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Sample records for pol helicase spike

  1. The helicase domain of Polθ counteracts RPA to promote alt-NHEJ.

    Science.gov (United States)

    Mateos-Gomez, Pedro A; Kent, Tatiana; Deng, Sarah K; McDevitt, Shane; Kashkina, Ekaterina; Hoang, Trung M; Pomerantz, Richard T; Sfeir, Agnel

    2017-12-01

    Mammalian polymerase theta (Polθ) is a multifunctional enzyme that promotes error-prone DNA repair by alternative nonhomologous end joining (alt-NHEJ). Here we present structure-function analyses that reveal that, in addition to the polymerase domain, Polθ-helicase activity plays a central role during double-strand break (DSB) repair. Our results show that the helicase domain promotes chromosomal translocations by alt-NHEJ in mouse embryonic stem cells and also suppresses CRISPR-Cas9- mediated gene targeting by homologous recombination (HR). In vitro assays demonstrate that Polθ-helicase activity facilitates the removal of RPA from resected DSBs to allow their annealing and subsequent joining by alt-NHEJ. Consistent with an antagonistic role for RPA during alt-NHEJ, inhibition of RPA1 enhances end joining and suppresses recombination. Taken together, our results reveal that the balance between HR and alt-NHEJ is controlled by opposing activities of Polθ and RPA, providing further insight into the regulation of repair-pathway choice in mammalian cells.

  2. Werner helicase wings DNA binding

    OpenAIRE

    Hoadley, Kelly A.; Keck, James L.

    2010-01-01

    In this issue of Structure, Kitano et al. describe the structure of the DNA-bound winged-helix domain from the Werner helicase. This structure of a RecQ/DNA complex offers insights into the DNA unwinding mechanisms of RecQ family helicases.

  3. XPD Helicase: Shifting the Inchworm into Reverse

    Science.gov (United States)

    Pugh, Robert A.

    2009-01-01

    Directional translocation by helicases results in duplex separation and displacement of bound proteins which allows for the DNA processing events associated with DNA repair, replication, recombination, and transcription. Unresolved questions regarding DNA helicases include: (1) how is directional translocation determined in SF2 helicases; (2) do…

  4. Mitochondrial helicases and mitochondrial genome maintenance

    DEFF Research Database (Denmark)

    de Souza-Pinto, Nadja C; Aamann, Maria Diget; Kulikowicz, Tomasz

    2010-01-01

    Helicases are essential enzymes that utilize the energy of nucleotide hydrolysis to drive unwinding of nucleic acid duplexes. Helicases play roles in all aspects of DNA metabolism including DNA repair, DNA replication and transcription. The subcellular locations and functions of several helicases...

  5. Helicases as molecular motors: An insight

    Science.gov (United States)

    Tuteja, Narendra; Tuteja, Renu

    2006-12-01

    Helicases are one of the smallest motors of biological system, which harness the chemical free energy of ATP hydrolysis to catalyze the opening of energetically stable duplex nucleic acids and thereby are involved in almost all aspect of nucleic acid metabolism including replication, repair, recombination, transcription, translation, and ribosome biogenesis. Basically, they break the hydrogen bonding between the duplex helix and translocate unidirectionally along the bound strand. Mostly all the helicases contain some conserved signature motifs, which act as an engine to power the unwinding. After the discovery of the first prokaryotic DNA helicase from Escherichia coli bacteria in 1976 and the first eukaryotic one from the lily plant in 1978, many more (>100) have been isolated. All the helicases share some common properties, including nucleic acid binding, NTP hydrolysis and unwinding of the duplex. Many helicases have been crystallized and their structures have revealed an underlying common structural fold for their function. The defects in helicases gene have also been reported to be responsible for variety of human genetic disorders, which can lead to cancer, premature aging or mental retardation. Recently, a new role of a helicase in abiotic stress signaling in plant has been discovered. Overall, helicases act as essential molecular tools for cellular machinery and help in maintaining the integrity of genome. Here an overview of helicases has been covered which includes history, biochemical assay, properties, classification, role in human disease and mechanism of unwinding and translocation.

  6. RNA Helicases at work: binding and rearranging

    Science.gov (United States)

    Jankowsky, Eckhard

    2010-01-01

    RNA helicases are ubiquitous, highly conserved enzymes that participate in nearly all aspects of RNA metabolism. These proteins bind or remodel RNA or RNA–protein complexes in an ATP-dependent fashion. How RNA helicases physically perform their cellular tasks has been a longstanding question, but in recent years, intriguing models have started to link structure, mechanism and biological function for some RNA helicases. This review outlines our current view on major structural and mechanistic themes of RNA helicase function, and on emerging physical models for cellular roles of these enzymes. PMID:20813532

  7. Purification and crystallization of Kokobera virus helicase

    Energy Technology Data Exchange (ETDEWEB)

    De Colibus, Luigi; Speroni, Silvia [Department of Genetics and Microbiology, University of Pavia, Via Ferrata 1, 27100 Pavia (Italy); Coutard, Bruno [Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS et Université Aix-Marseille I et II, ESIL, Campus de Luminy, 13288 Marseille CEDEX 09 (France); Forrester, Naomi L.; Gould, Ernest [Centre for Ecology and Hydrology (formerly Institute of Virology), Mansfield Road, Oxford OX1 3SR (United Kingdom); Canard, Bruno [Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS et Université Aix-Marseille I et II, ESIL, Campus de Luminy, 13288 Marseille CEDEX 09 (France); Mattevi, Andrea, E-mail: mattevi@ipvgen.unipv.it [Department of Genetics and Microbiology, University of Pavia, Via Ferrata 1, 27100 Pavia (Italy)

    2007-03-01

    Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method and exhibit a diffraction limit of 2.3 Å. Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. The flavivirus genus is characterized by a positive-sense single-stranded RNA genome. The unique open reading frame of the viral RNA is transcribed and translated as a single polyprotein which is post-translationally cleaved to yield three structural and seven nonstructural proteins, one of which is the NS3 gene that encodes a C-terminal helicase domain consisting of 431 amino acids. Helicase inhibitors are potential antiviral drugs as the helicase is essential to viral replication. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method. The crystals belong to space group P3{sub 1}21 (or P3{sub 2}21), with unit-cell parameters a = 88.6, c = 138.6 Å, and exhibit a diffraction limit of 2.3 Å.

  8. Purification and crystallization of Kokobera virus helicase

    International Nuclear Information System (INIS)

    De Colibus, Luigi; Speroni, Silvia; Coutard, Bruno; Forrester, Naomi L.; Gould, Ernest; Canard, Bruno; Mattevi, Andrea

    2007-01-01

    Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method and exhibit a diffraction limit of 2.3 Å. Kokobera virus is a mosquito-borne flavivirus belonging, like West Nile virus, to the Japanese encephalitis virus serocomplex. The flavivirus genus is characterized by a positive-sense single-stranded RNA genome. The unique open reading frame of the viral RNA is transcribed and translated as a single polyprotein which is post-translationally cleaved to yield three structural and seven nonstructural proteins, one of which is the NS3 gene that encodes a C-terminal helicase domain consisting of 431 amino acids. Helicase inhibitors are potential antiviral drugs as the helicase is essential to viral replication. Crystals of the Kokobera virus helicase domain were obtained by the hanging-drop vapour-diffusion method. The crystals belong to space group P3 1 21 (or P3 2 21), with unit-cell parameters a = 88.6, c = 138.6 Å, and exhibit a diffraction limit of 2.3 Å

  9. Deep Spiking Networks

    NARCIS (Netherlands)

    O'Connor, P.; Welling, M.

    2016-01-01

    We introduce an algorithm to do backpropagation on a spiking network. Our network is "spiking" in the sense that our neurons accumulate their activation into a potential over time, and only send out a signal (a "spike") when this potential crosses a threshold and the neuron is reset. Neurons only

  10. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  11. The function and architecture of DEAH/RHA helicases

    DEFF Research Database (Denmark)

    He, Yangzi; Andersen, Gregers Rom; Nielsen, Klaus Hvid

    2012-01-01

    Helicases are ubiquitous enzymes that participate in every aspect of nucleic acid metabolism. The DEAH/RHA family of helicases are involved in a variety of cellular processes including transcriptional and translational regulation, pre-mRNA splicing, pre-rRNA processing, mRNA export and decay......, in addition to the innate immune response. Recently, the first crystal structures of a DEAH/RHA helicase unveiled the unique structural features of this helicase family. These structures furthermore illuminate the molecular mechanism of these proteins and provide a framework for analysis of their interaction...

  12. Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair.

    Science.gov (United States)

    Beagan, Kelly; Armstrong, Robin L; Witsell, Alice; Roy, Upasana; Renedo, Nikolai; Baker, Amy E; Schärer, Orlando D; McVey, Mitch

    2017-05-01

    Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase θ (Pol θ), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol θ contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol θ. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol θ can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol θ and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance.

  13. Bypass of a protein barrier by a replicative DNA helicase

    NARCIS (Netherlands)

    Yardimci, Hasan; Wang, Xindan; Loveland, Anna B.; Tappin, Inger; Rudner, David Z.; Hurwitz, Jerard; van Oijen, Antoine M.; Walter, Johannes C.

    2012-01-01

    Replicative DNA helicases generally unwind DNA as a single hexamer that encircles and translocates along one strand of the duplex while excluding the complementary strand (known as steric exclusion). By contrast, large T antigen, the replicative DNA helicase of the simian virus 40 (SV40), is

  14. XPD helicase speeds through a molecular traffic jam.

    Science.gov (United States)

    Finkelstein, Ilya J; Greene, Eric C

    2009-09-11

    Helicases and other DNA translocases must travel along crowded substrates. In this issue, Honda et al. (2009) report that the archaeal XPD helicase can bypass a single-stranded DNA-binding protein without either molecule being ejected from the DNA.

  15. Structural basis of Zika virus helicase in recognizing its substrates

    Directory of Open Access Journals (Sweden)

    Hongliang Tian

    2016-07-01

    Full Text Available Abstract The recent explosive outbreak of Zika virus (ZIKV infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn2+ and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn2+. The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.

  16. Structural basis for the function of DEAH helicases

    DEFF Research Database (Denmark)

    He, Yangzi; Andersen, Gregers Rom; Nielsen, Klaus Hvid

    2010-01-01

    DEAH helicases participate in pre‐messenger RNA splicing and ribosome biogenesis. The structure of yeast Prp43p‐ADP reveals the homology of DEAH helicases to DNA helicases and the presence of an oligonucleotide‐binding motif. A β‐hairpin from the second RecA domain is wedged between two carboxy......‐terminal domains and blocks access to the occluded RNA binding site formed by the RecA domains and a C‐terminal domain. ATP binding and hydrolysis are likely to induce conformational changes in the hairpin that are important for RNA unwinding or ribonucleoprotein remodelling. The structure of Prp43p provides...

  17. A transcription fork model for Pol IV and Pol V-dependent RNA-directed DNA methylation.

    Science.gov (United States)

    Pikaard, C S; Haag, J R; Pontes, O M F; Blevins, T; Cocklin, R

    2012-01-01

    In Arabidopsis thaliana, nuclear multisubunit RNA polymerase IV (Pol IV) and RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) are required for the biogenesis of 24-nucleotide small interfering RNAs (siRNAs) that direct DNA methylation and transcriptional silencing at target loci transcribed by nuclear multisubunit RNA polymerase V (Pol V). Pol IV and RDR2 physically associate and RDR2's polymerase activity in vitro is dependent on Pol IV. RDR2 transcription of nascent Pol IV transcripts might result in discontinuous second strands, analogous to lagging-strand Okazaki fragments generated during DNA replication. In vitro, Pol V is unable to displace nontemplate DNA during transcriptional elongation. This suggests a need for DNA duplex unwinding by helper proteins, perhaps analogous to the helicase-mediated duplex unwinding that occurs at replication forks to enable leading strand synthesis by DNA polymerase ε. A multiprotein complex (DRD1, DMS3, DMS11, RDM1) known to enable Pol V transcription might facilitate duplex unwinding via ATP-dependent DNA translocase, single-stranded DNA binding, and cohesin-like strand capture activities. These considerations are discussed and incorporated into a "transcription fork" model for Pol IV and Pol V-dependent RNA-directed DNA methylation.

  18. The variational spiked oscillator

    International Nuclear Information System (INIS)

    Aguilera-Navarro, V.C.; Ullah, N.

    1992-08-01

    A variational analysis of the spiked harmonic oscillator Hamiltonian -d 2 / d x 2 + x 2 + δ/ x 5/2 , δ > 0, is reported in this work. A trial function satisfying Dirichlet boundary conditions is suggested. The results are excellent for a large range of values of the coupling parameter. (author)

  19. Response Features Determining Spike Times

    Directory of Open Access Journals (Sweden)

    Barry J. Richmond

    1999-01-01

    redundant with that carried by the coarse structure. Thus, the existence of precisely timed spike patterns carrying stimulus-related information does not imply control of spike timing at precise time scales.

  20. Spiking neural network for recognizing spatiotemporal sequences of spikes

    International Nuclear Information System (INIS)

    Jin, Dezhe Z.

    2004-01-01

    Sensory neurons in many brain areas spike with precise timing to stimuli with temporal structures, and encode temporally complex stimuli into spatiotemporal spikes. How the downstream neurons read out such neural code is an important unsolved problem. In this paper, we describe a decoding scheme using a spiking recurrent neural network. The network consists of excitatory neurons that form a synfire chain, and two globally inhibitory interneurons of different types that provide delayed feedforward and fast feedback inhibition, respectively. The network signals recognition of a specific spatiotemporal sequence when the last excitatory neuron down the synfire chain spikes, which happens if and only if that sequence was present in the input spike stream. The recognition scheme is invariant to variations in the intervals between input spikes within some range. The computation of the network can be mapped into that of a finite state machine. Our network provides a simple way to decode spatiotemporal spikes with diverse types of neurons

  1. Protein Displacement by Herpes Helicase-Primase and the Key Role of UL42 during Helicase-Coupled DNA Synthesis by the Herpes Polymerase.

    Science.gov (United States)

    Dickerson, Sarah Michelle; Kuchta, Robert D

    2017-05-30

    The herpes helicase-primase (UL5-UL8-UL52) very inefficiently unwinds double-stranded DNA. To better understand the mechanistic consequences of this inefficiency, we investigated protein displacement activity by UL5-UL8-UL52, as well as the impact of coupling DNA synthesis by the herpes polymerase with helicase activity. While the helicase can displace proteins bound to the lagging strand template, bound proteins significantly impede helicase activity. Remarkably, UL5-UL8-UL52, an extremely inefficient helicase, disrupts the exceptionally tight interaction between streptavidin and biotin on the lagging strand template. It also unwinds DNA containing streptavidin bound to the leading strand template, although it does not displace the streptavidin. These data suggest that the helicase may largely or completely wrap around the lagging strand template, with minimal interactions with the leading strand template. We utilized synthetic DNA minicircles to study helicase activity coupled with the herpes polymerase-processivity factor (UL30-UL42). Coupling greatly enhances unwinding of DNA, although bound proteins still inhibit helicase activity. Surprisingly, while UL30-UL42 and two noncognate polymerases (Klenow Fragment and T4 DNA polymerase) all stimulate unwinding of DNA by the helicase, the isolated UL30 polymerase (i.e., no UL42 processivity factor) binds to the replication fork but in a manner that is incompetent in terms of coupled helicase-polymerase activity.

  2. Use of a restriction enzyme-digested PCR product as substrate for helicase assays.

    Science.gov (United States)

    Shin, Jae-Ho; Reeve, John N; Kelman, Zvi

    2005-01-13

    DNA helicases play essential roles in many cellular processes. The currently available techniques to generate substrates for helicase assays are fairly complicated and need some expertise not available in all laboratories. Here, a PCR-based method to generate a substrate for a helicase assay is described, and its application for several archaeal, bacterial and viral enzymes is demonstrated.

  3. Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication

    Energy Technology Data Exchange (ETDEWEB)

    Hood, Iris V.; Berger, James M.

    2016-05-31

    Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of theStaphylococcus aureusreplicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association.

  4. Staphylococcus aureus helicase but not Escherichia coli helicase stimulates S. aureus primase activity and maintains initiation specificity.

    Science.gov (United States)

    Koepsell, Scott A; Larson, Marilynn A; Griep, Mark A; Hinrichs, Steven H

    2006-07-01

    Bacterial primases are essential for DNA replication due to their role in polymerizing the formation of short RNA primers repeatedly on the lagging-strand template and at least once on the leading-strand template. The ability of recombinant Staphylococcus aureus DnaG primase to utilize different single-stranded DNA templates was tested using oligonucleotides of the sequence 5'-CAGA (CA)5 XYZ (CA)3-3', where XYZ represented the variable trinucleotide. These experiments demonstrated that S. aureus primase synthesized RNA primers predominately on templates containing 5'-d(CTA)-3' or TTA and to a much lesser degree on GTA-containing templates, in contrast to results seen with the Escherichia coli DnaG primase recognition sequence 5'-d(CTG)-3'. Primer synthesis was initiated complementarily to the middle nucleotide of the recognition sequence, while the third nucleotide, an adenosine, was required to support primer synthesis but was not copied into the RNA primer. The replicative helicases from both S. aureus and E. coli were tested for their ability to stimulate either S. aureus or E. coli primase. Results showed that each bacterial helicase could only stimulate the cognate bacterial primase. In addition, S. aureus helicase stimulated the production of full-length primers, whereas E. coli helicase increased the synthesis of only short RNA polymers. These studies identified important differences between E. coli and S. aureus related to DNA replication and suggest that each bacterial primase and helicase may have adapted unique properties optimized for replication.

  5. MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

    Directory of Open Access Journals (Sweden)

    Mitali Das

    2014-01-01

    Full Text Available As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.

  6. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  7. Three-dimensional structure of N-terminal domain of DnaB helicase and helicase-primase interactions in Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Tara Kashav

    2009-10-01

    Full Text Available Replication initiation is a crucial step in genome duplication and homohexameric DnaB helicase plays a central role in the replication initiation process by unwinding the duplex DNA and interacting with several other proteins during the process of replication. N-terminal domain of DnaB is critical for helicase activity and for DnaG primase interactions. We present here the crystal structure of the N-terminal domain (NTD of H. pylori DnaB (HpDnaB helicase at 2.2 A resolution and compare the structural differences among helicases and correlate with the functional differences. The structural details of NTD suggest that the linker region between NTD and C-terminal helicase domain plays a vital role in accurate assembly of NTD dimers. The sequence analysis of the linker regions from several helicases reveals that they should form four helix bundles. We also report the characterization of H. pylori DnaG primase and study the helicase-primase interactions, where HpDnaG primase stimulates DNA unwinding activity of HpDnaB suggesting presence of helicase-primase cohort at the replication fork. The protein-protein interaction study of C-terminal domain of primase and different deletion constructs of helicase suggests that linker is essential for proper conformation of NTD to interact strongly with HpDnaG. The surface charge distribution on the primase binding surface of NTDs of various helicases suggests that DnaB-DnaG interaction and stability of the complex is most probably charge dependent. Structure of the linker and helicase-primase interactions indicate that HpDnaB differs greatly from E.coli DnaB despite both belong to gram negative bacteria.

  8. Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation.

    Science.gov (United States)

    Georgescu, Roxana; Yuan, Zuanning; Bai, Lin; de Luna Almeida Santos, Ruda; Sun, Jingchuan; Zhang, Dan; Yurieva, Olga; Li, Huilin; O'Donnell, Michael E

    2017-01-31

    The eukaryotic CMG (Cdc45, Mcm2-7, GINS) helicase consists of the Mcm2-7 hexameric ring along with five accessory factors. The Mcm2-7 heterohexamer, like other hexameric helicases, is shaped like a ring with two tiers, an N-tier ring composed of the N-terminal domains, and a C-tier of C-terminal domains; the C-tier contains the motor. In principle, either tier could translocate ahead of the other during movement on DNA. We have used cryo-EM single-particle 3D reconstruction to solve the structure of CMG in complex with a DNA fork. The duplex stem penetrates into the central channel of the N-tier and the unwound leading single-strand DNA traverses the channel through the N-tier into the C-tier motor, 5'-3' through CMG. Therefore, the N-tier ring is pushed ahead by the C-tier ring during CMG translocation, opposite the currently accepted polarity. The polarity of the N-tier ahead of the C-tier places the leading Pol ε below CMG and Pol α-primase at the top of CMG at the replication fork. Surprisingly, the new N-tier to C-tier polarity of translocation reveals an unforeseen quality-control mechanism at the origin. Thus, upon assembly of head-to-head CMGs that encircle double-stranded DNA at the origin, the two CMGs must pass one another to leave the origin and both must remodel onto opposite strands of single-stranded DNA to do so. We propose that head-to-head motors may generate energy that underlies initial melting at the origin.

  9. Inhibition of RNA Helicases of ssRNA+ Virus Belonging to Flaviviridae, Coronaviridae and Picornaviridae Families

    Directory of Open Access Journals (Sweden)

    Irene Briguglio

    2011-01-01

    Full Text Available Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families.

  10. A comprehensive web resource on RNA helicases from the baker's yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Linder, P; Gasteiger, E; Bairoch, A

    2000-04-01

    Members of the RNA helicase protein family are defined by several motifs that have been widely conserved during evolution. They are found in all organisms-from bacteria to humans-and many viruses. The minimum number of RNA helicases present within a eukaryotic cell can be predicted from the complete sequence of the Saccharomyces cerevisiae genome. Recent progress in the functional analysis of various family members has confirmed the significance of RNA helicases for most cellular RNA metabolic processes. We have assembled a web resource that focuses on RNA helicases from the budding yeast Saccharomyces cerevisiae. It includes descriptions of RNA helicases and their functions, links to sequence- and yeast-specific databases, an extensive list of references, and links to non-yeast helicase web resources. Copyright 2000 John Wiley & Sons, Ltd.

  11. DNA Structure Specificity Conferred on a Replicative Helicase by Its Loader*

    OpenAIRE

    Gupta, Milind K.; Atkinson, John; McGlynn, Peter

    2009-01-01

    Prokaryotic and eukaryotic replicative helicases can translocate along single-stranded and double-stranded DNA, with the central cavity of these multimeric ring helicases being able to accommodate both forms of DNA. Translocation by such helicases along single-stranded DNA results in the unwinding of forked DNA by steric exclusion and appears critical in unwinding of parental strands at the replication fork, whereas translocation over double-stranded DNA has no well-defined role. We have foun...

  12. Wavelet analysis of epileptic spikes

    CERN Document Server

    Latka, M; Kozik, A; West, B J; Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

    2003-01-01

    Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous, pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

  13. Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins

    Science.gov (United States)

    Samson, Rachel Y.; Abeyrathne, Priyanka D.; Bell, Stephen D.

    2015-01-01

    Summary Cellular DNA replication origins direct the recruitment of replicative helicases via the action of initiator proteins belonging to the AAA+ superfamily of ATPases. Archaea have a simplified subset of the eukaryotic DNA replication machinery proteins and possess initiators that appear ancestral to both eukaryotic Orc1 and Cdc6. We have reconstituted origin-dependent recruitment of the homohexameric archaeal MCM in vitro with purified recombinant proteins. Using this system, we reveal that archaeal Orc1-1 fulfills both Orc1 and Cdc6 functions by binding to a replication origin and directly recruiting MCM helicase. We identify the interaction interface between these proteins and reveal how ATP binding by Orc1-1 modulates recruitment of MCM. Additionally, we provide evidence that an open-ring form of the archaeal MCM homohexamer is loaded at origins. PMID:26725007

  14. RNA helicase domains of viral origin in proteins of insect retrotransposons: possible source for evolutionary advantages

    Directory of Open Access Journals (Sweden)

    Sergey Y. Morozov

    2017-08-01

    Full Text Available Recently, a novel phenomenon of horizontal gene transfer of helicase-encoding sequence from positive-stranded RNA viruses to LINE transposons in insect genomes was described. TRAS family transposons encoding an ORF2 protein, which comprised all typical functional domains and an additional helicase domain, were found to be preserved in many families during the evolution of the order Lepidoptera. In the present paper, in species of orders Hemiptera and Orthoptera, we found helicase domain-encoding sequences integrated into ORF1 of retrotransposons of the Jockey family. RNA helicases encoded by transposons of TRAS and Jockey families represented separate brunches in a phylogenetic tree of helicase domains and thus could be considered as independently originated in the evolution of insect transposons. Transcriptome database analyses revealed that both TRAS and Jockey transposons encoding the helicase domain represented transcribed genome sequences. Moreover, the transposon-encoded helicases were found to contain the full set of conserved motifs essential for their enzymatic activities. Taking into account the previously reported ability of RNA helicase encoded by TRAS ORF2 to suppress post-transcriptional RNA silencing, we propose possible scenarios of evolutionary fixation of actively expressed functional helicases of viral origin in insect retrotransposons as genetic elements advantageous for both transposons and their insect hosts.

  15. The annealing helicase and branch migration activities of Drosophila HARP.

    Directory of Open Access Journals (Sweden)

    George A Kassavetis

    Full Text Available HARP (SMARCAL1, MARCAL1 is an annealing helicase that functions in the repair and restart of damaged DNA replication forks through its DNA branch migration and replication fork regression activities. HARP is conserved among metazoans. HARP from invertebrates differs by the absence of one of the two HARP-specific domain repeats found in vertebrates. The annealing helicase and branch migration activity of invertebrate HARP has not been documented. We found that HARP from Drosophila melanogaster retains the annealing helicase activity of human HARP, the ability to disrupt D-loops and to branch migrate Holliday junctions, but fails to regress model DNA replication fork structures. A comparison of human and Drosophila HARP on additional substrates revealed that both HARPs are competent in branch migrating a bidirectional replication bubble composed of either DNA:DNA or RNA:DNA hybrid. Human, but not Drosophila, HARP is also capable of regressing a replication fork structure containing a highly stable poly rG:dC hybrid. Persistent RNA:DNA hybrids in vivo can lead to replication fork arrest and genome instability. The ability of HARP to strand transfer hybrids may signify a hybrid removal function for this enzyme, in vivo.

  16. Training spiking neural networks to associate spatio-temporal input-output spike patterns

    OpenAIRE

    Mohemmed, A; Schliebs, S; Matsuda, S; Kasabov, N

    2013-01-01

    In a previous work (Mohemmed et al., Method for training a spiking neuron to associate input–output spike trains) [1] we have proposed a supervised learning algorithm based on temporal coding to train a spiking neuron to associate input spatiotemporal spike patterns to desired output spike patterns. The algorithm is based on the conversion of spike trains into analogue signals and the application of the Widrow–Hoff learning rule. In this paper we present a mathematical formulation of the prop...

  17. Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3.

    Science.gov (United States)

    Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu

    2017-11-01

    The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å 2 intramolecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis -cleavage event. Although this conformation is incompatible with protease trans -cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis -cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different

  18. Primuline Derivatives That Mimic RNA to Stimulate Hepatitis C Virus NS3 Helicase-catalyzed ATP Hydrolysis*

    Science.gov (United States)

    Sweeney, Noreena L.; Shadrick, William R.; Mukherjee, Sourav; Li, Kelin; Frankowski, Kevin J.; Schoenen, Frank J.; Frick, David N.

    2013-01-01

    ATP hydrolysis fuels the ability of helicases and related proteins to translocate on nucleic acids and separate base pairs. As a consequence, nucleic acid binding stimulates the rate at which a helicase catalyzes ATP hydrolysis. In this study, we searched a library of small molecule helicase inhibitors for compounds that stimulate ATP hydrolysis catalyzed by the hepatitis C virus (HCV) NS3 helicase, which is an important antiviral drug target. Two compounds were found that stimulate HCV helicase-catalyzed ATP hydrolysis, both of which are amide derivatives synthesized from the main component of the yellow dye primuline. Both compounds possess a terminal pyridine moiety, which was critical for stimulation. Analogs lacking a terminal pyridine inhibited HCV helicase catalyzed ATP hydrolysis. Unlike other HCV helicase inhibitors, the stimulatory compounds differentiate between helicases isolated from various HCV genotypes and related viruses. The compounds only stimulated ATP hydrolysis catalyzed by NS3 purified from HCV genotype 1b. They inhibited helicases from other HCV genotypes (e.g. 1a and 2a) or related flaviviruses (e.g. Dengue virus). The stimulatory compounds interacted with HCV helicase in the absence of ATP with dissociation constants of about 2 μm. Molecular modeling and site-directed mutagenesis studies suggest that the stimulatory compounds bind in the HCV helicase RNA-binding cleft near key residues Arg-393, Glu-493, and Ser-231. PMID:23703611

  19. Molecular Dynamics of the ZIKA Virus NS3 Helicase

    Science.gov (United States)

    Raubenolt, Bryan; Rick, Steven; The Rick Group Team

    The recent outbreaks of the ZIKA virus (ZIKV) and its connection to microcephaly in newborns has raised its awareness as a global threat and many scientific research efforts are currently underway in attempt to create a vaccine. Molecular Dynamics is a powerful method of investigating the physical behavior of protein complexes. ZIKV is comprised of 3 structural and 7 nonstructural proteins. The NS3 helicase protein appears to play a significant role in the replication complex and its inhibition could be a crucial source of antiviral drug design. This research primarily focuses on studying the structural dynamics, over the course of few hundred nanoseconds, of NS3 helicase in the free state, as well as in complex form with human ssRNA, ATP, and an analogue of GTP. RMSD and RMSF plots of each simulation will provide details on the forces involved in the overall stability of the active and inactive states. Furthermore, free energy calculations on a per residue level will reveal the most interactive residues between states and ultimately the primary driving force behind these interactions. Together these analyses will provide highly relevant information on the binding surface chemistry and thus serve as the basis for potential drug design.

  20. Molecular determinants of nucleolar translocation of RNA helicase A

    International Nuclear Information System (INIS)

    Liu Zhe; Kenworthy, Rachael; Green, Christopher; Tang, Hengli

    2007-01-01

    RNA helicase A (RHA) is a member of the DEAH-box family of DNA/RNA helicases involved in multiple cellular processes and the life cycles of many viruses. The subcellular localization of RHA is dynamic despite its steady-state concentration in the nucleoplasm. We have previously shown that it shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus. Here, we investigate the molecular determinants for its translocation within the nucleus and, more specifically, its redistribution from the nucleoplasm to nucleolus or the perinucleolar region. We found that low temperature treatment, transcription inhibition or replication of hepatitis C virus caused the intranuclear redistribution of the protein, suggesting that RHA shuttles between the nucleolus and nucleoplasm and becomes trapped in the nucleolus or the perinucleolar region upon blockade of transport to the nucleoplasm. Both the NTD and ATPase activity were essential for RHA's transport to the nucleolus or perinucleolar region. One of the double-stranded RNA binding domains (dsRBD II) was also required for this nucleolar translocation (NoT) phenotype. RNA interference studies revealed that RHA is essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role

  1. Structural basis for DNA strand separation by a hexameric replicative helicase

    Science.gov (United States)

    Chaban, Yuriy; Stead, Jonathan A.; Ryzhenkova, Ksenia; Whelan, Fiona; Lamber, Ekaterina P.; Antson, Alfred; Sanders, Cyril M.; Orlova, Elena V.

    2015-01-01

    Hexameric helicases are processive DNA unwinding machines but how they engage with a replication fork during unwinding is unknown. Using electron microscopy and single particle analysis we determined structures of the intact hexameric helicase E1 from papillomavirus and two complexes of E1 bound to a DNA replication fork end-labelled with protein tags. By labelling a DNA replication fork with streptavidin (dsDNA end) and Fab (5′ ssDNA) we located the positions of these labels on the helicase surface, showing that at least 10 bp of dsDNA enter the E1 helicase via a side tunnel. In the currently accepted ‘steric exclusion’ model for dsDNA unwinding, the active 3′ ssDNA strand is pulled through a central tunnel of the helicase motor domain as the dsDNA strands are wedged apart outside the protein assembly. Our structural observations together with nuclease footprinting assays indicate otherwise: strand separation is taking place inside E1 in a chamber above the helicase domain and the 5′ passive ssDNA strands exits the assembly through a separate tunnel opposite to the dsDNA entry point. Our data therefore suggest an alternative to the current general model for DNA unwinding by hexameric helicases. PMID:26240379

  2. Two-state model for helicase translocation and unwinding of nucleic acids

    Science.gov (United States)

    Garai, Ashok; Chowdhury, Debashish; Betterton, M. D.

    2008-06-01

    Helicases are molecular motors that unwind double-stranded nucleic acids (dsNA), such as DNA and RNA. Typically a helicase translocates along one of the NA single strands while unwinding and uses adenosine triphosphate (ATP) hydrolysis as an energy source. Here we model a helicase motor that can switch between two states, which could represent two different points in the ATP hydrolysis cycle. Our model is an extension of the earlier Betterton-Jülicher model of helicases to incorporate switching between two states. The main predictions of the model are the speed of unwinding of the dsNA and fluctuations around the average unwinding velocity. Motivated by a recent claim that the NS3 helicase of Hepatitis C virus follows a flashing-ratchet mechanism, we have compared the experimental results for the NS3 helicase with a special limit of our model which corresponds to the flashing-ratchet scenario. Our model accounts for one key feature of the experimental data on NS3 helicase. However, contradictory observations in experiments carried out under different conditions limit the ability to compare the model to experiments.

  3. Neuronal coding and spiking randomness

    Czech Academy of Sciences Publication Activity Database

    Košťál, Lubomír; Lánský, Petr; Rospars, J. P.

    2007-01-01

    Roč. 26, č. 10 (2007), s. 2693-2988 ISSN 0953-816X R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) 1ET400110401; GA AV ČR(CZ) KJB100110701 Grant - others:ECO-NET(FR) 112644PF Institutional research plan: CEZ:AV0Z50110509 Keywords : spike train * variability * neurovědy Subject RIV: FH - Neurology Impact factor: 3.673, year: 2007

  4. Prospective Coding by Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Johanni Brea

    2016-06-01

    Full Text Available Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron's firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ.

  5. iSpike: a spiking neural interface for the iCub robot

    International Nuclear Information System (INIS)

    Gamez, D; Fidjeland, A K; Lazdins, E

    2012-01-01

    This paper presents iSpike: a C++ library that interfaces between spiking neural network simulators and the iCub humanoid robot. It uses a biologically inspired approach to convert the robot’s sensory information into spikes that are passed to the neural network simulator, and it decodes output spikes from the network into motor signals that are sent to control the robot. Applications of iSpike range from embodied models of the brain to the development of intelligent robots using biologically inspired spiking neural networks. iSpike is an open source library that is available for free download under the terms of the GPL. (paper)

  6. Information transmission with spiking Bayesian neurons

    International Nuclear Information System (INIS)

    Lochmann, Timm; Deneve, Sophie

    2008-01-01

    Spike trains of cortical neurons resulting from repeatedpresentations of a stimulus are variable and exhibit Poisson-like statistics. Many models of neural coding therefore assumed that sensory information is contained in instantaneous firing rates, not spike times. Here, we ask how much information about time-varying stimuli can be transmitted by spiking neurons with such input and output variability. In particular, does this variability imply spike generation to be intrinsically stochastic? We consider a model neuron that estimates optimally the current state of a time-varying binary variable (e.g. presence of a stimulus) by integrating incoming spikes. The unit signals its current estimate to other units with spikes whenever the estimate increased by a fixed amount. As shown previously, this computation results in integrate and fire dynamics with Poisson-like output spike trains. This output variability is entirely due to the stochastic input rather than noisy spike generation. As a result such a deterministic neuron can transmit most of the information about the time varying stimulus. This contrasts with a standard model of sensory neurons, the linear-nonlinear Poisson (LNP) model which assumes that most variability in output spike trains is due to stochastic spike generation. Although it yields the same firing statistics, we found that such noisy firing results in the loss of most information. Finally, we use this framework to compare potential effects of top-down attention versus bottom-up saliency on information transfer with spiking neurons

  7. Feature Representations for Neuromorphic Audio Spike Streams.

    Science.gov (United States)

    Anumula, Jithendar; Neil, Daniel; Delbruck, Tobi; Liu, Shih-Chii

    2018-01-01

    Event-driven neuromorphic spiking sensors such as the silicon retina and the silicon cochlea encode the external sensory stimuli as asynchronous streams of spikes across different channels or pixels. Combining state-of-art deep neural networks with the asynchronous outputs of these sensors has produced encouraging results on some datasets but remains challenging. While the lack of effective spiking networks to process the spike streams is one reason, the other reason is that the pre-processing methods required to convert the spike streams to frame-based features needed for the deep networks still require further investigation. This work investigates the effectiveness of synchronous and asynchronous frame-based features generated using spike count and constant event binning in combination with the use of a recurrent neural network for solving a classification task using N-TIDIGITS18 dataset. This spike-based dataset consists of recordings from the Dynamic Audio Sensor, a spiking silicon cochlea sensor, in response to the TIDIGITS audio dataset. We also propose a new pre-processing method which applies an exponential kernel on the output cochlea spikes so that the interspike timing information is better preserved. The results from the N-TIDIGITS18 dataset show that the exponential features perform better than the spike count features, with over 91% accuracy on the digit classification task. This accuracy corresponds to an improvement of at least 2.5% over the use of spike count features, establishing a new state of the art for this dataset.

  8. A mechanical mechanism for translocation of ring-shaped helicases on DNA and its demonstration in a macroscopic simulation system

    Science.gov (United States)

    Chou, Y. C.

    2018-04-01

    The asymmetry in the two-layered ring structure of helicases and the random thermal fluctuations of the helicase and DNA molecules are considered as the bases for the generation of the force required for translocation of the ring-shaped helicase on DNA. The helicase comprises a channel at its center with two unequal ends, through which strands of DNA can pass. The random collisions between the portion of the DNA strand in the central channel and the wall of the channel generate an impulsive force toward the small end. This impulsive force is the starting point for the helicase to translocate along the DNA with the small end in front. Such a physical mechanism may serve as a complementary for the chemomechanical mechanism of the translocation of helicase on DNA. When the helicase arrives at the junction of ssDNA and dsDNA (a fork), the collision between the helicase and the closest base pair may produce a sufficient impulsive force to break the weak hydrogen bond of the base pair. Thus, the helicase may advance and repeat the process of unwinding the dsDNA strand. This mechanism was tested in a macroscopic simulation system where the helicase was simulated using a truncated-cone structure and DNA was simulated with bead chains. Many features of translocation and unwinding such as translocation on ssDNA and dsDNA, unwinding of dsDNA, rewinding, strand switching, and Holliday junction resolution were reproduced.

  9. A role for the fission yeast Rqh1 helicase in chromosome segregation

    DEFF Research Database (Denmark)

    Win, Thein Z; Mankouri, Hocine W; Hickson, Ian D

    2005-01-01

    Schizosaccharomyces pombe Rqh1 protein is a member of the RecQ DNA helicase family. Members of this protein family are mutated in several human genome instability syndromes, including Bloom, Werner and Rothmund-Thomson syndromes. RecQ helicases participate in recombination repair of stalled......DNA repeat by deletion of reb1+ partially suppresses rqh1delta phenotypes. These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication. The chromosome segregation defects seen...... in the absence of functional RecQ helicases may contribute to the pathogenesis of human RecQ helicase disorders....

  10. Crystal structures of the methyltransferase and helicase from the ZIKA 1947 MR766 Uganda strain

    Energy Technology Data Exchange (ETDEWEB)

    Bukrejewska, Malgorzata; Derewenda, Urszula; Radwanska, Malwina; Engel, Daniel A.; Derewenda, Zygmunt S.

    2017-08-15

    Two nonstructural proteins encoded byZika virusstrain MR766 RNA, a methyltransferase and a helicase, were crystallized and their structures were solved and refined at 2.10 and 2.01 Å resolution, respectively. The NS5 methyltransferase contains a boundS-adenosyl-L-methionine (SAM) co-substrate. The NS3 helicase is in the apo form. Comparison with published crystal structures of the helicase in the apo, nucleotide-bound and single-stranded RNA (ssRNA)-bound states suggests that binding of ssRNA to the helicase may occur through conformational selection rather than induced fit.

  11. High-throughput screening assay of hepatitis C virus helicase inhibitors using fluorescence-quenching phenomenon

    International Nuclear Information System (INIS)

    Tani, Hidenori; Akimitsu, Nobuyoshi; Fujita, Osamu; Matsuda, Yasuyoshi; Miyata, Ryo; Tsuneda, Satoshi; Igarashi, Masayuki; Sekiguchi, Yuji; Noda, Naohiro

    2009-01-01

    We have developed a novel high-throughput screening assay of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase inhibitors using the fluorescence-quenching phenomenon via photoinduced electron transfer between fluorescent dyes and guanine bases. We prepared double-stranded DNA (dsDNA) with a 5'-fluorescent-dye (BODIPY FL)-labeled strand hybridized with a complementary strand, the 3'-end of which has guanine bases. When dsDNA is unwound by helicase, the dye emits fluorescence owing to its release from the guanine bases. Our results demonstrate that this assay is suitable for quantitative assay of HCV NS3 helicase activity and useful for high-throughput screening for inhibitors. Furthermore, we applied this assay to the screening for NS3 helicase inhibitors from cell extracts of microorganisms, and found several cell extracts containing potential inhibitors.

  12. Oxygen isotopic exchange probes of ATP hydrolysis by RNA helicases.

    Science.gov (United States)

    Hackney, David D

    2012-01-01

    It is often possible to obtain a detailed understanding of the forward steps in ATP hydrolysis because they are thermodynamically favored and usually occur rapidly. However, it is difficult to obtain the reverse rates for ATP resynthesis because they are thermodynamically disfavored and little of their product, ATP, accumulates. Isotopic exchange reactions provide access to these reverse reactions because isotopic changes accumulate over time due to multiple reversals of hydrolysis, even in the absence of net resynthesis of significant amounts of ATP. Knowledge of both the forward and reverse rates allows calculation of the free energy changes at each step and how it changes when coupled to an energy-requiring conformational step such as unwinding of an RNA helix. This chapter describes the principal types of oxygen isotopic exchange reactions that are applicable to ATPases, in general, and helicases, in particular, their application and their interpretation. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

    DEFF Research Database (Denmark)

    Huys, Raoul; Jirsa, Viktor K; Darokhan, Ziauddin

    2016-01-01

    by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point...

