiological and P300 amplitude and latency assessment. The results revealed a highly significant difference in P300 amplitude and latency between specific language impairment group and control group. There is also strong correlations between P300 latency and the grammatical closure, auditory sequential memory and sound blending, while significant correlation between the P300 amplitude and auditory association and verbal expression. Children with specific language impairment, in spite of the normal peripheral hearing, have evidence of cognitive and central auditory processing defects as evidenced by P300 auditory event related potential in the form of prolonged latency which indicate a

  10. Cortical activities of single-trial P300 amplitudes modulated by memory load using simultaneous EEG-fMRI

    Science.gov (United States)

    Zhang, Qiushi; Zhao, Xiaojie; Zhu, Chaozhe; Yang, Xueqian; Yao, Li

    2015-03-01

    The functional magnetic resonance imaging (fMRI) researches on working memory have found that activation of cortical areas appeared dependent on memory load, and event-related potentials (ERP) studies have demonstrated that amplitudes of P300 decreased significantly when working memory load increased. However, the cortical activities related with P300 amplitudes under different memory loads remains unclear. Joint fMRI and EEG analysis which fusions the time and spatial information in simultaneous EEG-fMRI recording can reveal the regional activation at each ERP time point. In this paper, we first used wavelet transform to obtain the single-trial amplitudes of P300 caused by a digital N-back task in the simultaneous EEG-fMRI recording as the ERP feature sequences. Then the feature sequences in 1-back condition and 3-back condition were introduced into general linear model (GLM) separately as parametric modulations to compare the cortical activation under different memory loads. The results showed that the average amplitudes of P300 in 3-back significantly decreased than that in 1-back, and the activities induced by ERP feature sequences in 3-back also significantly decreased than that in the 1-back, including the insular, anterior cingulate cortex, right inferior frontal gyrus, and medial frontal gyrus, which were relevant to the storage, monitoring, and manipulation of information in working memory task. Moreover, the difference in the activation caused by ERP feature showed a positive correlation with the difference in behavioral performance. These findings demonstrated the locations of P300 amplitudes differences modulated by the memory load and its relationship with the behavioral performance.

  11. Synthesis and bioactivity of novel histone acetylation inhibitors : potential new drugs for treatment of cancer and inflammation

    NARCIS (Netherlands)

    Ghizzoni, Massimo

    2011-01-01

    There is an increasing interest in histone acetyltransferases (HATs) as new therapeutic targets for treatment of diseases like, for example, inflammation and cancer. However, only few small and cell-permeable molecule inhibitors of HATs are currently available. The work described in this thesis

  12. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  13. Histone Deacetylase Inhibitors as Anticancer Drugs.

    Science.gov (United States)

    Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

    2017-07-01

    Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  14. Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation

    Energy Technology Data Exchange (ETDEWEB)

    McCullough, Cheryl E.; Song, Shufei; Shin, Michael H.; Johnson, F. Brad; Marmorstein, Ronen (UPENN)

    2016-07-05

    Many histone acetyltransferases undergo autoacetylation, either through chemical or enzymatic means, to potentiate enzymatic cognate substrate lysine acetylation, although the mode and molecular role of such autoacetylation is poorly understood. The MYST family of histone acetyltransferases is autoacetylated at an active site lysine residue to facilitate cognate substrate lysine binding and acetylation. Here, we report on a detailed molecular investigation of Lys-274 autoacetylation of the human MYST protein Males Absent on the First (hMOF). A mutational scan of hMOF Lys-274 reveals that all amino acid substitutions of this residue are able to bind cofactor but are significantly destabilized, both in vitro and in cells, and are catalytically inactive for cognate histone H4 peptide lysine acetylation. The x-ray crystal structure of a hMOF K274P mutant suggests that the reduced stability and catalytic activity stems from a disordering of the residue 274-harboring a α2-ÎČ7 loop. We also provide structural evidence that a C316S/E350Q mutant, which is defective for cognate substrate lysine acetylation; and biochemical evidence that a K268M mutant, which is defective for Lys-274 chemical acetylation in the context of a K274-peptide, can still undergo quantitative K274 autoacetylation. Together, these studies point to the critical and specific role of hMOF Lys-274 autoacetylation in hMOF stability and cognate substrate acetylation and argues that binding of Ac-CoA to hMOF likely drives Lys-274 autoacetylation for subsequent cognate substrate acetylation.

  15. Chromatin accessibility, p300, and histone acetylation define PML-RARalpha and AML1-ETO binding sites in acute myeloid leukemia.

    NARCIS (Netherlands)

    Saeed, S.; Logie, C.; Francoijs, K.J.; Frige, G.; Romanenghi, M.; Nielsen, F.G.G.; Raats, L.; Shahhoseini, M.; Huynen, M.A.; Altucci, L.; Minucci, S.; Martens, J.H.; Stunnenberg, H.G.

    2012-01-01

    Chromatin accessibility plays a key role in regulating cell type specific gene expression during hematopoiesis but has also been suggested to be aberrantly regulated during leukemogenesis. To understand the leukemogenic chromatin signature, we analyzed acute promyelocytic leukemia, a subtype of

  16. Combining the P300-complex trial-based concealed information test and the reaction time-based autobiographical implicit association test in concealed memory detection.

    Science.gov (United States)

    Hu, Xiaoqing; Rosenfeld, J Peter

    2012-08-01

    Despite the P300-concealed information test's validity in detecting concealed memory when it is conducted immediately after the mock crime, whether the P300-CIT's detection efficiency is moderated by time delay remains unknown. Here, we conducted a mock crime study in which guilty participants were tested immediately after the mock crime or 1 month later. An innocent group was also tested. Assuming that the autobiographical Implicit Association Test (aIAT) and the P300-CIT rely on nonoverlapping mechanisms for memory detection, participants were tested using both the P300-CIT and the reaction time (RT)-based aIAT. Results suggested that the sensitivity of both tests remains even after the 1-month delay. The indicators from the RT-aIAT and P300-CIT were uncorrelated, thus combining P300-CIT and aIAT data further increased the efficiency of memory detection. Copyright © 2012 Society for Psychophysiological Research.

  17. P300-amplitudes in upper limb amputees with and without phantom limb pain in a visual oddball paradigm.

    Science.gov (United States)

    Karl, Anke; Diers, Martin; Flor, Herta

    2004-07-01

    The aim of the study was to investigate to what extent cortical hyper-reactivity to visual stimuli is present in upper limb amputees. Five amputees with phantom limb pain (PLP), five amputees without PLP (Non-PLP) and 10 healthy controls (HC) were investigated using a visual oddball paradigm. Two hundred visual stimuli were presented with target stimuli occurring at a probability of 25% and standard stimuli at a probability of 75%. Event-related potentials were recorded from nine scalp positions (F3, F4, Fz, C3, C4, Cz, P3, P4, Pz). The PLP-patients had significantly higher P300-amplitudes to both types of stimuli compared to the non-PLP-patients. The HC were not significantly different from both amputee groups. P300-amplitude to targets at frontal sites in the hemisphere contralateral to the amputation was higher in the PLP patients. P300-latencies to target stimuli differed only at frontal sites with PLP-patients showing significantly longer latencies than non-PLP-patients. To standard stimuli, however, they showed significantly shorter latencies at central and parietal scalp positions. The HC had significantly shorter latencies than both amputee groups. The size of the P300-amplitude was positively correlated with the intensity of PLP. These findings suggest a higher magnitude of non-specific cortical excitability in amputees with PLP and a reduced excitability in amputees without PLP. This extends previous findings of differences in cortical excitability in PLP and non-PLP patients in the sensorimotor domain.

  18. Relation between P300 and event-related theta-band synchronization: a single-trial analysis.

    Science.gov (United States)

    Wang, Xue; Ding, Mingzhou

    2011-05-01

    Recent reports show that theta-band (4-7 Hz) power is enhanced by target detection in the standard oddball paradigm, which, together with increased P300, is considered as providing complementary neural mechanisms supporting memory and attention processes. We hypothesize that the increased theta event-related synchronization (ERS) may stem largely from not accounting for the trial-to-trial variability of the P300 evoked component and may not reflect a separate mechanism for target detection and related cognitive processing. EEG was recorded from healthy volunteers performing visual and auditory odd-ball tasks. Ongoing-activity was obtained using two methods: (a) subtracting the ASEO-estimated (analysis of single-trial event-related potentials and ongoing-activity) single-trial ERP from corresponding single-trial EEG time series and (b) subtracting the average event-related potential (AERP) from single-trial EEG time series. Event-related oscillatory activities obtained from the two methods were compared. The amount of power increase in the theta-band was greatly attenuated for the single-trial based method relative to the traditional AERP method. Our results suggest that the theta-ERS arises largely from not modeling the trial-to-trial variability of the P300. ERP components such as the P300 vary from trial-to-trial in both amplitude and latency. The traditional AERP method leaves traces of evoked responses in the residual data which can negatively impact the inference of ongoing oscillatory dynamics. Thus, caution should be exercised in interpreting such phenomena in basic and clinical contexts. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Evaluation of the Effect of Modafinil on Cognitive Functions in Patients with Idiopathic Hypersomnia with P300.

    Science.gov (United States)

    Yaman, Mehmet; Karakaya, Fatıma; Aydin, Tuğçe; Mayda, Hasan; GĂŒzel, Hail Ä°brahim; Kayaalp, Dilek

    2015-06-27

    Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy and other excessive sleepiness. Whereas favorable effects of modafinil on cognitive functions have been shown in a large number of studies, there are very few reports presenting the effects of modafinil electrophysiologically. The aim of this study was to investigate the effects of modafinil on auditory P300 latency and amplitude electrophysiologically. Eighteen patients (age range: 16-48 years) with a diagnosis of idiopathic hypersomnia (IH) were included in the present study. As a standard treatment, 200 mg/day modafinil was administered to each patient. The P300 auditory test was performed for each patient before and at the end of 1 week of modafinil treatment. After 1 week of modafinil treatment, mean P300 latencies (at all electrode sites) were significantly lower than the latencies before the treatment (P values for Fz, Cz and Pz recording sites were 0.039, 0.002, and 0.004, respectively). An increase in the P300 amplitudes was detected only at the Fz recording site, but not at Cz or Pz recording sites (P values for Fz, Cz, and Pz recording sites were 0.014, 0.100, and 0.05, respectively). One week of modafinil treatment improved the cognitive performance, alertness, and executive functions in IH patients. Our electrophysiologically obtained findings provide further confirmation for previous reports in which modafinil has been shown to exert favorable effects on cognitive performance, alertness, and executive functions.

  20. Simultaneous detection of P300 and steady-state visually evoked potentials for hybrid brain-computer interface.

    Science.gov (United States)

    Combaz, Adrien; Van Hulle, Marc M

    2015-01-01

    We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI. We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline. Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.

  1. Motor imagery, P300 and error-related EEG-based robot arm movement control for rehabilitation purpose.

    Science.gov (United States)

    Bhattacharyya, Saugat; Konar, Amit; Tibarewala, D N

    2014-12-01

    The paper proposes a novel approach toward EEG-driven position control of a robot arm by utilizing motor imagery, P300 and error-related potentials (ErRP) to align the robot arm with desired target position. In the proposed scheme, the users generate motor imagery signals to control the motion of the robot arm. The P300 waveforms are detected when the user intends to stop the motion of the robot on reaching the goal position. The error potentials are employed as feedback response by the user. On detection of error the control system performs the necessary corrections on the robot arm. Here, an AdaBoost-Support Vector Machine (SVM) classifier is used to decode the 4-class motor imagery and an SVM is used to decode the presence of P300 and ErRP waveforms. The average steady-state error, peak overshoot and settling time obtained for our proposed approach is 0.045, 2.8% and 44 s, respectively, and the average rate of reaching the target is 95%. The results obtained for the proposed control scheme make it suitable for designs of prosthetics in rehabilitative applications.