  14. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Tainer, John; Fan, Li; Fuss, Jill O.; Cheng, Quen J.; Arvai, Andrew S.; Hammel, Michal; Roberts, Victoria A.; Cooper, Priscilla K.; Tainer, John A.

    2008-06-02

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  15. Regulation of DEAH/RHA helicases by G-patch proteins.

    Science.gov (United States)

    Robert-Paganin, Julien; Réty, Stéphane; Leulliot, Nicolas

    2015-01-01

    RNA helicases from the DEAH/RHA family are present in all the processes of RNA metabolism. The function of two helicases from this family, Prp2 and Prp43, is regulated by protein partners containing a G-patch domain. The G-patch is a glycine-rich domain discovered by sequence alignment, involved in protein-protein and protein-nucleic acid interaction. Although it has been shown to stimulate the helicase's enzymatic activities, the precise role of the G-patch domain remains unclear. The role of G-patch proteins in the regulation of Prp43 activity has been studied in the two biological processes in which it is involved: splicing and ribosome biogenesis. Depending on the pathway, the activity of Prp43 is modulated by different G-patch proteins. A particular feature of the structure of DEAH/RHA helicases revealed by the Prp43 structure is the OB-fold domain in C-terminal part. The OB-fold has been shown to be a platform responsible for the interaction with G-patch proteins and RNA. Though there is still no structural data on the G-patch domain, in the current model, the interaction between the helicase, the G-patch protein, and RNA leads to a cooperative binding of RNA and conformational changes of the helicase.

  16. Translesion DNA polymerases Pol ζ, Pol η, Pol ι, Pol κ and Rev1 are ...

    Indian Academy of Sciences (India)

    MADU

    Kozmin S G, Pavlov Y I, Kunkel T A and Sage E 2003 Roles of Saccharomyces cerevisiae DNA polymerases Pol η and. Pol ζ in response to simulated sunlight; Nucleic Acids Res. 31. 4541–4552. Lawrence C W 2002 Cellular roles of DNA polymerase ζ and Rev. 1 protein; DNA Repair 1 425–435. Lemontt J F 1971 Mutants ...

  17. The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

    Science.gov (United States)

    Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

    2017-01-01

    Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition

  18. Robust spike-train learning in spike-event based weight update.

    Science.gov (United States)

    Shrestha, Sumit Bam; Song, Qing

    2017-12-01

    Supervised learning algorithms in a spiking neural network either learn a spike-train pattern for a single neuron receiving input spike-train from multiple input synapses or learn to output the first spike time in a feedforward network setting. In this paper, we build upon spike-event based weight update strategy to learn continuous spike-train in a spiking neural network with a hidden layer using a dead zone on-off based adaptive learning rate rule which ensures convergence of the learning process in the sense of weight convergence and robustness of the learning process to external disturbances. Based on different benchmark problems, we compare this new method with other relevant spike-train learning algorithms. The results show that the speed of learning is much improved and the rate of successful learning is also greatly improved. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Spiking Neuron Network Helmholtz Machine

    Directory of Open Access Journals (Sweden)

    Pavel eSountsov

    2015-04-01

    Full Text Available An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule.

  20. The Second Spiking Threshold: Dynamics of Laminar Network Spiking in the Visual Cortex

    DEFF Research Database (Denmark)

    Forsberg, Lars E.; Bonde, Lars H.; Harvey, Michael A.

    2016-01-01

    visually evoked spiking driven by sharp transients. Here we examine whether this second threshold exists outside the granular layer and examine details of transitions between spiking states in ferrets exposed to moving objects. We found the second threshold, separating spiking states evoked by stationary...

  1. Linking investment spikes and productivity growth

    NARCIS (Netherlands)

    Geylani, P.C.; Stefanou, S.E.

    2013-01-01

    We investigate the relationship between productivity growth and investment spikes using Census Bureau’s plant-level dataset for the U.S. food manufacturing industry. There are differences in productivity growth and investment spike patterns across different sub-industries and food manufacturing

  2. Stochastic Variational Learning in Recurrent Spiking Networks

    Directory of Open Access Journals (Sweden)

    Danilo eJimenez Rezende

    2014-04-01

    Full Text Available The ability to learn and perform statistical inference with biologically plausible recurrent network of spiking neurons is an important step towards understanding perception and reasoning. Here we derive and investigate a new learning rule for recurrent spiking networks with hidden neurons, combining principles from variational learning and reinforcement learning. Our network defines a generative model over spike train histories and the derived learning rule has the form of a local Spike Timing Dependent Plasticity rule modulated by global factors (neuromodulators conveying information about ``novelty on a statistically rigorous ground.Simulations show that our model is able to learn bothstationary and non-stationary patterns of spike trains.We also propose one experiment that could potentially be performed with animals in order to test the dynamics of the predicted novelty signal.

  3. DbpA is a region-specific RNA helicase.

    Science.gov (United States)

    Moore, Anthony F T; Gentry, Riley C; Koculi, Eda

    2017-03-01

    DbpA is a DEAD-box RNA helicase implicated in RNA structural rearrangements in the peptidyl transferase center. DbpA contains an RNA binding domain, responsible for tight binding of DbpA to hairpin 92 of 23S ribosomal RNA, and a RecA-like catalytic core responsible for double-helix unwinding. It is not known if DbpA unwinds only the RNA helices that are part of a specific RNA structure, or if DbpA unwinds any RNA helices within the catalytic core's grasp. In other words, it is not known if DbpA is a site-specific enzyme or region-specific enzyme. In this study, we used protein and RNA engineering to investigate if DbpA is a region-specific or a site-specific enzyme. Our data suggest that DbpA is a region-specific enzyme. This conclusion has an important implication for the physiological role of DbpA. It suggests that during ribosome assembly, DbpA could bind with its C-terminal RNA binding domain to hairpin 92, while its catalytic core may unwind any double-helices in its vicinity. The only requirement for a double-helix to serve as a DbpA substrate is for the double-helix to be positioned within the catalytic core's grasp. © 2016 Wiley Periodicals, Inc.

  4. Characterization of the Neisseria meningitidis Helicase RecG.

    Directory of Open Access Journals (Sweden)

    Getachew Tesfaye Beyene

    Full Text Available Neisseria meningitidis (Nm is a Gram-negative oral commensal that opportunistically can cause septicaemia and/or meningitis. Here, we overexpressed, purified and characterized the Nm DNA repair/recombination helicase RecG (RecGNm and examined its role during genotoxic stress. RecGNm possessed ATP-dependent DNA binding and unwinding activities in vitro on a variety of DNA model substrates including a Holliday junction (HJ. Database searching of the Nm genomes identified 49 single nucleotide polymorphisms (SNPs in the recGNm including 37 non-synonymous SNPs (nsSNPs, and 7 of the nsSNPs were located in the codons for conserved active site residues of RecGNm. A transient reduction in transformation of DNA was observed in the Nm ΔrecG strain as compared to the wildtype. The gene encoding recGNm also contained an unusually high number of the DNA uptake sequence (DUS that facilitate transformation in neisserial species. The differentially abundant protein profiles of the Nm wildtype and ΔrecG strains suggest that expression of RecGNm might be linked to expression of other proteins involved in DNA repair, recombination and replication, pilus biogenesis, glycan biosynthesis and ribosomal activity. This might explain the growth defect that was observed in the Nm ΔrecG null mutant.

  5. The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

    Directory of Open Access Journals (Sweden)

    Noonan James P

    2001-07-01

    Full Text Available Abstract Background Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10 or PML (promyelocytic leukemia nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. Results This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies.

  6. Serial Spike Time Correlations Affect Probability Distribution of Joint Spike Events.

    Science.gov (United States)

    Shahi, Mina; van Vreeswijk, Carl; Pipa, Gordon

    2016-01-01

    Detecting the existence of temporally coordinated spiking activity, and its role in information processing in the cortex, has remained a major challenge for neuroscience research. Different methods and approaches have been suggested to test whether the observed synchronized events are significantly different from those expected by chance. To analyze the simultaneous spike trains for precise spike correlation, these methods typically model the spike trains as a Poisson process implying that the generation of each spike is independent of all the other spikes. However, studies have shown that neural spike trains exhibit dependence among spike sequences, such as the absolute and relative refractory periods which govern the spike probability of the oncoming action potential based on the time of the last spike, or the bursting behavior, which is characterized by short epochs of rapid action potentials, followed by longer episodes of silence. Here we investigate non-renewal processes with the inter-spike interval distribution model that incorporates spike-history dependence of individual neurons. For that, we use the Monte Carlo method to estimate the full shape of the coincidence count distribution and to generate false positives for coincidence detection. The results show that compared to the distributions based on homogeneous Poisson processes, and also non-Poisson processes, the width of the distribution of joint spike events changes. Non-renewal processes can lead to both heavy tailed or narrow coincidence distribution. We conclude that small differences in the exact autostructure of the point process can cause large differences in the width of a coincidence distribution. Therefore, manipulations of the autostructure for the estimation of significance of joint spike events seem to be inadequate.

  7. Structure of a helicase–helicase loader complex reveals insights into the mechanism of bacterial primosome assembly

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bin; Eliason, William K.; Steitz, Thomas A.

    2013-09-19

    During the assembly of the bacterial loader-dependent primosome, helicase loader proteins bind to the hexameric helicase ring, deliver it onto the oriC DNA and then dissociate from the complex. Here, to provide a better understanding of this key process, we report the crystal structure of the ~570-kDa prepriming complex between the Bacillus subtilis loader protein and the Bacillus stearothermophilus helicase, as well as the helicase-binding domain of primase with a molar ratio of 6:6:3 at 7.5 Å resolution. The overall architecture of the complex exhibits a three-layered ring conformation. Moreover, the structure combined with the proposed model suggests that the shift from the ‘open-ring’ to the ‘open-spiral’ and then the ‘closed-spiral’ state of the helicase ring due to the binding of single-stranded DNA may be the cause of the loader release.

  8. Memristors Empower Spiking Neurons With Stochasticity

    KAUST Repository

    Al-Shedivat, Maruan

    2015-06-01

    Recent theoretical studies have shown that probabilistic spiking can be interpreted as learning and inference in cortical microcircuits. This interpretation creates new opportunities for building neuromorphic systems driven by probabilistic learning algorithms. However, such systems must have two crucial features: 1) the neurons should follow a specific behavioral model, and 2) stochastic spiking should be implemented efficiently for it to be scalable. This paper proposes a memristor-based stochastically spiking neuron that fulfills these requirements. First, the analytical model of the memristor is enhanced so it can capture the behavioral stochasticity consistent with experimentally observed phenomena. The switching behavior of the memristor model is demonstrated to be akin to the firing of the stochastic spike response neuron model, the primary building block for probabilistic algorithms in spiking neural networks. Furthermore, the paper proposes a neural soma circuit that utilizes the intrinsic nondeterminism of memristive switching for efficient spike generation. The simulations and analysis of the behavior of a single stochastic neuron and a winner-take-all network built of such neurons and trained on handwritten digits confirm that the circuit can be used for building probabilistic sampling and pattern adaptation machinery in spiking networks. The findings constitute an important step towards scalable and efficient probabilistic neuromorphic platforms. © 2011 IEEE.

  9. Factors correlated with volleyball spike velocity.

    Science.gov (United States)

    Forthomme, Bénédicte; Croisier, Jean-Louis; Ciccarone, Guido; Crielaard, Jean-Michel; Cloes, Marc

    2005-10-01

    Spike effectiveness represents a determining element in volleyball. To compete at a high level, the player must, in particular, produce a spike characterized by a high ball velocity. Some muscular and physical features could influence ball velocity during the volleyball spike. Descriptive laboratory study. A total of 19 male volleyball players from the 2 highest Belgian national divisions underwent an isokinetic assessment of the dominant shoulder and elbow. Ball velocity performance (radar gun) during a spike test, morphological feature, and jump capacity (ergo jump) of the player were measured. We tested the relationship between the isokinetic parameters or physical features and field performances represented by spike velocity. We also compared first-division and second-division player data. Spike velocity correlated significantly with strength performance of the dominant shoulder (internal rotators) and of the dominant elbow (flexors and extensors) in the concentric mode. Negative correlations were established with the concentric external rotator on internal rotator ratio at 400 deg/s and with the mixed ratio (external rotator at 60 deg/s in the eccentric mode on internal rotator at 240 deg/s in the concentric mode). Positive correlations appeared with both the volleyball players' jump capacity and body mass index. First-division players differed from second-division players by higher ball velocity and increased jump capacity. Some specific strength and physical characteristics correlated significantly with spike performance in high-level volleyball practice. Our results could provide useful information for training management and propose some reflections on injury prevention.

  10. Structure, function and evolution of the animal mitochondrial replicative DNA helicase.

    Science.gov (United States)

    Kaguni, Laurie S; Oliveira, Marcos T

    2016-01-01

    The mitochondrial replicative DNA helicase is essential for animal mitochondrial DNA (mtDNA) maintenance. Deleterious mutations in the gene that encodes it cause mitochondrial dysfunction manifested in developmental delays, defects and arrest, limited life span, and a number of human pathogenic phenotypes that are recapitulated in animals across taxa. In fact, the replicative mtDNA helicase was discovered with the identification of human disease mutations in its nuclear gene, and based upon its deduced amino acid sequence homology with bacteriophage T7 gene 4 protein (T7 gp4), a bi-functional primase-helicase. Since that time, numerous investigations of its structure, mechanism, and physiological relevance have been reported, and human disease alleles have been modeled in the human, mouse, and Drosophila systems. Here, we review this literature and draw evolutionary comparisons that serve to shed light on its divergent features.

  11. DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain.

    Science.gov (United States)

    Northall, Sarah J; Buckley, Ryan; Jones, Nathan; Penedo, J Carlos; Soultanas, Panos; Bolt, Edward L

    2017-09-01

    Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities. When isolated from the rest of Hel308, the WHD protein alone bound to duplex DNA but not ssDNA, and DNA binding by WHD protein was abolished by the same mutations as were analyzed in full-length Hel308. Isolated WHD from a human Hel308 homologue (HelQ) also bound to duplex DNA. By disrupting the interface between the Hel308 WHD and a RecA-like domain, a topology typical of Ski2 helicases, we show that this is crucial for ATPase and helicase activities. The data suggest a model in which the WHD promotes activity of Hel308 directly, through binding to duplex DNA that is distinct from ssDNA binding by core helicase, and indirectly through interaction with the RecA-like domain. We propose how the WHD may contribute to ssDNA translocation, resulting in DNA helicase activity or in removal of other DNA bound proteins by "reeling" ssDNA. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Stress-induced Oryza sativa BAT1 dual helicase exhibits unique bipolar translocation.

    Science.gov (United States)

    Tuteja, Narendra; Tarique, Mohammed; Trivedi, Dipesh Kumar; Sahoo, Ranjan Kumar; Tuteja, Renu

    2015-11-01

    HLA-B associated transcript 1 (BAT1) protein, also named as spliceosome RNA helicase UAP56, is a member of the DExD/H-box family of helicases. However, regulation under stress, biochemical properties, and functions of plant homologue of BAT1 are poorly understood. Here, we report the purification and detailed biochemical characterization of the Oryza sativa homologue of BAT1 (OsBAT1/UAP56) protein (52 kDa) and regulation of its transcript under abiotic stress. OsBAT1 transcript levels are enhanced in rice seedlings in response to abiotic stress including salt stress and abscisic acid. Purified OsBAT1 protein exhibits the DNA- and RNA-dependent ATPase, RNA helicase, and DNA- and RNA-binding activities. Interestingly OsBAT1 also exhibits unique DNA helicase activity, which has not been reported so far in any BAT1 homologue. Moreover, OsBAT1 translocates in both the 3' to 5' and 5' to 3' directions, which is also a unique property. The K m value for OsBAT1 DNA helicase is 0.9753 nM and for RNA helicase is 1.7536 nM, respectively. This study demonstrates several unique characteristics of OsBAT1 especially its ability to unwind both DNA and RNA duplexes; bipolar translocation and its transcript upregulation under abiotic stresses indicate that it is a multifunctional protein. Overall, this study represents significant contribution in advancing our knowledge regarding functions of OsBAT1 in RNA and DNA metabolism and its putative role in abiotic stress signaling in plants.

  13. Spike Bursts from an Excitable Optical System

    Science.gov (United States)

    Rios Leite, Jose R.; Rosero, Edison J.; Barbosa, Wendson A. S.; Tredicce, Jorge R.

    Diode Lasers with double optical feedback are shown to present power drop spikes with statistical distribution controllable by the ratio of the two feedback times. The average time between spikes and the variance within long time series are studied. The system is shown to be excitable and present bursting of spikes created with specific feedback time ratios and strength. A rate equation model, extending the Lang-Kobayashi single feedback for semiconductor lasers proves to match the experimental observations. Potential applications to construct network to mimic neural systems having controlled bursting properties in each unit will be discussed. Brazilian Agency CNPQ.

  14. Dissection of the functional domains of an archaeal holliday junction helicase

    DEFF Research Database (Denmark)

    Hong, Ye; Chu, Mingzhu; Li, Yansheng

    2012-01-01

    the hyperthermophilic archaeon Sulfolobus tokodaii (StoHjm) and its truncated derivatives, and characterization of the StoHjm proteins revealed that the N-terminal module (residues 1-431) alone was capable of ATP hydrolysis and DNA binding, while the C-terminal one (residues 415-704) was responsible for regulating...... the helicase activity. The region involved in StoHjm-StoHjc (Hjc from S. tokodaii) interaction was identified as part of domain II, domain III (Winged Helix motif), and domain IV (residues 366-645) for StoHjm. We present evidence supporting that StoHjc regulates the helicase activity of StoHjm by inducing...

  15. Cooperation of DNA-PKcs and WRN helicase in the maintenance of telomeric D-loops

    DEFF Research Database (Denmark)

    Kusumoto-Matsuo, Rika; Opresko, Patricia L; Ramsden, Dale

    2010-01-01

    Werner syndrome is an inherited human progeriod syndrome caused by mutations in the gene encoding the Werner Syndrome protein, WRN. It has both 3'-5' DNA helicase and exonuclease activities, and is suggested to have roles in many aspects of DNA metabolism, including DNA repair and telomere...... D-loop model substrate. In addition, the length of telomeric G-tails decreases in DNA-PKcs knockdown cells, and this phenotype is reversed by overexpression of WRN helicase. These results suggest that WRN and DNA-PKcs may cooperatively prevent G-tail shortening in vivo....

  16. Inferring oscillatory modulation in neural spike trains.

    Science.gov (United States)

    Arai, Kensuke; Kass, Robert E

    2017-10-01

    Oscillations are observed at various frequency bands in continuous-valued neural recordings like the electroencephalogram (EEG) and local field potential (LFP) in bulk brain matter, and analysis of spike-field coherence reveals that spiking of single neurons often occurs at certain phases of the global oscillation. Oscillatory modulation has been examined in relation to continuous-valued oscillatory signals, and independently from the spike train alone, but behavior or stimulus triggered firing-rate modulation, spiking sparseness, presence of slow modulation not locked to stimuli and irregular oscillations with large variability in oscillatory periods, present challenges to searching for temporal structures present in the spike train. In order to study oscillatory modulation in real data collected under a variety of experimental conditions, we describe a flexible point-process framework we call the Latent Oscillatory Spike Train (LOST) model to decompose the instantaneous firing rate in biologically and behaviorally relevant factors: spiking refractoriness, event-locked firing rate non-stationarity, and trial-to-trial variability accounted for by baseline offset and a stochastic oscillatory modulation. We also extend the LOST model to accommodate changes in the modulatory structure over the duration of the experiment, and thereby discover trial-to-trial variability in the spike-field coherence of a rat primary motor cortical neuron to the LFP theta rhythm. Because LOST incorporates a latent stochastic auto-regressive term, LOST is able to detect oscillations when the firing rate is low, the modulation is weak, and when the modulating oscillation has a broad spectral peak.

  17. Training Deep Spiking Neural Networks Using Backpropagation.

    Science.gov (United States)

    Lee, Jun Haeng; Delbruck, Tobi; Pfeiffer, Michael

    2016-01-01

    Deep spiking neural networks (SNNs) hold the potential for improving the latency and energy efficiency of deep neural networks through data-driven event-based computation. However, training such networks is difficult due to the non-differentiable nature of spike events. In this paper, we introduce a novel technique, which treats the membrane potentials of spiking neurons as differentiable signals, where discontinuities at spike times are considered as noise. This enables an error backpropagation mechanism for deep SNNs that follows the same principles as in conventional deep networks, but works directly on spike signals and membrane potentials. Compared with previous methods relying on indirect training and conversion, our technique has the potential to capture the statistics of spikes more precisely. We evaluate the proposed framework on artificially generated events from the original MNIST handwritten digit benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic vision sensor, in which the proposed method reduces the error rate by a factor of more than three compared to the best previous SNN, and also achieves a higher accuracy than a conventional convolutional neural network (CNN) trained and tested on the same data. We demonstrate in the context of the MNIST task that thanks to their event-driven operation, deep SNNs (both fully connected and convolutional) trained with our method achieve accuracy equivalent with conventional neural networks. In the N-MNIST example, equivalent accuracy is achieved with about five times fewer computational operations.

  18. Towards statistical summaries of spike train data.

    Science.gov (United States)

    Wu, Wei; Srivastava, Anuj

    2011-01-30

    Statistical inference has an important role in analysis of neural spike trains. While current approaches are mostly model-based, and designed for capturing the temporal evolution of the underlying stochastic processes, we focus on a data-driven approach where statistics are defined and computed in function spaces where individual spike trains are viewed as points. The first contribution of this paper is to endow spike train space with a parameterized family of metrics that takes into account different time warpings and generalizes several currently used metrics. These metrics are essentially penalized L(p) norms, involving appropriate functions of spike trains, with penalties associated with time-warpings. The second contribution of this paper is to derive a notion of a mean spike train in the case when p=2. We present an efficient recursive algorithm, termed Matching-Minimization algorithm, to compute the sample mean of a set of spike trains. The proposed metrics as well as the mean computations are demonstrated using an experimental recording from the motor cortex. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Macroscopic Description for Networks of Spiking Neurons

    Science.gov (United States)

    Montbrió, Ernest; Pazó, Diego; Roxin, Alex

    2015-04-01

    A major goal of neuroscience, statistical physics, and nonlinear dynamics is to understand how brain function arises from the collective dynamics of networks of spiking neurons. This challenge has been chiefly addressed through large-scale numerical simulations. Alternatively, researchers have formulated mean-field theories to gain insight into macroscopic states of large neuronal networks in terms of the collective firing activity of the neurons, or the firing rate. However, these theories have not succeeded in establishing an exact correspondence between the firing rate of the network and the underlying microscopic state of the spiking neurons. This has largely constrained the range of applicability of such macroscopic descriptions, particularly when trying to describe neuronal synchronization. Here, we provide the derivation of a set of exact macroscopic equations for a network of spiking neurons. Our results reveal that the spike generation mechanism of individual neurons introduces an effective coupling between two biophysically relevant macroscopic quantities, the firing rate and the mean membrane potential, which together govern the evolution of the neuronal network. The resulting equations exactly describe all possible macroscopic dynamical states of the network, including states of synchronous spiking activity. Finally, we show that the firing-rate description is related, via a conformal map, to a low-dimensional description in terms of the Kuramoto order parameter, called Ott-Antonsen theory. We anticipate that our results will be an important tool in investigating how large networks of spiking neurons self-organize in time to process and encode information in the brain.

  20. Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2-7 helicases.

    Science.gov (United States)

    Takara, Thomas J; Bell, Stephen P

    2011-11-01

    Eukaryotic origins of replication are selected by loading a head-to-head double hexamer of the Mcm2-7 replicative helicase around origin DNA. Cdt1 plays an essential but transient role during this event; however, its mechanism of action is unknown. Through analysis of Cdt1 mutations, we demonstrate that Cdt1 performs multiple functions during helicase loading. The C-terminus of Cdt1 binds Mcm2-7, and this interaction is required for efficient origin recruitment of both proteins. We show that origin recognition complex (ORC) and Cdc6 recruit multiple Cdt1 molecules to the origin during helicase loading, and disruption of this multi-Cdt1 intermediate prevents helicase loading. Although dispensable for loading Mcm2-7 double hexamers that are topologically linked to DNA, the essential N-terminal domain of Cdt1 is required to load Mcm2-7 complexes that are competent for association with the Cdc45 and GINS helicase-activating proteins and replication initiation. Our data support a model in which origin-bound ORC and Cdc6 recruit two Cdt1 molecules to initiate double-hexamer formation prior to helicase loading and demonstrate that Cdt1 influences the replication competence of loaded Mcm2-7 helicases.

  1. Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2–7 helicases

    Science.gov (United States)

    Takara, Thomas J; Bell, Stephen P

    2011-01-01

    Eukaryotic origins of replication are selected by loading a head-to-head double hexamer of the Mcm2–7 replicative helicase around origin DNA. Cdt1 plays an essential but transient role during this event; however, its mechanism of action is unknown. Through analysis of Cdt1 mutations, we demonstrate that Cdt1 performs multiple functions during helicase loading. The C-terminus of Cdt1 binds Mcm2–7, and this interaction is required for efficient origin recruitment of both proteins. We show that origin recognition complex (ORC) and Cdc6 recruit multiple Cdt1 molecules to the origin during helicase loading, and disruption of this multi-Cdt1 intermediate prevents helicase loading. Although dispensable for loading Mcm2–7 double hexamers that are topologically linked to DNA, the essential N-terminal domain of Cdt1 is required to load Mcm2–7 complexes that are competent for association with the Cdc45 and GINS helicase-activating proteins and replication initiation. Our data support a model in which origin-bound ORC and Cdc6 recruit two Cdt1 molecules to initiate double-hexamer formation prior to helicase loading and demonstrate that Cdt1 influences the replication competence of loaded Mcm2–7 helicases. PMID:22045335

  2. Helicase and polymerase move together close to the fork junction and copy DNA in one-nucleotide steps

    Science.gov (United States)

    Pandey, Manjula; Patel, Smita S.

    2014-01-01

    SUMMARY By simultaneously measuring DNA synthesis and dNTP hydrolysis, we show that T7 DNA polymerase and T7 gp4 helicase move in sync during leading strand synthesis taking one-nucleotide steps and hydrolyzing one dNTP per base-pair unwound-copied. The cooperative catalysis enables the helicase and polymerase to move at a uniformly fast rate without GC-dependency or idling with futile NTP hydrolysis. We show that the helicase and polymerase are located close to the replication fork junction. This architecture enables the polymerase to use its strand-displacement synthesis to increase the unwinding rate while the helicase aids this process by translocating along single-stranded DNA and trapping the unwound bases. Thus, in contrast to the helicase-only unwinding model, our results suggest a new model where the helicase and polymerase are moving in one-nucleotide steps and DNA synthesis drives fork unwinding and a role of the helicase is to trap the unwound bases and prevent DNA reannealing. PMID:24630996

  3. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation

    Science.gov (United States)

    Marintchev, Assen; Edmonds, Katherine A.; Marintcheva, Boriana; Hendrickson, Elthea; Oberer, Monika; Suzuki, Chikako; Herdy, Barbara; Sonenberg, Nahum; Wagner, Gerhard

    2009-01-01

    Summary The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. Remarkably, some of the interactions are continuously rearranged during the ATP binding/hydrolysis cycle of the helicase. We show that the accessory proteins modulate the affinity of eIF4A for ATP by interacting simultaneously with both helicase domains and promoting either the closed, ATP-bound conformation or the open, nucleotide-free conformation. The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning. PMID:19203580

  4. RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

    Science.gov (United States)

    Seo, Mihwa; Seo, Keunhee; Hwang, Wooseon; Koo, Hee Jung; Hahm, Jeong-Hoon; Yang, Jae-Seong; Han, Seong Kyu; Hwang, Daehee; Kim, Sanguk; Jang, Sung Key; Lee, Yoontae; Nam, Hong Gil; Lee, Seung-Jae V.

    2015-01-01

    The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans. PMID:26195740

  5. Helicase and Polymerase Move Together Close to the Fork Junction and Copy DNA in One-Nucleotide Steps

    Directory of Open Access Journals (Sweden)

    Manjula Pandey

    2014-03-01

    Full Text Available By simultaneously measuring DNA synthesis and dNTP hydrolysis, we show that T7 DNA polymerase and T7 gp4 helicase move in sync during leading-strand synthesis, taking one-nucleotide steps and hydrolyzing one dNTP per base-pair unwound/copied. The cooperative catalysis enables the helicase and polymerase to move at a uniformly fast rate without guanine:cytosine (GC dependency or idling with futile NTP hydrolysis. We show that the helicase and polymerase are located close to the replication fork junction. This architecture enables the polymerase to use its strand-displacement synthesis to increase the unwinding rate, whereas the helicase aids this process by translocating along single-stranded DNA and trapping the unwound bases. Thus, in contrast to the helicase-only unwinding model, our results suggest a model in which the helicase and polymerase are moving in one-nucleotide steps, DNA synthesis drives fork unwinding, and a role of the helicase is to trap the unwound bases and prevent DNA reannealing.

  6. Yeast as a model system to study RecQ helicase function

    DEFF Research Database (Denmark)

    Ashton, Thomas M; Hickson, Ian David

    2010-01-01

    Mutations in the highly conserved RecQ helicase, BLM, cause the rare cancer predisposition disorder, Bloom's syndrome. The orthologues of BLM in Saccharomyces cerevisiae and Schizosaccharomyces pombe are SGS1 and rqh1(+), respectively. Studies in these yeast species have revealed a plethora...

  7. A Small Molecule Inhibitor of the BLM Helicase Modulates Chromosome Stability in Human Cells

    DEFF Research Database (Denmark)

    Nguyen, Giang Huong; Dexheimer, Thomas S; Rosenthal, Andrew S

    2013-01-01

    The Bloom's syndrome protein, BLM, is a member of the conserved RecQ helicase family. Although cell lines lacking BLM exist, these exhibit progressive genomic instability that makes distinguishing primary from secondary effects of BLM loss problematic. In order to be able to acutely disable BLM...

  8. Dynamic DNA Helicase-DNA Polymerase Interactions Assure Processive Replication Fork Movement

    NARCIS (Netherlands)

    Hamdan, Samir M.; Johnson, Donald E.; Tanner, Nathan A.; Lee, Jong-Bong; Qimron, Udi; Tabor, Stanley; Oijen, Antoine M. van; Richardson, Charles C.

    2007-01-01

    A single copy of bacteriophage T7 DNA polymerase and DNA helicase advance the replication fork with a processivity greater than 17,000 nucleotides. Nonetheless, the polymerase transiently dissociates from the DNA without leaving the replisome. Ensemble and single-molecule techniques demonstrate that

  9. FBH1 Helicase Disrupts RAD51 Filaments in Vitro and Modulates Homologous Recombination in Mammalian Cells

    Czech Academy of Sciences Publication Activity Database

    Šimandlová, Jitka; Zagelbaum, J.; Payne, M.J.; Chu, W.K.; Shevelev, Igor; Hanada, K.; Chatterjee, S.; Reid, D.A.; Liu, Y.; Janščák, Pavel; Rothenberg, E.; Hickson, I.D.

    2013-01-01

    Roč. 288, č. 47 (2013), s. 34168-34180 ISSN 0021-9258 R&D Projects: GA ČR GAP305/10/0281 Institutional support: RVO:68378050 Keywords : DNA damage * DNA helicase * DNA recombination * DNA repair * DNA replication Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.600, year: 2013

  10. Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome

    DEFF Research Database (Denmark)

    Suhasini, Avvaru N; Rawtani, Nina A; Wu, Yuliang

    2011-01-01

    Bloom's syndrome (BS) and Fanconi anemia (FA) are autosomal recessive disorders characterized by cancer and chromosomal instability. BS and FA group J arise from mutations in the BLM and FANCJ genes, respectively, which encode DNA helicases. In this work, FANCJ and BLM were found to interact...

  11. BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation

    Czech Academy of Sciences Publication Activity Database

    Yodh, J.G.; Stevens, B.C.; Kanagaraj, R.; Janščák, Pavel; Ha, T.

    2009-01-01

    Roč. 28, č. 4 (2009), s. 405-416 ISSN 0261-4189 Institutional research plan: CEZ:AV0Z50520514 Keywords : Bloom syndrome * FRET * helicase * hRPA * single molecule Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.993, year: 2009

  12. Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis DNA helicase XPB.

    Science.gov (United States)

    Balasingham, Seetha V; Zegeye, Ephrem Debebe; Homberset, Håvard; Rossi, Marie L; Laerdahl, Jon K; Bohr, Vilhelm A; Tønjum, Tone

    2012-01-01

    XPB, also known as ERCC3 and RAD25, is a 3' → 5' DNA repair helicase belonging to the superfamily 2 of helicases. XPB is an essential core subunit of the eukaryotic basal transcription factor complex TFIIH. It has two well-established functions: in the context of damaged DNA, XPB facilitates nucleotide excision repair by unwinding double stranded DNA (dsDNA) surrounding a DNA lesion; while in the context of actively transcribing genes, XPB facilitates initiation of RNA polymerase II transcription at gene promoters. Human and other eukaryotic XPB homologs are relatively well characterized compared to conserved homologs found in mycobacteria and archaea. However, more insight into the function of bacterial helicases is central to understanding the mechanism of DNA metabolism and pathogenesis in general. Here, we characterized Mycobacterium tuberculosis XPB (Mtb XPB), a 3'→5' DNA helicase with DNA-dependent ATPase activity. Mtb XPB efficiently catalyzed DNA unwinding in the presence of significant excess of enzyme. The unwinding activity was fueled by ATP or dATP in the presence of Mg(2+)/Mn(2+). Consistent with the 3'→5' polarity of this bacterial XPB helicase, the enzyme required a DNA substrate with a 3' overhang of 15 nucleotides or more. Although Mtb XPB efficiently unwound DNA model substrates with a 3' DNA tail, it was not active on substrates containing a 3' RNA tail. We also found that Mtb XPB efficiently catalyzed ATP-independent annealing of complementary DNA strands. These observations significantly enhance our understanding of the biological roles of Mtb XPB.

  13. Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis DNA helicase XPB.

    Directory of Open Access Journals (Sweden)

    Seetha V Balasingham

    Full Text Available XPB, also known as ERCC3 and RAD25, is a 3' → 5' DNA repair helicase belonging to the superfamily 2 of helicases. XPB is an essential core subunit of the eukaryotic basal transcription factor complex TFIIH. It has two well-established functions: in the context of damaged DNA, XPB facilitates nucleotide excision repair by unwinding double stranded DNA (dsDNA surrounding a DNA lesion; while in the context of actively transcribing genes, XPB facilitates initiation of RNA polymerase II transcription at gene promoters. Human and other eukaryotic XPB homologs are relatively well characterized compared to conserved homologs found in mycobacteria and archaea. However, more insight into the function of bacterial helicases is central to understanding the mechanism of DNA metabolism and pathogenesis in general. Here, we characterized Mycobacterium tuberculosis XPB (Mtb XPB, a 3'→5' DNA helicase with DNA-dependent ATPase activity. Mtb XPB efficiently catalyzed DNA unwinding in the presence of significant excess of enzyme. The unwinding activity was fueled by ATP or dATP in the presence of Mg(2+/Mn(2+. Consistent with the 3'→5' polarity of this bacterial XPB helicase, the enzyme required a DNA substrate with a 3' overhang of 15 nucleotides or more. Although Mtb XPB efficiently unwound DNA model substrates with a 3' DNA tail, it was not active on substrates containing a 3' RNA tail. We also found that Mtb XPB efficiently catalyzed ATP-independent annealing of complementary DNA strands. These observations significantly enhance our understanding of the biological roles of Mtb XPB.

  14. The B. subtilis Accessory Helicase PcrA Facilitates DNA Replication through Transcription Units.

    Directory of Open Access Journals (Sweden)

    Christopher N Merrikh

    2015-06-01

    Full Text Available In bacteria the concurrence of DNA replication and transcription leads to potentially deleterious encounters between the two machineries, which can occur in either the head-on (lagging strand genes or co-directional (leading strand genes orientations. These conflicts lead to replication fork stalling and can destabilize the genome. Both eukaryotic and prokaryotic cells possess resolution factors that reduce the severity of these encounters. Though Escherichia coli accessory helicases have been implicated in the mitigation of head-on conflicts, direct evidence of these proteins mitigating co-directional conflicts is lacking. Furthermore, the endogenous chromosomal regions where these helicases act, and the mechanism of recruitment, have not been identified. We show that the essential Bacillus subtilis accessory helicase PcrA aids replication progression through protein coding genes of both head-on and co-directional orientations, as well as rRNA and tRNA genes. ChIP-Seq experiments show that co-directional conflicts at highly transcribed rRNA, tRNA, and head-on protein coding genes are major targets of PcrA activity on the chromosome. Partial depletion of PcrA renders cells extremely sensitive to head-on conflicts, linking the essential function of PcrA to conflict resolution. Furthermore, ablating PcrA's ATPase/helicase activity simultaneously increases its association with conflict regions, while incapacitating its ability to mitigate conflicts, and leads to cell death. In contrast, disruption of PcrA's C-terminal RNA polymerase interaction domain does not impact its ability to mitigate conflicts between replication and transcription, its association with conflict regions, or cell survival. Altogether, this work establishes PcrA as an essential factor involved in mitigating transcription-replication conflicts and identifies chromosomal regions where it routinely acts. As both conflicts and accessory helicases are found in all domains of life

  15. Role of the Pif1-PCNA Complex in Pol δ-Dependent Strand Displacement DNA Synthesis and Break-Induced Replication.

    Science.gov (United States)

    Buzovetsky, Olga; Kwon, Youngho; Pham, Nhung Tuyet; Kim, Claire; Ira, Grzegorz; Sung, Patrick; Xiong, Yong

    2017-11-14

    The S. cerevisiae Pif1 helicase functions with DNA polymerase (Pol) δ in DNA synthesis during break-induced replication (BIR), a conserved pathway responsible for replication fork repair and telomere recombination. Pif1 interacts with the DNA polymerase processivity clamp PCNA, but the functional significance of the Pif1-PCNA complex remains to be elucidated. Here, we solve the crystal structure of PCNA in complex with a non-canonical PCNA-interacting motif in Pif1. The structure guides the construction of a Pif1 mutant that is deficient in PCNA interaction. This mutation impairs the ability of Pif1 to enhance DNA strand displacement synthesis by Pol δ in vitro and also the efficiency of BIR in cells. These results provide insights into the role of the Pif1-PCNA-Pol δ ensemble during DNA break repair by homologous recombination. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Enhancement of Spike-Timing-Dependent Plasticity in Spiking Neural Systems with Noise.

    Science.gov (United States)

    Nobukawa, Sou; Nishimura, Haruhiko

    2016-08-01

    Synaptic plasticity is widely recognized to support adaptable information processing in the brain. Spike-timing-dependent plasticity, one subtype of plasticity, can lead to synchronous spike propagation with temporal spiking coding information. Recently, it was reported that in a noisy environment, like the actual brain, the spike-timing-dependent plasticity may be made efficient by the effect of stochastic resonance. In the stochastic resonance, the presence of noise helps a nonlinear system in amplifying a weak (under barrier) signal. However, previous studies have ignored the full variety of spiking patterns and many relevant factors in neural dynamics. Thus, in order to prove the physiological possibility for the enhancement of spike-timing-dependent plasticity by stochastic resonance, it is necessary to demonstrate that this stochastic resonance arises in realistic cortical neural systems. In this study, we evaluate this stochastic resonance phenomenon in the realistic cortical neural system described by the Izhikevich neuron model and compare the characteristics of typical spiking patterns of regular spiking, intrinsically bursting and chattering experimentally observed in the cortex.

  17. Spiking Neurons for Analysis of Patterns

    Science.gov (United States)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  18. Spike train encoding by regular-spiking cells of the visual cortex.

    Science.gov (United States)

    Carandini, M; Mechler, F; Leonard, C S; Movshon, J A

    1996-11-01

    1. To study the encoding of input currents into output spike trains by regular-spiking cells, we recorded intracellularly from slices of the guinea pig visual cortex while injecting step, sinusoidal, and broadband noise currents. 2. When measured with sinusoidal currents, the frequency tuning of the spike responses was markedly band-pass. The preferred frequency was between 8 and 30 Hz, and grew with stimulus amplitude and mean intensity. 3. Stimulation with broadband noise currents dramatically enhanced the gain of the spike responses at low and high frequencies, yielding an essentially flat frequency tuning between 0.1 and 130 Hz. 4. The averaged spike responses to sinusoidal currents exhibited two nonlinearities: rectification and spike synchronization. By contrast, no nonlinearity was evident in the averaged responses to broadband noise stimuli. 5. These properties of the spike responses were not present in the membrane potential responses. The latter were roughly linear, and their frequency tuning was low-pass and well fit by a single-compartment passive model of the cell membrane composed of a resistance and a capacitance in parallel (RC circuit). 6. To account for the spike responses, we used a "sandwich model" consisting of a low-pass linear filter (the RC circuit), a rectification nonlinearity, and a high-pass linear filter. The model is described by six parameters and predicts analog firing rates rather than discrete spikes. It provided satisfactory fits to the firing rate responses to steps, sinusoids, and broadband noise currents. 7. The properties of spike encoding are consistent with temporal nonlinearities of the visual responses in V1, such as the dependence of response frequency tuning and latency on stimulus contrast and bandwidth. We speculate that one of the roles of the high-frequency membrane potential fluctuations observed in vivo could be to amplify and linearize the responses to lower, stimulus-related frequencies.

  19. Epileptiform spike detection via convolutional neural networks

    DEFF Research Database (Denmark)

    Johansen, Alexander Rosenberg; Jin, Jing; Maszczyk, Tomasz

    2016-01-01

    The EEG of epileptic patients often contains sharp waveforms called "spikes", occurring between seizures. Detecting such spikes is crucial for diagnosing epilepsy. In this paper, we develop a convolutional neural network (CNN) for detecting spikes in EEG of epileptic patients in an automated...... fashion. The CNN has a convolutional architecture with filters of various sizes applied to the input layer, leaky ReLUs as activation functions, and a sigmoid output layer. Balanced mini-batches were applied to handle the imbalance in the data set. Leave-one-patient-out cross-validation was carried out...... to test the CNN and benchmark models on EEG data of five epilepsy patients. We achieved 0.947 AUC for the CNN, while the best performing benchmark model, Support Vector Machines with Gaussian kernel, achieved an AUC of 0.912....

  20. The electric potential of tripolar spikes

    International Nuclear Information System (INIS)

    Nocera, L.

    2010-01-01

    We present an analytical formula for the waveform of the electric potential associated with a tripolar spike in a plasma. This formula is based on the construction and on the subsequent solution of a differential equation for the waveform. We work out this equation as a direct consequence of the morphological and functional properties of the observed waveform, without making any reference to the velocity distributions of the electrons and of the ions which sustain the spike. In the approximation of small potential amplitudes, we solve this equation by quadrature. In particular, in the second order approximation, the solution of this equation is given in terms of elementary functions. This analytical solution is able to reproduce the potential waveforms associated with electron holes, ion holes, monotonic and nonmonotonic double layers and tripolar spikes, in excellent agreement with observations.

  1. Implementing Signature Neural Networks with Spiking Neurons.

    Science.gov (United States)

    Carrillo-Medina, José Luis; Latorre, Roberto

    2016-01-01

    Spiking Neural Networks constitute the most promising approach to develop realistic Artificial Neural Networks (ANNs). Unlike traditional firing rate-based paradigms, information coding in spiking models is based on the precise timing of individual spikes. It has been demonstrated that spiking ANNs can be successfully and efficiently applied to multiple realistic problems solvable with traditional strategies (e.g., data classification or pattern recognition). In recent years, major breakthroughs in neuroscience research have discovered new relevant computational principles in different living neural systems. Could ANNs benefit from some of these recent findings providing novel elements of inspiration? This is an intriguing question for the research community and the development of spiking ANNs including novel bio-inspired information coding and processing strategies is gaining attention. From this perspective, in this work, we adapt the core concepts of the recently proposed Signature Neural Network paradigm-i.e., neural signatures to identify each unit in the network, local information contextualization during the processing, and multicoding strategies for information propagation regarding the origin and the content of the data-to be employed in a spiking neural network. To the best of our knowledge, none of these mechanisms have been used yet in the context of ANNs of spiking neurons. This paper provides a proof-of-concept for their applicability in such networks. Computer simulations show that a simple network model like the discussed here exhibits complex self-organizing properties. The combination of multiple simultaneous encoding schemes allows the network to generate coexisting spatio-temporal patterns of activity encoding information in different spatio-temporal spaces. As a function of the network and/or intra-unit parameters shaping the corresponding encoding modality, different forms of competition among the evoked patterns can emerge even in the absence

  2. Span: spike pattern association neuron for learning spatio-temporal spike patterns.

    Science.gov (United States)

    Mohemmed, Ammar; Schliebs, Stefan; Matsuda, Satoshi; Kasabov, Nikola

    2012-08-01

    Spiking Neural Networks (SNN) were shown to be suitable tools for the processing of spatio-temporal information. However, due to their inherent complexity, the formulation of efficient supervised learning algorithms for SNN is difficult and remains an important problem in the research area. This article presents SPAN - a spiking neuron that is able to learn associations of arbitrary spike trains in a supervised fashion allowing the processing of spatio-temporal information encoded in the precise timing of spikes. The idea of the proposed algorithm is to transform spike trains during the learning phase into analog signals so that common mathematical operations can be performed on them. Using this conversion, it is possible to apply the well-known Widrow-Hoff rule directly to the transformed spike trains in order to adjust the synaptic weights and to achieve a desired input/output spike behavior of the neuron. In the presented experimental analysis, the proposed learning algorithm is evaluated regarding its learning capabilities, its memory capacity, its robustness to noisy stimuli and its classification performance. Differences and similarities of SPAN regarding two related algorithms, ReSuMe and Chronotron, are discussed.

  3. Improved SpikeProp for Using Particle Swarm Optimization

    Directory of Open Access Journals (Sweden)

    Falah Y. H. Ahmed

    2013-01-01

    Full Text Available A spiking neurons network encodes information in the timing of individual spike times. A novel supervised learning rule for SpikeProp is derived to overcome the discontinuities introduced by the spiking thresholding. This algorithm is based on an error-backpropagation learning rule suited for supervised learning of spiking neurons that use exact spike time coding. The SpikeProp is able to demonstrate the spiking neurons that can perform complex nonlinear classification in fast temporal coding. This study proposes enhancements of SpikeProp learning algorithm for supervised training of spiking networks which can deal with complex patterns. The proposed methods include the SpikeProp particle swarm optimization (PSO and angle driven dependency learning rate. These methods are presented to SpikeProp network for multilayer learning enhancement and weights optimization. Input and output patterns are encoded as spike trains of precisely timed spikes, and the network learns to transform the input trains into target output trains. With these enhancements, our proposed methods outperformed other conventional neural network architectures.

  4. DNA secondary structure of the released strand stimulates WRN helicase action on forked duplexes without coordinate action of WRN exonuclease

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byungchan, E-mail: bbccahn@mail.ulsan.ac.kr [Department of Life Sciences, University of Ulsan, Ulsan (Korea, Republic of); Bohr, Vilhelm A. [Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Aging, Baltimore, MD (United States)

    2011-08-12

    Highlights: {yields} In this study, we investigated the effect of a DNA secondary structure on the two WRN activities. {yields} We found that a DNA secondary structure of the displaced strand during unwinding stimulates WRN helicase without coordinate action of WRN exonuclease. {yields} These results imply that WRN helicase and exonuclease activities can act independently. -- Abstract: Werner syndrome (WS) is an autosomal recessive premature aging disorder characterized by aging-related phenotypes and genomic instability. WS is caused by mutations in a gene encoding a nuclear protein, Werner syndrome protein (WRN), a member of the RecQ helicase family, that interestingly possesses both helicase and exonuclease activities. Previous studies have shown that the two activities act in concert on a single substrate. We investigated the effect of a DNA secondary structure on the two WRN activities and found that a DNA secondary structure of the displaced strand during unwinding stimulates WRN helicase without coordinate action of WRN exonuclease. These results imply that WRN helicase and exonuclease activities can act independently, and we propose that the uncoordinated action may be relevant to the in vivo activity of WRN.

  5. Spike-timing theory of working memory.

    Directory of Open Access Journals (Sweden)

    Botond Szatmáry

    Full Text Available Working memory (WM is the part of the brain's memory system that provides temporary storage and manipulation of information necessary for cognition. Although WM has limited capacity at any given time, it has vast memory content in the sense that it acts on the brain's nearly infinite repertoire of lifetime long-term memories. Using simulations, we show that large memory content and WM functionality emerge spontaneously if we take the spike-timing nature of neuronal processing into account. Here, memories are represented by extensively overlapping groups of neurons that exhibit stereotypical time-locked spatiotemporal spike-timing patterns, called polychronous patterns; and synapses forming such polychronous neuronal groups (PNGs are subject to associative synaptic plasticity in the form of both long-term and short-term spike-timing dependent plasticity. While long-term potentiation is essential in PNG formation, we show how short-term plasticity can temporarily strengthen the synapses of selected PNGs and lead to an increase in the spontaneous reactivation rate of these PNGs. This increased reactivation rate, consistent with in vivo recordings during WM tasks, results in high interspike interval variability and irregular, yet systematically changing, elevated firing rate profiles within the neurons of the selected PNGs. Additionally, our theory explains the relationship between such slowly changing firing rates and precisely timed spikes, and it reveals a novel relationship between WM and the perception of time on the order of seconds.

  6. Physics of volleyball: Spiking with a purpose

    Science.gov (United States)

    Behroozi, F.

    1998-05-01

    A few weeks ago our volleyball coach telephoned me with a problem: How high should a player jump to "spike" a "set" ball so it would clear the net and land at a known distance on the other side of the net?

  7. Investment spikes in Dutch greenhouse horticulture

    NARCIS (Netherlands)

    Goncharova, N.; Oskam, A.; Oude Lansink, A.G.J.M.; Vlist, van der A.J.; Verstegen, J.A.A.M.

    2008-01-01

    The presence of investment cycles demonstrates the long-run policy of firms investing in particular periods (investment spikes) with lower or zero investment levels in between, which contradicts the smooth pattern predicted by a convex adjustment model. This paper investigates the spells between

  8. Food Price Spikes, Price Insulation, and Poverty

    OpenAIRE

    Anderson, Kym; Ivanic, Maros; Martin, Will

    2013-01-01

    This paper has two purposes. It first considers the impact on world food prices of the changes in restrictions on trade in staple foods during the 2008 world food price crisis. Those changes -- reductions in import protection or increases in export restraints -- were meant to partially insulate domestic markets from the spike in international prices. The authors find that this insulation a...

  9. Gymnosporia montana Benth.(Mountain Spike Thorn)

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 23; Issue 2. Gymnosporia montana Benth. (Mountain Spike Thorn). Flowering Trees Volume 23 Issue 2 February 2018 pp 245-245. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/023/02/0245-0245 ...

  10. Mycobacterium smegmatis SftH exemplifies a distinctive clade of superfamily II DNA-dependent ATPases with 3′ to 5′ translocase and helicase activities

    OpenAIRE

    Yakovleva, Lyudmila; Shuman, Stewart

    2012-01-01

    Bacterial DNA helicases are nucleic acid-dependent NTPases that play important roles in DNA replication, recombination and repair. We are interested in the DNA helicases of Mycobacteria, a genus of the phylum Actinobacteria, which includes the human pathogen Mycobacterium tuberculosis and its avirulent relative Mycobacterium smegmatis. Here, we identify and characterize M. smegmatis SftH, a superfamily II helicase with a distinctive domain structure, comprising an N-terminal NTPase domain and...

  11. FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells

    DEFF Research Database (Denmark)

    Simandlova, Jitka; Zagelbaum, Jennifer; Payne, Miranda J

    2013-01-01

    Efficient repair of DNA double strand breaks and interstrand cross-links requires the homologous recombination (HR) pathway, a potentially error-free process that utilizes a homologous sequence as a repair template. A key player in HR is RAD51, the eukaryotic ortholog of bacterial RecA protein. RAD....... Using a combination of molecular genetic, biochemical, and single-molecule biophysical techniques, we provide mechanistic insight into the mode of action of the FBH1 helicase as a regulator of RAD51-dependent HR in mammalian cells. We show that FBH1 binds directly to RAD51 and is able to disrupt RAD51...... filaments on DNA through its ssDNA translocase function. Consistent with this, a mutant mouse embryonic stem cell line with a deletion in the FBH1 helicase domain fails to limit RAD51 chromatin association and shows hyper-recombination. Our data are consistent with FBH1 restraining RAD51 DNA binding under...

  12. Cooperation of DNA-PKcs and WRN helicase in the maintenance of telomeric D-loops

    DEFF Research Database (Denmark)

    Kusumoto-Matsuo, Rika; Opresko, Patricia L; Ramsden, Dale

    2010-01-01

    Werner syndrome is an inherited human progeriod syndrome caused by mutations in the gene encoding the Werner Syndrome protein, WRN. It has both 3'-5' DNA helicase and exonuclease activities, and is suggested to have roles in many aspects of DNA metabolism, including DNA repair and telomere...... maintenance. The DNA-PK complex also functions in both DNA double strand break repair and telomere maintenance. Interaction between WRN and the DNA-PK complex has been reported in DNA double strand break repair, but their possible cooperation at telomeres has not been reported. This study analyzes thein vitro...... D-loop model substrate. In addition, the length of telomeric G-tails decreases in DNA-PKcs knockdown cells, and this phenotype is reversed by overexpression of WRN helicase. These results suggest that WRN and DNA-PKcs may cooperatively prevent G-tail shortening in vivo....

  13. Spiking Neural P Systems with Communication on Request.

    Science.gov (United States)

    Pan, Linqiang; Păun, Gheorghe; Zhang, Gexiang; Neri, Ferrante

    2017-12-01

    Spiking Neural [Formula: see text] Systems are Neural System models characterized by the fact that each neuron mimics a biological cell and the communication between neurons is based on spikes. In the Spiking Neural [Formula: see text] systems investigated so far, the application of evolution rules depends on the contents of a neuron (checked by means of a regular expression). In these [Formula: see text] systems, a specified number of spikes are consumed and a specified number of spikes are produced, and then sent to each of the neurons linked by a synapse to the evolving neuron. [Formula: see text]In the present work, a novel communication strategy among neurons of Spiking Neural [Formula: see text] Systems is proposed. In the resulting models, called Spiking Neural [Formula: see text] Systems with Communication on Request, the spikes are requested from neighboring neurons, depending on the contents of the neuron (still checked by means of a regular expression). Unlike the traditional Spiking Neural [Formula: see text] systems, no spikes are consumed or created: the spikes are only moved along synapses and replicated (when two or more neurons request the contents of the same neuron). [Formula: see text]The Spiking Neural [Formula: see text] Systems with Communication on Request are proved to be computationally universal, that is, equivalent with Turing machines as long as two types of spikes are used. Following this work, further research questions are listed to be open problems.

  14. Roles of the linker region of RNA helicase A in HIV-1 RNA metabolism.

    Directory of Open Access Journals (Sweden)

    Li Xing

    Full Text Available RNA helicase A (RHA promotes multiple steps in HIV-1 production including transcription and translation of viral RNA, annealing of primer tRNA(Lys3 to viral RNA, and elevating the ratio of unspliced to spliced viral RNA. At its amino terminus are two double-stranded RNA binding domains (dsRBDs that are essential for RHA-viral RNA interaction. Linking the dsRBDs to the core helicase domain is a linker region containing 6 predicted helices. Working in vitro with purified mutant RHAs containing deletions of individual helices reveals that this region may regulate the enzyme's helicase activity, since deletion of helix 2 or 3 reduces the rate of unwinding RNA by RHA. The biological significance of this finding was then examined during HIV-1 production. Deletions in the linker region do not significantly affect either RHA-HIV-1 RNA interaction in vivo or the incorporation of mutant RHAs into progeny virions. While the partial reduction in helicase activity of mutant RHA containing a deletion of helices 2 or 3 does not reduce the ability of RHA to stimulate viral RNA synthesis, the promotion of tRNA(Lys3 annealing to viral RNA is blocked. In contrast, deletion of helices 4 or 5 does not affect the ability of RHA to promote tRNA(Lys3 annealing, but reduces its ability to stimulate viral RNA synthesis. Additionally, RHA stimulation of viral RNA synthesis results in an increased ratio of unspliced to spliced viral RNA, and this increase is not inhibited by deletions in the linker region, nor is the pattern of splicing changed within the ∼ 4.0 kb or ∼ 1.8 kb HIV-1 RNA classes, suggesting that RHA's effect on suppressing splicing is confined mainly to the first 5'-splice donor site. Overall, the differential responses to the mutations in the linker region of RHA reveal that RHA participates in HIV-1 RNA metabolism by multiple distinct mechanisms.

  15. Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity

    Czech Academy of Sciences Publication Activity Database

    Schwendener, S.; Raynard, S.; Paliwal, S.; Cheng, A.; Kanagaraj, R.; Shevelev, Igor; Stark, J.M.; Sung, P.; Janscak, P.

    2010-01-01

    Roč. 285, č. 21 (2010), s. 15739-15745 ISSN 0021-9258 Grant - others:NIH(US) R01CA120954; NIH(US) ES015632; SNSF(CH) 3100A0-116008 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA helicase * double-strand breaks * homologous recombination Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.328, year: 2010

  16. Molecular insights into DNA interference by CRISPR-associated nuclease-helicase Cas3.

    Science.gov (United States)

    Gong, Bei; Shin, Minsang; Sun, Jiali; Jung, Che-Hun; Bolt, Edward L; van der Oost, John; Kim, Jeong-Sun

    2014-11-18

    Mobile genetic elements in bacteria are neutralized by a system based on clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins. Type I CRISPR-Cas systems use a "Cascade" ribonucleoprotein complex to guide RNA specifically to complementary sequence in invader double-stranded DNA (dsDNA), a process called "interference." After target recognition by Cascade, formation of an R-loop triggers recruitment of a Cas3 nuclease-helicase, completing the interference process by destroying the invader dsDNA. To elucidate the molecular mechanism of CRISPR interference, we analyzed crystal structures of Cas3 from the bacterium Thermobaculum terrenum, with and without a bound ATP analog. The structures reveal a histidine-aspartate (HD)-type nuclease domain fused to superfamily-2 (SF2) helicase domains and a distinct C-terminal domain. Binding of ATP analog at the interface of the SF2 helicase RecA-like domains rearranges a motif V with implications for the enzyme mechanism. The HD-nucleolytic site contains two metal ions that are positioned at the end of a proposed nucleic acid-binding tunnel running through the SF2 helicase structure. This structural alignment suggests a mechanism for 3' to 5' nucleolytic processing of the displaced strand of invader DNA that is coordinated with ATP-dependent 3' to 5' translocation of Cas3 along DNA. In agreement with biochemical studies, the presented Cas3 structures reveal important mechanistic details on the neutralization of genetic invaders by type I CRISPR-Cas systems.

  17. Evolution of the DEAD box helicase family in chicken: chickens have no DHX9 ortholog.

    Science.gov (United States)

    Sato, Haruko; Oshiumi, Hiroyuki; Takaki, Hiromi; Hikono, Hirokazu; Seya, Tsukasa

    2015-10-01

    Viral RNA represents a pattern molecule that can be recognized by RNA sensors in innate immunity. Humans and mice possess cytoplasmic DNA/RNA sensors for detecting viral replication. There are a number of DEAD (Asp-Glu-Ala-Asp; DExD/H) box-type helicases in mammals, among which retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA50) are indispensable for RNA sensing; however, they are functionally supported by a number of sensors that directly bind viral RNA or replicative RNA intermediates to convey signals to RIG-I and MDA5. Some DEAD box helicase members recognize DNA irrespective of the origin. These sensors transmit IFN-inducing signals through adaptors, including mitochondrial antiviral signaling. Viral double-stranded RNAs are reportedly sensed by the helicases DDX1, DDX21, DHX36, DHX9, DDX3, DDX41, LGP2 and DDX60, in addition to RIG-I and MDA5, and induce type I IFNs, thereby blocking viral replication. Humans and mice have all nucleic acid sensors listed here. In the RNA sensing system in chicken, it was found in the present study that most DEAD box helicases are conserved; however, DHX9 is genetically deficient in addition to reported RIG-I. Based on the current genome databases, similar DHX9 deficiency was observed in ducks and several other bird species. Because chicken, but not duck, was found to be deficient in RIG-I, the RNA-sensing system of chicken lacks RIG-I and DHX9 and is thus more fragile than that of duck or mammal. DHX9 may generally compensate for the function of RIG-I and deficiency of DHX9 possibly participates in exacerbations of viral infection such as influenza in chickens. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  18. The helicase DinG responds to stress due to DNA double strand breaks.

    Directory of Open Access Journals (Sweden)

    Stephan A Frye

    Full Text Available Neisseria meningitidis (Nm is a Gram-negative nasopharyngeal commensal that can cause septicaemia and meningitis. The neisserial DNA damage-inducible protein DinG is a helicase related to the mammalian helicases XPD and FANCJ. These helicases belong to superfamily 2, are ATP dependent and exert 5' → 3' directionality. To better understand the role of DinG in neisserial genome maintenance, the Nm DinG (DinGNm enzymatic activities were assessed in vitro and phenotypical characterization of a dinG null mutant (NmΔdinG was performed. Like its homologues, DinGNm possesses 5' → 3' directionality and prefers DNA substrates containing a 5'-overhang. ATPase activity of DinGNm is strictly DNA-dependent and DNA unwinding activity requires nucleoside triphosphate and divalent metal cations. DinGNm directly binds SSBNm with a Kd of 313 nM. Genotoxic stress analysis demonstrated that NmΔdinG was more sensitive to double-strand DNA breaks (DSB induced by mitomycin C (MMC than the Nm wildtype, defining the role of neisserial DinG in DSB repair. Notably, when NmΔdinG cells grown under MMC stress assessed by quantitative mass spectrometry, 134 proteins were shown to be differentially abundant (DA compared to unstressed NmΔdinG cells. Among the DNA replication, repair and recombination proteins affected, polymerase III subunits and recombinational repair proteins RuvA, RuvB, RecB and RecD were significantly down regulated while TopA and SSB were upregulated under stress condition. Most of the other DA proteins detected are involved in metabolic functions. The present study shows that the helicase DinG is probably involved in regulating metabolic pathways as well as in genome maintenance.

  19. The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability

    Czech Academy of Sciences Publication Activity Database

    Singh, D.K.; Popuri, V.; Kulikowicz, T.; Shevelev, Igor; Ghosh, A.K.; Ramamoorthy, M.; Rossi, M.L.; Janščák, Pavel; Croteau, D.L.; Bohr, V.A.

    2012-01-01

    Roč. 40, č. 14 (2012), s. 6632-6648 ISSN 0305-1048 R&D Projects: GA ČR GAP305/10/0281 Grant - others:NIH(US) Z01-AG000726-17 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : RecQ helicase * genome stability * BLM * RECQL4 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.278, year: 2012

  20. The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

    Energy Technology Data Exchange (ETDEWEB)

    Ziehr, Ben; Lenarcic, Erik; Cecil, Chad; Moorman, Nathaniel J., E-mail: nmoorman@med.unc.edu

    2016-02-15

    Human cytomegalovirus (HCMV) was recently shown to encode a large number of spliced mRNAs. While the nuclear export of unspliced viral transcripts has been extensively studied, the role of host mRNA export factors in HCMV mRNA trafficking remains poorly defined. We found that the eIF4AIII RNA helicase, a component of the exon junction complex, was necessary for efficient virus replication. Depletion of eIF4AIII limited viral DNA accumulation, export of viral mRNAs from the nucleus, and the production of progeny virus. However eIF4AIII was dispensable for the association of viral transcripts with ribosomes. We found that pateamine A, a natural compound that inhibits both eIF4AI/II and eIF4AIII, has potent antiviral activity and inhibits HCMV replication throughout the virus lytic cycle. Our results demonstrate that eIF4AIII is required for efficient HCMV replication, and suggest that eIF4A family helicases may be a new class of targets for the development of host-directed antiviral therapeutics. - Highlights: • The host eIF4AIII RNA helicase is required for efficient HCMV replication. • Depleting eIF4AIII inhibited the nuclear export of HCMV mRNAs. • HCMV mRNAs did not require eIF4AIII to associate with polyribosomes. • The eIF4A family helicases may be new targets for host-directed antiviral drugs.

  1. DEAD-box RNA helicase is dispensable for mitochondrial translation in Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Richterová, Lenka; Vávrová, Zuzana; Lukeš, Julius

    2011-01-01

    Roč. 127, č. 1 (2011), 300-303 ISSN 0014-4894 R&D Projects: GA ČR GA204/09/1667; GA MŠk LC07032; GA MŠk 2B06129 Institutional research plan: CEZ:AV0Z60220518 Keywords : Trypanosoma * Mitochondrial translation * RNA helicase * Cytochrome c oxidase * Mitochondrion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.122, year: 2011

  2. Distinct functions of human RecQ helicases during DNA replication

    Czech Academy of Sciences Publication Activity Database

    Urban, Václav; Dobrovolná, Jana; Janščák, Pavel

    2017-01-01

    Roč. 225, červen (2017), s. 20-26 ISSN 0301-4622 R&D Projects: GA ČR(CZ) GA14-05743S; GA MŠk LH14037 Institutional support: RVO:68378050 Keywords : DNA replication * Replication stress * RecQ helicases * Genomic instability * Cancer Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 2.402, year: 2016

  3. The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

    International Nuclear Information System (INIS)

    Ziehr, Ben; Lenarcic, Erik; Cecil, Chad; Moorman, Nathaniel J.

    2016-01-01

    Human cytomegalovirus (HCMV) was recently shown to encode a large number of spliced mRNAs. While the nuclear export of unspliced viral transcripts has been extensively studied, the role of host mRNA export factors in HCMV mRNA trafficking remains poorly defined. We found that the eIF4AIII RNA helicase, a component of the exon junction complex, was necessary for efficient virus replication. Depletion of eIF4AIII limited viral DNA accumulation, export of viral mRNAs from the nucleus, and the production of progeny virus. However eIF4AIII was dispensable for the association of viral transcripts with ribosomes. We found that pateamine A, a natural compound that inhibits both eIF4AI/II and eIF4AIII, has potent antiviral activity and inhibits HCMV replication throughout the virus lytic cycle. Our results demonstrate that eIF4AIII is required for efficient HCMV replication, and suggest that eIF4A family helicases may be a new class of targets for the development of host-directed antiviral therapeutics. - Highlights: • The host eIF4AIII RNA helicase is required for efficient HCMV replication. • Depleting eIF4AIII inhibited the nuclear export of HCMV mRNAs. • HCMV mRNAs did not require eIF4AIII to associate with polyribosomes. • The eIF4A family helicases may be new targets for host-directed antiviral drugs.

  4. Relocalization of nuclear DNA helicase II during the growth period of bovine oocytes

    Czech Academy of Sciences Publication Activity Database

    Baran, V.; Kovářová, Hana; Klíma, Jiří; Hozák, Pavel; Motlík, Jan

    2006-01-01

    Roč. 125, 1-2 (2006), s. 155-164 ISSN 0948-6143 R&D Projects: GA ČR GA523/03/0857 Grant - others:Slovenská Akademie věd(SK) VEGA 2/3065/23 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50390512 Keywords : DNA helicase II * fibroblasts * oocytes Subject RIV: EB - Genetics ; Molecular Biology Impact factor : 3.220, year: 2006

  5. Impact of spike train autostructure on probability distribution of joint spike events.

    Science.gov (United States)

    Pipa, Gordon; Grün, Sonja; van Vreeswijk, Carl

    2013-05-01

    The discussion whether temporally coordinated spiking activity really exists and whether it is relevant has been heated over the past few years. To investigate this issue, several approaches have been taken to determine whether synchronized events occur significantly above chance, that is, whether they occur more often than expected if the neurons fire independently. Most investigations ignore or destroy the autostructure of the spiking activity of individual cells or assume Poissonian spiking as a model. Such methods that ignore the autostructure can significantly bias the coincidence statistics. Here, we study the influence of the autostructure on the probability distribution of coincident spiking events between tuples of mutually independent non-Poisson renewal processes. In particular, we consider two types of renewal processes that were suggested as appropriate models of experimental spike trains: a gamma and a log-normal process. For a gamma process, we characterize the shape of the distribution analytically with the Fano factor (FFc). In addition, we perform Monte Carlo estimations to derive the full shape of the distribution and the probability for false positives if a different process type is assumed as was actually present. We also determine how manipulations of such spike trains, here dithering, used for the generation of surrogate data change the distribution of coincident events and influence the significance estimation. We find, first, that the width of the coincidence count distribution and its FFc depend critically and in a nontrivial way on the detailed properties of the structure of the spike trains as characterized by the coefficient of variation CV. Second, the dependence of the FFc on the CV is complex and mostly nonmonotonic. Third, spike dithering, even if as small as a fraction of the interspike interval, can falsify the inference on coordinated firing.

  6. Spike detection algorithm improvement, spike waveforms projections with PCA and hierarchical classification

    OpenAIRE

    Biffi, Emilia; Ghezzi, Diego; Pedrocchi, Alessandra; Ferrigno, Giancarlo

    2008-01-01

    Definition of single spikes from multiunit spike trains plays a critical role in neurophysiology and in neuroengineering. Moreover, long period analysis are needed to study synaptic plasticity effects and observe the long and medium term development on which all central nervous system (CNS) learning functions are based. Therefore, the increasing importance of long period recordings makes necessary on-line and real time analysis, memory use optimization and data transmission rate improvement. ...

  7. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    Werner syndrome (WS) is a severe recessive disorder characterized by premature aging, cancer predisposition and genomic instability. The gene mutated in WS encodes a bi-functional enzyme called WRN that acts as a RecQ-type DNA helicase and a 3'-5' exonuclease, but its exact role in DNA metabolism...... stimulate the helicase activity of WRN specifically on forked DNA structures with a 3'-single-stranded arm. The stimulatory effect of MutSalpha on WRN-mediated unwinding is enhanced by a G/T mismatch in the DNA duplex ahead of the fork. The MutLalpha protein known to bind to the MutS alpha......-heteroduplex complexes has no effect on WRN-mediated DNA unwinding stimulated by MutSalpha, nor does it affect DNA unwinding by WRN alone. Our data are consistent with results of genetic experiments in yeast suggesting that MMR factors act in conjunction with a RecQ-type helicase to reject recombination between...

  8. Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

    Energy Technology Data Exchange (ETDEWEB)

    Mir-Sanchis, Ignacio; Roman, Christina A.; Misiura, Agnieszka; Pigli, Ying Z.; Boyle-Vavra, Susan; Rice , Phoebe A. (UC)

    2016-08-29

    Methicillin-resistant Staphylococcus aureus (MRSA) is a public-health threat worldwide. Although the mobile genomic island responsible for this phenotype, staphylococcal cassette chromosome (SCC), has been thought to be nonreplicative, we predicted DNA-replication-related functions for some of the conserved proteins encoded by SCC. We show that one of these, Cch, is homologous to the self-loading initiator helicases of an unrelated family of genomic islands, that it is an active 3'-to-5' helicase and that the adjacent ORF encodes a single-stranded DNA–binding protein. Our 2.9-Å crystal structure of intact Cch shows that it forms a hexameric ring. Cch, like the archaeal and eukaryotic MCM-family replicative helicases, belongs to the pre–sensor II insert clade of AAA+ ATPases. Additionally, we found that SCC elements are part of a broader family of mobile elements, all of which encode a replication initiator upstream of their recombinases. Replication after excision would enhance the efficiency of horizontal gene transfer.

  9. Isolation and Characterization of Pepper Genes Interacting with the CMV-P1 Helicase Domain.

    Directory of Open Access Journals (Sweden)

    Yoomi Choi

    Full Text Available Cucumber mosaic virus (CMV is a destructive pathogen affecting Capsicum annuum (pepper production. The pepper Cmr1 gene confers resistance to most CMV strains, but is overcome by CMV-P1 in a process dependent on the CMV-P1 RNA1 helicase domain (P1 helicase. Here, to identify host factors involved in CMV-P1 infection in pepper, a yeast two-hybrid library derived from a C. annuum 'Bukang' cDNA library was screened, producing a total of 76 potential clones interacting with the P1 helicase. Beta-galactosidase filter lift assay, PCR screening, and sequencing analysis narrowed the candidates to 10 genes putatively involved in virus infection. The candidate host genes were silenced in Nicotiana benthamiana plants that were then inoculated with CMV-P1 tagged with the green fluorescent protein (GFP. Plants silenced for seven of the genes showed development comparable to N. benthamiana wild type, whereas plants silenced for the other three genes showed developmental defects including stunting and severe distortion. Silencing formate dehydrogenase and calreticulin-3 precursor led to reduced virus accumulation. Formate dehydrogenase-silenced plants showed local infection in inoculated leaves, but not in upper (systemic leaves. In the calreticulin-3 precursor-silenced plants, infection was not observed in either the inoculated or the upper leaves. Our results demonstrate that formate dehydrogenase and calreticulin-3 precursor are required for CMV-P1 infection.

  10. Helicase properties of the Escherichia coli UvrAb protein complex

    International Nuclear Information System (INIS)

    Oh, E.Y.; Grossman, L.

    1987-01-01

    The Escherichia coli UvrA protein has an associated ATPase activity with a turnover number affected by the presence of UvrB protein as well as by DNA. Specifically, the structure of DNA significantly influences the turnover rate of the UvrAB ATPase activity. Double-stranded DNA maximally activates the turnover rate 10-fold whereas single-stranded DNA maximally activates the turnover rate 20-fold, suggesting that the mode of interaction of UvrAB protein with different DNAs is distinctive. We have previously shown that the UvrAB protein complex, driven by the binding energy of ATP, can locally unwind supercoiled DNA. The nature of the DNA unwinding activity and single-stranded DNA activation of ATPase activity suggest potential helicase activity. In the presence of a number of helicase substrates, the UvrAB complex, indeed, manifests a strand-displacement activity-unwinding short duplexes and D-loop DNA, thereby generating component DNA structures. The energy for the activity is derived from ATP or dATP hydrolysis. Unlike the E. coli DnaB, the UvrAB helicase is sensitive to UV-induced photoproducts

  11. Novel benzoxazole inhibitor of dengue virus replication that targets the NS3 helicase.

    Science.gov (United States)

    Byrd, Chelsea M; Grosenbach, Douglas W; Berhanu, Aklile; Dai, Dongcheng; Jones, Kevin F; Cardwell, Kara B; Schneider, Christine; Yang, Guang; Tyavanagimatt, Shanthakumar; Harver, Chris; Wineinger, Kristin A; Page, Jessica; Stavale, Eric; Stone, Melialani A; Fuller, Kathleen P; Lovejoy, Candace; Leeds, Janet M; Hruby, Dennis E; Jordan, Robert

    2013-04-01

    Dengue virus (DENV) is the predominant mosquito-borne viral pathogen that infects humans with an estimated 50 to 100 million infections per year worldwide. Over the past 50 years, the incidence of dengue disease has increased dramatically and the virus is now endemic in more than 100 countries. Moreover, multiple serotypes of DENV are now found in the same geographic region, increasing the likelihood of more severe forms of disease. Despite extensive research, there are still no approved vaccines or therapeutics commercially available to treat DENV infection. Here we report the results of a high-throughput screen of a chemical compound library using a whole-virus assay that identified a novel small-molecule inhibitor of DENV, ST-610, that potently and selectively inhibits all four serotypes of DENV replication in vitro. Sequence analysis of drug-resistant virus isolates has identified a single point mutation, A263T, in the NS3 helicase domain that confers resistance to this compound. ST-610 inhibits DENV NS3 helicase RNA unwinding activity in a molecular-beacon-based helicase assay but does not inhibit nucleoside triphosphatase activity based on a malachite green ATPase assay. ST-610 is nonmutagenic, is well tolerated (nontoxic) in mice, and has shown efficacy in a sublethal murine model of DENV infection with the ability to significantly reduce viremia and viral load compared to vehicle controls.

  12. Stochastic spike synchronization in a small-world neural network with spike-timing-dependent plasticity.

    Science.gov (United States)

    Kim, Sang-Yoon; Lim, Woochang

    2018-01-01

    We consider the Watts-Strogatz small-world network (SWN) consisting of subthreshold neurons which exhibit noise-induced spikings. This neuronal network has adaptive dynamic synaptic strengths governed by the spike-timing-dependent plasticity (STDP). In previous works without STDP, stochastic spike synchronization (SSS) between noise-induced spikings of subthreshold neurons was found to occur in a range of intermediate noise intensities. Here, we investigate the effect of additive STDP on the SSS by varying the noise intensity. Occurrence of a "Matthew" effect in synaptic plasticity is found due to a positive feedback process. As a result, good synchronization gets better via long-term potentiation of synaptic strengths, while bad synchronization gets worse via long-term depression. Emergences of long-term potentiation and long-term depression of synaptic strengths are intensively investigated via microscopic studies based on the pair-correlations between the pre- and the post-synaptic IISRs (instantaneous individual spike rates) as well as the distributions of time delays between the pre- and the post-synaptic spike times. Furthermore, the effects of multiplicative STDP (which depends on states) on the SSS are studied and discussed in comparison with the case of additive STDP (independent of states). These effects of STDP on the SSS in the SWN are also compared with those in the regular lattice and the random graph. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Significance of monoclonal antibodies against the conserved epitopes within non-structural protein 3 helicase of hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Yixin Bian

    Full Text Available Nonstructural protein 3 (NS3 of hepatitis C virus (HCV, codes for protease and helicase carrying NTPase enzymatic activities, plays a crucial role in viral replication and an ideal target for diagnosis, antiviral therapy and vaccine development. In this study, monoclonal antibodies (mAbs to NS3 helicase were characterized by epitope mapping and biological function test. A total of 29 monoclonal antibodies were produced to the truncated NS3 helicase of HCV-1b (T1b-rNS3, aa1192-1459. Six mAbs recognized 8/29 16mer peptides, which contributed to identify 5 linear and 1 discontinuous putative epitope sequences. Seven mAbs reacted with HCV-2a JFH-1 infected Huh-7.5.1 cells by immunofluorescent staining, of which 2E12 and 3E5 strongly bound to the exposed linear epitope (1231PTGSGKSTK(1239 (EP05 or core motif (1373IPFYGKAI(1380 (EP21, respectively. Five other mAbs recognized semi-conformational or conformational epitopes of HCV helicase. MAb 2E12 binds to epitope EP05 at the ATP binding site of motif I in domain 1, while mAb 3E5 reacts with epitope EP21 close to helicase nucleotide binding region of domain 2. Epitope EP05 is totally conserved and EP21 highly conserved across HCV genotypes. These two epitope peptides reacted strongly with 59-79% chronic and weakly with 30-58% resolved HCV infected blood donors, suggesting that these epitopes were dominant in HCV infection. MAb 2E12 inhibited 50% of unwinding activity of NS3 helicase in vitro. Novel monoclonal antibodies recognize highly conserved epitopes at crucial functional sites within NS3 helicase, which may become important antibodies for diagnosis and antiviral therapy in chronic HCV infection.

  14. A holistic evolutionary and structural study of flaviviridae provides insights into the function and inhibition of HCV helicase

    Directory of Open Access Journals (Sweden)

    Dimitrios Vlachakis

    2013-05-01

    Full Text Available Viral RNA helicases are involved in duplex unwinding during the RNA replication of the virus. It is suggested that these helicases represent very promising antiviral targets. Viruses of the flaviviridae family are the causative agents of many common and devastating diseases, including hepatitis, yellow fever and dengue fever. As there is currently no available anti-Flaviviridae therapy, there is urgent need for the development of efficient anti-viral pharmaceutical strategies. Herein, we report the complete phylogenetic analysis across flaviviridae alongside a more in-depth evolutionary study that revealed a series of conserved and invariant amino acids that are predicted to be key to the function of the helicase. Structural molecular modelling analysis revealed the strategic significance of these residues based on their relative positioning on the 3D structures of the helicase enzymes, which may be used as pharmacological targets. We previously reported a novel series of highly potent HCV helicase inhibitors, and we now re-assess their antiviral potential using the 3D structural model of the invariant helicase residues. It was found that the most active compound of the series, compound C4, exhibited an IC50 in the submicromolar range, whereas its stereoisomer (compound C12 was completely inactive. Useful insights were obtained from molecular modelling and conformational search studies via molecular dynamics simulations. C12 tends to bend and lock in an almost “U” shape conformation, failing to establish vital interactions with the active site of HCV. On the contrary, C4 spends most of its conformational time in a straight, more rigid formation that allows it to successfully block the passage of the oligonucleotide in the ssRNA channel of the HCV helicase. This study paves the way and provides the necessary framework for the in-depth analysis required to enable the future design of new and potent anti-viral agents.

  15. Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone

    Science.gov (United States)

    Xia, Hongjie; Wang, Peipei; Wang, Guang-Chuan; Yang, Jie; Sun, Xianlin; Wu, Wenzhe; Qiu, Yang; Shu, Ting; Zhao, Xiaolu; Yin, Lei; Qin, Cheng-Feng; Hu, Yuanyang; Zhou, Xi

    2015-01-01

    RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our

  16. Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone.

    Directory of Open Access Journals (Sweden)

    Hongjie Xia

    2015-07-01

    Full Text Available RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71, which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3'-to-5' unwinds RNA helices in an adenosine triphosphate (ATP-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16, another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings

  17. Barbed micro-spikes for micro-scale biopsy

    Science.gov (United States)

    Byun, Sangwon; Lim, Jung-Min; Paik, Seung-Joon; Lee, Ahra; Koo, Kyo-in; Park, Sunkil; Park, Jaehong; Choi, Byoung-Doo; Seo, Jong Mo; Kim, Kyung-ah; Chung, Hum; Song, Si Young; Jeon, Doyoung; Cho, Dongil

    2005-06-01

    Single-crystal silicon planar micro-spikes with protruding barbs are developed for micro-scale biopsy and the feasibility of using the micro-spike as a micro-scale biopsy tool is evaluated for the first time. The fabrication process utilizes a deep silicon etch to define the micro-spike outline, resulting in protruding barbs of various shapes. Shanks of the fabricated micro-spikes are 3 mm long, 100 µm thick and 250 µm wide. Barbs protruding from micro-spike shanks facilitate the biopsy procedure by tearing off and retaining samples from target tissues. Micro-spikes with barbs successfully extracted tissue samples from the small intestines of the anesthetized pig, whereas micro-spikes without barbs failed to obtain a biopsy sample. Parylene coating can be applied to improve the biocompatibility of the micro-spike without deteriorating the biopsy function of the micro-spike. In addition, to show that the biopsy with the micro-spike can be applied to tissue analysis, samples obtained by micro-spikes were examined using immunofluorescent staining. Nuclei and F-actin of cells which are extracted by the micro-spike from a transwell were clearly visualized by immunofluorescent staining.