  2. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts.

    Science.gov (United States)

    Tong, Kwok-Man; Shieh, Dong-Chen; Chen, Chao-Ping; Tzeng, Chung-Yuh; Wang, Shun-Ping; Huang, Kui-Chou; Chiu, Yung-Cheng; Fong, Yi-Chin; Tang, Chih-Hsin

    2008-08-01

    Leptin, the adipocyte-secreted hormone that centrally regulates weight control, is known to function as an immunomodulatory regulator. We investigated the signaling pathway involved in IL-8 production caused by leptin in both rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). RASF and OASF expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. Leptin caused concentration- and time-dependent increases in IL-8 production. Leptin-mediated IL-8 production was attenuated by OBRl receptor antisense oligonucleotide, JAK2 inhibitor or STAT3 small interference RNA (siRNA). Transfection with insulin receptor substrate (IRS)-1 siRNA or dominant-negative mutant of p85 and Akt or pretreatment with phosphatidylinositol 3-kinase inhibitor (Ly294002 and wortmannin), Akt inhibitor, NF-kappaB inhibitor (PDTC) and NF-kappaB inhibitor peptide also inhibited the potentiating action of leptin. Stimulation of RASF with leptin activated IkappaB kinase alpha/beta (IKK alpha/beta), p65 phosphorylation at Ser(276), p65 translocation from the cytosol to the nucleus, and kappaB-luciferase activity. Moreover, pretreatment with p300 inhibitor (curcumin) also blocked IL-8 expression. The binding of p65 to the NF-kappaB elements, as well as the recruitment of p300 and the enhancement of histone H3 acetylation on the IL-8 promoter was enhanced by leptin, which was inhibited by wortmannin, Akt inhibitor or IRS-1 siRNA. These results suggest that leptin increased IL-8 production in synovial fibroblast via the OBRl/JAK2/STAT3 pathway, as well as the activation of IRS1/PI3K/Akt/NF-kappaB-dependent pathway and the subsequent recruitment of p300.

  3. Yeast phospholipase C is required for normal acetyl-CoA homeostasis and global histone acetylation.

    Science.gov (United States)

    Galdieri, Luciano; Chang, Jennifer; Mehrotra, Swati; Vancura, Ales

    2013-09-27

    Phospholipase C (Plc1p) is required for the initial step of inositol polyphosphate (InsP) synthesis, and yeast cells with deletion of the PLC1 gene are completely devoid of any InsPs and display aberrations in transcriptional regulation. Here we show that Plc1p is required for a normal level of histone acetylation; plc1Δ cells that do not synthesize any InsPs display decreased acetylation of bulk histones and global hypoacetylation of chromatin histones. In accordance with the role of Plc1p in supporting histone acetylation, plc1Δ mutation is synthetically lethal with mutations in several subunits of SAGA and NuA4 histone acetyltransferase (HAT) complexes. Conversely, the growth rate, sensitivity to multiple stresses, and the transcriptional defects of plc1Δ cells are partially suppressed by deletion of histone deacetylase HDA1. The histone hypoacetylation in plc1Δ cells is due to the defect in degradation of repressor Mth1p, and consequently lower expression of HXT genes and reduced conversion of glucose to acetyl-CoA, a substrate for HATs. The histone acetylation and transcriptional defects can be partially suppressed and the overall fitness improved in plc1Δ cells by increasing the cellular concentration of acetyl-CoA. Together, our data indicate that Plc1p and InsPs are required for normal acetyl-CoA homeostasis, which, in turn, regulates global histone acetylation.

  4. Yeast Phospholipase C Is Required for Normal Acetyl-CoA Homeostasis and Global Histone Acetylation*

    Science.gov (United States)

    Galdieri, Luciano; Chang, Jennifer; Mehrotra, Swati; Vancura, Ales

    2013-01-01

    Phospholipase C (Plc1p) is required for the initial step of inositol polyphosphate (InsP) synthesis, and yeast cells with deletion of the PLC1 gene are completely devoid of any InsPs and display aberrations in transcriptional regulation. Here we show that Plc1p is required for a normal level of histone acetylation; plc1Δ cells that do not synthesize any InsPs display decreased acetylation of bulk histones and global hypoacetylation of chromatin histones. In accordance with the role of Plc1p in supporting histone acetylation, plc1Δ mutation is synthetically lethal with mutations in several subunits of SAGA and NuA4 histone acetyltransferase (HAT) complexes. Conversely, the growth rate, sensitivity to multiple stresses, and the transcriptional defects of plc1Δ cells are partially suppressed by deletion of histone deacetylase HDA1. The histone hypoacetylation in plc1Δ cells is due to the defect in degradation of repressor Mth1p, and consequently lower expression of HXT genes and reduced conversion of glucose to acetyl-CoA, a substrate for HATs. The histone acetylation and transcriptional defects can be partially suppressed and the overall fitness improved in plc1Δ cells by increasing the cellular concentration of acetyl-CoA. Together, our data indicate that Plc1p and InsPs are required for normal acetyl-CoA homeostasis, which, in turn, regulates global histone acetylation. PMID:23913687

  5. Schistosoma mansoni histones: from transcription to chromatin regulation; an in silico analysis.

    Science.gov (United States)

    Anderson, LetĂ­cia; Pierce, Raymond J; Verjovski-Almeida, Sergio

    2012-06-01

    Schistosoma mansoni is a human endoparasite with a complex life cycle that also infects an invertebrate mollusk intermediate host and exhibits many diverse phenotypes. Its complexity is reflected in a large genome and different transcriptome profiles specific to each life cycle stage. Epigenetic regulation of gene expression such as the post-translational modification of histones has a significant impact on phenotypes, and this information storage function resides primarily at histone tails, which results in a varied histone code. Evidence of transcription of the different histone families at all life stages of the parasite was detected by a survey of transcriptome databases; manual curation of each gene prediction at the genome sequence level showed errors in the coding sequences of three of them. The biogenesis of histones is coupled to DNA replication, and a detailed in silico analysis of the specialized machinery of histone mRNA processing in the S. mansoni genome reveals that it is as conserved as in other eukaryotes, consisting in transcription factors and stem-loop binding proteins which recognize the stem loop structure at the histone mRNA 3'UTR. Histone modifying enzymes (HMEs) such as histone acetyltransferases, methyltransferases and deacetylases (HDACs) have been described in S. mansoni, and their potential as new therapeutic targets was evidenced with the apoptotic phenotype that resulted from HDAC inhibition. However, the overall regulation of transcription coupled with gene expression profiles correlated to histone modifications has not yet been characterized. Besides the interaction of HMEs with histones, many factors involved in cellular processes are known to bind to histones, and were identified here by an in silico analysis of the S. mansoni genome. Knowledge of the histone families opens up perspectives for further studies that will lead to a better identification of their post-translational modifications, their gene regulation and to the

  6. Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

    Science.gov (United States)

    Schunter, Sarah; Villa, Raffaella; Flynn, Victoria; Heidelberger, Jan B; Classen, Anne-Kathrin; Beli, Petra; Becker, Peter B

    2017-01-01

    The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

  7. Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Sarah Schunter

    Full Text Available The nuclear acetyltransferase MOF (KAT8 in mammals is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

  8. Analysis of the influence of bromazepam on cognitive performance through the visual evoked potential (P300 AnĂĄlise da influĂȘncia do bromazepam na performance cognitiva atravĂ©s do potencial evocado visual (P300

    Directory of Open Access Journals (Sweden)

    Fernanda Puga

    2005-06-01

    Full Text Available Benzodiazepines have been used in the pharmacological treatment of anxiety for over four decades. However, very few studies have combined bromazepam and event-related potentials (ERP. The present study aimed at investigating the modulatory effects of this drug on brain dynamics. Specifically, the effects of bromazepam (3mg on the P300 component of the ERP were tested in a double-blind experiment. The sample, consisting of 15 healthy subjects (7 male and 8 female, was submitted to a visual discrimination task, which employed the "oddball" paradigm. Electrophysiological (P300 and behavioral measures (stroop, digit span, and reaction time were analyzed across three experimental conditions: placebo 1, placebo 2, and bromazepam. Results suggest that the effects of bromazepam (3mg on cognitive processes are not apparent. In spite of what seems irrefutable in current literature, bromazepam did not produce evident effects on the behavioral and electrophysiological variables analyzed.BenzodiazepĂ­nicos tĂȘm sido utilizados no tratamento farmacolĂłgico da ansiedade hĂĄ mais de quatro dĂ©cadas. No entanto, poucos estudos tĂȘm combinado bromazepam e potencial evocado relacionado a evento (PRE. O presente estudo teve por objetivo investigar os efeitos modulatĂłrios desta droga na dinĂąmica cerebral. Especificamente, os efeitos de 3mg de bromazepam no componente P300 do PRE foram analisados em um experimento duplo-cego. A amostra consistiu de 15 sujeitos sadios (7 homens e 8 mulheres, submetidos a uma tarefa de discriminação visual utilizando o paradigma "oddball". Medidas eletrofisiolĂłgicas (P300 e comportamentais (stroop, digit span, e tempo de reação foram analisadas em trĂȘs condiçÔes experimentais: placebo 1, placebo 2 e bromazepam. Os resultados sugerem que os efeitos de 3mg de bromazepam em processos cognitivos nĂŁo sĂŁo aparentes. Apesar do que parece irrefutĂĄvel na literatura, o bromazepam nĂŁo produziu efeitos evidentes nas vari

  9. Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

    Science.gov (United States)

    Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

    2016-10-01

    Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction.

  10. Rapid Communication with a “P300” Matrix Speller Using Electrocorticographic Signals (ECoG)

    Science.gov (United States)

    Brunner, Peter; Ritaccio, Anthony L.; Emrich, Joseph F.; Bischof, Horst; Schalk, Gerwin

    2010-01-01

    A brain–computer interface (BCI) can provide a non-muscular communication channel to severely disabled people. One particular realization of a BCI is the P300 matrix speller that was originally described by Farwell and Donchin (1988). This speller uses event-related potentials (ERPs) that include the P300 ERP. All previous online studies of the P300 matrix speller used scalp-recorded electroencephalography (EEG) and were limited in their communication performance to only a few characters per minute. In our study, we investigated the feasibility of using electrocorticographic (ECoG) signals for online operation of the matrix speller, and determined associated spelling rates. We used the matrix speller that is implemented in the BCI2000 system. This speller used ECoG signals that were recorded from frontal, parietal, and occipital areas in one subject. This subject spelled a total of 444 characters in online experiments. The results showed that the subject sustained a rate of 17 characters/min (i.e., 69 bits/min), and achieved a peak rate of 22 characters/min (i.e., 113 bits/min). Detailed analysis of the results suggests that ERPs over visual areas (i.e., visual evoked potentials) contribute significantly to the performance of the matrix speller BCI system. Our results also point to potential reasons for the apparent advantages in spelling performance of ECoG compared to EEG. Thus, with additional verification in more subjects, these results may further extend the communication options for people with serious neuromuscular disabilities. PMID:21369351

  11. Avaliação auditiva central com BERA e P300 na Doença de Parkinson

    Directory of Open Access Journals (Sweden)

    Pineroli José C.A.