  18. The Mutation Frequency in Different Spike Categories in Barley

    DEFF Research Database (Denmark)

    Frydenberg, O.; Doll, Hans; Sandfær, J.

    1964-01-01

    After gamma irradiation of barley seeds, a comparison has been made between the chlorophyll-mutant frequencies in X1 spikes that had multicellular bud meristems in the seeds at the time of treatment (denoted as pre-formed spikes) and X1 spikes having no recognizable meristems at the time...

  19. Thermal impact on spiking properties in Hodgkin–Huxley neuron ...

    Indian Academy of Sciences (India)

    Abstract. The effect of environmental temperature on neuronal spiking behaviors is investigated by numerically simulating the temperature dependence of spiking threshold of the Hodgkin–Huxley neuron subject to synaptic stimulus. We find that the spiking threshold exhibits a global minimum in a specific temperature range ...

  20. Cytoplasmic tail of Coronavirus spike protein has intracellular ...

    Indian Academy of Sciences (India)

    58

    Transfection ability of YFP tagged spike protein constructs are much more efficient. 220 compared to wild type spike construct, the reasons for which are unclear (data not. 221 shown). Because of efficient detection of YFP fluorescence and the limitations of spike. 222 specific antibodies, we decided to use the YFP tagged ...

  1. X-ray structure of the pestivirus NS3 helicase and its conformation in solution.

    Science.gov (United States)

    Tortorici, M Alejandra; Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice; Rey, Félix A

    2015-04-01

    Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the

  2. Spiked instantons from intersecting D-branes

    Directory of Open Access Journals (Sweden)

    Nikita Nekrasov

    2017-01-01

    Full Text Available The moduli space of spiked instantons that arises in the context of the BPS/CFT correspondence [22] is realised as the moduli space of classical vacua, i.e. low-energy open string field configurations, of a certain stack of intersecting D1-branes and D5-branes in Type IIB string theory. The presence of a constant B-field induces an interesting dynamics involving the tachyon condensation.

  3. Non-singular spiked harmonic oscillator

    International Nuclear Information System (INIS)

    Aguilera-Navarro, V.C.; Guardiola, R.

    1990-01-01

    A perturbative study of a class of non-singular spiked harmonic oscillators defined by the hamiltonian H = d sup(2)/dr sup(2) + r sup(2) + λ/r sup(α) in the domain [0,∞] is carried out, in the two extremes of a weak coupling and a strong coupling regimes. A path has been found to connect both expansions for α near 2. (author)

  4. Genome-Wide Comparative In Silico Analysis of the RNA Helicase Gene Family in Zea mays and Glycine max: A Comparison with Arabidopsis and Oryza sativa

    Science.gov (United States)

    Huang, Jinguang; Zheng, Chengchao

    2013-01-01

    RNA helicases are enzymes that are thought to unwind double-stranded RNA molecules in an energy-dependent fashion through the hydrolysis of NTP. RNA helicases are associated with all processes involving RNA molecules, including nuclear transcription, editing, splicing, ribosome biogenesis, RNA export, and organelle gene expression. The involvement of RNA helicase in response to stress and in plant growth and development has been reported previously. While their importance in Arabidopsis and Oryza sativa has been partially studied, the function of RNA helicase proteins is poorly understood in Zea mays and Glycine max. In this study, we identified a total of RNA helicase genes in Arabidopsis and other crop species genome by genome-wide comparative in silico analysis. We classified the RNA helicase genes into three subfamilies according to the structural features of the motif II region, such as DEAD-box, DEAH-box and DExD/H-box, and different species showed different patterns of alternative splicing. Secondly, chromosome location analysis showed that the RNA helicase protein genes were distributed across all chromosomes with different densities in the four species. Thirdly, phylogenetic tree analyses identified the relevant homologs of DEAD-box, DEAH-box and DExD/H-box RNA helicase proteins in each of the four species. Fourthly, microarray expression data showed that many of these predicted RNA helicase genes were expressed in different developmental stages and different tissues under normal growth conditions. Finally, real-time quantitative PCR analysis showed that the expression levels of 10 genes in Arabidopsis and 13 genes in Zea mays were in close agreement with the microarray expression data. To our knowledge, this is the first report of a comparative genome-wide analysis of the RNA helicase gene family in Arabidopsis, Oryza sativa, Zea mays and Glycine max. This study provides valuable information for understanding the classification and putative functions of

  5. Genome-wide comparative in silico analysis of the RNA helicase gene family in Zea mays and Glycine max: a comparison with Arabidopsis and Oryza sativa.

    Science.gov (United States)

    Xu, Ruirui; Zhang, Shizhong; Huang, Jinguang; Zheng, Chengchao

    2013-01-01

    RNA helicases are enzymes that are thought to unwind double-stranded RNA molecules in an energy-dependent fashion through the hydrolysis of NTP. RNA helicases are associated with all processes involving RNA molecules, including nuclear transcription, editing, splicing, ribosome biogenesis, RNA export, and organelle gene expression. The involvement of RNA helicase in response to stress and in plant growth and development has been reported previously. While their importance in Arabidopsis and Oryza sativa has been partially studied, the function of RNA helicase proteins is poorly understood in Zea mays and Glycine max. In this study, we identified a total of RNA helicase genes in Arabidopsis and other crop species genome by genome-wide comparative in silico analysis. We classified the RNA helicase genes into three subfamilies according to the structural features of the motif II region, such as DEAD-box, DEAH-box and DExD/H-box, and different species showed different patterns of alternative splicing. Secondly, chromosome location analysis showed that the RNA helicase protein genes were distributed across all chromosomes with different densities in the four species. Thirdly, phylogenetic tree analyses identified the relevant homologs of DEAD-box, DEAH-box and DExD/H-box RNA helicase proteins in each of the four species. Fourthly, microarray expression data showed that many of these predicted RNA helicase genes were expressed in different developmental stages and different tissues under normal growth conditions. Finally, real-time quantitative PCR analysis showed that the expression levels of 10 genes in Arabidopsis and 13 genes in Zea mays were in close agreement with the microarray expression data. To our knowledge, this is the first report of a comparative genome-wide analysis of the RNA helicase gene family in Arabidopsis, Oryza sativa, Zea mays and Glycine max. This study provides valuable information for understanding the classification and putative functions of

  6. Basalt FRP Spike Repairing of Wood Beams

    Directory of Open Access Journals (Sweden)

    Luca Righetti

    2015-08-01

    Full Text Available This article describes aspects within an experimental program aimed at improving the structural performance of cracked solid fir-wood beams repaired with Basalt Fiber Reinforced Polymer (BFRP spikes. Fir wood is characterized by its low density, low compression strength, and high level of defects, and it is likely to distort when dried and tends to fail under tension due to the presence of cracks, knots, or grain deviation. The proposed repair technique consists of the insertion of BFRP spikes into timber beams to restore the continuity of cracked sections. The experimental efforts deal with the evaluation of the bending strength and deformation properties of 24 timber beams. An artificially simulated cracking was produced by cutting the wood beams in half or notching. The obtained results for the repaired beams were compared with those of solid undamaged and damaged beams, and increases of beam capacity, bending strength and of modulus of elasticity, and analysis of failure modes was discussed. For notched beams, the application of the BFRP spikes was able to restore the original bending capacity of undamaged beams, while only a small part of the original capacity was recovered for beams that were cut in half.

  7. Spiking Neural P Systems With Scheduled Synapses.

    Science.gov (United States)

    Cabarle, Francis George C; Adorna, Henry N; Jiang, Min; Zeng, Xiangxiang

    2017-12-01

    Spiking neural P systems (SN P systems) are models of computation inspired by biological spiking neurons. SN P systems have neurons as spike processors, which are placed on the nodes of a directed and static graph (the edges in the graph are the synapses). In this paper, we introduce a variant called SN P systems with scheduled synapses (SSN P systems). SSN P systems are inspired and motivated by the structural dynamism of biological synapses, while incorporating ideas from nonstatic (i.e., dynamic) graphs and networks. In particular, synapses in SSN P systems are available only at specific durations according to their schedules. The SSN P systems model is a response to the problem of introducing durations to synapses of SN P systems. Since SN P systems are in essence static graphs, it is natural to consider them for dynamic graphs also. We introduce local and global schedule types, also taking inspiration from the above-mentioned sources. We prove that SSN P systems are computationally universal as number generators and acceptors for both schedule types, under a normal form (i.e., a simplifying set of restrictions). The introduction of synapse schedules for either schedule type proves useful in programming the system, despite restrictions in the normal form.

  8. Expression, purification, crystallization and preliminary X-ray analysis of the RecQ helicase catalytic core from Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Chen, Sheng-Chia; Huang, Chi-Hung; Yang, Chia-Shin; Chang, Chi-Huang; Kuan, Shu-Min; Chan, Nei-Li; Chen, Yeh

    2012-01-01

    The DrRecQ helicase catalytic core has been crystallized to a resolution of 2.9 Å. The determination of its structure will lead to structural and functional insight into the DNA repair mechanism. The RecQ proteins are a highly conserved group of DNA helicases which play crucial roles in the maintenance of genome stability. DrRecQ from the radioresistant bacterium Deinococcus radiodurans is a special member of the RecQ family because it contains three Helicase-and-RNase-D-C-terminal (HRDC) domains at the C-terminus. The helicase catalytic core is essential for ATPase and DNA-unwinding activities. In this work, the helicase catalytic core of DrRecQ was expressed in Escherichia coli, purified and crystallized. Crystals were obtained using the sitting-drop vapour diffusion method and X-ray diffraction data were collected to 2.9 Å resolution. The crystals belong to space group P2 1 2 1 2 1 , with unit-cell parameters a = 84.75, b = 95.61, c = 183.83 Å

  9. Precise-Spike-Driven Synaptic Plasticity: Learning Hetero-Association of Spatiotemporal Spike Patterns

    Science.gov (United States)

    Yu, Qiang; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

    2013-01-01

    A new learning rule (Precise-Spike-Driven (PSD) Synaptic Plasticity) is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe. PMID:24223789

  10. Precise-spike-driven synaptic plasticity: learning hetero-association of spatiotemporal spike patterns.

    Directory of Open Access Journals (Sweden)

    Qiang Yu

    Full Text Available A new learning rule (Precise-Spike-Driven (PSD Synaptic Plasticity is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe.

  11. Precise-spike-driven synaptic plasticity: learning hetero-association of spatiotemporal spike patterns.

    Science.gov (United States)

    Yu, Qiang; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

    2013-01-01

    A new learning rule (Precise-Spike-Driven (PSD) Synaptic Plasticity) is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe.

  12. Nicotine-Mediated ADP to Spike Transition: Double Spiking in Septal Neurons.

    Science.gov (United States)

    Kodirov, Sodikdjon A; Wehrmeister, Michael; Colom, Luis

    2016-04-01

    The majority of neurons in lateral septum (LS) are electrically silent at resting membrane potential. Nicotine transiently excites a subset of neurons and occasionally leads to long lasting bursting activity upon longer applications. We have observed simultaneous changes in frequencies and amplitudes of spontaneous action potentials (AP) in the presence of nicotine. During the prolonged exposure, nicotine increased numbers of spikes within a burst. One of the hallmarks of nicotine effects was the occurrences of double spikes (known also as bursting). Alignment of 51 spontaneous spikes, triggered upon continuous application of nicotine, revealed that the slope of after-depolarizing potential gradually increased (1.4 vs. 3 mV/ms) and neuron fired the second AP, termed as double spiking. A transition from a single AP to double spikes increased the amplitude of after-hyperpolarizing potential. The amplitude of the second (premature) AP was smaller compared to the first one, and this correlation persisted in regard to their duration (half-width). A similar bursting activity in the presence of nicotine, to our knowledge, has not been reported previously in the septal structure in general and in LS in particular.

  13. A Rad53 Independent Function of Rad9 Becomes Crucial for Genome Maintenance in the Absence of the RecQ Helicase Sgs1

    DEFF Research Database (Denmark)

    Nielsen, Ida; Bentsen, Iben Bach; Andersen, Anni Hangaard

    2013-01-01

    The conserved family of RecQ DNA helicases consists of caretaker tumour suppressors, that defend genome integrity by acting on several pathways of DNA repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ helicase and it has been implicated in checkpoint responses...

  14. Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase

    DEFF Research Database (Denmark)

    Rosenthal, Andrew S; Dexheimer, Thomas S; Gileadi, Opher

    2013-01-01

    Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding comp...

  15. Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy

    Directory of Open Access Journals (Sweden)

    Naruo Yoshida

    2015-07-01

    Conclusions: The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan.

  16. Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons.

    Science.gov (United States)

    Grewe, Jan; Kruscha, Alexandra; Lindner, Benjamin; Benda, Jan

    2017-03-07

    Synchronous activity in populations of neurons potentially encodes special stimulus features. Selective readout of either synchronous or asynchronous activity allows formation of two streams of information processing. Theoretical work predicts that such a synchrony code is a fundamental feature of populations of spiking neurons if they operate in specific noise and stimulus regimes. Here we experimentally test the theoretical predictions by quantifying and comparing neuronal response properties in tuberous and ampullary electroreceptor afferents of the weakly electric fish Apteronotus leptorhynchus These related systems show similar levels of synchronous activity, but only in the more irregularly firing tuberous afferents a synchrony code is established, whereas in the more regularly firing ampullary afferents it is not. The mere existence of synchronous activity is thus not sufficient for a synchrony code. Single-cell features such as the irregularity of spiking and the frequency dependence of the neuron's transfer function determine whether synchronous spikes possess a distinct meaning for the encoding of time-dependent signals.

  17. Comparison of electrodialytic removal of Cu from spiked kaolinite, spiked soil and industrially polluted soil

    DEFF Research Database (Denmark)

    Ottosen, Lisbeth M.; Lepkova, Katarina; Kubal, Martin

    2006-01-01

    Electrokinetic remediation methods for removal of heavy metals from polluted soils have been subjected for quite intense research during the past years since these methods are well suitable for fine-grained soils where other remediation methods fail. Electrodialytic remediation is an electrokinetic...... remediation method which is based on applying an electric DC field and the use of ion exchange membranes that ensures the main transport of heavy metals to be out of the pollutes soil. An experimental investigation was made with electrodialytic removal of Cu from spiked kaolinite, spiked soil and industrially...... polluted soil under the same operational conditions (constant current density 0.2 mA/cm2 and duration 28 days). The results of the present paper show that caution must be taken when generalising results obtained in spiked kaolinite to remediation of industrially polluted soils, as it was shown...

  18. Diallel analysis to study the genetic makeup of spike and yield ...

    African Journals Online (AJOL)

    Five wheat genotypes were crossed in complete diallel fashion for gene action studies of spike length, spikelets per spike, grains per spike, grain weight per spike ... High magnitude of narrow sense heritability (h2n.s) was noticed for spikelets per spike (79%), and grains per spike (88%) thus illustrated fixable and additive ...

  19. The Q Motif Is Involved in DNA Binding but Not ATP Binding in ChlR1 Helicase.

    Directory of Open Access Journals (Sweden)

    Hao Ding

    Full Text Available Helicases are molecular motors that couple the energy of ATP hydrolysis to the unwinding of structured DNA or RNA and chromatin remodeling. The conversion of energy derived from ATP hydrolysis into unwinding and remodeling is coordinated by seven sequence motifs (I, Ia, II, III, IV, V, and VI. The Q motif, consisting of nine amino acids (GFXXPXPIQ with an invariant glutamine (Q residue, has been identified in some, but not all helicases. Compared to the seven well-recognized conserved helicase motifs, the role of the Q motif is less acknowledged. Mutations in the human ChlR1 (DDX11 gene are associated with a unique genetic disorder known as Warsaw Breakage Syndrome, which is characterized by cellular defects in genome maintenance. To examine the roles of the Q motif in ChlR1 helicase, we performed site directed mutagenesis of glutamine to alanine at residue 23 in the Q motif of ChlR1. ChlR1 recombinant protein was overexpressed and purified from HEK293T cells. ChlR1-Q23A mutant abolished the helicase activity of ChlR1 and displayed reduced DNA binding ability. The mutant showed impaired ATPase activity but normal ATP binding. A thermal shift assay revealed that ChlR1-Q23A has a melting point value similar to ChlR1-WT. Partial proteolysis mapping demonstrated that ChlR1-WT and Q23A have a similar globular structure, although some subtle conformational differences in these two proteins are evident. Finally, we found ChlR1 exists and functions as a monomer in solution, which is different from FANCJ, in which the Q motif is involved in protein dimerization. Taken together, our results suggest that the Q motif is involved in DNA binding but not ATP binding in ChlR1 helicase.

  20. Mutational analysis of an archaeal minichromosome maintenance protein exterior hairpin reveals critical residues for helicase activity and DNA binding

    Directory of Open Access Journals (Sweden)

    Brewster Aaron S

    2010-08-01

    Full Text Available Abstract Background The mini-chromosome maintenance protein (MCM complex is an essential replicative helicase for DNA replication in Archaea and Eukaryotes. While the eukaryotic complex consists of six homologous proteins (MCM2-7, the archaeon Sulfolobus solfataricus has only one MCM protein (ssoMCM, six subunits of which form a homohexamer. We have recently reported a 4.35Å crystal structure of the near full-length ssoMCM. The structure reveals a total of four β-hairpins per subunit, three of which are located within the main channel or side channels of the ssoMCM hexamer model generated based on the symmetry of the N-terminal Methanothermobacter thermautotrophicus (mtMCM structure. The fourth β-hairpin, however, is located on the exterior of the hexamer, near the exit of the putative side channels and next to the ATP binding pocket. Results In order to better understand this hairpin's role in DNA binding and helicase activity, we performed a detailed mutational and biochemical analysis of nine residues on this exterior β-hairpin (EXT-hp. We examined the activities of the mutants related to their helicase function, including hexamerization, ATPase, DNA binding and helicase activities. The assays showed that some of the residues on this EXT-hp play a role for DNA binding as well as for helicase activity. Conclusions These results implicate several current theories regarding helicase activity by this critical hexameric enzyme. As the data suggest that EXT-hp is involved in DNA binding, the results reported here imply that the EXT-hp located near the exterior exit of the side channels may play a role in contacting DNA substrate in a manner that affects DNA unwinding.

  1. Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

    Energy Technology Data Exchange (ETDEWEB)

    Möhlmann, Sina [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Mathew, Rebecca [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Neumann, Piotr; Schmitt, Andreas [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Lührmann, Reinhard [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@uni-goettingen.de [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

    2014-06-01

    The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

  2. In vivo mapping of the functional regions of the DEAD-box helicase Vasa

    Directory of Open Access Journals (Sweden)

    Mehrnoush Dehghani

    2015-03-01

    Full Text Available The maternally expressed Drosophila melanogaster DEAD-box helicase Vasa (Vas is necessary for many cellular and developmental processes, including specification of primordial germ cells (pole cells, posterior patterning of the embryo, piRNA-mediated repression of transposon-encoded mRNAs, translational activation of gurken (grk mRNA, and completion of oogenesis itself. Vas protein accumulates in the perinuclear nuage in nurse cells soon after their specification, and then at stage 10 Vas translocates to the posterior pole plasm of the oocyte. We produced a series of transgenic constructs encoding eGFP-Vas proteins carrying mutations affecting different regions of the protein, and analyzed in vivo which Vas functions each could support. We identified novel domains in the N- and C-terminal regions of the protein that are essential for localization, transposon repression, posterior patterning, and pole cell specification. One such functional region, the most C-terminal seven amino acids, is specific to Vas orthologues and is thus critical to distinguishing Vas from other closely related DEAD-box helicases. Surprisingly, we also found that many eGFP-Vas proteins carrying mutations that would be expected to abrogate DEAD-box helicase function localized to the nuage and posterior pole, and retained the capacity to support oogenesis, although they did not function in embryonic patterning, pole cell specification, grk activation, or transposon repression. We conclude from these experiments that Vas, a multifunctional protein, uses different domains and different molecular associations to carry out its various cellular and developmental roles.

  3. Solving constraint satisfaction problems with networks of spiking neurons

    Directory of Open Access Journals (Sweden)

    Zeno eJonke

    2016-03-01

    Full Text Available Network of neurons in the brain apply – unlike processors in our current generation ofcomputer hardware – an event-based processing strategy, where short pulses (spikes areemitted sparsely by neurons to signal the occurrence of an event at a particular point intime. Such spike-based computations promise to be substantially more power-efficient thantraditional clocked processing schemes. However it turned out to be surprisingly difficult todesign networks of spiking neurons that can solve difficult computational problems on the levelof single spikes (rather than rates of spikes. We present here a new method for designingnetworks of spiking neurons via an energy function. Furthermore we show how the energyfunction of a network of stochastically firing neurons can be shaped in a quite transparentmanner by composing the networks of simple stereotypical network motifs. We show that thisdesign approach enables networks of spiking neurons to produce approximate solutions todifficult (NP-hard constraint satisfaction problems from the domains of planning/optimizationand verification/logical inference. The resulting networks employ noise as a computationalresource. Nevertheless the timing of spikes (rather than just spike rates plays an essential rolein their computations. Furthermore, networks of spiking neurons carry out for the Traveling Salesman Problem a more efficient stochastic search for good solutions compared with stochastic artificial neural networks (Boltzmann machines and Gibbs sampling.

  4. Decrease in Lymphoid Specific Helicase and 5-hydroxymethylcytosine Is Associated with Metastasis and Genome Instability

    OpenAIRE

    Jia, Jiantao; Shi, Ying; Chen, Ling; Lai, Weiwei; Yan, Bin; Jiang, Yiqun; Xiao, Desheng; Xi, Sichuan; Cao, Ya; Liu, Shuang; Cheng, Yan; Tao, Yongguang

    2017-01-01

    DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change...

  5. New roles of the human Suv3 helicase in genome maintenance

    DEFF Research Database (Denmark)

    Venø, Susanne Trillingsgaard

    During her PhD studies, Susanne Trillingsgaard Venø carried out research into the role of the human Suv3 protein in stabilising the human genome – DNA. Suv3 is a helicase that separates the two strands of the DNA’s double helix. Throughout our lives, the DNA in our cells is constantly exposed...... maintenance. Based on these new research results, the Suv3 protein could be a valuable model for genome stability as an important factor in our understanding of why we get old....

  6. Dual Nuclease and Helicase Activities of Helicobacter pylori AddAB Are Required for DNA Repair, Recombination, and Mouse Infectivity*

    OpenAIRE

    Amundsen, Susan K.; Fero, Jutta; Salama, Nina R.; Smith, Gerald R.

    2009-01-01

    Helicobacter pylori infection of the human stomach is associated with disease-causing inflammation that elicits DNA damage in both bacterial and host cells. Bacteria must repair their DNA to persist. The H. pylori AddAB helicase-exonuclease is required for DNA repair and efficient stomach colonization. To dissect the role of each activity in DNA repair and infectivity, we altered the AddA and AddB nuclease (NUC) domains and the AddA helicase (HEL) domain by site-directed mutagenesis. Extracts...

  7. Substrate specific stimulation of NEIL1 by WRN but not the other human RecQ helicases

    DEFF Research Database (Denmark)

    Popuri, Venkateswarlu; Croteau, Deborah L; Bohr, Vilhelm A

    2010-01-01

    NEIL1, the mammalian homolog of Escherichia coli endonuclease VIII, is a DNA glycosylase that repairs ring-fragmented purines, saturated pyrimidines and several oxidative lesions like 5-hydroxyuracil, 5-hydroxycytosine, etc. Previous studies from our laboratory have shown that Werner Syndrome...... protein (WRN), one of the five human RecQ helicases, stimulates NEIL1 DNA glycosylase activity on oxidative DNA lesions. The goal of this study was to extend this observation and analyze the interaction between NEIL1 and all five human RecQ helicases. The DNA substrate specificity of the interaction...

  8. Spike-timing-dependent learning rule to encode spatiotemporal patterns in a network of spiking neurons

    Science.gov (United States)

    Yoshioka, Masahiko

    2002-01-01

    We study associative memory neural networks based on the Hodgkin-Huxley type of spiking neurons. We introduce the spike-timing-dependent learning rule, in which the time window with the negative part as well as the positive part is used to describe the biologically plausible synaptic plasticity. The learning rule is applied to encode a number of periodical spatiotemporal patterns, which are successfully reproduced in the periodical firing pattern of spiking neurons in the process of memory retrieval. The global inhibition is incorporated into the model so as to induce the gamma oscillation. The occurrence of gamma oscillation turns out to give appropriate spike timings for memory retrieval of discrete type of spatiotemporal pattern. The theoretical analysis to elucidate the stationary properties of perfect retrieval state is conducted in the limit of an infinite number of neurons and shows the good agreement with the result of numerical simulations. The result of this analysis indicates that the presence of the negative and positive parts in the form of the time window contributes to reduce the size of crosstalk term, implying that the time window with the negative and positive parts is suitable to encode a number of spatiotemporal patterns. We draw some phase diagrams, in which we find various types of phase transitions with change of the intensity of global inhibition.

  9. Spike Pattern Recognition for Automatic Collimation Alignment

    CERN Document Server

    Azzopardi, Gabriella; Salvachua Ferrando, Belen Maria; Mereghetti, Alessio; Redaelli, Stefano; CERN. Geneva. ATS Department

    2017-01-01

    The LHC makes use of a collimation system to protect its sensitive equipment by intercepting potentially dangerous beam halo particles. The appropriate collimator settings to protect the machine against beam losses relies on a very precise alignment of all the collimators with respect to the beam. The beam center at each collimator is then found by touching the beam halo using an alignment procedure. Until now, in order to determine whether a collimator is aligned with the beam or not, a user is required to follow the collimator’s BLM loss data and detect spikes. A machine learning (ML) model was trained in order to automatically recognize spikes when a collimator is aligned. The model was loosely integrated with the alignment implementation to determine the classification performance and reliability, without effecting the alignment process itself. The model was tested on a number of collimators during this MD and the machine learning was able to output the classifications in real-time.

  10. Eliminating thermal violin spikes from LIGO noise

    Energy Technology Data Exchange (ETDEWEB)

    Santamore, D. H.; Levin, Yuri

    2001-08-15

    We have developed a scheme for reducing LIGO suspension thermal noise close to violin-mode resonances. The idea is to monitor directly the thermally induced motion of a small portion of (a 'point' on) each suspension fiber, thereby recording the random forces driving the test-mass motion close to each violin-mode frequency. One can then suppress the thermal noise by optimally subtracting the recorded fiber motions from the measured motion of the test mass, i.e., from the LIGO output. The proposed method is a modification of an analogous but more technically difficult scheme by Braginsky, Levin and Vyatchanin for reducing broad-band suspension thermal noise. The efficiency of our method is limited by the sensitivity of the sensor used to monitor the fiber motion. If the sensor has no intrinsic noise (i.e. has unlimited sensitivity), then our method allows, in principle, a complete removal of violin spikes from the thermal-noise spectrum. We find that in LIGO-II interferometers, in order to suppress violin spikes below the shot-noise level, the intrinsic noise of the sensor must be less than {approx}2 x 10{sup -13} cm/Hz. This sensitivity is two orders of magnitude greater than that of currently available sensors.

  11. Eliminating thermal violin spikes from LIGO noise

    International Nuclear Information System (INIS)

    Santamore, D. H.; Levin, Yuri

    2001-01-01

    We have developed a scheme for reducing LIGO suspension thermal noise close to violin-mode resonances. The idea is to monitor directly the thermally induced motion of a small portion of (a 'point' on) each suspension fiber, thereby recording the random forces driving the test-mass motion close to each violin-mode frequency. One can then suppress the thermal noise by optimally subtracting the recorded fiber motions from the measured motion of the test mass, i.e., from the LIGO output. The proposed method is a modification of an analogous but more technically difficult scheme by Braginsky, Levin and Vyatchanin for reducing broad-band suspension thermal noise. The efficiency of our method is limited by the sensitivity of the sensor used to monitor the fiber motion. If the sensor has no intrinsic noise (i.e. has unlimited sensitivity), then our method allows, in principle, a complete removal of violin spikes from the thermal-noise spectrum. We find that in LIGO-II interferometers, in order to suppress violin spikes below the shot-noise level, the intrinsic noise of the sensor must be less than ∼2 x 10 -13 cm/Hz. This sensitivity is two orders of magnitude greater than that of currently available sensors

  12. Phase Diagram of Spiking Neural Networks

    Directory of Open Access Journals (Sweden)

    Hamed eSeyed-Allaei

    2015-03-01

    Full Text Available In computer simulations of spiking neural networks, often it is assumed that every two neurons of the network are connected by a probablilty of 2%, 20% of neurons are inhibitory and 80% are excitatory. These common values are based on experiments, observations. but here, I take a different perspective, inspired by evolution. I simulate many networks, each with a different set of parameters, and then I try to figure out what makes the common values desirable by nature. Networks which are configured according to the common values, have the best dynamic range in response to an impulse and their dynamic range is more robust in respect to synaptic weights. In fact, evolution has favored networks of best dynamic range. I present a phase diagram that shows the dynamic ranges of different networks of different parameteres. This phase diagram gives an insight into the space of parameters -- excitatory to inhibitory ratio, sparseness of connections and synaptic weights. It may serve as a guideline to decide about the values of parameters in a simulation of spiking neural network.

  13. Spiking Neural Network in Precision Agriculture

    Directory of Open Access Journals (Sweden)

    Nadia Adnan Shiltagh

    2015-07-01

    Full Text Available In this paper, precision agriculture system is introduced based on Wireless Sensor Network (WSN. Soil moisture considered one of environment factors that effect on crop. The period of irrigation must be monitored. Neural network capable of learning the behavior of the agricultural soil in absence of mathematical model. This paper introduced modified type of neural network that is known as Spiking Neural Network (SNN. In this work, the precision agriculture system is modeled, contains two SNNs which have been identified off-line based on logged data, one of these SNNs represents the monitor that located at sink where the period of irrigation is calculated and the other represents the soil. In addition, to reduce power consumption of sensor nodes Modified Chain-Cluster based Mixed (MCCM routing algorithm is used. According to MCCM, the sensors will send their packets that are less than threshold moisture level to the sink. The SNN with Modified Spike-Prop (MSP training algorithm is capable of identifying soil, irrigation periods and monitoring the soil moisture level, this means that SNN has the ability to be an identifier and monitor. By applying this system the particular agriculture area reaches to the desired moisture level.

  14. An Overview of Bayesian Methods for Neural Spike Train Analysis

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    2013-01-01

    Full Text Available Neural spike train analysis is an important task in computational neuroscience which aims to understand neural mechanisms and gain insights into neural circuits. With the advancement of multielectrode recording and imaging technologies, it has become increasingly demanding to develop statistical tools for analyzing large neuronal ensemble spike activity. Here we present a tutorial overview of Bayesian methods and their representative applications in neural spike train analysis, at both single neuron and population levels. On the theoretical side, we focus on various approximate Bayesian inference techniques as applied to latent state and parameter estimation. On the application side, the topics include spike sorting, tuning curve estimation, neural encoding and decoding, deconvolution of spike trains from calcium imaging signals, and inference of neuronal functional connectivity and synchrony. Some research challenges and opportunities for neural spike train analysis are discussed.

  15. A new supervised learning algorithm for spiking neurons.

    Science.gov (United States)

    Xu, Yan; Zeng, Xiaoqin; Zhong, Shuiming

    2013-06-01

    The purpose of supervised learning with temporal encoding for spiking neurons is to make the neurons emit a specific spike train encoded by the precise firing times of spikes. If only running time is considered, the supervised learning for a spiking neuron is equivalent to distinguishing the times of desired output spikes and the other time during the running process of the neuron through adjusting synaptic weights, which can be regarded as a classification problem. Based on this idea, this letter proposes a new supervised learning method for spiking neurons with temporal encoding; it first transforms the supervised learning into a classification problem and then solves the problem by using the perceptron learning rule. The experiment results show that the proposed method has higher learning accuracy and efficiency over the existing learning methods, so it is more powerful for solving complex and real-time problems.

  16. Effects of Spike Anticipation on the Spiking Dynamics of Neural Networks

    Directory of Open Access Journals (Sweden)

    Daniel ede Santos-Sierra

    2015-11-01

    Full Text Available Synchronization is one of the central phenomena involved in information processing in living systems. It is known that the nervous system requires the coordinated activity of both local and distant neural populations. Such an interplay allows to merge different information modalities in a whole processing supporting high-level mental skills as understanding, memory, abstraction, etc. Though the biological processes underlying synchronization in the brain are not fully understood there have been reported a variety of mechanisms supporting different types of synchronization both at theoretical and experimental level. One of the more intriguing of these phenomena is the anticipating synchronization, which has been recently reported in a pair of unidirectionally coupled artificial neurons under simple conditions cite{Pyragas}, where the slave neuron is able to anticipate in time the behaviour of the master one. In this paper we explore the effect of spike anticipation over the information processing performed by a neural network at functional and structural level. We show that the introduction of intermediary neurons in the network enhances spike anticipation and analyse how these variations in spike anticipation can significantly change the firing regime of the neural network according to its functional and structural properties. In addition we show that the interspike interval (ISI, one of the main features of the neural response associated to the information coding, can be closely related to spike anticipation by each spike, and how synaptic plasticity can be modulated through that relationship. This study has been performed through numerical simulation of a coupled system of Hindmarsh-Rose neurons.

  17. Multimodal imaging of spike propagation: a technical case report.

    Science.gov (United States)

    Tanaka, N; Grant, P E; Suzuki, N; Madsen, J R; Bergin, A M; Hämäläinen, M S; Stufflebeam, S M

    2012-06-01

    We report an 11-year-old boy with intractable epilepsy, who had cortical dysplasia in the right superior frontal gyrus. Spatiotemporal source analysis of MEG and EEG spikes demonstrated a similar time course of spike propagation from the superior to inferior frontal gyri, as observed on intracranial EEG. The tractography reconstructed from DTI showed a fiber connection between these areas. Our multimodal approach demonstrates spike propagation and a white matter tract guiding the propagation.

  18. Spike timing precision in the visual front-end

    OpenAIRE

    Borghuis, B.G. (Bart Gerard)

    2003-01-01

    This thesis describes a series of investigations into the reliability of neural responses in the primary visual pathway. The results described in subsequent chapters are primarily based on extracellular recordings from single neurons in anaesthetized cats and area MT of an awake monkey, and computational model analysis. Comparison of spike timing precision in recorded and Poisson-simulated spike trains shows that spike timing in the front-end visual system is considerably more precise than on...

  19. Spike sorting for polytrodes: a divide and conquer approach

    OpenAIRE

    Swindale, Nicholas V.; Spacek, Martin A.

    2014-01-01

    In order to determine patterns of neural activity, spike signals recorded by extracellular electrodes have to be clustered (sorted) with the aim of ensuring that each cluster represents all the spikes generated by an individual neuron. Many methods for spike sorting have been proposed but few are easily applicable to recordings from polytrodes which may have 16 or more recording sites. As with tetrodes, these are spaced sufficiently closely that signals from single neurons will usually be rec...

  20. Spike Frequency Adaptation in Neurons of the Central Nervous System.

    Science.gov (United States)

    Ha, Go Eun; Cheong, Eunji

    2017-08-01

    Neuronal firing patterns and frequencies determine the nature of encoded information of the neurons. Here we discuss the molecular identity and cellular mechanisms of spike-frequency adaptation in central nervous system (CNS) neurons. Calcium-activated potassium (K Ca ) channels such as BK Ca and SK Ca channels have long been known to be important mediators of spike adaptation via generation of a large afterhyperpolarization when neurons are hyper-activated. However, it has been shown that a strong hyperpolarization via these K Ca channels would cease action potential generation rather than reducing the frequency of spike generation. In some types of neurons, the strong hyperpolarization is followed by oscillatory activity in these neurons. Recently, spike-frequency adaptation in thalamocortical (TC) and CA1 hippocampal neurons is shown to be mediated by the Ca 2+ -activated Cl- channel (CACC), anoctamin-2 (ANO2). Knockdown of ANO2 in these neurons results in significantly reduced spike-frequency adaptation accompanied by increased number of spikes without shifting the firing mode, which suggests that ANO2 mediates a genuine form of spike adaptation, finely tuning the frequency of spikes in these neurons. Based on the finding of a broad expression of this new class of CACC in the brain, it can be proposed that the ANO2-mediated spike-frequency adaptation may be a general mechanism to control information transmission in the CNS neurons.

  1. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    is poorly understood. Here we show that WRN physically interacts with the MSH2/MSH6 (MutSalpha), MSH2/MSH3 (MutSbeta) and MLH1/PMS2 (MutLalpha) heterodimers that are involved in the initiation of mismatch repair (MMR) and the rejection of homeologous recombination. MutSalpha and MutSbeta can strongly......Werner syndrome (WS) is a severe recessive disorder characterized by premature aging, cancer predisposition and genomic instability. The gene mutated in WS encodes a bi-functional enzyme called WRN that acts as a RecQ-type DNA helicase and a 3'-5' exonuclease, but its exact role in DNA metabolism...... stimulate the helicase activity of WRN specifically on forked DNA structures with a 3'-single-stranded arm. The stimulatory effect of MutSalpha on WRN-mediated unwinding is enhanced by a G/T mismatch in the DNA duplex ahead of the fork. The MutLalpha protein known to bind to the MutS alpha...

  2. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair

    Science.gov (United States)

    Nimonkar, Amitabh V.; Özsoy, A. Zeynep; Genschel, Jochen; Modrich, Paul; Kowalczykowski, Stephen C.

    2008-01-01

    The error-free repair of double-stranded DNA breaks by homologous recombination requires processing of broken ends. These processed ends are substrates for assembly of DNA strand exchange proteins that mediate DNA strand invasion. Here, we establish that human BLM helicase, a member of the RecQ family, stimulates the nucleolytic activity of human exonuclease 1 (hExo1), a 5′→3′ double-stranded DNA exonuclease. The stimulation is specific because other RecQ homologs fail to stimulate hExo1. Stimulation of DNA resection by hExo1 is independent of BLM helicase activity and is, instead, mediated by an interaction between the 2 proteins. Finally, we show that DNA ends resected by hExo1 and BLM are used by human Rad51, but not its yeast or bacterial counterparts, to promote homologous DNA pairing. This in vitro system recapitulates initial steps of homologous recombination and provides biochemical evidence for a role of BLM and Exo1 in the initiation of recombinational DNA repair. PMID:18971343

  3. Sumoylation of RecQ helicase controls the fate of dysfunctional telomeres.

    Science.gov (United States)

    Rog, Ofer; Miller, Kyle M; Ferreira, Miguel Godinho; Cooper, Julia Promisel

    2009-03-13

    Genome stability depends upon the RecQ helicases, which are conserved from bacteria to man, but little is known about how their myriad activities are regulated. Fission yeast lacking the telomere protein Taz1 (mammalian TRF1/TRF2 ortholog) lose many hallmarks of telomeres, including accurate replication and local protection from DNA repair reactions. Here we show that the RecQ homolog, Rqh1, is sumoylated. Surprisingly, Rqh1 acts on taz1Delta telomeres in a deleterious way, promoting telomere breakage and entanglement. Mutation of Rqh1 sumoylation sites rescues taz1Delta cells from these hazards without dramatically affecting nontelomeric Rqh1 functions. The prominence of Rqh1 in the etiology of several different telomere defects supports the idea that they originate from a common underlying lesion--aberrant processing of the stalled telomeric replication forks that accumulate in the absence of Taz1. Our work underscores the principle that RecQ helicases are "double-edged swords" whose activity, while necessary for maintaining genome-wide stability, must be vigilantly controlled.

  4. CTXφ Replication Depends on the Histone-Like HU Protein and the UvrD Helicase.

    Directory of Open Access Journals (Sweden)

    Eriel Martínez

    2015-05-01

    Full Text Available The Vibrio cholerae bacterium is the agent of cholera. The capacity to produce the cholera toxin, which is responsible for the deadly diarrhea associated with cholera epidemics, is encoded in the genome of a filamentous phage, CTXφ. Rolling-circle replication (RCR is central to the life cycle of CTXφ because amplification of the phage genome permits its efficient integration into the genome and its packaging into new viral particles. A single phage-encoded HUH endonuclease initiates RCR of the proto-typical filamentous phages of enterobacteriaceae by introducing a nick at a specific position of the double stranded DNA form of the phage genome. The rest of the process is driven by host factors that are either essential or crucial for the replication of the host genome, such as the Rep SF1 helicase. In contrast, we show here that the histone-like HU protein of V. cholerae is necessary for the introduction of a nick by the HUH endonuclease of CTXφ. We further show that CTXφ RCR depends on a SF1 helicase normally implicated in DNA repair, UvrD, rather than Rep. In addition to CTXφ, we show that VGJφ, a representative member of a second family of vibrio integrative filamentous phages, requires UvrD and HU for RCR while TLCφ, a satellite phage, depends on Rep and is independent from HU.

  5. DRH1, a p68-related RNA helicase gene, is required for chromosome breakage in Tetrahymena

    Directory of Open Access Journals (Sweden)

    Stephen L. McDaniel

    2016-12-01

    Full Text Available The p68 DEAD box helicases comprise a widely conserved protein family involved in a large range of biological processes including transcription, splicing and translation. The genome of the ciliate Tetrahymena thermophile encodes two p68-like helicases, Drh1p and Lia2p. We show that DRH1 is essential for growth and completion of development. In growing cells, Drh1p is excluded from the nucleus and accumulates near cortical basal bodies. In contrast, during sexual reproduction, this protein localizes to meiotic micronuclei, initially in punctate foci in regions where centromeres and telomeres are known to reside and later in post-zygotic differentiating somatic macronuclei. Differentiation of the macronuclear genome involves extensive DNA rearrangements including fragmentation of the five pairs of germline-derived chromosomes into 180 chromosomal sub-fragments that are stabilized by de novo telomere deletion. In addition, thousands of internal eliminated sequences (IESs are excised from loci dispersed throughout the genome. Strains with DRH1 deleted from the germline nuclei, which do not express the protein during post-zygotic development, fail to fragment the developing macronuclear chromosomes. IES excision still occurs in the absence of DRH1 zygotic expression; thus, Drh1p is the first protein found to be specifically required for chromosome breakage but not DNA elimination.