    2002-01-01

    Full Text Available Introdução: A Doença de Parkinson (DP Ă© um dos distĂșrbios do movimento mais encontrados na população idosa. Cursa com perda progressiva e irreversĂ­vel de cĂ©lulas da substĂąncia negra (locus niger do mesencĂ©falo, o que resultarĂĄ numa diminuição da produção de dopamina, levando Ă  sintomatologia da DP. Objetivo: Averiguar a relevĂąncia de testes eletrofisiolĂłgicos, capazes de monitorar a integridade funcional das vias cerebrais, no diagnĂłstico e/ou prognĂłstico de pacientes com DP, uma vez que tais testes nĂŁo-invasivos sĂŁo de fĂĄcil aplicabilidade, rĂĄpidos e facilmente compreendidos por quem participa de sua aplicação. Forma de estudo: Prospectivo clĂ­nico randomizado. Material e MĂ©todo: Grupo de 32 pacientes com diagnĂłstico prĂ©vio de DP, submetidos aos testes de potencial evocado BERA e P300. Pacientes de ambos os sexos, entre 44 e 85 anos, com tempo de doença variando de 8 meses a 21 anos de evolução. Resultados: os valores do BERA e do P300 encontrados em pacientes com DP nĂŁo se mostraram diferentes dos limites de normalidade para a idade. ConclusĂŁo: Observou-se integridade das vias auditivas em pacientes portadores de DP. Uma vez que a latĂȘncia do P300 aumenta de forma linear com a idade, a partir dos 45 anos, aceitando-se um aumento de 1 a 1,5ms por anoÂč; observou-se integridade nas vias cerebrais que refletem a habilidade de performance cognitiva em pacientes portadores de DP sem comprometimento demencial exuberante.

  12. REHABILITATION OF PATIENTS WITH ENCEPHALOPATHY CAUSED BY ACUTE CHEMICAL AGENTS POISONING. P300 OF AUDITORY EVENT RELATED POTENTIALS AND ELECTROENCEPHALOGRAPHY

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    I. U. Berezina

    2014-01-01

    Full Text Available RELEVANCE. Patients with encephalopathy due to acute chemical agents poisoning have some brain functioning changes and a cognitive impairment during the rehabilitation program. These changes require correction of appropriate diagnostic protocol and treatment.AIM. The aim of this study was to estimate changes of electroencephalography (EEG and the P3 component of the event related potential (P300 ERP that are observed in patients with encephalopathy due to acute chemical agents poisoning during stage of rehabilitation.MATERIAL AND METHODS. The study was included 25 patients (age 37 (32; 51 poisoned different kind of neurotoxic substances (drugs, ethanol and complicated by toxic and hypoxic encephalopathy. They have got the treatment of encephalopathy by mexidol intravenously, mesodiencephalic modulation (MDM and hyperbaric oxygen therapy (HBOT. All patients were recoded EEG (electroencephalograph of “MBN” company, Russia and P300 ERP (“Neuron-Spectrum-5/EP” of “Neurosoft”, Russia according to the international recommendations of clinical neurophysiologists. Neuropsychological testing was used for the assessment of cognitive functions.RESULTS. There were some disturbances in primary electroencephalograms of all subjects. The follow-up EEG recording showed the main group of patients who had got the treatment (mexidol, MDM, HBOT had more often (11 patients the EEG improvements compared to the controls (1 patient. The main group had more rarely the EEG impairments compared to the control group. 6 patients of main group and 3 patients of controls did not have EEG changes during the follow-up EEG recordings. All controls and 17 patients of the main group patients had different cognitive disturbances. After the treatment 15 patients of the main group had improved on neuropsychological tests (MMSE, Munsterberg test, Schulte table, Number Connecting Test. They also had a decrease in the N200, P300 peak latency and an increase in the N200, P300

  13. Experimental Studies on Evaluation of TV Picture Degraded by Burst Noise Using Event Related Potential P300

    Science.gov (United States)

    Tanaka, Motoshi; Miyashita, Takayuki; Inoue, Hiroshi; Niiyama, Yoshitsugu

    As a fundamental study on the objective evaluation of TV picture degradation by electromagnetic noise with visual physiological information, the electroencephalogram (EEG) activity was measured when a still TV picture was degraded by the burst noise whose rms and duration were changed. A degradation was subjectively evaluated by three-grade impairment scale of “Not Annoying”, “Slightly Annoying”, and “Annoying”. Measured EEGs were analyzed by an averaging technique. In the results, the amplitude of the event related potential P300 becomes larger when the subjects feel the noise “Annoying”.

  14. Acetyltransferase SAS2 and sirtuin SIR2, respectively, control flocculation and biofilm formation in wine yeast.

    Science.gov (United States)

    Rodriguez, MarĂ­a E; Orozco, Helena; Cantoral, JesĂșs M; Matallana, Emilia; Aranda, AgustĂ­n

    2014-09-01

    Cell-to-cell and cell-to-environment interactions of microorganisms are of substantial relevance for their biotechnological use. In the yeast Saccharomyces cerevisiae, flocculation can be an advantage to clarify final liquid products after fermentation, and biofilm formation may be relevant for the encapsulation of strains of interest. The adhesion properties of wine yeast strains can be modified by the genetic manipulation of transcriptional regulatory proteins, such as histone deacetylases, and acetylases. Sirtuin SIR2 is essential for the formation of mat structures, a kind of biofilm that requires the expression of cell-wall protein FLO11 as its deletion reduces FLO11 expression, and adhesion of cells to themselves and to agar in a commercial wine strain. Deletion of acetyltransferase GCN5 leads to a similar phenotype. A naturally flocculant wine yeast strain called P2 was characterized. Its flocculation happens only during grape juice fermentation and is due to the presence of a highly transcribed version of flocculin FLO5, linked to the presence of a Ύ sequence in the promoter. Deletion of acetyltransferase SAS2 enhances this phenotype and maltose fermentation even more. Therefore, the manipulation of acetylation/deacetylation machinery members is a valid way to alter the interaction of industrial yeast to their environment. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  15. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    Energy Technology Data Exchange (ETDEWEB)

    He, Yuan [Northwest University, Xi’an 710069 (China); The University of York, York YO10 5DD (United Kingdom); Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J., E-mail: gideon.davies@york.ac.uk [The University of York, York YO10 5DD (United Kingdom); Northwest University, Xi’an 710069 (China)

    2014-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain.

  16. Asynchronous P300-based brain-computer interface to control a virtual environment: initial tests on end users.

    Science.gov (United States)

    Aloise, Fabio; Schettini, Francesca; AricĂČ, Pietro; Salinari, Serenella; Guger, Christoph; Rinsma, Johanna; Aiello, Marco; Mattia, Donatella; Cincotti, Febo

    2011-10-01

    Motor disability and/or ageing can prevent individuals from fully enjoying home facilities, thus worsening their quality of life. Advances in the field of accessible user interfaces for domotic appliances can represent a valuable way to improve the independence of these persons. An asynchronous P300-based Brain-Computer Interface (BCI) system was recently validated with the participation of healthy young volunteers for environmental control. In this study, the asynchronous P300-based BCI for the interaction with a virtual home environment was tested with the participation of potential end-users (clients of a Frisian home care organization) with limited autonomy due to ageing and/or motor disabilities. System testing revealed that the minimum number of stimulation sequences needed to achieve correct classification had a higher intra-subject variability in potential end-users with respect to what was previously observed in young controls. Here we show that the asynchronous modality performed significantly better as compared to the synchronous mode in continuously adapting its speed to the users' state. Furthermore, the asynchronous system modality confirmed its reliability in avoiding misclassifications and false positives, as previously shown in young healthy subjects. The asynchronous modality may contribute to filling the usability gap between BCI systems and traditional input devices, representing an important step towards their use in the activities of daily living.

  17. A P300-based brain-computer interface aimed at operating electronic devices at home for severely disabled people.

    Science.gov (United States)

    Corralejo, Rebeca; NicolĂĄs-Alonso, Luis F; Alvarez, Daniel; Hornero, Roberto

    2014-10-01

    The present study aims at developing and assessing an assistive tool for operating electronic devices at home by means of a P300-based brain-computer interface (BCI). Fifteen severely impaired subjects participated in the study. The developed tool allows users to interact with their usual environment fulfilling their main needs. It allows for navigation through ten menus and to manage up to 113 control commands from eight electronic devices. Ten out of the fifteen subjects were able to operate the proposed tool with accuracy above 77 %. Eight out of them reached accuracies higher than 95 %. Moreover, bitrates up to 20.1 bit/min were achieved. The novelty of this study lies in the use of an environment control application in a real scenario: real devices managed by potential BCI end-users. Although impaired users might not be able to set up this system without aid of others, this study takes a significant step to evaluate the degree to which such populations could eventually operate a stand-alone system. Our results suggest that neither the type nor the degree of disability is a relevant issue to suitably operate a P300-based BCI. Hence, it could be useful to assist disabled people at home improving their personal autonomy.

  18. An evaluation of training with an auditory P300 brain-computer interface for the Japanese Hiragana syllabary

    Directory of Open Access Journals (Sweden)

    Sebastian Halder

    2016-09-01

    Full Text Available Gaze-independent brain-computer interfaces (BCIs are a possible communication channel for persons with paralysis. We investigated if it is possible to use auditory stimuli to create a BCI for the Japanese Hiragana syllabary, which has 46 Hiragana characters. Additionally, we investigated if training has an effect on accuracy despite the high amount of different stimuli involved. Able-bodied participants (N=6 were asked to select 25 syllables (out of fifty possible choices using a two step procedure: first the consonant (ten choices and then the vowel (five choices. This was repeated on three separate days. Additionally, a person with spinal cord injury (SCI participated in the experiment. Four out of six healthy participants reached Hiragana syllable accuracies above 70% and the information transfer rate increased from 1.7 bits/min in the first session to 3.2 bits/min in the third session. The accuracy of the participant with SCI increased from 12% (0.2 bits/min to 56% (2 bits/min in session three. Reliable selections from a 10×5 matrix using auditory stimuli were possible and performance is increased by training. We were able to show that auditory P300 BCIs can be used for communication with up to fifty symbols. This enables the use of the technology of auditory P300 BCIs with a variety of applications.

  19. The impact of prior knowledge from participant instructions in a mock crime P300 Concealed Information Test.

    Science.gov (United States)

    Winograd, Michael R; Rosenfeld, J Peter

    2014-12-01

    In P300-Concealed Information Tests used with mock crime scenarios, the amount of detail revealed to a participant prior to the commission of the mock crime can have a serious impact on a study's validity. We predicted that exposure to crime details through instructions would bias detection rates toward enhanced sensitivity. In a 2 × 2 factorial design, participants were either informed (through mock crime instructions) or naĂŻve as to the identity of a to-be-stolen item, and then either committed (guilty) or did not commit (innocent) the crime. Results showed that prior knowledge of the stolen item was sufficient to cause 69% of innocent-informed participants to be incorrectly classified as guilty. Further, we found a trend toward enhanced detection rate for guilty-informed participants over guilty-naĂŻve participants. Results suggest that revealing details to participants through instructions biases detection rates in the P300-CIT toward enhanced sensitivity. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Latency of auditory P300 correlates with self-control as measured by the Sixteen Personality Factor Questionnaire.

    Science.gov (United States)

    Lee, Heon-Jeong; Kim, Leen; Han, Chang-Su; Kim, Yong-Ku; Kim, Seung-Hyun; Lee, Min-Soo; Joe, Sook-Haeng; Jung, In-Kwa

    2005-08-01

    The reception, processing, and storage of information about experience define personality. The present study investigated the relationship between auditory event-related potentials (AERP) and personality traits. The AERP were recorded using a standard auditory oddball paradigm, and personality was evaluated by Cattell's Sixteen Personality Factor Questionnaire (16PF) in 20 healthy young male subjects. The P300 latency was found to be significantly associated with rule consciousness (factor G in the 16PF), perfectionism (factor Q3), and self-control (factor SC): it was negatively correlated with G score (r = -0.56, P = 0.01), Q3 score (r = -0.67, P = 0.001), and SC score (r = -0.65, P = 0.002). Moreover, the P300 amplitude and N100 amplitude were negatively correlated with reasoning (factor B; r = -0.46, P = 0.044; and r = -0.72, P = 0.002, respectively). These results indicate that the personality traits of self-control, perfectionism, high superego, and reasoning are related to information processing in the brain.

  1. The Tax oncogene enhances ELL incorporation into p300 and P-TEFb containing protein complexes to activate transcription.

    Science.gov (United States)

    Fufa, Temesgen D; Byun, Jung S; Wakano, Clay; Fernandez, Alfonso G; Pise-Masison, Cynthia A; Gardner, Kevin

    2015-09-11

    The eleven-nineteen lysine-rich leukemia protein (ELL) is a key regulator of RNA polymerase II mediated transcription. ELL facilitates RNA polymerase II transcription pause site entry and release by dynamically interacting with p300 and the positive transcription elongation factor b (P-TEFb). In this study, we investigated the role of ELL during the HTLV-1 Tax oncogene induced transactivation. We show that ectopic expression of Tax enhances ELL incorporation into p300 and P-TEFb containing transcriptional complexes and the subsequent recruitment of these complexes to target genes in vivo. Depletion of ELL abrogates Tax induced transactivation of the immediate early genes Fos, Egr2 and NF-kB, suggesting that ELL is an essential cellular cofactor of the Tax oncogene. Thus, our study identifies a novel mechanism of ELL-dependent transactivation of immediate early genes by Tax and provides the rational for further defining the genome-wide targets of Tax and ELL. Published by Elsevier Inc.

  2. [Effects of noise exposure on event-related potential P300 and mechanism in hippocampus of rats].

    Science.gov (United States)

    Cui, Bo; Wu, Ming-quan; She, Xiao-jun; Liu, Hong-tao

    2009-08-01

    To study the effects of noise on event-related potential(ERP) and its mechanism in hippocampus in rats. Male SD rats were divided into 2 groups: control group (CG) and noise exposure group(NG). The rats in NG were exposed to white noise 105 dB SPL for 2.5 h/d x 20 d. P300 were recorded at parietal bone in rats. The Nissl body, NMDAR2B and [Ca2+]i of neurons in hippocampus were analyzed. The peak latency (PL) of ERP P3a, P3 and P3b in NG were significantly longer than that in CG in the 14th and 20th exposure day. The amount of Nissl body in dentate gyrus (DG) and CA1 region and NMDAR2B in DG, CA1 and CA3 region of hippocampus of NG were significantly decreased than those of CG as well, while the concentration of Ca2+ in neurons increased markedly in NG. Decreased Nissl body and NMDAR2B and increased [Ca2+]i in hippocampus in long-term noise exposed rats might cause the change of ERP P300.

  3. Memory timeline: Brain ERP C250 (not P300) is an early biomarker of short-term storage.

    Science.gov (United States)

    Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Dupree, Haley M; Antonsdottir, Inga M

    2015-04-16

    Brain event-related potentials (ERPs) offer a quantitative link between neurophysiological activity and cognitive performance. ERPs were measured while young adults performed a task that required storing a relevant stimulus in short-term memory. Using principal components analysis, ERP component C250 (maximum at 250 ms post-stimulus) was extracted from a set of ERPs that were separately averaged for various task conditions, including stimulus relevancy and stimulus sequence within a trial. C250 was more positive in response to task-specific stimuli that were successfully stored in short-term memory. This relationship between C250 and short-term memory storage of a stimulus was confirmed by a memory probe recall test where the behavioral recall of a stimulus was highly correlated with its C250 amplitude. ERP component P300 (and its subcomponents of P3a and P3b, which are commonly thought to represent memory operations) did not show a pattern of activation reflective of storing task-relevant stimuli. C250 precedes the P300, indicating that initial short-term memory storage may occur earlier than previously believed. Additionally, because C250 is so strongly predictive of a stimulus being stored in short-term memory, C250 may provide a strong index of early memory operations. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

    Science.gov (United States)

    Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

    2016-10-01

    Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

  5. Control or non-control state: that is the question! An asynchronous visual P300-based BCI approach

    Science.gov (United States)

    Pinegger, Andreas; Faller, Josef; Halder, Sebastian; Wriessnegger, Selina C.; MĂŒller-Putz, Gernot R.

    2015-02-01

    Objective. Brain-computer interfaces (BCI) based on event-related potentials (ERP) were proven to be a reliable synchronous communication method. For everyday life situations, however, this synchronous mode is impractical because the system will deliver a selection even if the user is not paying attention to the stimulation. So far, research into attention-aware visual ERP-BCIs (i.e., asynchronous ERP-BCIs) has led to variable success. In this study, we investigate new approaches for detection of user engagement. Approach. Classifier output and frequency-domain features of electroencephalogram signals as well as the hybridization of them were used to detect the user's state. We tested their capabilities for state detection in different control scenarios on offline data from 21 healthy volunteers. Main results. The hybridization of classifier output and frequency-domain features outperformed the results of the single methods, and allowed building an asynchronous P300-based BCI with an average correct state detection accuracy of more than 95%. Significance. Our results show that all introduced approaches for state detection in an asynchronous P300-based BCI can effectively avoid involuntary selections, and that the hybrid method is the most effective approach.

  6. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  7. Effects of acute oral Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers.

    Science.gov (United States)

    Roser, Patrik; Juckel, Georg; Rentzsch, Johannes; Nadulski, Thomas; Gallinat, JĂŒrgen; Stadelmann, Andreas M

    2008-08-01

    Reduced amplitudes of auditory evoked P300 are a robust finding in schizophrenic patients, indicating deficient attentional resource allocation and active working memory. Delta9-Tetrahydrocannabinol (Delta9-THC), the main active constituent of Cannabis sativa, has been known to acutely impair cognitive abilities in several domains, particularly in memory and attention. Given the psychotic-like effects of Delta9-THC, a cannabinoid hypothesis of schizophrenia has been proposed. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on P300 amplitude in 20 healthy volunteers (age 28.2+/-3.1 years, 10 male) by comparing Delta9-THC and standardized cannabis extract containing Delta9-THC and cannabidiol (CBD). P300 waves were recorded during a choice reaction task. As expected, Delta9-THC revealed a significant reduction of P300 amplitude at midline frontal, central, and parietal electrodes. CBD has been known to abolish many of the psychotropic effects of Delta9-THC, but, unexpectedly, failed to demonstrate a reversal of Delta9-THC-induced P300 reduction. Moreover, there were no correlations between cannabinoid plasma concentrations and P300 parameters. These data suggest that Delta(9)-THC may lead to acute impairment of attentional functioning and working memory. It can be speculated whether the lack of effect of CBD may be due to an insufficient dose used or to an involvement of neurotransmitter systems in P300 generation which are not influenced by CBD.

  8. Effects of caffeine on visual evoked potencial (P300 and neuromotor performance Efeitos da ingestĂŁo de cafeĂ­na no potencial evocado visual (p300 e no desempenho neuromotor

    Directory of Open Access Journals (Sweden)

    Andréa Camaz Deslandes

    2004-06-01

    Full Text Available The stimulant effects of caffeine on cognitive performance have been widely investigated. The visual evoked potential, specially the P300 component, has been used in studies that explain the stimulant mechanisms of caffeine through neurophysiological methods. In this context, the present study aimed to investigate electrophysiological changes (P300 latency and modification of cognitive and motor performance produced by caffeine. Fifteen healthy volunteers, 9 women and 6 men (26 ± 5 years, 67 ± 12.5kg were submitted three times to the following procedure: electroencefalographic recording, Word Color Stroop Test, and visual discrimination task. Subjects took a gelatin caffeine capsule (400 mg or a placebo (P1 and P2, in a randomized, crossover, double-blind design. A one-factor ANOVA and Tukey’ post hoc test were used to compare dependent variables on the C, P1 and P2 moments. The statistical analyses indicated a non-significant decrease in reaction time, Stroop execution time and latency at Cz on the caffeine moment when compared to the others. Moreover, a non-significant increase in Stroop raw score and latency at Pz could be observed. The only significant result was found at Fz. These findings suggest that the positive tendency of caffeine to improve cognitive performance is probably associated with changes in the frontal cortex, a widely recognized attention area.Os efeitos estimulantes da cafeĂ­na no desempenho cognitivo vĂȘm sendo amplamente investigados. O potencial evocado visual (P300 tem sido empregado em estudos recentes que buscam elucidar os mecanismos excitatĂłrios da cafeĂ­na atravĂ©s de mĂ©todos neurofisiolĂłgicos. Neste contexto, o presente estudo objetivou examinar as variaçÔes geradas pela cafeĂ­na em respostas eletrofisiolĂłgicas (latĂȘncia do P300 e determinar modificaçÔes no desempenho cognitivo e motor. Para tanto, 15 indivĂ­duos hĂ­gidos, sendo 9 mulheres e 6 homens (26 ± 5 anos, 67 ± 12,5 kg foram submetidos por

  9. Association between a cannabinoid receptor gene (CNR1) polymorphism and cannabinoid-induced alterations of the auditory event-related P300 potential.

    Science.gov (United States)

    Stadelmann, Andreas M; Juckel, Georg; Arning, Larissa; Gallinat, JĂŒrgen; Epplen, Jörg T; Roser, Patrik

    2011-05-27

    Numerous studies demonstrated a close relationship between cannabis abuse and schizophrenia with similar impairments in cognitive processing, particularly in P300 generation. Recently, an (AAT)n triplet repeat polymorphism within the cannabinoid receptor gene CNR1 has been found to be associated with both schizophrenia and substance dependence, and to modulate the P300 potential. As previously reported, both acute oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the main psychoactive constituent of cannabis, and standardized cannabis extract containing Δ(9)-THC and cannabidiol (CBD) revealed a significant reduction of P300 amplitudes in healthy subjects but did not show any differences among each other. The aim of this study was to investigate whether the (AAT)n polymorphism differentially modulates the effects of Δ(9)-THC and cannabis extract on P300 generation in 20 healthy volunteers during an auditory choice reaction task. For the >10/>10 genotype, there was a significant decrease of P300 amplitude as well as a significant prolongation of P300 latency under pure Δ(9)-THC but not under cannabis extract. Moreover, we found a significant correlation between the number of AAT repeats and P300 variables for the Δ(9)-THC condition. Our data thus indicate that the CNR1 gene seems to be involved in the regulation of the P300 wave as a marker of selective attention and working memory. Moreover, it appears that variations within CNR1 may differentially alter the sensitivity to the acute effects of cannabinoids on P300 generation in healthy subjects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. BOLD response to deviant face detection informed by P300 event-related potential parameters: a simultaneous ERP-fMRI study.