  6. The nuclear import of RNA helicase A is mediated by importin-α3

    International Nuclear Information System (INIS)

    Aratani, Satoko; Oishi, Takayuki; Fujita, Hidetoshi; Nakazawa, Minako; Fujii, Ryouji; Imamoto, Naoko; Yoneda, Yoshihiro; Fukamizu, Akiyoshi; Nakajima, Toshihiro

    2006-01-01

    RNA helicase A (RHA), an ATPase/helicase, regulates the gene expression at various steps including transcriptional activation and RNA processing. RHA is known to shuttle between the nucleus and cytoplasm. We identified the nuclear localization signal (NLS) of RHA and analyzed the nuclear import mechanisms. The NLS of RHA (RHA-NLS) consisting of 19 amino acid residues is highly conserved through species and does not have the consensus classical NLS. In vitro nuclear import assays revealed that the nuclear import of RHA was Ran-dependent and mediated with the classical importin-α/β-dependent pathway. The binding assay indicated that the basic residues in RHA-NLS were used for interaction with importin-α. Furthermore, the nuclear import of RHA-NLS was supported by importin-α1 and preferentially importin-α3. Our results indicate that the nuclear import of RHA is mediated by the importin-α3/importin-β-dependent pathway and suggest that the specificity for importin may regulate the functions of cargo proteins

  7. An antiviral response directed by PKR phosphorylation of the RNA helicase A.

    Directory of Open Access Journals (Sweden)

    Anthony J Sadler

    2009-02-01

    Full Text Available The double-stranded RNA-activated protein kinase R (PKR is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2alpha to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA. Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR-mediated type 1 human immunodeficiency virus (HIV-1 gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism.

  8. AMORE Mo-99 Spike Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Youker, Amanda J. [Argonne National Lab. (ANL), Argonne, IL (United States); Krebs, John F. [Argonne National Lab. (ANL), Argonne, IL (United States); Quigley, Kevin J. [Argonne National Lab. (ANL), Argonne, IL (United States); Byrnes, James P. [Argonne National Lab. (ANL), Argonne, IL (United States); Rotsch, David A [Argonne National Lab. (ANL), Argonne, IL (United States); Brossard, Thomas [Argonne National Lab. (ANL), Argonne, IL (United States); Wesolowski, Kenneth [Argonne National Lab. (ANL), Argonne, IL (United States); Alford, Kurt [Argonne National Lab. (ANL), Argonne, IL (United States); Chemerisov, Sergey [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-09-27

    With funding from the National Nuclear Security Administrations Material Management and Minimization Office, Argonne National Laboratory (Argonne) is providing technical assistance to help accelerate the U.S. production of Mo-99 using a non-highly enriched uranium (non-HEU) source. A potential Mo-99 production pathway is by accelerator-initiated fissioning in a subcritical uranyl sulfate solution containing low enriched uranium (LEU). As part of the Argonne development effort, we are undertaking the AMORE (Argonne Molybdenum Research Experiment) project, which is essentially a pilot facility for all phases of Mo-99 production, recovery, and purification. Production of Mo-99 and other fission products in the subcritical target solution is initiated by putting an electron beam on a depleted uranium (DU) target; the fast neutrons produced in the DU target are thermalized and lead to fissioning of U-235. At the end of irradiation, Mo is recovered from the target solution and separated from uranium and most of the fission products by using a titania column. The Mo is stripped from the column with an alkaline solution. After acidification of the Mo product solution from the recovery column, the Mo is concentrated (and further purified) in a second titania column. The strip solution from the concentration column is then purified with the LEU Modified Cintichem process. A full description of the process can be found elsewhere [1–3]. The initial commissioning steps for the AMORE project include performing a Mo-99 spike test with pH 1 sulfuric acid in the target vessel without a beam on the target to demonstrate the initial Mo separation-and-recovery process, followed by the concentration column process. All glovebox operations were tested with cold solutions prior to performing the Mo-99 spike tests. Two Mo-99 spike tests with pH 1 sulfuric acid have been performed to date. Figure 1 shows the flow diagram for the remotely operated Mo-recovery system for the AMORE project

  9. Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. I: Spike Generating Models on Converging Motifs

    OpenAIRE

    Bi, Zedong; Zhou, Changsong

    2016-01-01

    In neural systems, synaptic plasticity is usually driven by spike trains. Due to the inherent noises of neurons and synapses as well as the randomness of connection details, spike trains typically exhibit variability such as spatial randomness and temporal stochasticity, resulting in variability of synaptic changes under plasticity, which we call efficacy variability. How the variability of spike trains influences the efficacy variability of synapses remains unclear. In this paper, we try to...

  10. [Wide QRS tachycardia preceded by pacemaker spikes].

    Science.gov (United States)

    Romero, M; Aranda, A; Gómez, F J; Jurado, A

    2014-04-01

    The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  11. The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients

    DEFF Research Database (Denmark)

    Jensen, Martin Borch; Dunn, Christopher A; Keijzers, Guido

    2012-01-01

    -dead, had marginal ATPase activity and may be structurally compromised, while the other two showed greatly reduced helicase and ATPase activities. The remaining biochemical activities and ability to recruit to damage sites were not significantly impaired for any of the mutants. Our findings demonstrate...

  12. The RecQ helicase-topoisomerase III-Rmi1 complex: a DNA structure-specific 'dissolvasome'?

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Hickson, Ian D

    2007-01-01

    RecQ helicases, together with topoisomerase III and Rmi1 family proteins, form an evolutionarily conserved complex that is essential for the maintenance of genome integrity. This complex, which we term RTR, is capable of, or has been implicated in, the processing of a diverse array of DNA...

  13. Single molecule measurements of DNA helicase activity with magnetic tweezers and t-test based step-finding analysis

    Science.gov (United States)

    Seol, Yeonee; Strub, Marie-Paule; Neuman, Keir C.

    2016-01-01

    Magnetic tweezers is a versatile and easy to implement single-molecule technique that has become increasingly prevalent in the study of nucleic acid based molecular motors. Here, we provide a description of the magnetic tweezers instrument and guidelines for measuring and analyzing DNA helicase activity. Along with experimental methods, we describe a robust method of single-molecule trajectory analysis based on the Student’s t-test that accommodates continuous transitions in addition to the discrete transitions assumed in most widely employed analysis routines. To illustrate the single-molecule unwinding assay and the analysis routine, we provide DNA unwinding measurements of Escherichia coli RecQ helicase under a variety of conditions (Na+, ATP, temperature, and DNA substrate geometry). These examples reveal that DNA unwinding measurements under various conditions can aid in elucidating the unwinding mechanism of DNA helicase but also emphasize that environmental effects on DNA helicase activity must be considered in relation to in vivo activity and mechanism. PMID:27131595

  14. Effects of the NUP98-DDX10 oncogene on primary human CD34+ cells: role of a conserved helicase motif.

    Science.gov (United States)

    Yassin, E R; Abdul-Nabi, A M; Takeda, A; Yaseen, N R

    2010-05-01

    NUP98 gene rearrangements occur in acute myeloid leukemia and result in the expression of fusion proteins. One of the most frequent is NUP98-DDX10 that fuses a portion of NUP98 to a portion of DDX10, a putative DEAD-box RNA helicase. Here, we show that NUP98-DDX10 dramatically increases proliferation and self-renewal of primary human CD34+ cells, and disrupts their erythroid and myeloid differentiation. It localizes to their nuclei and extensively deregulates gene expression. Comparison to another leukemogenic NUP98 fusion, NUP98-HOXA9, reveals a number of genes deregulated by both oncoproteins, including HOX genes, COX-2, MYCN, ANGPT1, REN, HEY1, SOX4 and others. These genes may account for the similar leukemogenic properties of NUP98 fusion oncogenes. The YIHRAGRTAR sequence in the DDX10 portion of NUP98-DDX10 represents a major motif shared by DEAD-box RNA helicases that is required for ATP binding, RNA-binding and helicase functions. Mutating this motif diminished the in vitro transforming ability of NUP98-DDX10, indicating that it has a role in leukemogenesis. These data show for the first time the in vitro transforming ability of NUP98-DDX10 and show that it is partially dependent on one of the consensus helicase motifs of DDX10. They also point to common pathways that may underlie leukemogenesis by different NUP98 fusions.

  15. RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis

    DEFF Research Database (Denmark)

    Di Marco, Stefano; Hasanova, Zdenka; Kanagaraj, Radhakrishnan

    2017-01-01

    The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent...

  16. Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs

    DEFF Research Database (Denmark)

    Nguyen, Giang Huong; Tang, Weiliang; Robles, Ana I

    2014-01-01

    Bloom syndrome is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition, and caused by mutations in the gene encoding the Bloom syndrome, RecQ helicase-like (BLM) protein. To determine whether altered gene expression might be responsible for pathologic...

  17. Hrq1, a Homolog of the Human RecQ4 Helicase, Acts Catalytically and Structurally to Promote Genome Integrity

    Directory of Open Access Journals (Sweden)

    Matthew L. Bochman

    2014-01-01

    Full Text Available Human RecQ4 (hRecQ4 affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3′-5′ helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres in vivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to a role in ICL repair and/or suppression of de novo telomere addition.

  18. Neuronal spike sorting based on radial basis function neural networks

    Directory of Open Access Journals (Sweden)

    Taghavi Kani M

    2011-02-01

    Full Text Available "nBackground: Studying the behavior of a society of neurons, extracting the communication mechanisms of brain with other tissues, finding treatment for some nervous system diseases and designing neuroprosthetic devices, require an algorithm to sort neuralspikes automatically. However, sorting neural spikes is a challenging task because of the low signal to noise ratio (SNR of the spikes. The main purpose of this study was to design an automatic algorithm for classifying neuronal spikes that are emitted from a specific region of the nervous system."n "nMethods: The spike sorting process usually consists of three stages: detection, feature extraction and sorting. We initially used signal statistics to detect neural spikes. Then, we chose a limited number of typical spikes as features and finally used them to train a radial basis function (RBF neural network to sort the spikes. In most spike sorting devices, these signals are not linearly discriminative. In order to solve this problem, the aforesaid RBF neural network was used."n "nResults: After the learning process, our proposed algorithm classified any arbitrary spike. The obtained results showed that even though the proposed Radial Basis Spike Sorter (RBSS reached to the same error as the previous methods, however, the computational costs were much lower compared to other algorithms. Moreover, the competitive points of the proposed algorithm were its good speed and low computational complexity."n "nConclusion: Regarding the results of this study, the proposed algorithm seems to serve the purpose of procedures that require real-time processing and spike sorting.

  19. A robust and biologically plausible spike pattern recognition network.

    Science.gov (United States)

    Larson, Eric; Perrone, Ben P; Sen, Kamal; Billimoria, Cyrus P

    2010-11-17

    The neural mechanisms that enable recognition of spiking patterns in the brain are currently unknown. This is especially relevant in sensory systems, in which the brain has to detect such patterns and recognize relevant stimuli by processing peripheral inputs; in particular, it is unclear how sensory systems can recognize time-varying stimuli by processing spiking activity. Because auditory stimuli are represented by time-varying fluctuations in frequency content, it is useful to consider how such stimuli can be recognized by neural processing. Previous models for sound recognition have used preprocessed or low-level auditory signals as input, but complex natural sounds such as speech are thought to be processed in auditory cortex, and brain regions involved in object recognition in general must deal with the natural variability present in spike trains. Thus, we used neural recordings to investigate how a spike pattern recognition system could deal with the intrinsic variability and diverse response properties of cortical spike trains. We propose a biologically plausible computational spike pattern recognition model that uses an excitatory chain of neurons to spatially preserve the temporal representation of the spike pattern. Using a single neural recording as input, the model can be trained using a spike-timing-dependent plasticity-based learning rule to recognize neural responses to 20 different bird songs with >98% accuracy and can be stimulated to evoke reverse spike pattern playback. Although we test spike train recognition performance in an auditory task, this model can be applied to recognize sufficiently reliable spike patterns from any neuronal system.

  20. Spike sorting for polytrodes: a divide and conquer approach

    Directory of Open Access Journals (Sweden)

    Nicholas V. Swindale

    2014-02-01

    Full Text Available In order to determine patterns of neural activity, spike signals recorded by extracellular electrodes have to be clustered (sorted with the aim of ensuring that each cluster represents all the spikes generated by an individual neuron. Many methods for spike sorting have been proposed but few are easily applicable to recordings from polytrodes which may have 16 or more recording sites. As with tetrodes, these are spaced sufficiently closely that signals from single neurons will usually be recorded on several adjacent sites. Although this offers a better chance of distinguishing neurons with similarly shaped spikes, sorting is difficult in such cases because of the high dimensionality of the space in which the signals must be classified. This report details a method for spike sorting based on a divide and conquer approach. Clusters are initially formed by assigning each event to the channel on which it is largest. Each channel-based cluster is then sub-divided into as many distinct clusters as possible. These are then recombined on the basis of pairwise tests into a final set of clusters. Pairwise tests are also performed to establish how distinct each cluster is from the others. A modified gradient ascent clustering (GAC algorithm is used to do the clustering. The method can sort spikes with minimal user input in times comparable to real time for recordings lasting up to 45 minutes. Our results illustrate some of the difficulties inherent in spike sorting, including changes in spike shape over time. We show that some physiologically distinct units may have very similar spike shapes. We show that RMS measures of spike shape similarity are not sensitive enough to discriminate clusters that can otherwise be separated by principal components analysis. Hence spike sorting based on least-squares matching to templates may be unreliable. Our methods should be applicable to tetrodes and scaleable to larger multi-electrode arrays (MEAs.

  1. Spike sorting for polytrodes: a divide and conquer approach.

    Science.gov (United States)

    Swindale, Nicholas V; Spacek, Martin A

    2014-01-01

    In order to determine patterns of neural activity, spike signals recorded by extracellular electrodes have to be clustered (sorted) with the aim of ensuring that each cluster represents all the spikes generated by an individual neuron. Many methods for spike sorting have been proposed but few are easily applicable to recordings from polytrodes which may have 16 or more recording sites. As with tetrodes, these are spaced sufficiently closely that signals from single neurons will usually be recorded on several adjacent sites. Although this offers a better chance of distinguishing neurons with similarly shaped spikes, sorting is difficult in such cases because of the high dimensionality of the space in which the signals must be classified. This report details a method for spike sorting based on a divide and conquer approach. Clusters are initially formed by assigning each event to the channel on which it is largest. Each channel-based cluster is then sub-divided into as many distinct clusters as possible. These are then recombined on the basis of pairwise tests into a final set of clusters. Pairwise tests are also performed to establish how distinct each cluster is from the others. A modified gradient ascent clustering (GAC) algorithm is used to do the clustering. The method can sort spikes with minimal user input in times comparable to real time for recordings lasting up to 45 min. Our results illustrate some of the difficulties inherent in spike sorting, including changes in spike shape over time. We show that some physiologically distinct units may have very similar spike shapes. We show that RMS measures of spike shape similarity are not sensitive enough to discriminate clusters that can otherwise be separated by principal components analysis (PCA). Hence spike sorting based on least-squares matching to templates may be unreliable. Our methods should be applicable to tetrodes and scalable to larger multi-electrode arrays (MEAs).

  2. Clustering predicts memory performance in networks of spiking and non-spiking neurons

    Directory of Open Access Journals (Sweden)

    Weiliang eChen

    2011-03-01

    Full Text Available The problem we address in this paper is that of finding effective and parsimonious patterns of connectivity in sparse associative memories. This problem must be addressed in real neuronal systems, so that results in artificial systems could throw light on real systems. We show that there are efficient patterns of connectivity and that these patterns are effective in models with either spiking or non-spiking neurons. This suggests that there may be some underlying general principles governing good connectivity in such networks. We also show that the clustering of the network, measured by Clustering Coefficient, has a strong linear correlation to the performance of associative memory. This result is important since a purely static measure of network connectivity appears to determine an important dynamic property of the network.

  3. Analysis of the Enzymatic Activity of an NS3 Helicase Genotype 3a Variant Sequence Obtained from a Relapse Patient.

    Directory of Open Access Journals (Sweden)

    Paola J S Provazzi

    Full Text Available The hepatitis C virus (HCV is a species of diverse genotypes that infect over 170 million people worldwide, causing chronic inflammation, cirrhosis and hepatocellular carcinoma. HCV genotype 3a is common in Brazil, and it is associated with a relatively poor response to current direct-acting antiviral therapies. The HCV NS3 protein cleaves part of the HCV polyprotein, and cellular antiviral proteins. It is therefore the target of several HCV drugs. In addition to its protease activity, NS3 is also an RNA helicase. Previously, HCV present in a relapse patient was found to harbor a mutation known to be lethal to HCV genotype 1b. The point mutation encodes the amino acid substitution W501R in the helicase RNA binding site. To examine how the W501R substitution affects NS3 helicase activity in a genotype 3a background, wild type and W501R genotype 3a NS3 alleles were sub-cloned, expressed in E. coli, and the recombinant proteins were purified and characterized. The impact of the W501R allele on genotype 2a and 3a subgenomic replicons was also analyzed. Assays monitoring helicase-catalyzed DNA and RNA unwinding revealed that the catalytic efficiency of wild type genotype 3a NS3 helicase was more than 600 times greater than the W501R protein. Other assays revealed that the W501R protein bound DNA less than 2 times weaker than wild type, and both proteins hydrolyzed ATP at similar rates. In Huh7.5 cells, both genotype 2a and 3a subgenomic HCV replicons harboring the W501R allele showed a severe defect in replication. Since the W501R allele is carried as a minor variant, its replication would therefore need to be attributed to the trans-complementation by other wild type quasispecies.

  4. No WIMP mini-spikes in dwarf spheroidal galaxies

    NARCIS (Netherlands)

    Wanders, M.; Bertone, G.; Volonteri, M.; Weniger, C.

    2015-01-01

    The formation of black holes inevitably affects the distribution of dark and baryonic matter in their vicinity, leading to an enhancement of the dark matter density, called spike, and if dark matter is made of WIMPs, to a strong enhancement of the dark matter annihilation rate. Spikes at the center

  5. Grain price spikes and beggar-thy-neighbor policy responses

    DEFF Research Database (Denmark)

    Boysen, Ole; Jensen, Hans Grinsted

    Upward spikes in the international price of food in recent years led some countries to raise export barriers, thereby exacerbating both the price spike and reducing the terms of trade for food-importing countries (beggaring their neighbors). At the same time, and for similar political...

  6. Spiking and bursting patterns of fractional-order Izhikevich model

    Science.gov (United States)

    Teka, Wondimu W.; Upadhyay, Ranjit Kumar; Mondal, Argha

    2018-03-01

    Bursting and spiking oscillations play major roles in processing and transmitting information in the brain through cortical neurons that respond differently to the same signal. These oscillations display complex dynamics that might be produced by using neuronal models and varying many model parameters. Recent studies have shown that models with fractional order can produce several types of history-dependent neuronal activities without the adjustment of several parameters. We studied the fractional-order Izhikevich model and analyzed different kinds of oscillations that emerge from the fractional dynamics. The model produces a wide range of neuronal spike responses, including regular spiking, fast spiking, intrinsic bursting, mixed mode oscillations, regular bursting and chattering, by adjusting only the fractional order. Both the active and silent phase of the burst increase when the fractional-order model further deviates from the classical model. For smaller fractional order, the model produces memory dependent spiking activity after the pulse signal turned off. This special spiking activity and other properties of the fractional-order model are caused by the memory trace that emerges from the fractional-order dynamics and integrates all the past activities of the neuron. On the network level, the response of the neuronal network shifts from random to scale-free spiking. Our results suggest that the complex dynamics of spiking and bursting can be the result of the long-term dependence and interaction of intracellular and extracellular ionic currents.

  7. Interictal spike EEG source analysis in hypothalamic hamartoma epilepsy.

    Science.gov (United States)

    Leal, Alberto J R; Passão, Vitorina; Calado, Eulália; Vieira, José P; Silva Cunha, João P

    2002-12-01

    The epilepsy associated with the hypothalamic hamartomas constitutes a syndrome with peculiar seizures, usually refractory to medical therapy, mild cognitive delay, behavioural problems and multifocal spike activity in the scalp electroencephalogram (EEG). The cortical origin of spikes has been widely assumed but not specifically demonstrated. We present results of a source analysis of interictal spikes from 4 patients (age 2-25 years) with epilepsy and hypothalamic hamartoma, using EEG scalp recordings (32 electrodes) and realistic boundary element models constructed from volumetric magnetic resonance imaging (MRIs). Multifocal spike activity was the most common finding, distributed mainly over the frontal and temporal lobes. A spike classification based on scalp topography was done and averaging within each class performed to improve the signal to noise ratio. Single moving dipole models were used, as well as the Rap-MUSIC algorithm. All spikes with good signal to noise ratio were best explained by initial deep sources in the neighbourhood of the hamartoma, with late sources located in the cortex. Not a single patient could have his spike activity explained by a combination of cortical sources. Overall, the results demonstrate a consistent origin of spike activity in the subcortical region in the neighbourhood of the hamartoma, with late spread to cortical areas.

  8. Spike protection device for electronics and communication appliances

    African Journals Online (AJOL)

    Experience shows that most failures of electronic and communication equipment result from damage caused by external electrical disturbances in the form of overvoltage, undervoltage, surge, sag, spike, or voltage dropout (blackout), the status of which is determined by the amplitude and duration of the disturbance. Spikes ...

  9. Diagrammatic scale for the assessment of blast on wheat spikes

    Directory of Open Access Journals (Sweden)

    João Leodato Nunes Maciel

    2013-09-01

    Full Text Available The correct quantification of blast caused by the fungus Magnaporthe oryzae on wheat (Triticum aestivum spikes is an important component to understand the development of this disease aimed at its control. Visual quantification based on a diagrammatic scale can be a practical and efficient strategy that has already proven to be useful against several plant pathosystems, including diseases affecting wheat spikes like glume blotch and fusarium head blight. Spikes showing different disease severity values were collected from a wheat field with the aim of elaborating a diagrammatic scale to quantify blast severity on wheat spikes. The spikes were photographed and blast severity was determined by using resources of the software ImageJ. A diagrammatic scale was developed with the following disease severity values: 3.7, 7.5, 21.4, 30.5, 43.8, 57.3, 68.1, 86.0, and 100.0%. An asymptomatic spike was added to the scale. Scale validation was performed by eight people who estimated blast severity by using digitalized images of 40 wheat spikes. The precision and the accuracy of the evaluations varied according to the rater (0.82spikes.

  10. SPIKY: a graphical user interface for monitoring spike train synchrony

    Science.gov (United States)

    Mulansky, Mario; Bozanic, Nebojsa

    2015-01-01

    Techniques for recording large-scale neuronal spiking activity are developing very fast. This leads to an increasing demand for algorithms capable of analyzing large amounts of experimental spike train data. One of the most crucial and demanding tasks is the identification of similarity patterns with a very high temporal resolution and across different spatial scales. To address this task, in recent years three time-resolved measures of spike train synchrony have been proposed, the ISI-distance, the SPIKE-distance, and event synchronization. The Matlab source codes for calculating and visualizing these measures have been made publicly available. However, due to the many different possible representations of the results the use of these codes is rather complicated and their application requires some basic knowledge of Matlab. Thus it became desirable to provide a more user-friendly and interactive interface. Here we address this need and present SPIKY, a graphical user interface that facilitates the application of time-resolved measures of spike train synchrony to both simulated and real data. SPIKY includes implementations of the ISI-distance, the SPIKE-distance, and the SPIKE-synchronization (an improved and simplified extension of event synchronization) that have been optimized with respect to computation speed and memory demand. It also comprises a spike train generator and an event detector that makes it capable of analyzing continuous data. Finally, the SPIKY package includes additional complementary programs aimed at the analysis of large numbers of datasets and the estimation of significance levels. PMID:25744888

  11. Cytoplasmic tail of coronavirus spike protein has intracellular

    Indian Academy of Sciences (India)

    Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spikeprotein is localized in the ER or ERGIC compartment and OC43 spike protein is predominantly localized in thelysosome. Differential localization can be explained by signal sequence. The sequence alignment ...

  12. Recrutamento político

    OpenAIRE

    Norris, Pippa

    2013-01-01

    O objetivo principal deste artigo é apresentar uma breve revisão da literatura sobre recrutamento político e oferecer alguns critérios empíricos para análise. A partir de uma perspectiva integrada, nos estabelecemos um modelo de análise que trabalha com a estrutural social e as instituições políticas. O modelo de oferta e demanda foi mobilizado para relacionar os inputs do background social e as possíveis consequências nas instituições. Os dados apresentados provém de uma diversidade de fonte...

  13. Spectral components of cytosolic [Ca2+] spiking in neurons

    DEFF Research Database (Denmark)

    Kardos, J; Szilágyi, N; Juhász, G

    1998-01-01

    We show here, by means of evolutionary spectral analysis and synthesis of cytosolic Ca2+ ([Ca2+]c) spiking observed at the single cell level using digital imaging fluorescence microscopy of fura-2-loaded mouse cerebellar granule cells in culture, that [Ca2+]c spiking can be resolved into evolutio......We show here, by means of evolutionary spectral analysis and synthesis of cytosolic Ca2+ ([Ca2+]c) spiking observed at the single cell level using digital imaging fluorescence microscopy of fura-2-loaded mouse cerebellar granule cells in culture, that [Ca2+]c spiking can be resolved...... into evolutionary spectra of a characteristic set of frequencies. Non-delayed small spikes on top of sustained [Ca2+]c were synthesized by a main component frequency, 0.132+/-0.012 Hz, showing its maximal amplitude in phase with the start of depolarization (25 mM KCI) combined with caffeine (10 mM) application...

  14. Spike detection II: automatic, perception-based detection and clustering.

    Science.gov (United States)

    Wilson, S B; Turner, C A; Emerson, R G; Scheuer, M L

    1999-03-01

    We developed perception-based spike detection and clustering algorithms. The detection algorithm employs a novel, multiple monotonic neural network (MMNN). It is tested on two short-duration EEG databases containing 2400 spikes from 50 epilepsy patients and 10 control subjects. Previous studies are compared for database difficulty and reliability and algorithm accuracy. Automatic grouping of spikes via hierarchical clustering (using topology and morphology) is visually compared with hand marked grouping on a single record. The MMNN algorithm is found to operate close to the ability of a human expert while alleviating problems related to overtraining. The hierarchical and hand marked spike groupings are found to be strikingly similar. An automatic detection algorithm need not be as accurate as a human expert to be clinically useful. A user interface that allows the neurologist to quickly delete artifacts and determine whether there are multiple spike generators is sufficient.

  15. A supervised learning rule for classification of spatiotemporal spike patterns.

    Science.gov (United States)

    Lilin Guo; Zhenzhong Wang; Adjouadi, Malek

    2016-08-01

    This study introduces a novel supervised algorithm for spiking neurons that take into consideration synapse delays and axonal delays associated with weights. It can be utilized for both classification and association and uses several biologically influenced properties, such as axonal and synaptic delays. This algorithm also takes into consideration spike-timing-dependent plasticity as in Remote Supervised Method (ReSuMe). This paper focuses on the classification aspect alone. Spiked neurons trained according to this proposed learning rule are capable of classifying different categories by the associated sequences of precisely timed spikes. Simulation results have shown that the proposed learning method greatly improves classification accuracy when compared to the Spike Pattern Association Neuron (SPAN) and the Tempotron learning rule.

  16. The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas

    Directory of Open Access Journals (Sweden)

    Bhattacharya Chitralekha

    2012-11-01

    Full Text Available Abstract Background Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival. Methods Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma. Result The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis. Conclusion To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome

  17. Obtaining Arbitrary Prescribed Mean Field Dynamics for Recurrently Coupled Networks of Type-I Spiking Neurons with Analytically Determined Weights

    Directory of Open Access Journals (Sweden)

    Wilten eNicola

    2016-02-01

    Full Text Available A fundamental question in computational neuroscience is how to connect a network of spiking neurons to produce desired macroscopic or mean field dynamics. One possible approach is through the Neural Engineering Framework (NEF. The NEF approach requires quantities called decoders which are solved through an optimization problem requiring large matrix inversion. Here, we show how a decoder can be obtained analytically for type I and certain type II firing rates as a function of the heterogeneity of its associated neuron. These decoders generate approximants for functions that converge to the desired function in mean-squared error like 1/N, where N is the number of neurons in the network. We refer to these decoders as scale-invariant decoders due to their structure. These decoders generate weights for a network of neurons through the NEF formula for weights. These weights force the spiking network to have arbitrary and prescribed mean field dynamics. The weights generated with scale-invariant decoders all lie on low dimensional hypersurfaces asymptotically. We demonstrate the applicability of these scale-invariant decoders and weight surfaces by constructing networks of spiking theta neurons that replicate the dynamics of various well known dynamical systems such as the neural integrator, Van der Pol system and the Lorenz system. As these decoders are analytically determined and non-unique, the weights are also analytically determined and non-unique. We discuss the implications for measured weights of neuronal networks

  18. Acquisition of full-length viral helicase domains by insect retrotransposon-encoded polypeptides

    Directory of Open Access Journals (Sweden)

    Ekaterina eLazareva

    2015-12-01

    Full Text Available Recent metagenomic studies in insects identified many sequences unexpectedly closely related to plant virus genes. Here we describe a new example of this kind, insect R1 LINEs with an additional C-terminal domain in their open reading frame 2. This domain is similar to NTPase/helicase (SF1H domains, which are found in replicative proteins encoded by plant viruses of the genus Tobamovirus. We hypothesize that the SF1H domain could be acquired by LINEs, directly or indirectly, upon insect feeding on virus-infected plants. Possible functions of this domain in LINE transposition and involvement in LINEs counteraction the silencing-based cell defense against retrotransposons are discussed.

  19. The role of RecQ helicases in non-homologous end-joining

    DEFF Research Database (Denmark)

    Keijzers, Guido; Maynard, Scott; Shamanna, Raghavendra A

    2014-01-01

    -strand break repair. Double-strand breaks can be repaired by homologous recombination (HR) using sister chromatids as templates to facilitate precise DNA repair, or by an HR-independent mechanism known as non-homologous end-joining (NHEJ) (error-prone). NHEJ is a non-templated DNA repair process, in which DNA...... termini are directly ligated. Canonical NHEJ requires DNA-PKcs and Ku70/80, while alternative NHEJ pathways are DNA-PKcs and Ku70/80 independent. This review discusses the role of RecQ helicases in NHEJ, alternative (or back-up) NHEJ (B-NHEJ) and microhomology-mediated end-joining (MMEJ) in V(D)J...... recombination, class switch recombination and telomere maintenance....

  20. Insights into the architecture of the replicative helicase from the structure of an archaeal MCM homolog.

    Science.gov (United States)

    Bae, Brian; Chen, Yi-Hsing; Costa, Alessandro; Onesti, Silvia; Brunzelle, Joseph S; Lin, Yuyen; Cann, Isaac K O; Nair, Satish K

    2009-02-13

    The minichromosome maintenance (MCM) proteins, members of the AAA+ (ATPase associated with diverse cellular activities) superfamily, are believed to constitute the replicative helicase in eukaryotic and archaeal species. Here, we present the 1.9 A resolution crystal structure of a monomeric MCM homolog from Methanopyrus kandleri, the first crystallographic structure of a full-length MCM. We also present an 18 A cryo-electron microscopy reconstruction of the hexameric MCM from Methanothermobacter thermautotrophicus, and fit the atomic resolution crystal structure into the reconstruction in order to generate an atomic model for the oligomeric assembly. These structural data reveal a distinct active site topology consisting of a unique arrangement of critical determinants. The structures also provide a molecular framework for understanding the functional contributions of trans-acting elements that facilitate intersubunit crosstalk in response to DNA binding and ATP hydrolysis.

  1. The helicase senataxin suppresses the antiviral transcriptional response and controls viral biogenesis

    Science.gov (United States)

    Miller, Matthew S.; Rialdi, Alexander; Ho, Jessica Sook Yuin; Tilove, Micah; Martinez-Gil, Luis; Moshkina, Natasha P.; Peralta, Zuleyma; Noel, Justine; Melegari, Camilla; Maestre, Ana; Mitsopoulos, Panagiotis; Madrenas, Joaquín; Heinz, Sven; Benner, Chris; Young, John A. T.; Feagins, Alicia R.; Basler, Christopher; Fernandez-Sesma, Ana; Becherel, Olivier J.; Lavin, Martin F.; van Bakel, Harm; Marazzi, Ivan

    2015-01-01

    The human helicase senataxin (SETX) is implicated in the neurodegenerative diseases amyotrophic lateral sclerosis (ALS4) and ataxia with oculomotor apraxia (AOA2). Here, we reveal a role for SETX in controlling the antiviral response. Cells depleted for SETX and AOA2 patient-derived SETX-deficient cells exhibit increased expression of antiviral mediators in response to infection. Mechanistically, we propose a model whereby SETX attenuates RNA polymerase II (RNAPII) activity at genes stimulated upon viral sensing, thus controlling the magnitude of the host response to pathogens and the biogenesis of numerous RNA viruses (e. g. Influenza A virus and West Nile virus). Our data indicate a potentially causal link between SETX inborn errors, susceptibility to infection and development of neurologic disorders. PMID:25822250

  2. Recrutamento político

    Directory of Open Access Journals (Sweden)

    Pippa Norris

    2013-06-01

    Full Text Available O objetivo principal deste artigo é apresentar uma breve revisão da literatura sobre recrutamento político e oferecer alguns critérios empíricos para análise. A partir de uma perspectiva integrada, nos estabelecemos um modelo de análise que trabalha com a estrutural social e as instituições políticas. O modelo de oferta e demanda foi mobilizado para relacionar os inputs do background social e as possíveis consequências nas instituições. Os dados apresentados provém de uma diversidade de fontes e privilegiaram os processos de inclusão de mulheres em diferentes tipos de democracias e sociedades. Os resultados mostram que somente através da interação da estrutural social com as demandas institucionais é possível conhecer o resultado final da representatividade e os filtros do recrutamento político. Além disso, os dados nos permitiram desvendar um incremento da participação das bases sociais do partido no processo de nominação de candidatos. Concluímos que o processo de seleção de candidatos é uma das mais técnicas e privadas funções dos partidos políticos. O aumento da oferta e o estreitamento da demanda tem promovido uma série de consequências para a democracia representativa, como a inserção de mulheres ao mesmo tempo em que se profissionalizam os partidos políticos..

  3. Uroguanylin induces electroencephalographic spikes in rats

    Directory of Open Access Journals (Sweden)

    MDA. Teixeira

    Full Text Available Uroguanylin (UGN is an endogenous peptide that acts on membrane-bound guanylate cyclase receptors of intestinal and renal cells increasing cGMP production and regulating electrolyte and water epithelial transport. Recent research works demonstrate the expression of this peptide and its receptor in the central nervous system. The current work was undertaken in order to evaluate modifications of electroencephalographic spectra (EEG in anesthetized Wistar rats, submitted to intracisternal infusion of uroguanylin (0.0125 nmoles/min or 0.04 nmoles/min. The current observations demonstrate that 0.0125 nmoles/min and 0.04 nmoles/min intracisternal infusion of UGN significantly enhances amplitude and frequency of sharp waves and evoked spikes (p = 0.03. No statistical significance was observed on absolute alpha and theta spectra amplitude. The present data suggest that UGN acts on bioelectrogenesis of cortical cells by inducing hypersynchronic firing of neurons. This effect is blocked by nedocromil, suggesting that UGN acts by increasing the activity of chloride channels.

  4. Retinitis Pigmentosa Mutations in Bad Response to Refrigeration 2 (Brr2) Impair ATPase and Helicase Activity.

    Science.gov (United States)

    Ledoux, Sarah; Guthrie, Christine

    2016-06-03

    Brr2 is an RNA-dependent ATPase required to unwind the U4/U6 snRNA duplex during spliceosome assembly. Mutations within the ratchet helix of the Brr2 RNA binding channel result in a form of degenerative human blindness known as retinitis pigmentosa (RP). The biochemical consequences of these mutations on Brr2's RNA binding, helicase, and ATPase activity have not yet been characterized. Therefore, we identified the largest construct of Brr2 that is soluble in vitro, which truncates the first 247 amino acids of the N terminus (Δ247-Brr2), to characterize the effects of the RP mutations on Brr2 activity. The Δ247-Brr2 RP mutants exhibit a gradient of severity of weakened RNA binding, reduced helicase activity, and reduced ATPase activity compared with wild type Δ247-Brr2. The globular C-terminal Jab1/Mpn1-like domain of Prp8 increases the ability of Δ247-Brr2 to bind the U4/U6 snRNA duplex at high pH and increases Δ247-Brr2's RNA-dependent ATPase activity and the extent of RNA unwinding. However, this domain of Prp8 does not differentially affect the Δ247-Brr2 RP mutants compared with the wild type Δ247-Brr2. When stimulated by Prp8, wild type Δ247-Brr2 is able to unwind long stable duplexes in vitro, and even the RP mutants capable of binding RNA with tight affinity are incapable of fully unwinding short duplex RNAs. Our data suggest that the RP mutations within the ratchet helix impair Brr2 translocation through RNA helices. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. The ATP-Dependent RNA Helicase DDX3X Modulates Herpes Simplex Virus 1 Gene Expression.

    Science.gov (United States)

    Khadivjam, Bita; Stegen, Camille; Hogue-Racine, Marc-Aurèle; El Bilali, Nabil; Döhner, Katinka; Sodeik, Beate; Lippé, Roger

    2017-04-15

    The human protein DDX3X is a DEAD box ATP-dependent RNA helicase that regulates transcription, mRNA maturation, and mRNA export and translation. DDX3X concomitantly modulates the replication of several RNA viruses and promotes innate immunity. We previously showed that herpes simplex virus 1 (HSV-1), a human DNA virus, incorporates DDX3X into its mature particles and that DDX3X is required for optimal HSV-1 infectivity. Here, we show that viral gene expression, replication, and propagation depend on optimal DDX3X protein levels. Surprisingly, DDX3X from incoming viral particles was not required for the early stages of the HSV-1 infection, but, rather, the protein controlled the assembly of new viral particles. This was independent of the previously reported ability of DDX3X to stimulate interferon type I production. Instead, both the lack and overexpression of DDX3X disturbed viral gene transcription and thus subsequent genome replication. This suggests that in addition to its effect on RNA viruses, DDX3X impacts DNA viruses such as HSV-1 by an interferon-independent pathway. IMPORTANCE Viruses interact with a variety of cellular proteins to complete their life cycle. Among them is DDX3X, an RNA helicase that participates in most aspects of RNA biology, including transcription, splicing, nuclear export, and translation. Several RNA viruses and a limited number of DNA viruses are known to manipulate DDX3X for their own benefit. In contrast, DDX3X is also known to promote interferon production to limit viral propagation. Here, we show that DDX3X, which we previously identified in mature HSV-1 virions, stimulates HSV-1 gene expression and, consequently, virion assembly by a process that is independent of its ability to promote the interferon pathway. Copyright © 2017 American Society for Microbiology.

  6. Vaccinia virions lacking the RNA helicase nucleoside triphosphate phosphohydrolase II are defective in early transcription.

    Science.gov (United States)

    Gross, C H; Shuman, S

    1996-12-01

    Temperature-sensitive mutations (ts10, ts18, and ts39) of the vaccinia virus RNA helicase nucleoside triphosphate phosphohydrolase II (NPH-II) result in the production of noninfectious progeny virions at the restrictive temperature. The noninfectious mutant particles contain the wild-type complement of virion core and envelope polypeptides, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of Western blot (immunoblot) analysis indicate that these particles lack NPH-II, whereas other enzymatic components of the virus core are present. These components include the following: DNA-dependent RNA polymerase subunits rpo147, rpo132, rpo94, rpo35, rpo30, rpo22, and rpo18; early transcription initiation factor subunits A8 and D6; mRNA capping enzyme subunits D1 and D12; RNA cap 2'-O-methyltransferase; A18 DNA helicase; DNA-dependent ATPase NPH-I; and DNA topoisomerase. Although RNA polymerase is encapsidated by the mutant viruses, mRNA synthesis in vitro by permeabilized mutant virions is only 5 to 20% that of the wild-type virus, as judged by nucleoside monophosphate incorporation into acid-insoluble material. Moreover, the transcripts synthesized by the mutant particles are longer than normal and remain virion associated. Transcription initiation by mutant virions occurs accurately at an endogenous genomic promoter, albeit at reduced levels (1 to 7%) compared with that of wild-type virions. In contrast, extracts of the mutant virions catalyze the wild-type level of transcription from an exogenous template containing an early promoter. We conclude that NPH-II is required for early mRNA synthesis uniquely in the context of the virus particle. Possible roles in transcription termination and RNA transport are discussed.

  7. Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

    Science.gov (United States)

    Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

    2014-02-05

    The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Generalized analog thresholding for spike acquisition at ultralow sampling rates.

    Science.gov (United States)

    He, Bryan D; Wein, Alex; Varshney, Lav R; Kusuma, Julius; Richardson, Andrew G; Srinivasan, Lakshminarayan

    2015-07-01

    Efficient spike acquisition techniques are needed to bridge the divide from creating large multielectrode arrays (MEA) to achieving whole-cortex electrophysiology. In this paper, we introduce generalized analog thresholding (gAT), which achieves millisecond temporal resolution with sampling rates as low as 10 Hz. Consider the torrent of data from a single 1,000-channel MEA, which would generate more than 3 GB/min using standard 30-kHz Nyquist sampling. Recent neural signal processing methods based on compressive sensing still require Nyquist sampling as a first step and use iterative methods to reconstruct spikes. Analog thresholding (AT) remains the best existing alternative, where spike waveforms are passed through an analog comparator and sampled at 1 kHz, with instant spike reconstruction. By generalizing AT, the new method reduces sampling rates another order of magnitude, detects more than one spike per interval, and reconstructs spike width. Unlike compressive sensing, the new method reveals a simple closed-form solution to achieve instant (noniterative) spike reconstruction. The base method is already robust to hardware nonidealities, including realistic quantization error and integration noise. Because it achieves these considerable specifications using hardware-friendly components like integrators and comparators, generalized AT could translate large-scale MEAs into implantable devices for scientific investigation and medical technology. Copyright © 2015 the American Physiological Society.

  9. Predictive coding of dynamical variables in balanced spiking networks.

    Science.gov (United States)

    Boerlin, Martin; Machens, Christian K; Denève, Sophie

    2013-01-01

    Two observations about the cortex have puzzled neuroscientists for a long time. First, neural responses are highly variable. Second, the level of excitation and inhibition received by each neuron is tightly balanced at all times. Here, we demonstrate that both properties are necessary consequences of neural networks that represent information efficiently in their spikes. We illustrate this insight with spiking networks that represent dynamical variables. Our approach is based on two assumptions: We assume that information about dynamical variables can be read out linearly from neural spike trains, and we assume that neurons only fire a spike if that improves the representation of the dynamical variables. Based on these assumptions, we derive a network of leaky integrate-and-fire neurons that is able to implement arbitrary linear dynamical systems. We show that the membrane voltage of the neurons is equivalent to a prediction error about a common population-level signal. Among other things, our approach allows us to construct an integrator network of spiking neurons that is robust against many perturbations. Most importantly, neural variability in our networks cannot be equated to noise. Despite exhibiting the same single unit properties as widely used population code models (e.g. tuning curves, Poisson distributed spike trains), balanced networks are orders of magnitudes more reliable. Our approach suggests that spikes do matter when considering how the brain computes, and that the reliability of cortical representations could have been strongly underestimated.

  10. A method for decoding the neurophysiological spike-response transform.

    Science.gov (United States)

    Stern, Estee; García-Crescioni, Keyla; Miller, Mark W; Peskin, Charles S; Brezina, Vladimir

    2009-11-15

    Many physiological responses elicited by neuronal spikes-intracellular calcium transients, synaptic potentials, muscle contractions-are built up of discrete, elementary responses to each spike. However, the spikes occur in trains of arbitrary temporal complexity, and each elementary response not only sums with previous ones, but can itself be modified by the previous history of the activity. A basic goal in system identification is to characterize the spike-response transform in terms of a small number of functions-the elementary response kernel and additional kernels or functions that describe the dependence on previous history-that will predict the response to any arbitrary spike train. Here we do this by developing further and generalizing the "synaptic decoding" approach of Sen et al. (1996). Given the spike times in a train and the observed overall response, we use least-squares minimization to construct the best estimated response and at the same time best estimates of the elementary response kernel and the other functions that characterize the spike-response transform. We avoid the need for any specific initial assumptions about these functions by using techniques of mathematical analysis and linear algebra that allow us to solve simultaneously for all of the numerical function values treated as independent parameters. The functions are such that they may be interpreted mechanistically. We examine the performance of the method as applied to synthetic data. We then use the method to decode real synaptic and muscle contraction transforms.

  11. Bursts generate a non-reducible spike-pattern code

    Directory of Open Access Journals (Sweden)

    Hugo G Eyherabide

    2009-05-01

    Full Text Available On the single-neuron level, precisely timed spikes can either constitute firing-rate codes or spike-pattern codes that utilize the relative timing between consecutive spikes. There has been little experimental support for the hypothesis that such temporal patterns contribute substantially to information transmission. Using grasshopper auditory receptors as a model system, we show that correlations between spikes can be used to represent behaviorally relevant stimuli. The correlations reflect the inner structure of the spike train: a succession of burst-like patterns. We demonstrate that bursts with different spike counts encode different stimulus features, such that about 20% of the transmitted information corresponds to discriminating between different features, and the remaining 80% is used to allocate these features in time. In this spike-pattern code, the "what" and the "when" of the stimuli are encoded in the duration of each burst and the time of burst onset, respectively. Given the ubiquity of burst firing, we expect similar findings also for other neural systems.

  12. A Simple Deep Learning Method for Neuronal Spike Sorting

    Science.gov (United States)

    Yang, Kai; Wu, Haifeng; Zeng, Yu

    2017-10-01

    Spike sorting is one of key technique to understand brain activity. With the development of modern electrophysiology technology, some recent multi-electrode technologies have been able to record the activity of thousands of neuronal spikes simultaneously. The spike sorting in this case will increase the computational complexity of conventional sorting algorithms. In this paper, we will focus spike sorting on how to reduce the complexity, and introduce a deep learning algorithm, principal component analysis network (PCANet) to spike sorting. The introduced method starts from a conventional model and establish a Toeplitz matrix. Through the column vectors in the matrix, we trains a PCANet, where some eigenvalue vectors of spikes could be extracted. Finally, support vector machine (SVM) is used to sort spikes. In experiments, we choose two groups of simulated data from public databases availably and compare this introduced method with conventional methods. The results indicate that the introduced method indeed has lower complexity with the same sorting errors as the conventional methods.

  13. Automated spike preparation system for Isotope Dilution Mass Spectrometry (IDMS)

    International Nuclear Information System (INIS)

    Maxwell, S.L. III; Clark, J.P.

    1990-01-01

    Isotope Dilution Mass Spectrometry (IDMS) is a method frequently employed to measure dissolved, irradiated nuclear materials. A known quantity of a unique isotope of the element to be measured (referred to as the ''spike'') is added to the solution containing the analyte. The resulting solution is chemically purified then analyzed by mass spectrometry. By measuring the magnitude of the response for each isotope and the response for the ''unique spike'' then relating this to the known quantity of the ''spike'', the quantity of the nuclear material can be determined. An automated spike preparation system was developed at the Savannah River Site (SRS) to dispense spikes for use in IDMS analytical methods. Prior to this development, technicians weighed each individual spike manually to achieve the accuracy required. This procedure was time-consuming and subjected the master stock solution to evaporation. The new system employs a high precision SMI Model 300 Unipump dispenser interfaced with an electronic balance and a portable Epson HX-20 notebook computer to automate spike preparation

  14. Grain price spikes and beggar-thy-neighbor policy responses

    DEFF Research Database (Denmark)

    Boysen, Ole; Jensen, Hans Grinsted

    Upward spikes in the international price of food in recent years led some countries to raise export barriers, thereby exacerbating both the price spike and reducing the terms of trade for food-importing countries (beggaring their neighbors). At the same time, and for similar political......-economy reasons, numerous food-importing countries reduced or suspended their import tariffs, and some even provided food import subsidies -- which also exacerbated the international price spike, thus turning the terms of trade even further against food-importing countries. This issue became a major item...

  15. Boobs, Boxing, and Bombs: Problematizing the Entertainment of Spike TV

    OpenAIRE

    Walton, Gerald; Potvin, L.

    2009-01-01

    Spike is the only television network in North America “for men.” Its motto, “Get more action,” is suggestive of pursuits of various forms of violence. We conceptualize Spike not as trivial entertainment, but rather as a form of pop culture that erodes the gains of feminists who have challenged the prevalence of normalized hegemonic masculinity (HM). Our paper highlights themes of Spike content, and connects those themes to the literature on HM. Moreover, we validate the identities and lives ...

  16. Heterogeneity of Purkinje cell simple spike-complex spike interactions: zebrin- and non-zebrin-related variations.

    Science.gov (United States)

    Tang, Tianyu; Xiao, Jianqiang; Suh, Colleen Y; Burroughs, Amelia; Cerminara, Nadia L; Jia, Linjia; Marshall, Sarah P; Wise, Andrew K; Apps, Richard; Sugihara, Izumi; Lang, Eric J

    2017-08-01

    Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike-complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre- and post-complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions. Purkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS-associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the

  17. Perceptron learning rule derived from spike-frequency adaptation and spike-time-dependent plasticity.

    Science.gov (United States)

    D'Souza, Prashanth; Liu, Shih-Chii; Hahnloser, Richard H R

    2010-03-09

    It is widely believed that sensory and motor processing in the brain is based on simple computational primitives rooted in cellular and synaptic physiology. However, many gaps remain in our understanding of the connections between neural computations and biophysical properties of neurons. Here, we show that synaptic spike-time-dependent plasticity (STDP) combined with spike-frequency adaptation (SFA) in a single neuron together approximate the well-known perceptron learning rule. Our calculations and integrate-and-fire simulations reveal that delayed inputs to a neuron endowed with STDP and SFA precisely instruct neural responses to earlier arriving inputs. We demonstrate this mechanism on a developmental example of auditory map formation guided by visual inputs, as observed in the external nucleus of the inferior colliculus (ICX) of barn owls. The interplay of SFA and STDP in model ICX neurons precisely transfers the tuning curve from the visual modality onto the auditory modality, demonstrating a useful computation for multimodal and sensory-guided processing.

  18. Stochastic optimal control of single neuron spike trains

    DEFF Research Database (Denmark)

    Iolov, Alexandre; Ditlevsen, Susanne; Longtin, Andrë

    2014-01-01

    stimulation of a neuron to achieve a target spike train under the physiological constraint to not damage tissue. Approach. We pose a stochastic optimal control problem to precisely specify the spike times in a leaky integrate-and-fire (LIF) model of a neuron with noise assumed to be of intrinsic or synaptic...... to the spike times (open-loop control). Main results. We have developed a stochastic optimal control algorithm to obtain precise spike times. It is applicable in both the supra-threshold and sub-threshold regimes, under open-loop and closed-loop conditions and with an arbitrary noise intensity; the accuracy...... into account physiological constraints on the control. A precise and robust targeting of neural activity based on stochastic optimal control has great potential for regulating neural activity in e.g. prosthetic applications and to improve our understanding of the basic mechanisms by which neuronal firing...

  19. Higher Order Spike Synchrony in Prefrontal Cortex during visual memory

    Directory of Open Access Journals (Sweden)

    Gordon ePipa

    2011-06-01

    Full Text Available Precise temporal synchrony of spike firing has been postulated as an important neuronal mechanism for signal integration and the induction of plasticity in neocortex. As prefrontal cortex plays an important role in organizing memory and executive functions, the convergence of multiple visual pathways onto PFC predicts that neurons should preferentially synchronize their spiking when stimulus information is processed. Furthermore, synchronous spike firing should intensify if memory processes require the induction of neuronal plasticity, even if this is only for short-term. Here we show with multiple simultaneously recorded units in ventral prefrontal cortex that neurons participate in 3 ms precise synchronous discharges distributed across multiple sites separated by at least 500 µm. The frequency of synchronous firing is modulated by behavioral performance and is specific for the memorized visual stimuli. In particular, during the memory period in which activity is not stimulus driven, larger groups of up to 7 sites exhibit performance dependent modulation of their spike synchronization.

  20. Sonar target localization based on spike coded spectrograms

    Directory of Open Access Journals (Sweden)

    Bertrand FONTAINE

    2006-12-01

    Full Text Available Target location is coded into the pattern of spikes that run up the auditory nerve to the bat's brain. Realistic scenes containing multiple, closely spaced, reflectors give rise to complex echo signals consisting of multiple filtered copies of the bat's own vocalisation. Some of this filtering is due to the directivity of the bat’s reception system i.e., the outer ears, and some of it is due to sound absorption and the reflection process. The analysis below concentrates on the conspicuous ridges (notches these filter operations give rise to in the time-frequency representation of the echo as produced by the bat's inner ear. Assuming multiple threshold detecting neurons for each frequency channel it is shown how the distribution of spike times within the generated spike bursts is linked to the presence and characteristics of these notches. A neural network decoding the spike bursts in terms of target location is described.

  1. Saccharomyces cerevisiae Hrq1 helicase activity is affected by the sequence but not the length of single-stranded DNA.

    Science.gov (United States)

    Rogers, Cody M; Bochman, Matthew L

    2017-05-13

    Mutations in the human RecQ4 DNA helicase are associated with three different diseases characterized by genomic instability. To gain insight into how RecQ4 dysfunction leads to these pathologies, several groups have used the Saccharomyces cerevisiae RecQ4 homolog Hrq1 as an experimental model. Hrq1 displays many of the same functions as RecQ4 in vivo and in vitro. However, there is some disagreement in the literature about the effects of single-stranded DNA (ssDNA) length on Hrq1 helicase activity and the ability of Hrq1 to anneal complementary ssDNA oligonucleotides into duplex DNA. Here, we present a side-by-side comparison of Hrq1 and RecQ4 helicase activity, demonstrating that in both cases, long random-sequence 3' ssDNA tails inhibit DNA unwinding in vitro in a length-dependent manner. This appears to be due to the formation of secondary structures in the random-sequence ssDNA because Hrq1 preferentially unwound poly(dT)-tailed forks independent of ssDNA length. Further, RecQ4 is capable of ssDNA strand annealing and annealing-dependent strand exchange, but Hrq1 lacks these activities. These results establish the importance of DNA sequence in Hrq1 helicase activity, and the absence of Hrq1 strand annealing activity explains the previously identified discrepancies between S. cerevisiae Hrq1 and human RecQ4. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Essential and distinct roles of the F-box and helicase domains of Fbh1 in DNA damage repair

    Directory of Open Access Journals (Sweden)

    Shinagawa Hideo

    2008-03-01

    Full Text Available Abstract Background DNA double-strand breaks (DSBs are induced by exogenous insults such as ionizing radiation and chemical exposure, and they can also arise as a consequence of stalled or collapsed DNA replication forks. Failure to repair DSBs can lead to genomic instability or cell death and cancer in higher eukaryotes. The Schizosaccharomyces pombe fbh1 gene encodes an F-box DNA helicase previously described to play a role in the Rhp51 (an orthologue of S. cerevisiae RAD51-dependent recombinational repair of DSBs. Fbh1 fused to GFP localizes to discrete nuclear foci following DNA damage. Results To determine the functional roles of the highly conserved F-box and helicase domains, we have characterized fbh1 mutants carrying specific mutations in these domains. We show that the F-box mutation fbh1-fb disturbs the nuclear localization of Fbh1, conferring an fbh1 null-like phenotype. Moreover, nuclear foci do not form in fbh1-fb cells with DNA damage even if Fbh1-fb is targeted to the nucleus by fusion to a nuclear localization signal sequence. In contrast, the helicase mutation fbh1-hl causes the accumulation of Fbh1 foci irrespective of the presence of DNA damage and confers damage sensitivity greater than that conferred by the null allele. Additional mutation of the F-box alleviates the hypermorphic phenotype of the fbh1-hl mutant. Conclusion These results suggest that the F-box and DNA helicase domains play indispensable but distinct roles in Fbh1 function. Assembly of the SCFFbh1 complex is required for both the nuclear localization and DNA damage-induced focus formation of Fbh1 and is therefore prerequisite for the Fbh1 recombination function.

  3. DEAD-Box RNA Helicases are among the Constituents of the Tobacco Pollen mRNA Storing Bodies

    Czech Academy of Sciences Publication Activity Database

    Hafidh, Said; Potěšil, D.; Zdráhal, Z.; Honys, David

    2013-01-01

    Roč. 1, č. 3 (2013) ISSN 2329-9029 R&D Projects: GA ČR GPP501/11/P321; GA ČR(CZ) GAP501/11/1462; GA MŠk(CZ) ED1.1.00/02.0068; GA MŠk(CZ) LD13049 Institutional support: RVO:61389030 Keywords : Translation * mRNA storage * RNA helicase Subject RIV: EB - Genetics ; Molecular Biology

  4. Spatiotemporal Dynamics and Reliable Computations in Recurrent Spiking Neural Networks

    Science.gov (United States)

    Pyle, Ryan; Rosenbaum, Robert

    2017-01-01

    Randomly connected networks of excitatory and inhibitory spiking neurons provide a parsimonious model of neural variability, but are notoriously unreliable for performing computations. We show that this difficulty is overcome by incorporating the well-documented dependence of connection probability on distance. Spatially extended spiking networks exhibit symmetry-breaking bifurcations and generate spatiotemporal patterns that can be trained to perform dynamical computations under a reservoir computing framework.

  5. Spike Neural Models Part II: Abstract Neural Models

    OpenAIRE

    Johnson, Melissa G.; Chartier, Sylvain

    2018-01-01

    Neurons are complex cells that require a lot of time and resources to model completely. In spiking neural networks (SNN) though, not all that complexity is required. Therefore simple, abstract models are often used. These models save time, use less computer resources, and are easier to understand. This tutorial presents two such models: Izhikevich's model, which is biologically realistic in the resulting spike trains but not in the parameters, and the Leaky Integrate and Fire (LIF) model whic...

  6. Characteristics of Spike motion in World top lever volleyball players

    OpenAIRE

    黒川, 貞生; 森田, 恭光; 亀ヶ谷, 純一; 加藤, 浩人; 松井, 泰二; 鈴木, 陽一; 矢島, 忠明

    2008-01-01

    The purpose of this study was to investigate the characteristics of spike motion in world top level volleyball players. Front- and back-spike motions were recorded by high-speed video camera system operating at 250Hz to obtain three dimensional coordinates of the body segments and the center of the ball. The velocity of the ball, wrist, shoulder and trunk twist angle was calculated using motion analyzer. There is no significant relationship between the initial ball velocity and the velocity o...

  7. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKES-WAVES ACTIVITY DURING SLEEP

    OpenAIRE

    E. D. Belousova

    2012-01-01

    The author represents the review and discussion of current scientific literature devoted to epileptic encephalopathy with continuous spikes-waves activity during sleep — the special form of partly reversible age-dependent epileptic encephalopathy, characterized by triad of symptoms: continuous prolonged epileptiform (spike-wave) activity on EEG in sleep, epileptic seizures and cognitive disorders. The author describes the aspects of classification, pathogenesis and etiology, prevalence, clini...

  8. Nonlinear evolution of single spike in Richtmyer-Meshkov instability

    International Nuclear Information System (INIS)

    Fukuda, Y.; Nishihara, K.; Wouchuk, J.G.

    2000-01-01

    Nonlinear evolution of single spike structure and vortex in the Richtmyer-Meshkov instability is investigated with the use of a two-dimensional hydrodynamic code. It is shown that singularity appears in the vorticity left by transmitted and reflected shocks at a corrugated interface. This singularity results in opposite sign of vorticity along the interface that causes double spiral structure of the spike. (authors)

  9. The Omega-Infinity Limit of Single Spikes

    CERN Document Server

    Axenides, Minos; Linardopoulos, Georgios

    A new infinite-size limit of strings in RxS2 is presented. The limit is obtained from single spike strings by letting their angular velocity omega become infinite. We derive the energy-momenta relation of omega-infinity single spikes as their linear velocity v-->1 and their angular momentum J-->1. Generally, the v-->1, J-->1 limit of single spikes is singular and has to be excluded from the spectrum and be studied separately. We discover that the dispersion relation of omega-infinity single spikes contains logarithms in the limit J-->1. This result is somewhat surprising, since the logarithmic behavior in the string spectra is typically associated with their motion in non-compact spaces such as AdS. Omega-infinity single spikes seem to completely cover the surface of the 2-sphere they occupy, so that they may essentially be viewed as some sort of "brany strings". A proof of the sphere-filling property of omega-infinity single spikes is given in the appendix.

  10. Automatic fitting of spiking neuron models to electrophysiological recordings

    Directory of Open Access Journals (Sweden)

    Cyrille Rossant

    2010-03-01

    Full Text Available Spiking models can accurately predict the spike trains produced by cortical neurons in response to somatically injected currents. Since the specific characteristics of the model depend on the neuron, a computational method is required to fit models to electrophysiological recordings. The fitting procedure can be very time consuming both in terms of computer simulations and in terms of code writing. We present algorithms to fit spiking models to electrophysiological data (time-varying input and spike trains that can run in parallel on graphics processing units (GPUs. The model fitting library is interfaced with Brian, a neural network simulator in Python. If a GPU is present it uses just-in-time compilation to translate model equations into optimized code. Arbitrary models can then be defined at script level and run on the graphics card. This tool can be used to obtain empirically validated spiking models of neurons in various systems. We demonstrate its use on public data from the INCF Quantitative Single-Neuron Modeling 2009 competition by comparing the performance of a number of neuron spiking models.

  11. Absolute Ca Isotopic Measurement Using an Improved Double Spike Technique

    Directory of Open Access Journals (Sweden)

    Jason Jiun-San Shen

    2009-01-01

    Full Text Available A new vector analytical method has been developed in order to obtain the true isotopic composition of the 42Ca-48Ca double spike. This is achieved by using two different sample-spike mixtures combined with the double spike and natural Ca data. Be cause the natural sample (two mixtures and the spike should all lie on a single mixing line, we are able to con strain the true isotopic composition of our double spike using this new approach. Once the isotopic composition of the Ca double spike is established, we are able to obtain the true Ca isotopic composition of the NIST Ca standard SRM915a, 40Ca/44Ca = 46.537 ± 2 (2sm, n = 55, 42Ca/44Ca = 0.31031 ± 1, 43Ca/44Ca = 0.06474 ± 1, and 48Ca/44Ca = 0.08956 ± 1. De spite an off set of 1.3% in 40Ca/44Ca between our result and the previously re ported value (Russell et al. 1978, our data indicate an off set of 1.89__in 40Ca/44Ca between SRM915a and seawater, entirely consistent with the published results.

  12. Structure of the frequency-interacting RNA helicase: a protein interaction hub for the circadian clock

    Energy Technology Data Exchange (ETDEWEB)

    Conrad, Karen S.; Hurley, Jennifer M.; Widom, Joanne; Ringelberg, Carol S.; Loros, Jennifer J.; Dunlap, Jay C.; Crane, Brian R.

    2016-06-23

    In the Neurospora crassa circadian clock, a protein complex of frequency (FRQ), casein kinase 1a (CK1a), and the FRQ-interacting RNA Helicase (FRH) rhythmically represses gene expression by the white-collar complex (WCC). FRH crystal structures in several conformations and bound to ADP/RNA reveal differences between FRH and the yeast homolog Mtr4 that clarify the distinct role of FRH in the clock. The FRQ-interacting region at the FRH N-terminus has variable structure in the absence of FRQ. A known mutation that disrupts circadian rhythms (R806H) resides in a positively charged surface of the KOW domain, far removed from the helicase core. Here, we show that changes to other similarly located residues modulate interactions with the WCC and FRQ. A V142G substitution near the N-terminus also alters FRQ and WCC binding to FRH, but produces an unusual short clock period. Finally, these data support the assertion that FRH helicase activity does not play an essential role in the clock, but rather FRH acts to mediate contacts among FRQ, CK1a and the WCC through interactions involving its N-terminus and KOW module.

  13. Binding Affinities among DNA Helicase-Primase, DNA Polymerase, and Replication Intermediates in the Replisome of Bacteriophage T7*

    Science.gov (United States)

    Zhang, Huidong; Tang, Yong; Lee, Seung-Joo; Wei, Zeliang; Cao, Jia; Richardson, Charles C.

    2016-01-01

    The formation of a replication loop on the lagging strand facilitates coordinated synthesis of the leading- and lagging-DNA strands and provides a mechanism for recycling of the lagging-strand DNA polymerase. As an Okazaki fragment is completed, the loop is released, and a new loop is formed as the synthesis of a new Okazaki fragment is initiated. Loop release requires the dissociation of the complex formed by the interactions among helicase, DNA polymerase, and DNA. The completion of the Okazaki fragment may result in either a nick or a single-stranded DNA region. In the replication system of bacteriophage T7, the dissociation of the polymerase from either DNA region is faster than that observed for the dissociation of the helicase from DNA polymerase, implying that the replication loop is released more likely through the dissociation of the lagging-strand DNA from polymerase, retaining the polymerase at replication fork. Both dissociation of DNA polymerase from DNA and that of helicase from a DNA polymerase·DNA complex are much faster at a nick DNA region than the release from a ssDNA region. These results suggest that the replication loop is released as a result of the nick formed when the lagging-strand DNA polymerase encounters the previously synthesized Okazaki fragment, releasing lagging-strand DNA and retaining DNA polymerase at the replication fork for the synthesis of next Okazaki fragment. PMID:26620561

  14. Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required for development and stress resilience

    Directory of Open Access Journals (Sweden)

    Cecilia Zampedri

    2016-10-01

    Full Text Available Stress granules are cytoplasmic foci that directly respond to the protein synthesis status of the cell. Various environmental insults, such as oxidative stress or extreme heat, block protein synthesis; consequently, mRNA will stall in translation, and stress granules will immediately form and become enriched with mRNAs. P54 DEAD box RNA helicases are components of RNA granules such as P-bodies and stress granules. We studied the expression, in cytoplasmic foci, of both zebrafish P54 RNA helicases (P54a and P54b during development and found that they are expressed in cytoplasmic granules under both normal conditions and stress conditions. In zebrafish embryos exposed to heat shock, some proportion of P54a and P54b helicases move to larger granules that exhibit the properties of genuine stress granules. Knockdown of P54a and/or P54b in zebrafish embryos produces developmental abnormalities restricted to the posterior trunk; further, these embryos do not form stress granules, and their survival upon exposure to heat-shock conditions is compromised. Our observations fit the model that cells lacking stress granules have no resilience or ability to recover once the stress has ended, indicating that stress granules play an essential role in the way organisms adapt to a changing environment.

  15. Structural Studies of RNA Helicases Involved in Eukaryotic Pre-mRNA Splicing, Ribosome Biogenesis, and Translation Initiation

    DEFF Research Database (Denmark)

    He, Yangzi

    and ligates the neighbouring exons to generate mature mRNAs. Prp43 is an RNA helicase of the DEAH/RHA family. In yeast, once mRNAs are released, Prp43 catalyzes the disassembly of spliceosomes. The 18S, 5.8S and 25S rRNAs are transcribed as a single polycistronic transcript—the 35S pre......-rRNA. It is nucleolytically cleaved and chemically modified to generate mature rRNAs, which assemble with ribosomal proteins to form the ribosome. Prp43 is required for the processing of the 18S rRNA. Using X-ray crystallography, I determined a high resolution structure of Prp43 bound to ADP, the first structure of a DEAH....../RHA helicase. It defined the conserved structural features of all DEAH/RHA helicases, and unveiled a novel nucleotide binding site. Additionally a preliminary low resolution structure of a ternary complex comprising Prp43, a non-hydrolyzable ATP analogue, and a single-stranded RNA, was obtained. The ribosome...

  16. Weighted spiking neural P systems with structural plasticity working in sequential mode based on maximum spike number

    Science.gov (United States)

    Sun, Mingming; Qu, Jianhua

    2017-10-01

    Spiking neural P systems (SNP systems, in short) are a group of parallel and distributed computing devices inspired by the function and structure of spiking neurons. Recently, a new variant of SNP systems, called SNP systems with structural plasticity (SNPSP systems, in short) was proposed. In SNPSP systems, neuron can use plasticity ru les to create and delete synapses. In this work, we consider many restrictions sequentiality on SNPSP systems: (1) neuron with the maximum number of spikes is chosen to fire; (2) we use the weighted synapses. Specifically, we investigate the computational power of weighted SNPSP systems working in the sequential mode based on maximum spike number (WSNPSPM systems, in short) and we proved that SNPSP systems with these new restrictions are universal as generating devices.

  17. Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

    Science.gov (United States)

    Bi, Zedong; Zhou, Changsong

    2016-01-01

    Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations) influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP) and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded), by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF) neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy). PMID:27555816

  18. Spike Pattern Structure Influences Synaptic Efficacy Variability Under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

    Directory of Open Access Journals (Sweden)

    Zedong Bi

    2016-08-01

    Full Text Available Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded, by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy.

  19. Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

    OpenAIRE

    Bi, Zedong; Zhou, Changsong

    2016-01-01

    Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations) influence the efficacy variability under pair-wis...

  20. Stress-Induced Impairment of a Working Memory Task: Role of Spiking Rate and Spiking History Predicted Discharge

    Science.gov (United States)

    Devilbiss, David M.; Jenison, Rick L.; Berridge, Craig W.

    2012-01-01

    Stress, pervasive in society, contributes to over half of all work place accidents a year and over time can contribute to a variety of psychiatric disorders including depression, schizophrenia, and post-traumatic stress disorder. Stress impairs higher cognitive processes, dependent on the prefrontal cortex (PFC) and that involve maintenance and integration of information over extended periods, including working memory and attention. Substantial evidence has demonstrated a relationship between patterns of PFC neuron spiking activity (action-potential discharge) and components of delayed-response tasks used to probe PFC-dependent cognitive function in rats and monkeys. During delay periods of these tasks, persistent spiking activity is posited to be essential for the maintenance of information for working memory and attention. However, the degree to which stress-induced impairment in PFC-dependent cognition involves changes in task-related spiking rates or the ability for PFC neurons to retain information over time remains unknown. In the current study, spiking activity was recorded from the medial PFC of rats performing a delayed-response task of working memory during acute noise stress (93 db). Spike history-predicted discharge (SHPD) for PFC neurons was quantified as a measure of the degree to which ongoing neuronal discharge can be predicted by past spiking activity and reflects the degree to which past information is retained by these neurons over time. We found that PFC neuron discharge is predicted by their past spiking patterns for nearly one second. Acute stress impaired SHPD, selectively during delay intervals of the task, and simultaneously impaired task performance. Despite the reduction in delay-related SHPD, stress increased delay-related spiking rates. These findings suggest that neural codes utilizing SHPD within PFC networks likely reflects an additional important neurophysiological mechanism for maintenance of past information over time. Stress

  1. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Jacob Thomas

    Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  2. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Science.gov (United States)

    Thomas, Jacob; Lee, Catherine A; Grossman, Alan D

    2013-01-01

    Integrative and conjugative elements (ICEs) are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT) by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP), encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  3. Joint Probability-Based Neuronal Spike Train Classification

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2009-01-01

    Full Text Available Neuronal spike trains are used by the nervous system to encode and transmit information. Euclidean distance-based methods (EDBMs have been applied to quantify the similarity between temporally-discretized spike trains and model responses. In this study, using the same discretization procedure, we developed and applied a joint probability-based method (JPBM to classify individual spike trains of slowly adapting pulmonary stretch receptors (SARs. The activity of individual SARs was recorded in anaesthetized, paralysed adult male rabbits, which were artificially-ventilated at constant rate and one of three different volumes. Two-thirds of the responses to the 600 stimuli presented at each volume were used to construct three response models (one for each stimulus volume consisting of a series of time bins, each with spike probabilities. The remaining one-third of the responses where used as test responses to be classified into one of the three model responses. This was done by computing the joint probability of observing the same series of events (spikes or no spikes, dictated by the test response in a given model and determining which probability of the three was highest. The JPBM generally produced better classification accuracy than the EDBM, and both performed well above chance. Both methods were similarly affected by variations in discretization parameters, response epoch duration, and two different response alignment strategies. Increasing bin widths increased classification accuracy, which also improved with increased observation time, but primarily during periods of increasing lung inflation. Thus, the JPBM is a simple and effective method performing spike train classification.

  4. The expanding functions of cellular helicases: the tombusvirus RNA replication enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box RNA helicases to promote viral asymmetric RNA replication.

    Directory of Open Access Journals (Sweden)

    Nikolay Kovalev

    2014-04-01

    Full Text Available Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC, template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3' terminal promoter region in the viral minus-strand (-RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5' proximal RIII(- replication enhancer (REN element in the TBSV (-RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (-RNA could unwind the dsRNA structure within the RIII(- REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(- REN in stimulation of plus-strand (+RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(- REN that promotes bringing the 5' and 3' terminal (-RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+-strand synthesis, thus resulting in asymmetrical viral replication.

  5. The expanding functions of cellular helicases: the tombusvirus RNA replication enhancer co-opts the plant eIF4AIII-like AtRH2 and the DDX5-like AtRH5 DEAD-box RNA helicases to promote viral asymmetric RNA replication.

    Science.gov (United States)

    Kovalev, Nikolay; Nagy, Peter D

    2014-04-01

    Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3' terminal promoter region in the viral minus-strand (-)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5' proximal RIII(-) replication enhancer (REN) element in the TBSV (-)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (-)RNA could unwind the dsRNA structure within the RIII(-) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(-) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(-) REN that promotes bringing the 5' and 3' terminal (-)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.

  6. Benchmarking Spike-Based Visual Recognition: A Dataset and Evaluation

    Science.gov (United States)

    Liu, Qian; Pineda-García, Garibaldi; Stromatias, Evangelos; Serrano-Gotarredona, Teresa; Furber, Steve B.

    2016-01-01

    Today, increasing attention is being paid to research into spike-based neural computation both to gain a better understanding of the brain and to explore biologically-inspired computation. Within this field, the primate visual pathway and its hierarchical organization have been extensively studied. Spiking Neural Networks (SNNs), inspired by the understanding of observed biological structure and function, have been successfully applied to visual recognition and classification tasks. In addition, implementations on neuromorphic hardware have enabled large-scale networks to run in (or even faster than) real time, making spike-based neural vision processing accessible on mobile robots. Neuromorphic sensors such as silicon retinas are able to feed such mobile systems with real-time visual stimuli. A new set of vision benchmarks for spike-based neural processing are now needed to measure progress quantitatively within this rapidly advancing field. We propose that a large dataset of spike-based visual stimuli is needed to provide meaningful comparisons between different systems, and a corresponding evaluation methodology is also required to measure the performance of SNN models and their hardware implementations. In this paper we first propose an initial NE (Neuromorphic Engineering) dataset based on standard computer vision benchmarksand that uses digits from the MNIST database. This dataset is compatible with the state of current research on spike-based image recognition. The corresponding spike trains are produced using a range of techniques: rate-based Poisson spike generation, rank order encoding, and recorded output from a silicon retina with both flashing and oscillating input stimuli. In addition, a complementary evaluation methodology is presented to assess both model-level and hardware-level performance. Finally, we demonstrate the use of the dataset and the evaluation methodology using two SNN models to validate the performance of the models and their hardware

  7. Direct detection of nasal Staphylococcus aureus carriage via helicase-dependent isothermal amplification and chip hybridization

    Directory of Open Access Journals (Sweden)

    Frech Georges C

    2012-08-01

    Full Text Available Abstract Background The bacterium Staphylococcus aureus constitutes one of the most important causes of nosocomial infections. One out of every three individuals naturally carries S. aureus in their anterior nares, and nasal carriage is associated with a significantly higher infection rate in hospital settings. Nasal carriage can be either persistent or intermittent, and it is the persistent carriers who, as a group, are at the highest risk of infection and who have the highest nasal S. aureus cell counts. Prophylactic decolonization of S. aureus from patients’ noses is known to reduce the incidence of postsurgical infections, and there is a clear rationale for rapid identification of nasal S. aureus carriers among hospital patients. Findings A molecular diagnostic assay was developed which is based on helicase-dependent target amplification and amplicon detection by chip hybridization to a chip surface, producing a visible readout. Nasal swabs from 70 subjects were used to compare the molecular assay against culturing on “CHROMagar Staph aureus” agar plates. The overall relative sensitivity was 89%, and the relative specificity was 94%. The sensitivity rose to 100% when excluding low-count subjects (S. aureus colony-forming units per swab. Conclusions This molecular assay is much faster than direct culture and has sensitivity that is appropriate for identification of high-count (>100 S. aureus colony-forming units per swab nasal S. aureus carriers who are at greatest risk for nosocomial infections.

  8. AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms.

    Directory of Open Access Journals (Sweden)

    Chloe Girard

    2015-07-01

    Full Text Available Meiotic crossovers (COs generate genetic diversity and are critical for the correct completion of meiosis in most species. Their occurrence is tightly constrained but the mechanisms underlying this limitation remain poorly understood. Here we identified the conserved AAA-ATPase FIDGETIN-LIKE-1 (FIGL1 as a negative regulator of meiotic CO formation. We show that Arabidopsis FIGL1 limits CO formation genome-wide, that FIGL1 controls dynamics of the two conserved recombinases DMC1 and RAD51 and that FIGL1 hinders the interaction between homologous chromosomes, suggesting that FIGL1 counteracts DMC1/RAD51-mediated inter-homologue strand invasion to limit CO formation. Further, depleting both FIGL1 and the previously identified anti-CO helicase FANCM synergistically increases crossover frequency. Additionally, we showed that the effect of mutating FANCM on recombination is much lower in F1 hybrids contrasting from the phenotype of inbred lines, while figl1 mutation equally increases crossovers in both contexts. This shows that the modes of action of FIGL1 and FANCM are differently affected by genomic contexts. We propose that FIGL1 and FANCM represent two successive barriers to CO formation, one limiting strand invasion, the other disassembling D-loops to promote SDSA, which when both lifted, leads to a large increase of crossovers, without impairing meiotic progression.

  9. Remodeling and Control of Homologous Recombination by DNA Helicases and Translocases that Target Recombinases and Synapsis

    Science.gov (United States)

    Northall, Sarah J.; Ivančić-Baće, Ivana; Soultanas, Panos; Bolt, Edward L.

    2016-01-01

    Recombinase enzymes catalyse invasion of single-stranded DNA (ssDNA) into homologous duplex DNA forming “Displacement loops” (D-loops), a process called synapsis. This triggers homologous recombination (HR), which can follow several possible paths to underpin DNA repair and restart of blocked and collapsed DNA replication forks. Therefore, synapsis can be a checkpoint for controlling whether or not, how far, and by which pathway, HR proceeds to overcome an obstacle or break in a replication fork. Synapsis can be antagonized by limiting access of a recombinase to ssDNA and by dissociation of D-loops or heteroduplex formed by synapsis. Antagonists include DNA helicases and translocases that are identifiable in eukaryotes, bacteria and archaea, and which target synaptic and pre-synaptic DNA structures thereby controlling HR at early stages. Here we survey these events with emphasis on enabling DNA replication to be resumed from sites of blockage or collapse. We also note how knowledge of anti-recombination activities could be useful to improve efficiency of CRISPR-based genome editing. PMID:27548227

  10. RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

    Science.gov (United States)

    Xie, Min; Vesuna, Farhad; Tantravedi, Saritha; Bol, Guus M.; Heerma van Voss, Marise R.; Nugent, Katriana; Malek, Reem; Gabrielson, Kathleen; van Diest, Paul J.; Tran, Phuoc T.; Raman, Venu

    2017-01-01

    Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. RK-33 treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) decreased proliferation and induced a G1 phase cell-cycle arrest. Conversely, the low DDX3–expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a radiosensitizer. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer. PMID:27634756

  11. Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Kylie L. Gorringe

    2008-11-01

    Full Text Available Chromodomain, helicase, DNA binding 5 (CHD5 is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04. The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.

  12. Analysis of the RNA helicase p68 (Ddx5) as a transcriptional regulator.

    Science.gov (United States)

    Nicol, Samantha M; Fuller-Pace, Frances V

    2010-01-01

    The DEAD box RNA helicase p68 (Ddx5) has been demonstrated to act as a transcriptional co-activator for a number of highly regulated transcription factors (e.g. estrogen receptor alpha and the tumour suppressor p53) and to be recruited to promoters of genes that are responsive to activation of these transcription factors, suggesting that it may play a role in transcription initiation. We have investigated the function of p68 as a co-activator of the tumour suppressor p53, with a particular emphasis on the importance of p68 in the induction of p53 transcriptional activity by DNA damage. These studies have involved RNAi-mediated suppression of p68 in cells expressing wild-type p53 and determining its effect on the expression of cellular p53 target genes in response to DNA damage. Additionally a significant amount of our research has focused on the study of the role of p68 in transcriptional initiation; this has included an investigation of the recruitment of p68 to the promoters of p53-responsive genes and of the importance of p68 in influencing recruitment of p53. Here we present detailed methods for RNAi knock-down of p68 expression, determination of its effect on expression of p53-responsive genes by quantitative RT-PCR and Western blotting, and chromatin immunoprecipitation techniques for determining recruitment of p68 and p53 to p53-responsive promoters.

  13. Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster.

    Science.gov (United States)

    Shiraki, K

    2017-11-01

    Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs) inhibit the progression of the replication fork, an initial step in DNA synthesis to separate the double strand into two single strands. The HPIs amenamevir and pritelivir have a novel mechanism of action, once-daily administration with nonrenal excretory characteristics, and clinical efficacy for genital herpes. Amenamevir exhibits anti-VZV and anti-HSV activity while pritelivir only has anti-HSV activity. A clinical trial of amenamevir for herpes zoster has been completed, and amenamevir has been licensed and successfully used in 20,000 patients with herpes zoster so far in Japan. We have characterized the features of the antiviral action of amenamevir and, unlike acyclovir, the drug's antiviral activity is not influenced by the viral replication cycle. Amenamevir is opening a new era of antiherpes therapy. Copyright 2017 Clarivate Analytics.