    Science.gov (United States)

    Campanella, Salvatore; Bourguignon, Mathieu; Peigneux, Philippe; Metens, Thierry; Nouali, Mustapha; Goldman, Serge; Verbanck, Paul; De TiĂšge, Xavier

    2013-05-01

    Faces are multi-dimensional stimuli conveying parallel information about identity and emotion. Although event-related potential (ERP) studies have disclosed a P300 component in oddball responses to both deviant identity and emotional target faces, it is hypothesized that partially different neural processes should subtend emotion vs. identity within the core network of face processing. In the present study, we used simultaneous ERP-fMRI recordings and ERP-informed analysis of functional magnetic resonance imaging (fMRI) data to evidence the specific neural networks underlying P300 generation in response to different deviant emotional vs. identity faces. 18 participants were scanned during a visual oddball task in which they had to detect 3 types of deviant faces representing a change in emotion-fear or happiness-or in identity, within a series of frequent neutral ones. Amplitude and latency parameters of the P300 component, recorded for each type of deviant faces, were used to constrain fMRI analyses. Analysis of fMRI data informed by single-trial parameters of the P300 component disclosed specific activation patterns for fearful, happy and identity deviant faces. For fearful faces, P300 amplitudes were associated with BOLD changes in the left fusiform gyrus whereas latencies were linked to left superior orbito-frontal and right fusiform activations. P300 amplitude modulations for happy deviant faces involved the left posterior cingulate gyrus and right parahippocampal regions whereas P300 latencies related to the right insula and left caudate regions. Finally, identity deviant faces were associated with widespread activities involving cortical and subcortical regions when P300 amplitudes were considered, and P300 latencies were associated with activity in right hippocampal/parahippocampal regions. Our results suggest the existence of differential cerebral functional processes involved in the responses to deviant face stimuli, depending on the quality of the

  11. Evaluation of P300 components for emotion-loaded visual event-related potential in elderly subjects, including those with dementia.

    Science.gov (United States)

    Asaumi, Yasue; Morita, Kiichiro; Nakashima, Youko; Muraoka, Akemi; Uchimura, Naohisa

    2014-07-01

    In the present study, the P300 component of the emotion-loaded visual event-related potential in response to photographs of babies crying or smiling was measured to evaluate cognitive function in elderly subjects, including those with dementia. The subjects were 48 elderly people who consulted a memory disorder clinic. The visual event-related potential was measured using oddball tasks. Brain waves were recorded from four sites. We analyzed the P300 amplitude and latency. Subjects were divided into three groups (the dementia with Alzheimer's disease group [ADG]; the intermediate group [MG], and the healthy group [HG]) based on the Revised Hasegawa Dementia Scale, Mini-mental State Examination scores and the Clinical Dementia Rating. For all subjects, there was a significant positive correlation between P300 latency and Z-score of voxel-based specific regional analysis for Alzheimer's disease for crying or smiling faces. There was a negative correlation between P300 amplitude and Z-score for the crying face. MG subjects were divided into two groups (high risk: HRMG, low risk: LRMG) based on Z-scores (HRMG ≄ 2.0). The P300 amplitude of ADG was significantly smaller than that of HG, and the P300 latency of ADG was significantly longer than those of other groups for crying or smiling faces. The P300 latency of HRMG was significantly longer than that of LRMG for the smiling face. Furthermore, the P300 latency for the crying face was significantly shorter than that for the smiling face in HG and ADG. These findings suggest that analysis of P300 components of the emotion-loaded visual event-related potential may be a useful neuropsychological index for the diagnosis of Alzheimer's disease and high-risk subjects. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  12. SnapShot: histone modifications

    National Research Council Canada - National Science Library

    Huang, He; Sabari, Benjamin R; Garcia, Benjamin A; Allis, C David; Zhao, Yingming

    2014-01-01

    Histone proteins are decorated by a variety of protein posttranslational modifications called histone marks that modulate chromatin structure and function, contributing to the cellular gene expression program...

  13. Pushing the P300-based brain-computer interface beyond 100 bpm: extending performance guided constraints into the temporal domain.

    Science.gov (United States)

    Townsend, G; Platsko, V

    2016-04-01

    A new presentation paradigm for the P300-based brain-computer interface (BCI) referred to as the 'asynchronous paradigm' (ASP) is introduced and studied. It is based on the principle of performance guided constraints (Townsend et al 2012 Neurosci. Lett. 531 63-8) extended from the spatial domain into the temporal domain. The traditional constraint of flashing targets in predefined constant epochs of time is eliminated and targets flash asynchronously with timing based instead on constraints intended to improve performance. We propose appropriate temporal constraints to derive the ASP and compare its performance to that of the 'checkerboard paradigm' (CBP), which has previously been shown to be superior to the standard 'row/column paradigm' introduced by Farwell and Donchin (1988 Electroencephalogr. Clin. Neurophysiol. 70 510-23). Ten participants were tested in the ASP and CBP conditions both with traditional flashing items and with flashing faces in place of the targets (see Zhang et al 2012 J. Neural Eng. 9 026018; Kaufmann and KĂŒbler 2014 J. Neural Eng. 11 ; Chen et al 2015 J. Neurosci. Methods 239 18-27). Eleven minutes of calibration data were used as input to a stepwise linear discriminant analysis to derive classification coefficients used for online classification. Accuracy was consistently high for both paradigms (87% and 93%) while information transfer rate was 45% higher for the ASP than the CBP. In a free spelling task, one subject spelled a 66 character sentence (from a 72 item matrix) with 100% accuracy in 3 min and 24 s demonstrating a practical throughput of 120 bits per minute (bpm) with a theoretical upper bound of 258 bpm. The subject repeated the task three times in a row without error. This work represents an advance in P300 speller technology and raises the ceiling that was being reached on P300-based BCIs. Most importantly, the research presented here is a novel and effective general strategy for organising timing for flashing items. The ASP

  14. The p300 event-related potential technique for libido assessment in women with hypoactive sexual desire disorder.

    Science.gov (United States)

    Vardi, Yoram; Sprecher, Elliot; Gruenwald, Ilan; Yarnitsky, David; Gartman, Irena; Granovsky, Yelena

    2009-06-01

    There is a need for an objective technique to assess the degree of hypoactive sexual desire disorder (HSDD). Recently, we described such a methodology (event-related potential technique [ERP]) based on recording of p300 electroencephalography (EEG) waves elicited by auditory stimuli during synchronous exposure to erotic films. To compare sexual interest of sexually healthy women to females with sexual dysfunction (FSD) using ERP, and to explore whether FSD women with and without HSDD would respond differently to two different types of erotic stimuli-films containing (I) or not containing (NI) sexual intercourse scenes. Twenty-two women with FSD, of which nine had HSDD only, and 30 sexually healthy women were assessed by the Female Sexual Functioning Index. ERP methodology was performed applying erotic NI or I films. Significant differences in percent of auditory p300 amplitude reduction (PR) in response to erotic stimuli within and between all three groups for each film type. PRs to each film type were similar in sexually healthy women (60.6% +/- 40.3 (NI) and 51.7% +/- 32.3 [I]), while in women with FSD, reduction was greater when viewing the NI vs. I erotic films (71.4% +/- 41.0 vs. 37.7% +/- 45.7; P = 0.0099). This difference was mainly due to the greater PR of the subgroup with HSDD in response to NI vs. I films (77.7% +/- 46.7 vs. 17.0% +/- 50.3) than in the FSD women without HSDD group or the sexually healthy women (67.5% +/- 38.7 vs. 50.4% +/- 39.4 respectively), P = 0.0084. For comparisons, we used the mixed-model one-way analysis of variance. Differences in neurophysiological response patterns between sexually healthy vs. sexually dysfunctional females may point to a specific inverse discrimination ability for sexually relevant information in the subgroup of women with HSDD. These findings suggest that the p300 ERP technique could be used as an objective quantitative tool for libido assessment in sexually dysfunctional women.

  15. Improving the accessibility at home: implementation of a domotic application using a p300-based brain computer interface system

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    Rebeca Corralejo Palacios

    2012-05-01

    Full Text Available The aim of this study was to develop a Brain Computer Interface (BCI application to control domotic devices usually present at home. Previous studies have shown that people with severe disabilities, both physical and cognitive ones, do not achieve high accuracy results using motor imagery-based BCIs. To overcome this limitation, we propose the implementation of a BCI application using P300 evoked potentials, because neither extensive training nor extremely high concentration level are required for this kind of BCIs. The implemented BCI application allows to control several devices as TV, DVD player, mini Hi-Fi system, multimedia hard drive, telephone, heater, fan and lights. Our aim is that potential users, i.e. people with severe disabilities, are able to achieve high accuracy. Therefore, this domotic BCI application is useful to increase

  16. Selección de Canales en Sistemas BCI basados en Potenciales P300 mediante Inteligencia de Enjambre

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    V. Martínez-Cagigal

    2017-10-01

    Full Text Available Resumen: Los sistemas Brain-Computer Interface (BCI se definen como sistemas de comunicación que monitorizan la actividad cerebral y traducen determinadas características, correspondientes a las intenciones del usuario, en comandos de control de un dispositivo. La selección de canales en los sistemas BCI es fundamental para evitar el sobre-entrenamiento del clasificador, reducir la carga computacional y aumentar la comodidad del usuario. A pesar de que se han desarrollado varios algoritmos con anterioridad para tal fin, las metaheurísticas basadas en inteligencia de enjambre aÃÂșn no han sido suficientemente explotadas en los sistemas BCI basados en potenciales P300. En este estudio se muestra una comparativa entre cinco métodos de enjambre, basados en el comportamiento de sistemas biológicos, aplicados con el objetivo de optimizar la selección de canales en este tipo de sistemas. Los métodos se han evaluado sobre la base de datos de la ñ€œIII BCI Competition 2005ñ€, reportando precisiones similares o, en algunos casos, incluso mÃ¥s altas que las obtenidas sin realizar ningÃÂșn tipo de selección. Dado que los cinco métodos se han demostrado capaces de disminuir drÃ¥sticamente los 64 canales originales a menos de la mitad sin comprometer el rendimiento del sistema, así como de superar el conjunto típico de 8 canales y el método backward elimination, se concluye que todos ellos son adecuados para su aplicación en la selección de canales en sistemas P300-BCI. Abstract: Brain-Computer Interfaces (BCI are direct communication pathways between the brain and the environment that translate certain features, which correspond to usersñ€™ intentions, into device control commands. Channel selection in BCI systems is essential to avoid over-fitting, to reduce the computational cost and to increase the usersñ€™ comfort. Although several algorithms have previously developed for that purpose

  17. AGO2 Negatively Regulates Type I Interferon Signaling Pathway by Competition Binding IRF3 with CBP/p300

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    Shengyu Wang

    2017-05-01

    Full Text Available Viral infection triggers a series of signaling cascades and host innate immune responses, including interferon (IFN production, which depends on coordinated activity of multiple transcription factors. IFN regulatory factor 3 (IRF3 and transcriptional coactivator CREB binding protein (CBP and/or p300 are core factors that participate in transcriptional complex formation in the nucleus. In general, cells balance the production of IFNs through suppressive and stimulative mechanisms, but viral infections can disrupt such equilibrium. This study determined that H5N1 viral infection reduced the distribution of human argonaute 2 (AGO2 in A549 cell nucleus. AGO2 did not block phosphorylation, nuclear translocation, and DNA binding ability of IRF3 but inhibited its association with CBP. Therefore, this newly revealed mechanism shows that cellular response leads to transfer of AGO2 from cell nucleus and promotes IFN-ÎČ expression to increase host survival during viral infection.