  14. Functional Dynamics of Hexameric Helicase Probed by Hydrogen Exchange and Simulation

    Science.gov (United States)

    Radou, Gaël; Dreyer, Frauke N.; Tuma, Roman; Paci, Emanuele

    2014-01-01

    The biological function of large macromolecular assemblies depends on their structure and their dynamics over a broad range of timescales; for this reason, it is a significant challenge to investigate these assemblies using conventional experimental techniques. One of the most promising experimental techniques is hydrogen-deuterium exchange detected by mass spectrometry. Here, we describe to our knowledge a new computational method for quantitative interpretation of deuterium exchange kinetics and apply it to a hexameric viral helicase P4 that unwinds and translocates RNA into a virus capsid at the expense of ATP hydrolysis. Room-temperature dynamics probed by a hundred nanoseconds of all-atom molecular dynamics simulations is sufficient to predict the exchange kinetics of most sequence fragments and provide a residue-level interpretation of the low-resolution experimental results. The strategy presented here is also a valuable tool to validate experimental data, e.g., assignments, and to probe mechanisms that cannot be observed by x-ray crystallography, or that occur over timescales longer than those that can be realistically simulated, such as the opening of the hexameric ring. PMID:25140434

  15. UPF1 helicase promotes TSN-mediated miRNA decay.

    Science.gov (United States)

    Elbarbary, Reyad A; Miyoshi, Keita; Hedaya, Omar; Myers, Jason R; Maquat, Lynne E

    2017-07-15

    While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of miRNAs that contain CA and/or UA dinucleotides. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, we report here that cellular TumiD requires UPF1. Results from experiments using AGO2-loaded miRNAs in duplex with target mRNAs indicate that UPF1 can dissociate miRNAs from their mRNA targets, making the miRNAs susceptible to TumiD. miR-seq (deep sequencing of miRNAs) data reveal that the degradation of ∼50% of candidate TumiD targets in T24 human urinary bladder cancer cells is augmented by UPF1. We illustrate the physiological relevance by demonstrating that UPF1-augmented TumiD promotes the invasion of T24 cells in part by degrading anti-invasive miRNAs so as to up-regulate the expression of proinvasive proteins. © 2017 Elbarbary et al.; Published by Cold Spring Harbor Laboratory Press.

  16. A rapid Salmonella detection method involving thermophilic helicase-dependent amplification and a lateral flow assay.

    Science.gov (United States)

    Du, Xin-Jun; Zhou, Tian-Jiao; Li, Ping; Wang, Shuo

    2017-08-01

    Salmonella is a major foodborne pathogen that is widespread in the environment and can cause serious human and animal disease. Since conventional culture methods to detect Salmonella are time-consuming and laborious, rapid and accurate techniques to detect this pathogen are critically important for food safety and diagnosing foodborne illness. In this study, we developed a rapid, simple and portable Salmonella detection strategy that combines thermophilic helicase-dependent amplification (tHDA) with a lateral flow assay to provide a detection result based on visual signals within 90 min. Performance analyses indicated that the method had detection limits for DNA and pure cultured bacteria of 73.4-80.7 fg and 35-40 CFU, respectively. Specificity analyses showed no cross reactions with Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Enterobacter aerogenes, Shigella and Campylobacter jejuni. The results for detection in real food samples showed that 1.3-1.9 CFU/g or 1.3-1.9 CFU/mL of Salmonella in contaminated chicken products and infant nutritional cereal could be detected after 2 h of enrichment. The same amount of Salmonella in contaminated milk could be detected after 4 h of enrichment. This tHDA-strip can be used for the rapid detection of Salmonella in food samples and is particularly suitable for use in areas with limited equipment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Decrease in Lymphoid Specific Helicase and 5-hydroxymethylcytosine Is Associated with Metastasis and Genome Instability.

    Science.gov (United States)

    Jia, Jiantao; Shi, Ying; Chen, Ling; Lai, Weiwei; Yan, Bin; Jiang, Yiqun; Xiao, Desheng; Xi, Sichuan; Cao, Ya; Liu, Shuang; Cheng, Yan; Tao, Yongguang

    2017-01-01

    DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change in 5-hmC levels in cancer and associated metastasis is not well defined. We report that the level of 5-hmC was decreased in metastatic tissues of nasopharyngeal carcinoma, breast cancer, and colon cancer relative to that in non-metastasis tumor tissues. Furthermore, our data show that TET2, but not TET3, interacted with LSH, whereas LSH increased TET2 expression through silencing miR-26b-5p and miR-29c-5p. Finally, LSH promoted genome stability by silencing satellite expression by affecting 5-hmC levels in pericentromeric satellite repeats, and LSH was resistant to cisplatin-induced DNA damage. Our data indicate that 5-hmC might serve as a metastasis marker for cancer and that the decreased expression of LSH is likely one of the mechanisms of genome instability underlying 5-hmC loss in cancer.

  18. Structural investigations of the Bacillus subtilis SPP1 phage G39P helicase inhibitor loading protein

    CERN Document Server

    Bailey, S

    2002-01-01

    The Bacillus subtilis SPPI phage encoded protein G39P is a loader and inhibitor of the phage G40P replicative helicase involved in the initiation of phage DNA replication. The 2.4A crystal structure of a C-terminal truncated variant of G39P was solved using multiple wavelength anomalous dispersion exploiting the anomalous signal of seleno- methionine substituted protein. Inspection of the electron density maps revealed the asymmetric unit contained three independent G39P monomers, composed of 3 alpha-helices and their connecting loops. However, the model only accounted for the first 67 residues of the protein, as there was no interpretable electron density for residues 68 to 112. A preliminary NMR investigation revealed the C-terminal region of the protein had rapid internal motion and formed no well-defined stable fold that involved immobilized side chains. This is consistent with the X-ray analysis that displayed no electron density for these residues. A detailed comparison of NMR spectra from the C-termina...

  19. Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis and viral infection

    Directory of Open Access Journals (Sweden)

    YASUO eARIUMI

    2014-12-01

    Full Text Available The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-ß-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon regulatory factor (IRF 3 and type I interferon (IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus (HIV-1, hepatitis C virus (HCV, hepatitis B virus (HBV, and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.

  20. Spike morphology in blast-wave-driven instability experiments

    International Nuclear Information System (INIS)

    Kuranz, C. C.; Drake, R. P.; Grosskopf, M. J.; Fryxell, B.; Budde, A.; Hansen, J. F.; Miles, A. R.; Plewa, T.; Hearn, N.; Knauer, J.

    2010-01-01

    The laboratory experiments described in the present paper observe the blast-wave-driven Rayleigh-Taylor instability with three-dimensional (3D) initial conditions. About 5 kJ of energy from the Omega laser creates conditions similar to those of the He-H interface during the explosion phase of a supernova. The experimental target is a 150 μm thick plastic disk followed by a low-density foam. The plastic piece has an embedded, 3D perturbation. The basic structure of the pattern is two orthogonal sine waves where each sine wave has an amplitude of 2.5 μm and a wavelength of 71 μm. In some experiments, an additional wavelength is added to explore the interaction of modes. In experiments with 3D initial conditions the spike morphology differs from what has been observed in other Rayleigh-Taylor experiments and simulations. Under certain conditions, experimental radiographs show some mass extending from the interface to the shock front. Current simulations show neither the spike morphology nor the spike penetration observed in the experiments. The amount of mass reaching the shock front is analyzed and potential causes for the spike morphology and the spikes reaching the shock are discussed. One such hypothesis is that these phenomena may be caused by magnetic pressure, generated by an azimuthal magnetic field produced by the plasma dynamics.

  1. A proteomic study of spike development inhibition in bread wheat.

    Science.gov (United States)

    Zheng, Yong-Sheng; Guo, Jun-Xian; Zhang, Jin-Peng; Gao, Ai-Nong; Yang, Xin-Ming; Li, Xiu-Quan; Liu, Wei-Hua; Li, Li-Hui

    2013-09-01

    Spike development in wheat is a complicated development process and determines the wheat propagation and survival. We report herein a proteomic study on the bread wheat mutant strain 5660M underlying spike development inhibition. A total of 121 differentially expressed proteins, which were involved in cold stress response, protein folding and assembly, cell-cycle regulation, scavenging of ROS, and the autonomous pathway were identified using MS/MS and database searching. We found that cold responsive proteins were highly expressed in the mutant in contrast to those expressed in the wild-type line. Particularly, the autonomous pathway protein FVE, which modulates flowering, was dramatically downregulated and closely related to the spike development inhibition phenotype of 5660M. A quantitative RT-PCR study demonstrated that the transcription of the FVE and other six genes in the autonomous pathway and downstream flowering regulators were all markedly downregulated. The results indicate that spike development of 5660M cannot complete the floral transition. FVE might play an important role in the spikes development of the wheat. Our results provide the theory basis for studying floral development and transition in the reproductive growth period, and further analysis of wheat yield formation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Multiplexed Spike Coding and Adaptation in the Thalamus

    Directory of Open Access Journals (Sweden)

    Rebecca A. Mease

    2017-05-01

    Full Text Available High-frequency “burst” clusters of spikes are a generic output pattern of many neurons. While bursting is a ubiquitous computational feature of different nervous systems across animal species, the encoding of synaptic inputs by bursts is not well understood. We find that bursting neurons in the rodent thalamus employ “multiplexing” to differentially encode low- and high-frequency stimulus features associated with either T-type calcium “low-threshold” or fast sodium spiking events, respectively, and these events adapt differently. Thus, thalamic bursts encode disparate information in three channels: (1 burst size, (2 burst onset time, and (3 precise spike timing within bursts. Strikingly, this latter “intraburst” encoding channel shows millisecond-level feature selectivity and adapts across statistical contexts to maintain stable information encoded per spike. Consequently, calcium events both encode low-frequency stimuli and, in parallel, gate a transient window for high-frequency, adaptive stimulus encoding by sodium spike timing, allowing bursts to efficiently convey fine-scale temporal information.

  3. ViSAPy: A Python tool for biophysics-based generation of virtual spiking activity for evaluation of spike-sorting algorithms

    OpenAIRE

    Hagen, Espen; Ness, Torbjørn V.; Khosrowshahi, Amir; Sørensen, Christina; Fyhn, Marianne; Hafting, Torkel; Franke, Felix; Einevoll, Gaute T.

    2015-01-01

    Background: New, silicon-based multielectrodes comprising hundreds or more electrode contacts offer the possibility to record spike trains from thousands of neurons simultaneously. This potential cannot be realized unless accurate, reliable automated methods for spike sorting are developed, in turn requiring benchmarking data sets with known ground-truth spike times.New method: We here present a general simulation tool for computing benchmarking data for evaluation of spike-sorting algorithms...

  4. Mycobacterium smegmatis Lhr Is a DNA-dependent ATPase and a 3'-to-5' DNA translocase and helicase that prefers to unwind 3'-tailed RNA:DNA hybrids.

    Science.gov (United States)

    Ordonez, Heather; Shuman, Stewart

    2013-05-17

    We are interested in the distinctive roster of helicases of Mycobacterium, a genus of the phylum Actinobacteria that includes the human pathogen Mycobacterium tuberculosis and its avirulent relative Mycobacterium smegmatis. Here, we identify and characterize M. smegmatis Lhr as the exemplar of a novel clade of superfamily II helicases, by virtue of its biochemical specificities and signature domain organization. Lhr is a 1507-amino acid monomeric nucleic acid-dependent ATPase that uses the energy of ATP hydrolysis to drive unidirectional 3'-to-5' translocation along single strand DNA and to unwind duplexes en route. The ATPase is more active in the presence of calcium than magnesium. ATP hydrolysis is triggered by either single strand DNA or single strand RNA, yet the apparent affinity for a DNA activator is 11-fold higher than for an RNA strand of identical size and nucleobase sequence. Lhr is 8-fold better at unwinding an RNA:DNA hybrid than it is at displacing a DNA:DNA duplex of identical nucleobase sequence. The truncated derivative Lhr-(1-856) is an autonomous ATPase, 3'-to-5' translocase, and RNA:DNA helicase. Lhr-(1-856) is 100-fold better RNA:DNA helicase than DNA:DNA helicase. Lhr homologs are found in bacteria representing eight different phyla, being especially prevalent in Actinobacteria (including M. tuberculosis) and Proteobacteria (including Escherichia coli).

  5. Spike Pattern Structure Influences Synaptic Efficacy Variability Under STDP and Synaptic Homeostasis. I: Spike Generating Models on Converging Motifs

    Directory of Open Access Journals (Sweden)

    Zedong eBi

    2016-02-01

    Full Text Available In neural systems, synaptic plasticity is usually driven by spike trains. Due to the inherent noises of neurons and synapses as well as the randomness of connection details, spike trains typically exhibit variability such as spatial randomness and temporal stochasticity, resulting in variability of synaptic changes under plasticity, which we call efficacy variability. How the variability of spike trains influences the efficacy variability of synapses remains unclear. In this paper, we try to understand this influence under pair-wise additive spike-timing dependent plasticity (STDP when the mean strength of plastic synapses into a neuron is bounded (synaptic homeostasis. Specifically, we systematically study, analytically and numerically, how four aspects of statistical features, i.e. synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations, as well as their interactions influence the efficacy variability in converging motifs (simple networks in which one neuron receives from many other neurons. Neurons (including the post-synaptic neuron in a converging motif generate spikes according to statistical models with tunable parameters. In this way, we can explicitly control the statistics of the spike patterns, and investigate their influence onto the efficacy variability, without worrying about the feedback from synaptic changes onto the dynamics of the post-synaptic neuron. We separate efficacy variability into two parts: the drift part (DriftV induced by the heterogeneity of change rates of different synapses, and the diffusion part (DiffV induced by weight diffusion caused by stochasticity of spike trains. Our main findings are: (1 synchronous firing and burstiness tend to increase DiffV, (2 heterogeneity of rates induces DriftV when potentiation and depression in STDP are not balanced, and (3 heterogeneity of cross-correlations induces DriftV together with heterogeneity of rates. We anticipate our

  6. Sangres políticas

    Directory of Open Access Journals (Sweden)

    Gabriel Gatti

    2018-03-01

    Full Text Available Trabajamos en las tensiones entre dos continentes en permanente disputa: “sangre” y “política”, “realidad” y “dispositivo”, “naturaleza” y “cultura”. Son viejos asuntos, y viejas tensiones, pero que no dejan de actualizarse y que ahora se manifiestan por doquier en cuestiones como la biometría, los mapas genéticos, la identificación de desaparecidos, las políticas de la identidad indígena o de género o de menores o de drogas, la gestación subrogada o la gestión de la marginalidad. Los diez textos recogidos en este número especial discuten desde una mirada interdisciplinaria sobre la presencia de la sangre —en sus distintas declinaciones— en la definición contemporánea de lo que entendemos por identidad, derechos humanos o ciudadanía.

  7. Grain price spikes and beggar-thy-neighbor policy responses

    DEFF Research Database (Denmark)

    Jensen, Hans Grinsted; Anderson, Kym

    2017-01-01

    When prices spike in international grain markets, national governments often reduce the extent to which that spike affects their domestic food markets. Those actions exacerbate the price spike and international welfare transfer associated with that terms of trade change. Several recent analyses...... have assessed the extent to which those policies contributed to the 2006–08 international price rises but only by focusing on one commodity or by using a back-of-the envelope (BOTE) method. The present more comprehensive analysis uses a global, economy-wide model that is able to take account...... of the interactions between markets for farm products that are closely related in production and/or consumption and able to estimate the impacts of those insulating policies on grain prices and on the grain trade and economic welfare of the world's various countries. Our results support the conclusion from earlier...

  8. Grain price spikes and beggar-thy-neighbor policy responses

    DEFF Research Database (Denmark)

    Jensen, Hans Grinsted; Anderson, Kym

    When prices spike in international grain markets, national governments often reduce the extent to which that spike affects their domestic food markets. Those actions exacerbate the price spike and international welfare transfer associated with that terms of trade change. Several recent analyses...... have assessed the extent to which those policies contributed to the 2006-08 international price rise, but only by focusing on one commodity or using a back-of-the envelope (BOTE) method. This paper provides a more-comprehensive analysis using a global economy-wide model that is able to take account...... of the interactions between markets for farm products that are closely related in production and/or consumption, and able to estimate the impacts of those insulating policies on grain prices and on the grain trade and economic welfare of the world’s various countries. Our results support the conclusion from earlier...

  9. Spikes and memory in (Nord Pool) electricity price spot prices

    DEFF Research Database (Denmark)

    Proietti, Tomasso; Haldrup, Niels; Knapik, Oskar

    from the normal price, where the latter is defined as the expectation arising from a model accounting for long memory at the zero and at the weekly seasonal frequencies, given the knowledge of the past realizations. Hence, a spike is associated to a time series innovation with size larger than......Electricity spot prices are subject to transitory sharp movements commonly referred to as spikes. The paper aims at assessing their effects on model based inferences and predictions, with reference to the Nord Pool power exchange. We identify a spike as a price value which deviates substantially...... a specified threshold. The latter regulates the robustness of the estimates of the underlying price level and it is chosen by a data driven procedure that focuses on the ability to predict future prices. The normal price is computed by a modified Kalman filter, which robustifies the inferences by cleaning...

  10. Inherently stochastic spiking neurons for probabilistic neural computation

    KAUST Repository

    Al-Shedivat, Maruan

    2015-04-01

    Neuromorphic engineering aims to design hardware that efficiently mimics neural circuitry and provides the means for emulating and studying neural systems. In this paper, we propose a new memristor-based neuron circuit that uniquely complements the scope of neuron implementations and follows the stochastic spike response model (SRM), which plays a cornerstone role in spike-based probabilistic algorithms. We demonstrate that the switching of the memristor is akin to the stochastic firing of the SRM. Our analysis and simulations show that the proposed neuron circuit satisfies a neural computability condition that enables probabilistic neural sampling and spike-based Bayesian learning and inference. Our findings constitute an important step towards memristive, scalable and efficient stochastic neuromorphic platforms. © 2015 IEEE.

  11. Evaluation of the uranium double spike technique for environmental monitoring

    International Nuclear Information System (INIS)

    Hemberger, P.H.; Rokop, D.J.; Efurd, D.W.; Roensch, F.R.; Smith, D.H.; Turner, M.L.; Barshick, C.M.; Bayne, C.K.

    1998-01-01

    Use of a uranium double spike in analysis of environmental samples showed that a 235 U enrichment of 1% ( 235 U/ 238 U = 0.00732) can be distinguished from natural ( 235 U/ 238 U = 0.00725). Experiments performed jointly at Los Alamos National Laboratory (LANL) and Oak Ridge National Laboratory (ORNL) used a carefully calibrated double spike of 233 U and 236 U to obtain much better precision than is possible using conventional analytical techniques. A variety of different sampling media (vegetation and swipes) showed that, provided sufficient care is exercised in choice of sample type, relative standard deviations of less than ± 0.5% can be routinely obtained. This ability, unavailable without use of the double spike, has enormous potential significance in the detection of undeclared nuclear facilities

  12. A Hybrid Setarx Model for Spikes in Tight Electricity Markets

    Directory of Open Access Journals (Sweden)

    Carlo Lucheroni

    2012-01-01

    Full Text Available The paper discusses a simple looking but highly nonlinear regime-switching, self-excited threshold model for hourly electricity prices in continuous and discrete time. The regime structure of the model is linked to organizational features of the market. In continuous time, the model can include spikes without using jumps, by defining stochastic orbits. In passing from continuous time to discrete time, the stochastic orbits survive discretization and can be identified again as spikes. A calibration technique suitable for the discrete version of this model, which does not need deseasonalization or spike filtering, is developed, tested and applied to market data. The discussion of the properties of the model uses phase-space analysis, an approach uncommon in econometrics. (original abstract

  13. A Cross-Correlated Delay Shift Supervised Learning Method for Spiking Neurons with Application to Interictal Spike Detection in Epilepsy.

    Science.gov (United States)

    Guo, Lilin; Wang, Zhenzhong; Cabrerizo, Mercedes; Adjouadi, Malek

    2017-05-01

    This study introduces a novel learning algorithm for spiking neurons, called CCDS, which is able to learn and reproduce arbitrary spike patterns in a supervised fashion allowing the processing of spatiotemporal information encoded in the precise timing of spikes. Unlike the Remote Supervised Method (ReSuMe), synapse delays and axonal delays in CCDS are variants which are modulated together with weights during learning. The CCDS rule is both biologically plausible and computationally efficient. The properties of this learning rule are investigated extensively through experimental evaluations in terms of reliability, adaptive learning performance, generality to different neuron models, learning in the presence of noise, effects of its learning parameters and classification performance. Results presented show that the CCDS learning method achieves learning accuracy and learning speed comparable with ReSuMe, but improves classification accuracy when compared to both the Spike Pattern Association Neuron (SPAN) learning rule and the Tempotron learning rule. The merit of CCDS rule is further validated on a practical example involving the automated detection of interictal spikes in EEG records of patients with epilepsy. Results again show that with proper encoding, the CCDS rule achieves good recognition performance.

  14. Upper limb biomechanics during the volleyball serve and spike.

    Science.gov (United States)

    Reeser, Jonathan C; Fleisig, Glenn S; Bolt, Becky; Ruan, Mianfang

    2010-09-01

    The shoulder is the third-most commonly injured body part in volleyball, with the majority of shoulder problems resulting from chronic overuse. Significant kinetic differences exist among specific types of volleyball serves and spikes. Controlled laboratory study. Fourteen healthy female collegiate volleyball players performed 5 successful trials of 4 skills: 2 directional spikes, an off-speed roll shot, and the float serve. Volunteers who were competent in jump serves (n, 5) performed 5 trials of that skill. A 240-Hz 3-dimensional automatic digitizing system captured each trial. Multivariate analysis of variance and post hoc paired t tests were used to compare kinetic parameters for the shoulder and elbow across all the skills (except the jump serve). A similar statistical analysis was performed for upper extremity kinematics. Forces, torques, and angular velocities at the shoulder and elbow were lowest for the roll shot and second-lowest for the float serve. No differences were detected between the cross-body and straight-ahead spikes. Although there was an insufficient number of participants to statistically analyze the jump serve, the data for it appear similar to those of the cross-body and straight-ahead spikes. Shoulder abduction at the instant of ball contact was approximately 130° for all skills, which is substantially greater than that previously reported for female athletes performing tennis serves or baseball pitches. Because shoulder kinetics were greatest during spiking, the volleyball player with symptoms of shoulder overuse may wish to reduce the number of repetitions performed during practice. Limiting the number of jump serves may also reduce the athlete's risk of overuse-related shoulder dysfunction. Volleyball-specific overhead skills, such as the spike and serve, produce considerable upper extremity force and torque, which may contribute to the risk of shoulder injury.

  15. Stochastic hybrid model of spontaneous dendritic NMDA spikes

    International Nuclear Information System (INIS)

    Bressloff, Paul C; Newby, Jay M

    2014-01-01

    Following recent advances in imaging techniques and methods of dendritic stimulation, active voltage spikes have been observed in thin dendritic branches of excitatory pyramidal neurons, where the majority of synapses occur. The generation of these dendritic spikes involves both Na + ion channels and M-methyl-D-aspartate receptor (NMDAR) channels. During strong stimulation of a thin dendrite, the resulting high levels of glutamate, the main excitatory neurotransmitter in the central nervous system and an NMDA agonist, modify the current-voltage (I–V) characteristics of an NMDAR so that it behaves like a voltage-gated Na + channel. Hence, the NMDARs can fire a regenerative dendritic spike, just as Na + channels support the initiation of an action potential following membrane depolarization. However, the duration of the dendritic spike is of the order 100 ms rather than 1 ms, since it involves slow unbinding of glutamate from NMDARs rather than activation of hyperpolarizing K + channels. It has been suggested that dendritic NMDA spikes may play an important role in dendritic computations and provide a cellular substrate for short-term memory. In this paper, we consider a stochastic, conductance-based model of dendritic NMDA spikes, in which the noise originates from the stochastic opening and closing of a finite number of Na + and NMDA receptor ion channels. The resulting model takes the form of a stochastic hybrid system, in which membrane voltage evolves according to a piecewise deterministic dynamics that is coupled to a jump Markov process describing the opening and closing of the ion channels. We formulate the noise-induced initiation and termination of a dendritic spike in terms of a first-passage time problem, under the assumption that glutamate unbinding is negligible, which we then solve using a combination of WKB methods and singular perturbation theory. Using a stochastic phase-plane analysis we then extend our analysis to take proper account of the

  16. Bayesian Inference for Structured Spike and Slab Priors

    DEFF Research Database (Denmark)

    Andersen, Michael Riis; Winther, Ole; Hansen, Lars Kai

    2014-01-01

    Sparse signal recovery addresses the problem of solving underdetermined linear inverse problems subject to a sparsity constraint. We propose a novel prior formulation, the structured spike and slab prior, which allows to incorporate a priori knowledge of the sparsity pattern by imposing a spatial...... Gaussian process on the spike and slab probabilities. Thus, prior information on the structure of the sparsity pattern can be encoded using generic covariance functions. Furthermore, we provide a Bayesian inference scheme for the proposed model based on the expectation propagation framework. Using...

  17. Spike propagation in driven chain networks with dominant global inhibition

    International Nuclear Information System (INIS)

    Chang Wonil; Jin, Dezhe Z.

    2009-01-01

    Spike propagation in chain networks is usually studied in the synfire regime, in which successive groups of neurons are synaptically activated sequentially through the unidirectional excitatory connections. Here we study the dynamics of chain networks with dominant global feedback inhibition that prevents the synfire activity. Neural activity is driven by suprathreshold external inputs. We analytically and numerically demonstrate that spike propagation along the chain is a unique dynamical attractor in a wide parameter regime. The strong inhibition permits a robust winner-take-all propagation in the case of multiple chains competing via the inhibition.

  18. A Spiking Neural Network in sEMG Feature Extraction.

    Science.gov (United States)

    Lobov, Sergey; Mironov, Vasiliy; Kastalskiy, Innokentiy; Kazantsev, Victor

    2015-11-03

    We have developed a novel algorithm for sEMG feature extraction and classification. It is based on a hybrid network composed of spiking and artificial neurons. The spiking neuron layer with mutual inhibition was assigned as feature extractor. We demonstrate that the classification accuracy of the proposed model could reach high values comparable with existing sEMG interface systems. Moreover, the algorithm sensibility for different sEMG collecting systems characteristics was estimated. Results showed rather equal accuracy, despite a significant sampling rate difference. The proposed algorithm was successfully tested for mobile robot control.

  19. Method for spiking soil samples with organic compounds

    DEFF Research Database (Denmark)

    Brinch, Ulla C; Ekelund, Flemming; Jacobsen, Carsten S

    2002-01-01

    We examined the harmful side effects on indigenous soil microorganisms of two organic solvents, acetone and dichloromethane, that are normally used for spiking of soil with polycyclic aromatic hydrocarbons for experimental purposes. The solvents were applied in two contamination protocols to either...... higher than in control soil, probably due mainly to release of predation from indigenous protozoa. In order to minimize solvent effects on indigenous soil microorganisms when spiking native soil samples with compounds having a low water solubility, we propose a common protocol in which the contaminant...

  20. Nanomechanical microcantilever operated in vibration modes with use of RNA aptamer as receptor molecules for label-free detection of HCV helicase.

    Science.gov (United States)

    Hwang, Kyo Seon; Lee, Sang-Myung; Eom, Kilho; Lee, Jeong Hoon; Lee, Yoon-Sik; Park, Jung Ho; Yoon, Dae Sung; Kim, Tae Song

    2007-11-30

    We report the nanomechanical microcantilevers operated in vibration modes (oscillation) with use of RNA aptamers as receptor molecules for label-free detection of hepatitis C virus (HCV) helicase. The nanomechanical detection principle is that the ligand-receptor binding on the microcantilever surface induces the dynamic response change of microcantilevers. We implemented the label-free detection of HCV helicase in the low concentration as much as 100 pg/ml from measuring the dynamic response change of microcantilevers. Moreover, from the recent studies showing that the ligand-receptor binding generates the surface stress on the microcantilever, we estimate the surface stress, on the oscillating microcantilevers, induced by ligand-receptor binding, i.e. binding between HCV helicase and RNA aptamer. In this article, it is suggested that the oscillating microcantilevers with use of RNA aptamers as receptor molecules may enable one to implement the sensitive label-free detection of very small amount of small-scale proteins.

  1. Política, marketing e neoliberalismo

    Directory of Open Access Journals (Sweden)

    Pedro Roberto Ferreira

    2004-07-01

    Full Text Available O texto contém uma análise da relação política e sua possível consciência no seu momento específico compreendido pelo processo eleitoral (Londrina - eleições 92. Como este processo eleitoral em nossos dias, nutre-se de algumas técnicas conhecidas como Marketing Político-Eleitoral, e de como estas, contribuem para uma dinâmica de esvaziamento da vida política propriamente dita. Procura ainda, conectar esse esvaziamento político e suas consequências, com o avanço da concepção neoliberal cujo ápice parece fazer coincidir a política como mais uma manifestação de Mercado.

  2. Toxicity of nickel-spiked freshwater sediments to benthic invertebrates-Spiking methodology, species sensitivity, and nickel bioavailability

    Science.gov (United States)

    Besser, John M.; Brumbaugh, William G.; Kemble, Nile E.; Ivey, Chris D.; Kunz, James L.; Ingersoll, Christopher G.; Rudel, David

    2011-01-01

    This report summarizes data from studies of the toxicity and bioavailability of nickel in nickel-spiked freshwater sediments. The goal of these studies was to generate toxicity and chemistry data to support development of broadly applicable sediment quality guidelines for nickel. The studies were conducted as three tasks, which are presented here as three chapters: Task 1, Development of methods for preparation and toxicity testing of nickel-spiked freshwater sediments; Task 2, Sensitivity of benthic invertebrates to toxicity of nickel-spiked freshwater sediments; and Task 3, Effect of sediment characteristics on nickel bioavailability. Appendices with additional methodological details and raw chemistry and toxicity data for the three tasks are available online at http://pubs.usgs.gov/sir/2011/5225/downloads/.

  3. Mycobacterium tuberculosis DinG is a structure-specific helicase that unwinds G4 DNA: implications for targeting G4 DNA as a novel therapeutic approach.

    Science.gov (United States)

    Thakur, Roshan Singh; Desingu, Ambika; Basavaraju, Shivakumar; Subramanya, Shreelakshmi; Rao, Desirazu N; Nagaraju, Ganesh

    2014-09-05

    The significance of G-quadruplexes and the helicases that resolve G4 structures in prokaryotes is poorly understood. The Mycobacterium tuberculosis genome is GC-rich and contains >10,000 sequences that have the potential to form G4 structures. In Escherichia coli, RecQ helicase unwinds G4 structures. However, RecQ is absent in M. tuberculosis, and the helicase that participates in G4 resolution in M. tuberculosis is obscure. Here, we show that M. tuberculosis DinG (MtDinG) exhibits high affinity for ssDNA and ssDNA translocation with a 5' → 3' polarity. Interestingly, MtDinG unwinds overhangs, flap structures, and forked duplexes but fails to unwind linear duplex DNA. Our data with DNase I footprinting provide mechanistic insights and suggest that MtDinG is a 5' → 3' polarity helicase. Notably, in contrast to E. coli DinG, MtDinG catalyzes unwinding of replication fork and Holliday junction structures. Strikingly, we find that MtDinG resolves intermolecular G4 structures. These data suggest that MtDinG is a multifunctional structure-specific helicase that unwinds model structures of DNA replication, repair, and recombination as well as G4 structures. We finally demonstrate that promoter sequences of M. tuberculosis PE_PGRS2, mce1R, and moeB1 genes contain G4 structures, implying that G4 structures may regulate gene expression in M. tuberculosis. We discuss these data and implicate targeting G4 structures and DinG helicase in M. tuberculosis could be a novel therapeutic strategy for culminating the infection with this pathogen. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Fractal dimension analysis for spike detection in low SNR extracellular signals.

    Science.gov (United States)

    Salmasi, Mehrdad; Büttner, Ulrich; Glasauer, Stefan

    2016-06-01

    Many algorithms have been suggested for detection and sorting of spikes in extracellular recording. Nevertheless, it is still challenging to detect spikes in low signal-to-noise ratios (SNR). We propose a spike detection algorithm that is based on the fractal properties of extracellular signals and can detect spikes in low SNR regimes. Semi-intact spikes are low-amplitude spikes whose shapes are almost preserved. The detection of these spikes can significantly enhance the performance of multi-electrode recording systems. Semi-intact spikes are simulated by adding three noise components to a spike train: thermal noise, inter-spike noise, and spike-level noise. We show that simulated signals have fractal properties which make them proper candidates for fractal analysis. Then we use fractal dimension as the main core of our spike detection algorithm and call it fractal detector. The performance of the fractal detector is compared with three frequently used spike detectors. We demonstrate that in low SNR, the fractal detector has the best performance and results in the highest detection probability. It is shown that, in contrast to the other three detectors, the performance of the fractal detector is independent of inter-spike noise power and that variations in spike shape do not alter its performance. Finally, we use the fractal detector for spike detection in experimental data and similar to simulations, it is shown that the fractal detector has the best performance in low SNR regimes. The detection of low-amplitude spikes provides more information about the neural activity in the vicinity of the recording electrodes. Our results suggest using the fractal detector as a reliable and robust method for detecting semi-intact spikes in low SNR extracellular signals.

  5. microRNAs targeting DEAD-box helicases are involved in salinity stress response in rice (Oryza sativa L.

    Directory of Open Access Journals (Sweden)

    Macovei Anca

    2012-10-01

    Full Text Available Abstract Background Rice (Oryza sativa L., one of the most important food crop in the world, is considered to be a salt-sensitive crop. Excess levels of salt adversely affect all the major metabolic activities, including cell wall damage, cytoplasmic lysis and genomic stability. In order to cope with salt stress, plants have evolved high degrees of developmental plasticity, including adaptation via cascades of molecular networks and changes in gene expression profiles. Posttranscriptional regulation, through the activity of microRNAs, also plays an important role in the plant response to salinity conditions. MicroRNAs are small endogenous RNAs that modulate gene expression and are involved in the most essential physiological processes, including plant development and adaptation to environmental changes. Results In the present study, we investigated the expression profiles of osa-MIR414, osa-MIR408 and osa-MIR164e along with their targeted genes, under salinity stress conditions in wild type and transgenic rice plants ectopically expressing the PDH45 (Pea DNA Helicase gene. The present miRNAs were predicted to target the OsABP (ATP-Binding Protein, OsDSHCT (DOB1/SK12/helY-like DEAD-box Helicase and OsDBH (DEAD-Box Helicase genes, included in the DEAD-box helicase family. An in silico characterization of the proteins was performed and the miRNAs predicted targets were validated by RLM-5′RACE. The qRT-PCR analysis showed that the OsABP, OsDBH and OsDSHCT genes were up-regulated in response to 100 and 200 mM NaCl treatments. The present study also highlighted an increased accumulation of the gene transcripts in wild type plants, with the exception of the OsABP mRNA which showed the highest level (15.1-fold change compared to control in the transgenic plants treated with 200 mM NaCl. Salinity treatments also affected the expression of osa-MIR414, osa-MIR164e and osa-MIR408, found to be significantly down-regulated, although the changes in mi

  6. Helicase domain encoded by Cucumber mosaic virus RNA1 determines systemic infection of Cmr1 in pepper.

    Directory of Open Access Journals (Sweden)

    Won-Hee Kang

    Full Text Available The Cmr1 gene in peppers confers resistance to Cucumber mosaic virus isolate-P0 (CMV-P0. Cmr1 restricts the systemic spread of CMV strain-Fny (CMV-Fny, whereas this gene cannot block the spread of CMV isolate-P1 (CMV-P1 to the upper leaves, resulting in systemic infection. To identify the virulence determinant of CMV-P1, six reassortant viruses and six chimeric viruses derived from CMV-Fny and CMV-P1 cDNA clones were used. Our results demonstrate that the C-terminus of the helicase domain encoded by CMV-P1 RNA1 determines susceptibility to systemic infection, and that the helicase domain contains six different amino acid substitutions between CMV-Fny and CMV-P1(. To identify the key amino acids of the helicase domain determining systemic infection with CMV-P1, we then constructed amino acid substitution mutants. Of the mutants tested, amino acid residues at positions 865, 896, 957, and 980 in the 1a protein sequence of CMV-P1 affected the systemic infection. Virus localization studies with GFP-tagged CMV clones and in situ localization of virus RNA revealed that these four amino acid residues together form the movement determinant for CMV-P1 movement from the epidermal cell layer to mesophyll cell layers. Quantitative real-time PCR revealed that CMV-P1 and a chimeric virus with four amino acid residues of CMV-P1 accumulated more genomic RNA in inoculated leaves than did CMV-Fny, indicating that those four amino acids are also involved in virus replication. These results demonstrate that the C-terminal region of the helicase domain is responsible for systemic infection by controlling virus replication and cell-to-cell movement. Whereas four amino acids are responsible for acquiring virulence in CMV-Fny, six amino acid (positions at 865, 896, 901, 957, 980 and 993 substitutions in CMV-P1 were required for complete loss of virulence in 'Bukang'.

  7. Differential Involvement of the Five RNA Helicases in Adaptation of Bacillus cereus ATCC 14579 to Low Growth Temperatures ▿

    OpenAIRE

    Pandiani, Franck; Brillard, Julien; Bornard, Isabelle; Michaud, Caroline; Chamot, Stéphanie; Nguyen-the, Christophe; Broussolle, Véronique

    2010-01-01

    Bacillus cereus ATCC 14579 possesses five RNA helicase-encoding genes overexpressed under cold growth conditions. Out of the five corresponding mutants, only the {Delta}cshA, {Delta}cshB, and {Delta}cshC strains were cold sensitive. Growth of the {Delta}cshA strain was also reduced at 30°C but not at 37°C. The cold phenotype was restored with the cshA gene for the {Delta}cshA strain and partially for the {Delta}cshB strain but not for the {Delta}cshC strain, suggesting different functions at ...

  8. microRNAs targeting DEAD-box helicases are involved in salinity stress response in rice (Oryza sativa L.).

    Science.gov (United States)

    Macovei, Anca; Tuteja, Narendra

    2012-10-08

    Rice (Oryza sativa L.), one of the most important food crop in the world, is considered to be a salt-sensitive crop. Excess levels of salt adversely affect all the major metabolic activities, including cell wall damage, cytoplasmic lysis and genomic stability. In order to cope with salt stress, plants have evolved high degrees of developmental plasticity, including adaptation via cascades of molecular networks and changes in gene expression profiles. Posttranscriptional regulation, through the activity of microRNAs, also plays an important role in the plant response to salinity conditions. MicroRNAs are small endogenous RNAs that modulate gene expression and are involved in the most essential physiological processes, including plant development and adaptation to environmental changes. In the present study, we investigated the expression profiles of osa-MIR414, osa-MIR408 and osa-MIR164e along with their targeted genes, under salinity stress conditions in wild type and transgenic rice plants ectopically expressing the PDH45 (Pea DNA Helicase) gene. The present miRNAs were predicted to target the OsABP (ATP-Binding Protein), OsDSHCT (DOB1/SK12/helY-like DEAD-box Helicase) and OsDBH (DEAD-Box Helicase) genes, included in the DEAD-box helicase family. An in silico characterization of the proteins was performed and the miRNAs predicted targets were validated by RLM-5'RACE. The qRT-PCR analysis showed that the OsABP, OsDBH and OsDSHCT genes were up-regulated in response to 100 and 200 mM NaCl treatments. The present study also highlighted an increased accumulation of the gene transcripts in wild type plants, with the exception of the OsABP mRNA which showed the highest level (15.1-fold change compared to control) in the transgenic plants treated with 200 mM NaCl. Salinity treatments also affected the expression of osa-MIR414, osa-MIR164e and osa-MIR408, found to be significantly down-regulated, although the changes in miRNA expression were limited. Osa-MIR414, osa-MIR164

  9. Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing

    Czech Academy of Sciences Publication Activity Database

    Paliwal, S.; Kanagaraj, R.; Sturzenegger, A.; Burdová, Kamila; Janščák, Pavel

    2014-01-01

    Roč. 42, č. 4 (2014), s. 2380-2390 ISSN 0305-1048 R&D Projects: GA ČR GA204/09/0565; GA ČR GAP305/10/0281 Grant - others:Swiss National Science Foundation(CH) 31003A-129747; Swiss National Science Foundation(CH) 31003A_146206 Institutional support: RVO:68378050 Keywords : Human RECQ5 helicase * DNA double-strand breaks * mitotic homologous recombination Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.112, year: 2014

  10. Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

    Directory of Open Access Journals (Sweden)

    M.A.C. Smith

    2005-07-01

    Full Text Available Werner syndrome (WS is a premature aging disease caused by a mutation in the WRN gene. The gene was identified in 1996 and its product acts as a DNA helicase and exonuclease. Some specific WRN polymorphic variants were associated with increased risk for cardiovascular diseases. The identification of genetic polymorphisms as risk factors for complex diseases affecting older people can improve their prevention, diagnosis and prognosis. We investigated WRN codon 1367 polymorphism in 383 residents in a district of the city of São Paulo, who were enrolled in an Elderly Brazilian Longitudinal Study. Their mean age was 79.70 ± 5.32 years, ranging from 67 to 97. This population was composed of 262 females (68.4% and 121 males (31.6% of European (89.2%, Japanese (3.3%, Middle Eastern (1.81%, and mixed and/or other origins (5.7%. There are no studies concerning this polymorphism in Brazilian population. These subjects were evaluated clinically every two years. The major health problems and morbidities affecting this cohort were cardiovascular diseases (21.7%, hypertension (83.7%, diabetes (63.3%, obesity (41.23%, dementia (8.0%, depression (20.0%, and neoplasia (10.8%. Their prevalence is similar to some urban elderly Brazilian samples. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. Allele frequencies were 0.788 for the cysteine and 0.211 for the arginine. Genotype distributions were within that expected for the Hardy-Weinberg equilibrium. Female gender was associated with hypertension and obesity. Logistic regression analysis did not detect significant association between the polymorphism and morbidity. These findings confirm those from Europeans and differ from Japanese population.