  18. Optimizing the stimulus presentation paradigm design for the P300-based brain-computer interface using performance prediction

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    Mainsah, B. O.; Reeves, G.; Collins, L. M.; Throckmorton, C. S.

    2017-08-01

    Objective. The role of a brain-computer interface (BCI) is to discern a user’s intended message or action by extracting and decoding relevant information from brain signals. Stimulus-driven BCIs, such as the P300 speller, rely on detecting event-related potentials (ERPs) in response to a user attending to relevant or target stimulus events. However, this process is error-prone because the ERPs are embedded in noisy electroencephalography (EEG) data, representing a fundamental problem in communication of the uncertainty in the information that is received during noisy transmission. A BCI can be modeled as a noisy communication system and an information-theoretic approach can be exploited to design a stimulus presentation paradigm to maximize the information content that is presented to the user. However, previous methods that focused on designing error-correcting codes failed to provide significant performance improvements due to underestimating the effects of psycho-physiological factors on the P300 ERP elicitation process and a limited ability to predict online performance with their proposed methods. Maximizing the information rate favors the selection of stimulus presentation patterns with increased target presentation frequency, which exacerbates refractory effects and negatively impacts performance within the context of an oddball paradigm. An information-theoretic approach that seeks to understand the fundamental trade-off between information rate and reliability is desirable. Approach. We developed a performance-based paradigm (PBP) by tuning specific parameters of the stimulus presentation paradigm to maximize performance while minimizing refractory effects. We used a probabilistic-based performance prediction method as an evaluation criterion to select a final configuration of the PBP. Main results. With our PBP, we demonstrate statistically significant improvements in online performance, both in accuracy and spelling rate, compared to the conventional

  19. Optimizing the stimulus presentation paradigm design for the P300-based brain-computer interface using performance prediction.

    Science.gov (United States)

    Mainsah, B O; Reeves, G; Collins, L M; Throckmorton, C S

    2017-08-01

    The role of a brain-computer interface (BCI) is to discern a user's intended message or action by extracting and decoding relevant information from brain signals. Stimulus-driven BCIs, such as the P300 speller, rely on detecting event-related potentials (ERPs) in response to a user attending to relevant or target stimulus events. However, this process is error-prone because the ERPs are embedded in noisy electroencephalography (EEG) data, representing a fundamental problem in communication of the uncertainty in the information that is received during noisy transmission. A BCI can be modeled as a noisy communication system and an information-theoretic approach can be exploited to design a stimulus presentation paradigm to maximize the information content that is presented to the user. However, previous methods that focused on designing error-correcting codes failed to provide significant performance improvements due to underestimating the effects of psycho-physiological factors on the P300 ERP elicitation process and a limited ability to predict online performance with their proposed methods. Maximizing the information rate favors the selection of stimulus presentation patterns with increased target presentation frequency, which exacerbates refractory effects and negatively impacts performance within the context of an oddball paradigm. An information-theoretic approach that seeks to understand the fundamental trade-off between information rate and reliability is desirable. We developed a performance-based paradigm (PBP) by tuning specific parameters of the stimulus presentation paradigm to maximize performance while minimizing refractory effects. We used a probabilistic-based performance prediction method as an evaluation criterion to select a final configuration of the PBP. With our PBP, we demonstrate statistically significant improvements in online performance, both in accuracy and spelling rate, compared to the conventional row-column paradigm. By accounting for

  20. Structural insight into histone recognition by the ING PHD fingers.

    Science.gov (United States)

    Champagne, Karen S; Kutateladze, Tatiana G

    2009-05-01

    The Inhibitor of Growth (ING) tumor suppressors are implicated in oncogenesis, control of DNA damage repair, cellular senescence and apoptosis. All members of the ING family contain unique amino-terminal regions and a carboxy-terminal plant homeodomain (PHD) finger. While the amino-terminal domains associate with a number of protein effectors including distinct components of histone deacetylase (HDAC) and histone acetyltransferase (HAT) complexes, the PHD finger binds strongly and specifically to histone H3 trimethylated at lysine 4 (H3K4me3). In this review we describe the molecular mechanism of H3K4me3 recognition by the ING1-5 PHD fingers, analyze the determinants of the histone specificity and compare the biological activities and structures within subsets of PHD fingers. The atomic-resolution structures of the ING PHD fingers in complex with a H3K4me3 peptide reveal that the histone tail is bound in a large and deep binding site encompassing nearly one-third of the protein surface. An extensive network of intermolecular hydrogen bonds, hydrophobic and cation-pi contacts, and complementary surface interactions coordinate the first six residues of the H3K4me3 peptide. The trimethylated Lys4 occupies an elongated groove, formed by the highly conserved aromatic and hydrophobic residues of the PHD finger, whereas the adjacent groove accommodates Arg2. The two grooves are connected by a narrow channel, the small size of which defines the PHD finger's specificity, excluding interactions with other modified histone peptides. Binding of the ING PHD fingers to H3K4me3 plays a critical role in regulating chromatin acetylation. The ING proteins function as tethering molecules that physically link the HDAC and HAT enzymatic complexes to chromatin. In this review we also highlight progress recently made in understanding the molecular basis underlying biological and tumorigenic activities of the ING tumor suppressors.

  1. Identification and Characterization of Histone Deacetylases in Tomato (Solanum lycopersicum

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    Linmao eZhao

    2015-01-01

    Full Text Available Histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in the regulation of eukaryotic gene activity. Histone acetylation and deacetylation are catalyzed by histone acetyltransferases and histone deacetylases (HDACs, respectively. A growing number of studies have demonstrated the importance of histone deacetylation/acetylation on genome stability, transcriptional regulation, development and response to stress in Arabidopsis. However, the biological functions of HDACs in tomato have not been investigated previously. Fifteen HDACs identified from tomato (Solanum Lycopersicum can be grouped into RPD3/HDA1, SIR2 and HD2 families based on phylogenetic analysis. Meanwhile, ten members of the RPD3/HDA1 family can be further subdivided into four groups, namely Class I, Class II, Class III and Class IV. High similarities of protein sequences and conserved domains were identified among SlHDACs and their homologs in Arabidopsis. Most SlHDACs were expressed in all tissues examined with different transcript abundance. Transient expression in Arabidopsis protoplasts showed that SlHDA8, SlHDA1, SlHDA5, SlSRT1 and members of the HD2 family were localized to the nucleus, whereas SlHDA3 and SlHDA4 were localized in both the cytoplasm and nucleus. The difference in the expression patterns and subcellular localization of SlHDACs suggest that they may play distinct functions in tomato. Furthermore, we found that three members of the RPD3/HDA1 family, SlHDA1, SIHDA3 and SlHDA4, interacted with TAG1 (TOMATO AGAMOUS1 and TM29 (TOMATO MADS BOX29, two MADS-box proteins associated with tomato reproductive developmentindicating that these HDACs may be involved in gene regulation in reproductive development.

  2. Solar Simulated Ultraviolet Radiation Induces Global Histone Hypoacetylation in Human Keratinocytes.

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    Xiaoru Zhang

    Full Text Available Ultraviolet radiation (UVR from sunlight is the primary effector of skin DNA damage. Chromatin remodeling and histone post-translational modification (PTM are critical factors in repairing DNA damage and maintaining genomic integrity, however, the dynamic changes of histone marks in response to solar UVR are not well characterized. Here we report global changes in histone PTMs induced by solar simulated UVR (ssUVR. A decrease in lysine acetylation of histones H3 and H4, particularly at positions of H3 lysine 9, lysine 56, H4 lysine 5, and lysine 16, was found in human keratinocytes exposed to ssUVR. These acetylation changes were highly associated with ssUVR in a dose-dependent and time-specific manner. Interestingly, H4K16ac, a mark that is crucial for higher order chromatin structure, exhibited a persistent reduction by ssUVR that was transmitted through multiple cell divisions. In addition, the enzymatic activities of histone acetyltransferases were significantly reduced in irradiated cells, which may account for decreased global acetylation. Moreover, depletion of histone deacetylase SIRT1 in keratinocytes rescued ssUVR-induced H4K16 hypoacetylation. These results indicate that ssUVR affects both HDAC and HAT activities, leading to reduced histone acetylation.

  3. Solar Simulated Ultraviolet Radiation Induces Global Histone Hypoacetylation in Human Keratinocytes.

    Science.gov (United States)

    Zhang, Xiaoru; Kluz, Thomas; Gesumaria, Lisa; Matsui, Mary S; Costa, Max; Sun, Hong

    2016-01-01

    Ultraviolet radiation (UVR) from sunlight is the primary effector of skin DNA damage. Chromatin remodeling and histone post-translational modification (PTM) are critical factors in repairing DNA damage and maintaining genomic integrity, however, the dynamic changes of histone marks in response to solar UVR are not well characterized. Here we report global changes in histone PTMs induced by solar simulated UVR (ssUVR). A decrease in lysine acetylation of histones H3 and H4, particularly at positions of H3 lysine 9, lysine 56, H4 lysine 5, and lysine 16, was found in human keratinocytes exposed to ssUVR. These acetylation changes were highly associated with ssUVR in a dose-dependent and time-specific manner. Interestingly, H4K16ac, a mark that is crucial for higher order chromatin structure, exhibited a persistent reduction by ssUVR that was transmitted through multiple cell divisions. In addition, the enzymatic activities of histone acetyltransferases were significantly reduced in irradiated cells, which may account for decreased global acetylation. Moreover, depletion of histone deacetylase SIRT1 in keratinocytes rescued ssUVR-induced H4K16 hypoacetylation. These results indicate that ssUVR affects both HDAC and HAT activities, leading to reduced histone acetylation.

  4. Genome-Wide Identification of Histone Modifiers and Their Expression Patterns during Fruit Abscission in Litchi

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    Jianguo Li

    2017-04-01

    Full Text Available Modifications to histones, including acetylation and methylation processes, play crucial roles in the regulation of gene expression in plant development as well as in stress responses. However, limited information on the enzymes catalyzing histone acetylation and methylation in non-model plants is currently available. In this study, several histone modifier (HM types, including six histone acetyltransferases (HATs, 11 histone deacetylases (HDACs, 48 histone methyltransferases (HMTs, and 22 histone demethylases (HDMs, are identified in litchi (Litchi chinensis Sonn. cv. Feizixiao based on similarities in their sequences to homologs in Arabidopsis (A. thaliana, tomato (Solanum lycopersicum, and rice (Oryza sativa. Phylogenetic analyses reveal that HM enzymes can be grouped into four HAT, two HDAC, two HMT, and two HDM subfamilies, respectively, while further expression profile analyses demonstrate that 17 HMs were significantly altered during fruit abscission in two field treatments. Analyses reveal that these genes exhibit four distinct patterns of expression in response to fruit abscission, while an in vitro assay was used to confirm the HDAC activity of LcHDA2, LcHDA6, and LcSRT2. Our findings are the first in-depth analysis of HMs in the litchi genome, and imply that some are likely to play important roles in fruit abscission in this commercially important plant.

  5. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1ÎČ expression in a rat model of neuroinflammation

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    Soliman Mahmoud L

    2012-03-01

    Full Text Available Abstract Background Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression. Methods In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1ÎČ expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively. Results We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9, histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1ÎČ protein

  6. The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: a meta-analytic investigation.

    Science.gov (United States)

    Euser, Anja S; Arends, Lidia R; Evans, Brittany E; Greaves-Lord, Kirstin; Huizink, Anja C; Franken, Ingmar H A

    2012-01-01

    Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to phenotype and can aid in discovering the genetic etiology of a disorder. There are currently very few suitable endophenotypes available for substance use disorders (SUD). The amplitude of the P300 event-related brain potential is a possible candidate. The present study determined whether the P300 amplitude fulfils two fundamental criteria for an endophenotype: (1) an association with the disorder (disease marker), and (2) presence in unaffected biological relatives of those who have the disorder (vulnerability marker). For this purpose, two separate meta-analyses were performed. Meta-analysis 1 investigated the P300 amplitude in relation to SUD in 39 studies and Meta-analysis 2 investigated P300 amplitude in relation to a family history (FH+) of SUD in 35 studies. The findings indicate that a reduced P300 amplitude is significantly associated with SUD (d=0.51) and, though to a lesser extent, with a FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300 amplitude and SUD is significantly larger for participants that were exclusively recruited from treatment facilities (d=0.67) than by other methods (i.e., community samples and family studies; d=0.45 and 0.32, respectively), and larger for abstinent SUD patients (d=0.71) than for current substance users (d=0.37). Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be present in FH+ females (d=-0.07). Taken together, these results suggest that P300 amplitude reduction can be both a useful disease and vulnerability marker and is a promising neurobiological endophenotype for SUD, though only in males. Implications and future directions are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. State and trait markers of emotionally charged visual event-related potentials (P300) in drug-naĂŻve schizophrenia.

    Science.gov (United States)

    Mori, Keiichiro; Morita, Kiichiro; Shoji, Yoshihisa; Matsuoka, Toshimasa; Fujiki, Ryo; Uchimura, Naohisa

    2012-06-01

    In the present study, we investigated the changes in P3 component in the emotionally charged visual event-related potentials (ERP) in 30 drug-naïve schizophrenic patients for up to 1 year. Visual oddball event-related potential was recorded from six recording sites for crying baby or smiling baby photographs. ERP were recorded before the treatment (session 1 [S1]), after 3 months (session 2 [S2]), and after 12 months (session 3 [S3]), as well as in 30 healthy subjects. Before taking medicine, there were no significant differences in the P300 amplitude between viewing photographs of a crying and a smiling baby. The P300 amplitude was significantly larger at S2 and S3 than at S1 for a crying baby, while there was no significant difference among sessions for a smiling baby after medication. A significant difference of the P300 amplitude was only observed between S3 and healthy subjects for a smiling baby. The P300 latency only when viewing a smiling face became significantly longer at S3 than those at S1 and S2. A significant negative correlation was obtained between the P300 amplitude changes upon viewing crying faces and negative syndrome score changes at the Pz site. The P300 amplitude induced by crying-face stimuli may be a state marker and the P300 amplitude caused by smiling-face stimuli may be a trait marker during recovery in schizophrenic patients. Atypical antipsychotic medications may be useful and may recover cognitive function reflected by the emotionally charged visual P300 components in schizophrenic patients. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

  8. Evaluation of cognitive performance by using P300 auditory event related potentials (ERPs) in patients with growth hormone (GH) deficiency and acromegaly.

    Science.gov (United States)

    Tanriverdi, F; Yapislar, H; Karaca, Z; Unluhizarci, K; Suer, C; Kelestimur, F

    2009-02-01

    Impaired cognitive performance has been demonstrated in adults with GH deficiency and acromegaly by using different neuropsychological tests. P300 event related potential (ERP) application is a well established neurophysiological approach in the assessment of cognitive performance. Evaluation of cognitive performance by using P300 ERPs has not been reported in acromegaly, and the comparisons of the P300 ERPs between the patients with GH deficiency and GH excess have not been done yet. Therefore present study was designed to investigate the effects of GH deficiency and GH excess on cognitive performance by using P300 ERPs. The study comprised 19 patients with severe GH deficiency, 18 acromegalic patients and 16 age, education and sex matched healthy controls. Baseline auditory ERPs were obtained at Fz (frontal), Cz (central), Pz (parietal) and Oz (occipital) electrode sites in GH deficient group, GH excess group and control group. There was a significant difference between mean serum IGF-I levels in the GH deficient and acromegalic patients (48+/-38 ng/ml and 742+/-272 ng/ml, respectively) (P=0.01). The mean P300 latency of the patients with GH deficiency was significantly (P=0.0001) prolonged when compared with that of normal controls and acromegalic patients at all electrode sites. The mean P300 amplitude of the patients with acromegaly was significantly (P=0.005) lower when compared with that of normal controls and GH deficient patients at all electrode sites. Using ERPs recordings, the present study indicates the prolongation of P300 latencies in patients with severe GH deficiency and reduction of P300 amplitudes in patients with acromegaly. This study provides the electrophysiological evidence for the presence of cognitive dysfunction in both GH deficiency and GH excess, and different components of the cognitive performance are impaired in these conditions.

  9. The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors.

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    Linya You

    2015-03-01

    Full Text Available Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1 is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.

  10. Using event-related potential P300 as an electrophysiological marker for differential diagnosis and to predict the progression of mild cognitive impairment: a meta-analysis.

    Science.gov (United States)

    Jiang, Shixiang; Qu, Changda; Wang, Fengjun; Liu, Yupeng; Qiao, Zhengxue; Qiu, Xiaohui; Yang, Xiuxian; Yang, Yanjie

    2015-07-01

    P300 event-related potential component may sensitively predict mild cognitive impairment (MCI) progression. Here, pooled effect size estimates of P300 amplitude and latency were computed at midline electrodes among controls, MCI patients, and Alzheimer's disease (AD) patients. Baseline data were compared to one-year follow-up data. MCI patients showed decreased P300 amplitude and prolonged latency compared to controls. Pooled standardized mean differences (SMDs) were -0.67 (95 % CI -1.12 to -0.23, P = 0.003) and 0.90 (95 % CI 0.66-1.14, P P300 latency decreased in MCI compared to AD patients where the pooled SMD was -0.52 (95 % CI -0.85 to -0.18, P = 0.003). Amplitude and latency differed between MCI baseline and follow-up. Pooled SMDs were 0.47 (95 % CI 0.29 to -0.65, P P300 latency existed compared to control and AD patients. P300 latency may therefore be a sensitive indicator for early cognitive decline or disease progression in MCI patients and identifying elderly patient progression to MCI and/or AD.

  11. The clinical utility of the auditory P300 latency subcomponent event-related potential in preclinical diagnosis of patients with mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Howe, Aaron S; Bani-Fatemi, Ali; De Luca, Vincenzo

    2014-04-01

    The present meta-analysis investigated the clinical utility of the auditory P300 latency event-related potential in differentiating patients with Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and unaffected controls. Effect size estimates were computed from mean P300 latency measurements at midline electrodes between patients and unaffected controls using the random effects restricted maximum likelihood model. The effects of clinical and ERP/EEG methological variables were assessed in a moderator analysis. P300 latency was found to be significantly prolonged in patients with AD (and MCI) compared to unaffected controls. Shortened P300 latencies were observed when comparing patients with MCI to patients with AD. Clinically relevant differences in P300 latency effect sizes were associated with mean age, interstimulus interval, stimulus difference, target frequency, reference electrode, and sampling rate. The meta-analytic findings provide robust statistical evidence for the use of the auditory P300 latency subcomponent as a biological marker of prodromal AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Synthetic histone code.

    Science.gov (United States)

    Fischle, Wolfgang; Mootz, Henning D; Schwarzer, Dirk

    2015-10-01

    Chromatin is the universal template of genetic information in all eukaryotic cells. This complex of DNA and histone proteins not only packages and organizes genomes but also regulates gene expression. A multitude of posttranslational histone modifications and their combinations are thought to constitute a code for directing distinct structural and functional states of chromatin. Methods of protein chemistry, including protein semisynthesis, amber suppression technology, and cysteine bioconjugation, have enabled the generation of so-called designer chromatin containing histones in defined and homogeneous modification states. Several of these approaches have matured from proof-of-concept studies into efficient tools and technologies for studying the biochemistry of chromatin regulation and for interrogating the histone code. We summarize pioneering experiments and recent developments in this exciting field of chemical biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation

    DEFF Research Database (Denmark)

    Malatesta, Martina; Steinhauer, Cornelia; Mohammad, Faizaan

    2013-01-01

    as in several cancers, including brain tumors like medulloblastoma and glioblastoma. Inhibition of aberrant Hh-Gli signaling has, thus, emerged as an attractive approach for anticancer therapy; however, the mechanisms that mediate Hh-Gli signaling in vertebrates remain poorly understood. Here, we show...... apoptosis. In addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh-Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh target gene promoters. Finally, we observed that PCAF silencing reduces the tumor-forming potential of neural stem cells...

  14. African swine fever virus blocks the host cell antiviral inflammatory response through a direct inhibition of PKC-theta-mediated p300 transactivation.

    Science.gov (United States)

    Granja, Aitor G; SĂĄnchez, Elena G; Sabina, Prado; Fresno, Manuel; Revilla, Yolanda

    2009-01-01

    During a viral infection, reprogramming of the host cell gene expression pattern is required to establish an adequate antiviral response. The transcriptional coactivators p300 and CREB binding protein (CBP) play a central role in this regulation by promoting the assembly of transcription enhancer complexes to specific promoters of immune and proinflammatory genes. Here we show that the protein A238L encoded by African swine fever virus counteracts the host cell inflammatory response through the control of p300 transactivation during the viral infection. We demonstrate that A238L inhibits the expression of the inflammatory regulators cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-alpha) by preventing the recruitment of p300 to the enhanceosomes formed on their promoters. Furthermore, we report that A238L inhibits p300 activity during the viral infection and that its amino-terminal transactivation domain is essential in the A238L-mediated inhibition of the inflammatory response. Importantly, we found that the residue serine 384 of p300 is required for the viral protein to accomplish its inhibitory function and that ectopically expressed PKC-theta completely reverts this inhibition, thus indicating that this signaling pathway is disrupted by A238L during the viral infection. Furthermore, we show here that A238L does not affect PKC-theta enzymatic activity, but the molecular mechanism of this viral inhibition relies on the lack of interaction between PKC-theta and p300. These findings shed new light on how viruses alter the host cell antiviral gene expression pattern through the blockade of the p300 activity, which represents a new and sophisticated viral mechanism to evade the inflammatory and immune defense responses.

  15. Preliminary investigation of plasma levels of sex hormones and human growth factor(s, and P300 latency as correlates to cognitive decline as a function of gender

    Directory of Open Access Journals (Sweden)

    Kerner Mallory M

    2009-07-01

    Full Text Available Abstract Background Aging is marked by declines in levels of many sex hormones and growth factors, as well as in cognitive function. The P300 event-related potential has been established as a predictor of cognitive decline. We decided to determine if this measure, as well as 2 standard tests of memory and attention, may be correlated with serum levels of sex hormones and growth factors, and if there are any generalizations that could be made based on these parameters and the aging process. Findings In this large clinically based preliminary study several sex-stratified associations between hormone levels and cognition were observed, including (1 for males aged 30 to 49, both IGF-1 and IGFBP-3 significantly associated negatively with prolonged P300 latency; (2 for males aged 30 to 49, the spearman correlation between prolonged P300 latency and low free testosterone was significant; (3 for males aged 60 to 69, there was a significant negative correlation between P300 latency and DHEA levels; (4 for females aged 50 to 59 IGFBP-3 significantly associated negatively with prolonged P300 latency; (5 for females at all age periods, estrogen and progesterone were uncorrelated with P300 latency; and (6 for females aged 40 to 69, there was significant negative correlation between DHEA levels and P300 latency. Moreover there were no statistically significant correlations between any hormone and Wechsler Memory Scale-III (WMS-111. However, in females, there was a significant positive correlation between estrogen levels and the number of Attention Deficit Disorder (ADD complaints. Conclusion Given certain caveats including confounding factors involving psychiatric and other chronic diseases as well as medications, the results may still have important value. If these results could be confirmed in a more rigorously controlled investigation, it may have important value in the diagnosis, prevention and treatment of cognitive impairments and decline.

  16. Interaction of the transactivation domain of B-Myb with the TAZ2 domain of the coactivator p300: molecular features and properties of the complex.

    Directory of Open Access Journals (Sweden)

    Ojore Oka

    Full Text Available The transcription factor B-Myb is a key regulator of the cell cycle in vertebrates, with activation of transcription involving the recognition of specific DNA target sites and the recruitment of functional partner proteins, including the coactivators p300 and CBP. Here we report the results of detailed studies of the interaction between the transactivation domain of B-Myb (B-Myb TAD and the TAZ2 domain of p300. The B-Myb TAD was characterized using circular dichroism, fluorescence and NMR spectroscopy, which revealed that the isolated domain exists as a random coil polypeptide. Pull-down and spectroscopic experiments clearly showed that the B-Myb TAD binds to p300 TAZ2 to form a moderately tight (K(d ~1.0-10 ”M complex, which results in at least partial folding of the B-Myb TAD. Significant changes in NMR spectra of p300 TAZ2 suggest that the B-Myb TAD binds to a relatively large patch on the surface of the domain (~1200 Å(2. The apparent B-Myb TAD binding site on p300 TAZ2 shows striking similarity to the surface of CBP TAZ2 involved in binding to the transactivation domain of the transcription factor signal transducer and activator of transcription 1 (STAT1, which suggests that the structure of the B-Myb TAD-p300 TAZ2 complex may share many features with that reported for STAT1 TAD-p300 TAZ2.

  17. Effect of the green/blue flicker matrix for P300-based brain–computer interface: an EEG–fMRI study.

    Directory of Open Access Journals (Sweden)

    Shiro eIkegami

    2012-07-01

    Full Text Available The visual P300 brain–computer interface (BCI, a popular system for EEG-based BCI, utilizes the P300 event-related potential to select an icon arranged in a flicker matrix. In the conventional P300 BCI speller paradigm, white/gray luminance intensification of each row/column in the matrix is used. In an earlier study, we applied green/blue luminance and chromatic change in the P300 BCI system and reported that this luminance and chromatic flicker matrix was associated with better performance and greater subject comfort compared with the conventional white/gray luminance flicker matrix. In this study, we used simultaneous EEG-fMRI recordings to identify brain areas that were more enhanced in the green/blue flicker matrix than in the white/gray flicker matrix, as these may highlight areas devoted to improved P300-BCI performance. The peak of the positive wave in the EEG data was detected under both conditions, and the peak amplitudes were larger at the parietal and occipital electrodes, particularly in the late components, under the green/blue condition than under the white/gray condition. fMRI data showed activation in the bilateral parietal and occipital cortices, and these areas, particularly those in the right hemisphere, were more activated under the green/blue condition than under the white/gray condition. The parietal and occipital regions more involved in the green/blue condition were part of the areas devoted to conventional P300s. These results suggest that the green/blue flicker matrix was useful for enhancing the so-called P300 responses.

  18. Cognitive assessment in Amyotrophic Lateral Sclerosis by means of P300-Brain Computer Interface: a preliminary study.

    Science.gov (United States)

    Poletti, Barbara; Carelli, Laura; Solca, Federica; Lafronza, Annalisa; Pedroli, Elisa; Faini, Andrea; Zago, Stefano; Ticozzi, Nicola; Meriggi, Paolo; Cipresso, Pietro; Lulé, Dorothée; Ludolph, Albert C; Riva, Giuseppe; Silani, Vincenzo

    To investigate the use of P300-based Brain Computer Interface (BCI) technology for the administration of motor-verbal free cognitive tests in Amyotrophic Lateral Sclerosis (ALS). We recruited 15 ALS patients and 15 age- and education-matched healthy subjects. All participants underwent a BCI-based neuropsychological assessment, together with two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI-Y) and a usability questionnaire. For patients, clinical and respiratory examinations were also performed, together with a behavioural assessment (FBI). Correlations were observed between standard cognitive and BCI-based neuropsychological assessment, mainly concerning execution times in the ALS group. Moreover, patients provided positive rates concerning the BCI perceived usability and subjective experience. Finally, execution times at the BCI-based neuropsychological assessment were useful to discriminate patients from controls, with patients achieving lower processing speed than controls regarding executive functions. The developed motor-verbal free neuropsychological battery represents an innovative approach, that could provide relevant information for clinical practice and ethical issues. Its use for cognitive evaluation throughout the course of ALS, currently not available by means of standard assessment, must be addressed in further longitudinal validation studies. Further work will be aimed at refining the developed system and enlarging the cognitive spectrum investigated.

  19. A novel P300-based brain-computer interface stimulus presentation paradigm: moving beyond rows and columns

    Science.gov (United States)

    Townsend, G.; LaPallo, B.K.; Boulay, C.B.; Krusienski, D.J.; Frye, G.E.; Hauser, C.K.; Schwartz, N.E.; Vaughan, T.M.; Wolpaw, J.R.; Sellers, E.W.

    2010-01-01

    Objective An electroencephalographic brain-computer interface (BCI) can provide a non-muscular means of communication for people with amyotrophic lateral sclerosis (ALS) or other neuromuscular disorders. We present a novel P300-based BCI stimulus presentation – the checkerboard paradigm (CBP). CBP performance is compared to that of the standard row/column paradigm (RCP) introduced by Farwell and Donchin (1988). Methods Using an 8×9 matrix of alphanumeric characters and keyboard commands, 18 participants used the CBP and RCP in counter-balanced fashion. With approximately 9 – 12 minutes of calibration data, we used a stepwise linear discriminant analysis for online classification of subsequent data. Results Mean online accuracy was significantly higher for the CBP, 92%, than for the RCP, 77%. Correcting for extra selections due to errors, mean bit rate was also significantly higher for the CBP, 23 bits/min, than for the RCP, 17 bits/min. Moreover, the two paradigms produced significantly different waveforms. Initial tests with three advanced ALS participants produced similar results. Furthermore, these individuals preferred the CBP to the RCP. Conclusions These results suggest that the CBP is markedly superior to the RCP in performance and user acceptability. Significance The CBP has the potential to provide a substantially more effective BCI than the RCP. This is especially important for people with severe neuromuscular disabilities. PMID:20347387

  20. Effects of a psychophysiological system for adaptive automation on performance, workload, and the event-related potential P300 component

    Science.gov (United States)

    Prinzel, Lawrence J 3rd; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    The present study examined the effects of an electroencephalographic- (EEG-) based system for adaptive automation on tracking performance and workload. In addition, event-related potentials (ERPs) to a secondary task were derived to determine whether they would provide an additional degree of workload specificity. Participants were run in an adaptive automation condition, in which the system switched between manual and automatic task modes based on the value of each individual's own EEG engagement index; a yoked control condition; or another control group, in which task mode switches followed a random pattern. Adaptive automation improved performance and resulted in lower levels of workload. Further, the P300 component of the ERP paralleled the sensitivity to task demands of the performance and subjective measures across conditions. These results indicate that it is possible to improve performance with a psychophysiological adaptive automation system and that ERPs may provide an alternative means for distinguishing among levels of cognitive task demand in such systems. Actual or potential applications of this research include improved methods for assessing operator workload and performance.

  1. Automation of a chloramphenicol acetyltransferase assay.

    Science.gov (United States)

    Chauchereau, A; Astinotti, D; Bouton, M M

    1990-08-01

    Accurate quantification of chloramphenicol acetyltransferase (CAT) enzyme activity in a large number of samples has been achieved through robotization of a CAT assay on a laboratory workstation (Biomek 1000). The basic principle of this CAT assay relies on the selective diffusion of [3H]acetylchloramphenicol into a water-immiscible liquid scintillation cocktail. This methodology gives unique characteristics to this robotized protocol by allowing complete control over the kinetics of the CAT enzymatic reaction which is a critical parameter in the CAT assay. Thus it has been possible to optimize the CAT assay for every processed sample, through real time monitoring of the enzymatic reaction, and to achieve maximum accuracy in CAT quantification. Moreover the sensitivity of this automated assay is high (detection threshold; 10(-4) CAT unit), and the sample processing is fast (approximately 125 samples per hour). Compared to other CAT assay protocols currently used, our robotized technique offers major advantages in terms of CAT quantification, and sets new standards for CAT assay productivity.

  2. N-acetyltransferase polymorphism among northern Sudanese.

    Science.gov (United States)

    Al-Yahyaee, Said; Gaffar, Uzma; Al-Ameri, Maryam M; Qureshi, Mansoor; Zadjali, Fahad; Ali, Baderldin H; Bayoumi, Riad

    2007-08-01

    Interindividual and interethnic differences in allele frequencies of N-acetyltransferase (NAT2) single nucleotide polymorphisms (SNPs) are responsible for phenotypic variability of adverse drug reactions and susceptibility to cancer. We genotyped the seven NAT2 common SNPs in 127 randomly selected unrelated northern Sudanese subjects using allele-specific and RFLP polymerase chain reaction (PCR) based methods. Molecular genotyping was enough to designate alleles for 41 individuals unambiguously, whereas 63 individuals' alleles were inferred from haplotypes previously described. In the remaining 23 individuals, however, the phase of the SNPs could not be decided because of multiple SNP heterozygotes. Using computational methods in the HAP and Phase programs, we confirmed the inferred alleles of the 62 individuals and predicted the remaining 23 ambiguous alleles. Twelve NAT2 alleles were identified. Four alleles coded for rapid acetylators (18%), and eight alleles coded for slow acetylators (82%). Two genotypes coded for rapid acetylation (3.9%), 10 for intermediate acetylation (27.6%), and 13 for slow acetylation (68.5%). The G191A African SNP and the G857A predominantly Asian SNP were each detected at a low frequency of 3.1%. The combination of molecular and computational analysis was useful in resolving ambiguous genotypes of NAT2 in multiple SNP heterozygotes. Among the northern Sudanese the SNPs associated with slow acetylation are more prevalent than in Caucasians and Asians. This and other African studies are suggestive of an African origin for NAT