  11. The roles of the Saccharomyces cerevisiae RecQ helicase SGS1 in meiotic genome surveillance.

    Directory of Open Access Journals (Sweden)

    Amit Dipak Amin

    2010-11-01

    Full Text Available The Saccharomyces cerevisiae RecQ helicase Sgs1 is essential for mitotic and meiotic genome stability. The stage at which Sgs1 acts during meiosis is subject to debate. Cytological experiments showed that a deletion of SGS1 leads to an increase in synapsis initiation complexes and axial associations leading to the proposal that it has an early role in unwinding surplus strand invasion events. Physical studies of recombination intermediates implicate it in the dissolution of double Holliday junctions between sister chromatids.In this work, we observed an increase in meiotic recombination between diverged sequences (homeologous recombination and an increase in unequal sister chromatid events when SGS1 is deleted. The first of these observations is most consistent with an early role of Sgs1 in unwinding inappropriate strand invasion events while the second is consistent with unwinding or dissolution of recombination intermediates in an Mlh1- and Top3-dependent manner. We also provide data that suggest that Sgs1 is involved in the rejection of 'second strand capture' when sequence divergence is present. Finally, we have identified a novel class of tetrads where non-sister spores (pairs of spores where each contains a centromere marker from a different parent are inviable. We propose a model for this unusual pattern of viability based on the inability of sgs1 mutants to untangle intertwined chromosomes. Our data suggest that this role of Sgs1 is not dependent on its interaction with Top3. We propose that in the absence of SGS1 chromosomes may sometimes remain entangled at the end of pre-meiotic replication. This, combined with reciprocal crossing over, could lead to physical destruction of the recombined and entangled chromosomes. We hypothesise that Sgs1, acting in concert with the topoisomerase Top2, resolves these structures.This work provides evidence that Sgs1 interacts with various partner proteins to maintain genome stability throughout

  12. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer.

    Science.gov (United States)

    Heerma van Voss, Marise R; Vesuna, Farhad; Trumpi, Kari; Brilliant, Justin; Berlinicke, Cynthia; de Leng, Wendy; Kranenburg, Onno; Offerhaus, G Johan; Bürger, Horst; van der Wall, Elsken; van Diest, Paul J; Raman, Venu

    2015-09-29

    Identifying druggable targets in the Wnt-signaling pathway can optimize colorectal cancer treatment. Recent studies have identified a member of the RNA helicase family DDX3 (DDX3X) as a multilevel activator of Wnt signaling in cells without activating mutations in the Wnt-signaling pathway. In this study, we evaluated whether DDX3 plays a role in the constitutively active Wnt pathway that drives colorectal cancer. We determined DDX3 expression levels in 303 colorectal cancers by immunohistochemistry. 39% of tumors overexpressed DDX3. High cytoplasmic DDX3 expression correlated with nuclear β-catenin expression, a marker of activated Wnt signaling. Functionally, we validated this finding in vitro and found that inhibition of DDX3 with siRNA resulted in reduced TCF4-reporter activity and lowered the mRNA expression levels of downstream TCF4-regulated genes. In addition, DDX3 knockdown in colorectal cancer cell lines reduced proliferation and caused a G1 arrest, supporting a potential oncogenic role of DDX3 in colorectal cancer. RK-33 is a small molecule inhibitor designed to bind to the ATP-binding site of DDX3. Treatment of colorectal cancer cell lines and patient-derived 3D cultures with RK-33 inhibited growth and promoted cell death with IC50 values ranging from 2.5 to 8 μM. The highest RK-33 sensitivity was observed in tumors with wild-type APC-status and a mutation in CTNNB1. Based on these results, we conclude that DDX3 has an oncogenic role in colorectal cancer. Inhibition of DDX3 with the small molecule inhibitor RK-33 causes inhibition of Wnt signaling and may therefore be a promising future treatment strategy for a subset of colorectal cancers.

  13. Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Daino

    Full Text Available BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1 and plays an important role in BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast cancer tumorigenesis remain unclear. To explore the function of BRIP1 in acinar morphogenesis of mammary epithelial cells, we generated BRIP1-knockdown MCF-10A cells by short hairpin RNA (shRNA-mediated RNA interference and examined its effect in a three-dimensional culture model. Genome-wide gene expression profiling by microarray and quantitative RT-PCR were performed to identify alterations in gene expression in BRIP1-knockdown cells compared with control cells. The microarray data were further investigated using the pathway analysis and Gene Set Enrichment Analysis (GSEA for pathway identification. BRIP1 knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference induced neoplastic-like changes such as abnormal cell adhesion, increased cell proliferation, large and irregular-shaped acini, invasive growth, and defective lumen formation. Differentially expressed genes, including MCAM, COL8A1, WIPF1, RICH2, PCSK5, GAS1, SATB1, and ELF3, in BRIP1-knockdown cells compared with control cells were categorized into several functional groups, such as cell adhesion, polarity, growth, signal transduction, and developmental process. Signaling-pathway analyses showed dysregulation of multiple cellular signaling pathways, involving LPA receptor, Myc, Wnt, PI3K, PTEN as well as DNA damage response, in BRIP1-knockdown cells. Loss of BRIP1 thus disrupts normal mammary morphogenesis and causes neoplastic-like changes, possibly via dysregulating multiple cellular signaling pathways functioning in the normal development of mammary glands.

  14. Spiking Activity of a LIF Neuron in Distributed Delay Framework

    Directory of Open Access Journals (Sweden)

    Saket Kumar Choudhary

    2016-06-01

    Full Text Available Evolution of membrane potential and spiking activity for a single leaky integrate-and-fire (LIF neuron in distributed delay framework (DDF is investigated. DDF provides a mechanism to incorporate memory element in terms of delay (kernel function into a single neuron models. This investigation includes LIF neuron model with two different kinds of delay kernel functions, namely, gamma distributed delay kernel function and hypo-exponential distributed delay kernel function. Evolution of membrane potential for considered models is studied in terms of stationary state probability distribution (SPD. Stationary state probability distribution of membrane potential (SPDV for considered neuron models are found asymptotically similar which is Gaussian distributed. In order to investigate the effect of membrane potential delay, rate code scheme for neuronal information processing is applied. Firing rate and Fano-factor for considered neuron models are calculated and standard LIF model is used for comparative study. It is noticed that distributed delay increases the spiking activity of a neuron. Increase in spiking activity of neuron in DDF is larger for hypo-exponential distributed delay function than gamma distributed delay function. Moreover, in case of hypo-exponential delay function, a LIF neuron generates spikes with Fano-factor less than 1.

  15. Bayesian Inference for Structured Spike and Slab Priors

    DEFF Research Database (Denmark)

    Andersen, Michael Riis; Winther, Ole; Hansen, Lars Kai

    2014-01-01

    Sparse signal recovery addresses the problem of solving underdetermined linear inverse problems subject to a sparsity constraint. We propose a novel prior formulation, the structured spike and slab prior, which allows to incorporate a priori knowledge of the sparsity pattern by imposing a spatial...

  16. Proficiency test on incurred and spiked pesticide residues in cereals

    DEFF Research Database (Denmark)

    Poulsen, Mette Erecius; Christensen, Hanne Bjerre; Herrmann, Susan Strange

    2009-01-01

    A proficiency test on incurred and spiked pesticide residues in wheat was organised in 2008. The test material was grown in 2007 and treated in the field with 14 pesticides formulations containing the active substances, alpha-cypermethrin, bifentrin, carbendazim, chlormequat, chlorpyrifos-methyl,...

  17. Cochlear spike synchronization and neuron coincidence detection model

    Science.gov (United States)

    Bader, Rolf

    2018-02-01

    Coincidence detection of a spike pattern fed from the cochlea into a single neuron is investigated using a physical Finite-Difference model of the cochlea and a physiologically motivated neuron model. Previous studies have shown experimental evidence of increased spike synchronization in the nucleus cochlearis and the trapezoid body [Joris et al., J. Neurophysiol. 71(3), 1022-1036 and 1037-1051 (1994)] and models show tone partial phase synchronization at the transition from mechanical waves on the basilar membrane into spike patterns [Ch. F. Babbs, J. Biophys. 2011, 435135]. Still the traveling speed of waves on the basilar membrane cause a frequency-dependent time delay of simultaneously incoming sound wavefronts up to 10 ms. The present model shows nearly perfect synchronization of multiple spike inputs as neuron outputs with interspike intervals (ISI) at the periodicity of the incoming sound for frequencies from about 30 to 300 Hz for two different amounts of afferent nerve fiber neuron inputs. Coincidence detection serves here as a fusion of multiple inputs into one single event enhancing pitch periodicity detection for low frequencies, impulse detection, or increased sound or speech intelligibility due to dereverberation.

  18. A memristive spiking neuron with firing rate coding

    Directory of Open Access Journals (Sweden)

    Marina eIgnatov

    2015-10-01

    Full Text Available Perception, decisions, and sensations are all encoded into trains of action potentials in the brain. The relation between stimulus strength and all-or-nothing spiking of neurons is widely believed to be the basis of this coding. This initiated the development of spiking neuron models; one of today's most powerful conceptual tool for the analysis and emulation of neural dynamics. The success of electronic circuit models and their physical realization within silicon field-effect transistor circuits lead to elegant technical approaches. Recently, the spectrum of electronic devices for neural computing has been extended by memristive devices, mainly used to emulate static synaptic functionality. Their capabilities for emulations of neural activity were recently demonstrated using a memristive neuristor circuit, while a memristive neuron circuit has so far been elusive. Here, a spiking neuron model is experimentally realized in a compact circuit comprising memristive and memcapacitive devices based on the strongly correlated electron material vanadium dioxide (VO2 and on the chemical electromigration cell Ag/TiO2-x/Al. The circuit can emulate dynamical spiking patterns in response to an external stimulus including adaptation, which is at the heart of firing rate coding as first observed by E.D. Adrian in 1926.

  19. Spike-timing-based computation in sound localization.

    Directory of Open Access Journals (Sweden)

    Dan F M Goodman

    2010-11-01

    Full Text Available Spike timing is precise in the auditory system and it has been argued that it conveys information about auditory stimuli, in particular about the location of a sound source. However, beyond simple time differences, the way in which neurons might extract this information is unclear and the potential computational advantages are unknown. The computational difficulty of this task for an animal is to locate the source of an unexpected sound from two monaural signals that are highly dependent on the unknown source signal. In neuron models consisting of spectro-temporal filtering and spiking nonlinearity, we found that the binaural structure induced by spatialized sounds is mapped to synchrony patterns that depend on source location rather than on source signal. Location-specific synchrony patterns would then result in the activation of location-specific assemblies of postsynaptic neurons. We designed a spiking neuron model which exploited this principle to locate a variety of sound sources in a virtual acoustic environment using measured human head-related transfer functions. The model was able to accurately estimate the location of previously unknown sounds in both azimuth and elevation (including front/back discrimination in a known acoustic environment. We found that multiple representations of different acoustic environments could coexist as sets of overlapping neural assemblies which could be associated with spatial locations by Hebbian learning. The model demonstrates the computational relevance of relative spike timing to extract spatial information about sources independently of the source signal.

  20. Sleep deprivation and spike-wave discharges in epileptic rats

    NARCIS (Netherlands)

    Drinkenburg, W.H.I.M.; Coenen, A.M.L.; Vossen, J.M.H.; Luijtelaar, E.L.J.M. van

    1995-01-01

    The effects of sleep deprivation were studied on the occurrence of spike-wave discharges in the electroencephalogram of rats of the epileptic WAG/Rij strain, a model for absence epilepsy. This was done before, during and after a period of 12 hours of near total sleep deprivation. A substantial

  1. Event-driven contrastive divergence for spiking neuromorphic systems.

    Science.gov (United States)

    Neftci, Emre; Das, Srinjoy; Pedroni, Bruno; Kreutz-Delgado, Kenneth; Cauwenberghs, Gert

    2013-01-01

    Restricted Boltzmann Machines (RBMs) and Deep Belief Networks have been demonstrated to perform efficiently in a variety of applications, such as dimensionality reduction, feature learning, and classification. Their implementation on neuromorphic hardware platforms emulating large-scale networks of spiking neurons can have significant advantages from the perspectives of scalability, power dissipation and real-time interfacing with the environment. However, the traditional RBM architecture and the commonly used training algorithm known as Contrastive Divergence (CD) are based on discrete updates and exact arithmetics which do not directly map onto a dynamical neural substrate. Here, we present an event-driven variation of CD to train a RBM constructed with Integrate & Fire (I&F) neurons, that is constrained by the limitations of existing and near future neuromorphic hardware platforms. Our strategy is based on neural sampling, which allows us to synthesize a spiking neural network that samples from a target Boltzmann distribution. The recurrent activity of the network replaces the discrete steps of the CD algorithm, while Spike Time Dependent Plasticity (STDP) carries out the weight updates in an online, asynchronous fashion. We demonstrate our approach by training an RBM composed of leaky I&F neurons with STDP synapses to learn a generative model of the MNIST hand-written digit dataset, and by testing it in recognition, generation and cue integration tasks. Our results contribute to a machine learning-driven approach for synthesizing networks of spiking neurons capable of carrying out practical, high-level functionality.

  2. Thermal impact on spiking properties in Hodgkin-Huxley neuron ...

    Indian Academy of Sciences (India)

    Thermal impact on spiking properties in Hodgkin-Huxley neuron with synaptic stimulus. Shenbing ... Department of Physical Science and Technology, Wuhan University of Technology, Wuhan, 430070, China; State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan, 430070, China ...

  3. Fast computation with spikes in a recurrent neural network

    International Nuclear Information System (INIS)

    Jin, Dezhe Z.; Seung, H. Sebastian

    2002-01-01

    Neural networks with recurrent connections are sometimes regarded as too slow at computation to serve as models of the brain. Here we analytically study a counterexample, a network consisting of N integrate-and-fire neurons with self excitation, all-to-all inhibition, instantaneous synaptic coupling, and constant external driving inputs. When the inhibition and/or excitation are large enough, the network performs a winner-take-all computation for all possible external inputs and initial states of the network. The computation is done very quickly: As soon as the winner spikes once, the computation is completed since no other neurons will spike. For some initial states, the winner is the first neuron to spike, and the computation is done at the first spike of the network. In general, there are M potential winners, corresponding to the top M external inputs. When the external inputs are close in magnitude, M tends to be larger. If M>1, the selection of the actual winner is strongly influenced by the initial states. If a special relation between the excitation and inhibition is satisfied, the network always selects the neuron with the maximum external input as the winner

  4. A memristive spiking neuron with firing rate coding.

    Science.gov (United States)

    Ignatov, Marina; Ziegler, Martin; Hansen, Mirko; Petraru, Adrian; Kohlstedt, Hermann

    2015-01-01

    Perception, decisions, and sensations are all encoded into trains of action potentials in the brain. The relation between stimulus strength and all-or-nothing spiking of neurons is widely believed to be the basis of this coding. This initiated the development of spiking neuron models; one of today's most powerful conceptual tool for the analysis and emulation of neural dynamics. The success of electronic circuit models and their physical realization within silicon field-effect transistor circuits lead to elegant technical approaches. Recently, the spectrum of electronic devices for neural computing has been extended by memristive devices, mainly used to emulate static synaptic functionality. Their capabilities for emulations of neural activity were recently demonstrated using a memristive neuristor circuit, while a memristive neuron circuit has so far been elusive. Here, a spiking neuron model is experimentally realized in a compact circuit comprising memristive and memcapacitive devices based on the strongly correlated electron material vanadium dioxide (VO2) and on the chemical electromigration cell Ag/TiO2-x /Al. The circuit can emulate dynamical spiking patterns in response to an external stimulus including adaptation, which is at the heart of firing rate coding as first observed by E.D. Adrian in 1926.

  5. Event-Driven Contrastive Divergence for Spiking Neuromorphic Systems

    Directory of Open Access Journals (Sweden)

    Emre eNeftci

    2014-01-01

    Full Text Available Restricted Boltzmann Machines (RBMs and Deep Belief Networks have been demonstrated to perform efficiently in variety of applications, such as dimensionality reduction, feature learning, and classification. Their implementation on neuromorphic hardware platforms emulating large-scale networks of spiking neurons can have significant advantages from the perspectives of scalability, power dissipation and real-time interfacing with the environment. However the traditional RBM architecture and the commonly used training algorithm known as Contrastive Divergence (CD are based on discrete updates and exact arithmetics which do not directly map onto a dynamical neural substrate. Here, we present an event-driven variation of CD to train a RBM constructed with Integrate & Fire (I&F neurons, that is constrained by the limitations of existing and near future neuromorphic hardware platforms. Our strategy is based on neural sampling, which allows us to synthesize a spiking neural network that samples from a target Boltzmann distribution. The reverberating activity of the network replaces the discrete steps of the CD algorithm, while Spike Time Dependent Plasticity (STDP carries out the weight updates in an online, asynchronous fashion.We demonstrate our approach by training an RBM composed of leaky I&F neurons with STDP synapses to learn a generative model of the MNIST hand-written digit dataset, and by testing it in recognition, generation and cue integration tasks. Our results contribute to a machine learning-driven approach for synthesizing networks of spiking neurons capable of carrying out practical, high-level functionality.

  6. Stochastic resonance in noisy spiking retinal and sensory neuron models.

    Science.gov (United States)

    Patel, Ashok; Kosko, Bart

    2005-01-01

    Two new theorems show that small amounts of additive white noise can improve the bit count or mutual information of several popular models of spiking retinal neurons and spiking sensory neurons. The first theorem gives necessary and sufficient conditions for this noise benefit or stochastic resonance (SR) effect for subthreshold signals in a standard family of Poisson spiking models of retinal neurons. The result holds for all types of finite-variance noise and for all types of infinite-variance stable noise: SR occurs if and only if a sum of noise means or location parameters falls outside a 'forbidden interval' of values. The second theorem gives a similar forbidden-interval sufficient condition for the SR effect for several types of spiking sensory neurons that include the Fitzhugh-Nagumo neuron, the leaky integrate-and-fire neuron, and the reduced Type I neuron model if the additive noise is Gaussian white noise. Simulations show that neither the forbidden-interval condition nor Gaussianity is necessary for the SR effect.

  7. Effect of Rolandic Spikes on ADHD Impulsive Behavior

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-01-01

    Full Text Available The association of Rolandic spikes with the neuropsychological profile of children with attention deficit hyperactivity disorder (ADHD was studied in a total of 48 patients at JW Goethe-University, Frankfurt/Main; and Central Institute of Mental Health, Mannheim, Germany.

  8. Edad y cultura política

    Directory of Open Access Journals (Sweden)

    MANUEL JUSTEL

    1992-01-01

    Full Text Available En este artículo se analiza la evolución de algunos aspectos de la cultura política y democrática durante los años ochenta: información y competencia política, participación política, actitudes hacia los partidos y orientaciones políticas. Los datos proceden de sendas encuestas realizadas en 1980 y 1989. Mediante análisis de cohortes de edad, controlando sexo y nivel de estudios, se comprueba el grado diferencial de expansión de actitudes democráticas en los grupos de edad, controlando sexo y nivel de estudios, se comprueba el grado diferencial de expansión de actitudes democráticas en los grupos de edad, el efecto homogeneizador que conlleva y el influjo estratégico de la educación. En el marco teórico de la socialización política en edad adulta y de las relaciones entre sistema social y sistema político, se interpretan los cambios de actitudes distinguiendo efectos de ciclo vital, de cohorte y de periodo. Al mismo tiempo, se discuten algunas consecuencias políticas del envejecimiento poblacional y se constata de un grado notable de plasticidad actitudinal y de adhesión creciente a la democracia de las cohortes de edad avanzada.

  9. Critical slowing down governs the transition to neuron spiking.

    Directory of Open Access Journals (Sweden)

    Christian Meisel

    2015-02-01

    Full Text Available Many complex systems have been found to exhibit critical transitions, or so-called tipping points, which are sudden changes to a qualitatively different system state. These changes can profoundly impact the functioning of a system ranging from controlled state switching to a catastrophic break-down; signals that predict critical transitions are therefore highly desirable. To this end, research efforts have focused on utilizing qualitative changes in markers related to a system's tendency to recover more slowly from a perturbation the closer it gets to the transition--a phenomenon called critical slowing down. The recently studied scaling of critical slowing down offers a refined path to understand critical transitions: to identify the transition mechanism and improve transition prediction using scaling laws. Here, we outline and apply this strategy for the first time in a real-world system by studying the transition to spiking in neurons of the mammalian cortex. The dynamical system approach has identified two robust mechanisms for the transition from subthreshold activity to spiking, saddle-node and Hopf bifurcation. Although theory provides precise predictions on signatures of critical slowing down near the bifurcation to spiking, quantitative experimental evidence has been lacking. Using whole-cell patch-clamp recordings from pyramidal neurons and fast-spiking interneurons, we show that 1 the transition to spiking dynamically corresponds to a critical transition exhibiting slowing down, 2 the scaling laws suggest a saddle-node bifurcation governing slowing down, and 3 these precise scaling laws can be used to predict the bifurcation point from a limited window of observation. To our knowledge this is the first report of scaling laws of critical slowing down in an experiment. They present a missing link for a broad class of neuroscience modeling and suggest improved estimation of tipping points by incorporating scaling laws of critical slowing

  10. Supervised Learning in Spiking Neural Networks for Precise Temporal Encoding.

    Science.gov (United States)

    Gardner, Brian; Grüning, André

    2016-01-01

    Precise spike timing as a means to encode information in neural networks is biologically supported, and is advantageous over frequency-based codes by processing input features on a much shorter time-scale. For these reasons, much recent attention has been focused on the development of supervised learning rules for spiking neural networks that utilise a temporal coding scheme. However, despite significant progress in this area, there still lack rules that have a theoretical basis, and yet can be considered biologically relevant. Here we examine the general conditions under which synaptic plasticity most effectively takes place to support the supervised learning of a precise temporal code. As part of our analysis we examine two spike-based learning methods: one of which relies on an instantaneous error signal to modify synaptic weights in a network (INST rule), and the other one relying on a filtered error signal for smoother synaptic weight modifications (FILT rule). We test the accuracy of the solutions provided by each rule with respect to their temporal encoding precision, and then measure the maximum number of input patterns they can learn to memorise using the precise timings of individual spikes as an indication of their storage capacity. Our results demonstrate the high performance of the FILT rule in most cases, underpinned by the rule's error-filtering mechanism, which is predicted to provide smooth convergence towards a desired solution during learning. We also find the FILT rule to be most efficient at performing input pattern memorisations, and most noticeably when patterns are identified using spikes with sub-millisecond temporal precision. In comparison with existing work, we determine the performance of the FILT rule to be consistent with that of the highly efficient E-learning Chronotron rule, but with the distinct advantage that our FILT rule is also implementable as an online method for increased biological realism.

  11. Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy.

    Science.gov (United States)

    Yoshida, Naruo; Hirata, Hirokuni; Watanabe, Mineaki; Sugiyama, Kumiya; Arima, Masafumi; Fukushima, Yasutsugu; Ishii, Yoshiki

    2015-07-01

    Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P venom (R = 0.78) in improvement testing and conventional testing. To determine specificity, 20 volunteers who had never experienced a Hymenoptera sting were all negative for sIgE against these venoms in both improvement and conventional testing. Improved sensitivity was seen in 8 patients negative for sIgE against both venoms in conventional testing, while improvement testing revealed sIgE against hornet or paper wasp venom in 5 (total 38 (92.7%)) patients. The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  12. Assembly of spikes into coronavirus particles is mediated by the carboxy-terminal domain of the spike protein

    NARCIS (Netherlands)

    Godeke, G J; de Haan, Cornelis A M; Rossen, J W; Vennema, H; Rottier, P J

    The type I glycoprotein S of coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. Here we demonstrate that incorporation is mediated by the short carboxy-terminal segment comprising the transmembrane and

  13. A Cold-Inducible DEAD-Box RNA Helicase from Arabidopsis thaliana Regulates Plant Growth and Development under Low Temperature.

    Science.gov (United States)

    Liu, Yuelin; Tabata, Daisuke; Imai, Ryozo

    2016-01-01

    DEAD-box RNA helicases comprise a large family and are involved in a range of RNA processing events. Here, we identified one of the Arabidopsis thaliana DEAD-box RNA helicases, AtRH7, as an interactor of Arabidopsis COLD SHOCK DOMAIN PROTEIN 3 (AtCSP3), which is an RNA chaperone involved in cold adaptation. Promoter:GUS transgenic plants revealed that AtRH7 is expressed ubiquitously and that its levels of the expression are higher in rapidly growing tissues. Knockout mutant lines displayed several morphological alterations such as disturbed vein pattern, pointed first true leaves, and short roots, which resemble ribosome-related mutants of Arabidopsis. In addition, aberrant floral development was also observed in rh7 mutants. When the mutants were germinated at low temperature (12°C), both radicle and first leaf emergence were severely delayed; after exposure of seedlings to a long period of cold, the mutants developed aberrant, fewer, and smaller leaves. RNA blots and circular RT-PCR revealed that 35S and 18S rRNA precursors accumulated to higher levels in the mutants than in WT under both normal and cold conditions, suggesting the mutants are partially impaired in pre-rRNA processing. Taken together, the results suggest that AtRH7 affects rRNA biogenesis and plays an important role in plant growth under cold.

  14. Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9.

    Science.gov (United States)

    Capitanio, Juliana S; Montpetit, Ben; Wozniak, Richard W

    2017-02-21

    Beyond their role at nuclear pore complexes, some nucleoporins function in the nucleoplasm. One such nucleoporin, Nup98, binds chromatin and regulates gene expression. To gain insight into how Nup98 contributes to this process, we focused on identifying novel binding partners and understanding the significance of these interactions. Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription. Consistent with these observations, our analysis revealed that Nup98 and DHX9 bind interdependently to similar gene loci and their transcripts. Based on our results, we propose that Nup98 functions as a co-factor that regulates DHX9 and, potentially, other RNA helicases.

  15. CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A

    Directory of Open Access Journals (Sweden)

    Jennifer Chu

    2016-06-01

    Full Text Available Targeting translation initiation is an emerging anti-neoplastic strategy that capitalizes on de-regulated upstream MAPK and PI3K-mTOR signaling pathways in cancers. A key regulator of translation that controls ribosome recruitment flux is eukaryotic initiation factor (eIF 4F, a hetero-trimeric complex composed of the cap binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Small molecule inhibitors targeting eIF4F display promising anti-neoplastic activity in preclinical settings. Among these are some rocaglate family members that are well tolerated in vivo, deplete eIF4F of its eIF4A helicase subunit, have shown activity as single agents in several xenograft models, and can reverse acquired resistance to MAPK and PI3K-mTOR targeted therapies. Herein, we highlight the power of using genetic complementation approaches and CRISPR/Cas9-mediated editing for drug-target validation ex vivo and in vivo, linking the anti-tumor properties of rocaglates to eIF4A inhibition.

  16. A Cold-Inducible DEAD-Box RNA Helicase from Arabidopsis thaliana Regulates Plant Growth and Development under Low Temperature.

    Directory of Open Access Journals (Sweden)

    Yuelin Liu

    Full Text Available DEAD-box RNA helicases comprise a large family and are involved in a range of RNA processing events. Here, we identified one of the Arabidopsis thaliana DEAD-box RNA helicases, AtRH7, as an interactor of Arabidopsis COLD SHOCK DOMAIN PROTEIN 3 (AtCSP3, which is an RNA chaperone involved in cold adaptation. Promoter:GUS transgenic plants revealed that AtRH7 is expressed ubiquitously and that its levels of the expression are higher in rapidly growing tissues. Knockout mutant lines displayed several morphological alterations such as disturbed vein pattern, pointed first true leaves, and short roots, which resemble ribosome-related mutants of Arabidopsis. In addition, aberrant floral development was also observed in rh7 mutants. When the mutants were germinated at low temperature (12°C, both radicle and first leaf emergence were severely delayed; after exposure of seedlings to a long period of cold, the mutants developed aberrant, fewer, and smaller leaves. RNA blots and circular RT-PCR revealed that 35S and 18S rRNA precursors accumulated to higher levels in the mutants than in WT under both normal and cold conditions, suggesting the mutants are partially impaired in pre-rRNA processing. Taken together, the results suggest that AtRH7 affects rRNA biogenesis and plays an important role in plant growth under cold.

  17. Dissociation from DNA of Type III Restriction–Modification enzymes during helicase-dependent motion and following endonuclease activity

    Science.gov (United States)

    Tóth, Júlia; van Aelst, Kara; Salmons, Hannah; Szczelkun, Mark D.

    2012-01-01

    DNA cleavage by the Type III Restriction–Modification (RM) enzymes requires the binding of a pair of RM enzymes at two distant, inversely orientated recognition sequences followed by helicase-catalysed ATP hydrolysis and long-range communication. Here we addressed the dissociation from DNA of these enzymes at two stages: during long-range communication and following DNA cleavage. First, we demonstrated that a communicating species can be trapped in a DNA domain without a recognition site, with a non-specific DNA association lifetime of ∼200 s. If free DNA ends were present the lifetime became too short to measure, confirming that ends accelerate dissociation. Secondly, we observed that Type III RM enzymes can dissociate upon DNA cleavage and go on to cleave further DNA molecules (they can ‘turnover’, albeit inefficiently). The relationship between the observed cleavage rate and enzyme concentration indicated independent binding of each site and a requirement for simultaneous interaction of at least two enzymes per DNA to achieve cleavage. In light of various mechanisms for helicase-driven motion on DNA, we suggest these results are most consistent with a thermally driven random 1D search model (i.e. ‘DNA sliding’). PMID:22523084

  18. Dissociation from DNA of Type III Restriction-Modification enzymes during helicase-dependent motion and following endonuclease activity.

    Science.gov (United States)

    Tóth, Júlia; van Aelst, Kara; Salmons, Hannah; Szczelkun, Mark D

    2012-08-01

    DNA cleavage by the Type III Restriction-Modification (RM) enzymes requires the binding of a pair of RM enzymes at two distant, inversely orientated recognition sequences followed by helicase-catalysed ATP hydrolysis and long-range communication. Here we addressed the dissociation from DNA of these enzymes at two stages: during long-range communication and following DNA cleavage. First, we demonstrated that a communicating species can be trapped in a DNA domain without a recognition site, with a non-specific DNA association lifetime of ∼ 200 s. If free DNA ends were present the lifetime became too short to measure, confirming that ends accelerate dissociation. Secondly, we observed that Type III RM enzymes can dissociate upon DNA cleavage and go on to cleave further DNA molecules (they can 'turnover', albeit inefficiently). The relationship between the observed cleavage rate and enzyme concentration indicated independent binding of each site and a requirement for simultaneous interaction of at least two enzymes per DNA to achieve cleavage. In light of various mechanisms for helicase-driven motion on DNA, we suggest these results are most consistent with a thermally driven random 1D search model (i.e. 'DNA sliding').

  19. Investigation of Current Spike Phenomena During Heavy Ion Irradiation of NAND Flash Memories

    Science.gov (United States)

    Oldham, Timothy R.; Berg, Melanie; Friendlich, Mark; Wilcox, Ted; Seidleck, Christina; LaBel, Kenneth A.; Irom, Farokh; Buchner, Steven P.; McMorrow, Dale; Mavis, David G.; hide

    2011-01-01

    A series of heavy ion and laser irradiations were performed to investigate previously reported current spikes in flash memories. High current events were observed, however, none matches the previously reported spikes. Plausible mechanisms are discussed.

  20. Fuels and Petroleum, Oil & Lubricants (POL) Laboratories

    Data.gov (United States)

    Federal Laboratory Consortium — The Fuels and Lubricants Technology Team operates and maintains the Fuels and POL Labs at TARDEC. Lab experts adhere to standardized American Society for Testing and...

  1. Estimating short-term synaptic plasticity from pre- and postsynaptic spiking

    Science.gov (United States)

    Malyshev, Aleksey; Stevenson, Ian H.

    2017-01-01

    Short-term synaptic plasticity (STP) critically affects the processing of information in neuronal circuits by reversibly changing the effective strength of connections between neurons on time scales from milliseconds to a few seconds. STP is traditionally studied using intracellular recordings of postsynaptic potentials or currents evoked by presynaptic spikes. However, STP also affects the statistics of postsynaptic spikes. Here we present two model-based approaches for estimating synaptic weights and short-term plasticity from pre- and postsynaptic spike observations alone. We extend a generalized linear model (GLM) that predicts postsynaptic spiking as a function of the observed pre- and postsynaptic spikes and allow the connection strength (coupling term in the GLM) to vary as a function of time based on the history of presynaptic spikes. Our first model assumes that STP follows a Tsodyks-Markram description of vesicle depletion and recovery. In a second model, we introduce a functional description of STP where we estimate the coupling term as a biophysically unrestrained function of the presynaptic inter-spike intervals. To validate the models, we test the accuracy of STP estimation using the spiking of pre- and postsynaptic neurons with known synaptic dynamics. We first test our models using the responses of layer 2/3 pyramidal neurons to simulated presynaptic input with different types of STP, and then use simulated spike trains to examine the effects of spike-frequency adaptation, stochastic vesicle release, spike sorting errors, and common input. We find that, using only spike observations, both model-based methods can accurately reconstruct the time-varying synaptic weights of presynaptic inputs for different types of STP. Our models also capture the differences in postsynaptic spike responses to presynaptic spikes following short vs long inter-spike intervals, similar to results reported for thalamocortical connections. These models may thus be useful

  2. a la política emancipatoria

    Directory of Open Access Journals (Sweden)

    Benjamín Arditi

    2007-01-01

    Full Text Available Este artículo explora la persistencia de la agitación en políticas de emancipación. Polemiza con la caracterización que hace Bismarck acerca de la política como “arte de lo posible” que fue retomada posteriormente como consigna por el realismo político. También toma distancia de las visiones escatológicas de la emancipación del tipo que asociamos con el jacobinismo. El propósito de esto es desestabilizar las fronteras entre lo posible y lo imposible y entre política revolucionaria y no revolucionaria. La agitación no es un remanente incómodo de la política caliente de antaño sino que sobrevive como periferia interna de la política institucional en democracias liberales. Funciona como un síntoma que impide el cierre de la política en un esquema plenamente normalizado o, lo que es igual, la agitación en combinación con la política emancipatoria hace surgir la “acontecimentalidad” del acontecimiento y permite vislumbrar el papel de lo imposible. Esto me permite introducir posteriormente una definición mínima de emancipación como disputa acerca de si las condiciones actuales impulsan o dañan la igualdad y la libertad, y si otro mundo es o no posible.

  3. Unique Helicase Determinants in the Essential Conjugative TraI Factor from Salmonella enterica Serovar Typhimurium Plasmid pCU1

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, Krystle J.; Nash, Rebekah P.; Redinbo, Mathew R. (UNC)

    2014-06-16

    The widespread development of multidrug-resistant bacteria is a major health emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic resistance genes, also encode the protein factors necessary to orchestrate the propagation of plasmid DNA between bacterial cells through conjugative transfer. Successful conjugative DNA transfer depends on key catalytic components to nick one strand of the duplex DNA plasmid and separate the DNA strands while cell-to-cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA-nicking relaxase and ATP-dependent helicase domains within a single, 1,078-residue polypeptide. In this work, we unraveled the helicase determinants of Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation assays. TraI binds DNA substrates with high affinity in a manner influenced by nucleic acid length and the presence of a DNA hairpin structure adjacent to the nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short (144-residue) domain at the extreme C terminus of the protein severely diminishes ATP-dependent strand separation. Collectively, these data define the helicase motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a previously uncharacterized C-terminal functional domain that uncouples ATP hydrolysis from strand separation activity.

  4. Mycobacterium smegmatis SftH exemplifies a distinctive clade of superfamily II DNA-dependent ATPases with 3' to 5' translocase and helicase activities.

    Science.gov (United States)

    Yakovleva, Lyudmila; Shuman, Stewart

    2012-08-01

    Bacterial DNA helicases are nucleic acid-dependent NTPases that play important roles in DNA replication, recombination and repair. We are interested in the DNA helicases of Mycobacteria, a genus of the phylum Actinobacteria, which includes the human pathogen Mycobacterium tuberculosis and its avirulent relative Mycobacterium smegmatis. Here, we identify and characterize M. smegmatis SftH, a superfamily II helicase with a distinctive domain structure, comprising an N-terminal NTPase domain and a C-terminal DUF1998 domain (containing a putative tetracysteine metal-binding motif). We show that SftH is a monomeric DNA-dependent ATPase/dATPase that translocates 3' to 5' on single-stranded DNA and has 3' to 5' helicase activity. SftH homologs are found in bacteria representing 12 different phyla, being especially prevalent in Actinobacteria (including M. tuberculosis). SftH homologs are evident in more than 30 genera of Archaea. Among eukarya, SftH homologs are present in plants and fungi.

  5. A temperature-sensitive allele of a putative mRNA splicing helicase down-regulates many cell wall genes and causes radial swelling in Arabidopsis thaliana.

    Science.gov (United States)

    Howles, Paul A; Gebbie, Leigh K; Collings, David A; Varsani, Arvind; Broad, Ronan C; Ohms, Stephen; Birch, Rosemary J; Cork, Ann H; Arioli, Tony; Williamson, Richard E

    2016-05-01

    The putative RNA helicase encoded by the Arabidopsis gene At1g32490 is a homolog of the yeast splicing RNA helicases Prp2 and Prp22. We isolated a temperature-sensitive allele (rsw12) of the gene in a screen for root radial swelling mutants. Plants containing this allele grown at the restrictive temperature showed weak radial swelling, were stunted with reduced root elongation, and contained reduced levels of cellulose. The role of the protein was further explored by microarray analysis. By using both fold change cutoffs and a weighted gene coexpression network analysis (WGCNA) to investigate coexpression of genes, we found that the radial swelling phenotype was not linked to genes usually associated with primary cell wall biosynthesis. Instead, the mutation has strong effects on expression of secondary cell wall related genes. Many genes potentially associated with secondary walls were present in the most significant WGCNA module, as were genes coding for arabinogalactans and proteins with GPI anchors. The proportion of up-regulated genes that possess introns in rsw12 was above that expected if splicing was unrelated to the activity of the RNA helicase, suggesting that the helicase does indeed play a role in splicing in Arabidopsis. The phenotype may be due to a change in the expression of one or more genes coding for cell wall proteins.

  6. Arabidopsis RecQsim, a plant-specific member of the RecQ helicase family, can suppress the MMS hypersensitivity of the yeast sgs1 mutant

    NARCIS (Netherlands)

    Bagherieh-Najjar, MB; de Vries, OMH; Kroon, JTM; Wright, EL; Elborough, KM; Hille, J; Dijkwel, PP

    The Arabidopsis genome contains seven genes that belong to the RecQ family of ATP-dependent DNA helicases. RecQ members in Saccharomyces cerevisiae (SGS1) and man (WRN, BLM and RecQL4) are involved in DNA recombination, repair and genome stability maintenance, but little is known about the function

  7. Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer.

    Science.gov (United States)

    Arora, Arvind; Abdel-Fatah, Tarek M A; Agarwal, Devika; Doherty, Rachel; Moseley, Paul M; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Alshareeda, Alaa T; Rakha, Emad A; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-04-01

    Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM mRNA expression in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1,950) and validated in an external dataset of 2,413 tumors. BLM protein level was evaluated in the Nottingham Tenovus series comprising 1,650 breast tumors. BLM mRNA overexpression was significantly associated with high histologic grade, larger tumor size, estrogen receptor-negative (ER(-)), progesterone receptor-negative (PR(-)), and triple-negative phenotypes (ps < 0.0001). BLM mRNA overexpression was also linked to aggressive molecular phenotypes, including PAM50.Her2 (P < 0.0001), PAM50.Basal (P < 0.0001), and PAM50.LumB (P < 0.0001) and Genufu subtype (ER(+)/Her2(-)/high proliferation; P < 0.0001). PAM50.LumA tumors and Genufu subtype (ER(+)/Her2(-)/low proliferation) were more likely to express low levels of BLM mRNA (ps < 0.0001). Integrative molecular clusters (intClust) intClust.1 (P < 0.0001), intClust.5 (P < 0.0001), intClust.9 (P < 0.0001), and intClust.10 (P < 0.0001) were also more likely in tumors with high BLM mRNA expression. BLM mRNA overexpression was associated with poor breast cancer-specific survival (BCSS; ps < 0.000001). At the protein level, altered subcellular localization with high cytoplasmic BLM and low nuclear BLM was linked to aggressive phenotypes. In multivariate analysis, BLM mRNA and BLM protein levels independently influenced BCSS. This is the first and the largest study to provide evidence that BLM is a promising biomarker in breast cancer. ©2015 American Association for Cancer Research.

  8. A 41 μW real-time adaptive neural spike classifier

    NARCIS (Netherlands)

    Zjajo, A.; van Leuken, T.G.R.M.

    2016-01-01

    Robust, power- and area-efficient spike classifier, capable of accurate identification of the neural spikes even for low SNR, is a prerequisite for the real-time, implantable, closed-loop brain-machine interface. In this paper, we propose an easily-scalable, 128-channel, programmable, neural spike

  9. Intracellular transport of recombinant coronavirus spike proteins: implications for virus assembly

    NARCIS (Netherlands)

    Horzinek, M.C.; Vennema, H.; Heijnen, L.; Zijderveld, A.; Spaan, W.J.M.

    1990-01-01

    Coronavirus spike protein genes were expressed in vitro by using the recombinant vaccinia virus expression system. Recombinant spike proteins were expressed at the cell surface and induced cell fusion in a host-cell-dependent fashion. The intracellular transport of recombinant spike proteins was

  10. The Ripple Pond: Enabling Spiking Networks to See

    Directory of Open Access Journals (Sweden)

    Saeed eAfshar

    2013-11-01

    Full Text Available We present the biologically inspired Ripple Pond Network (RPN, a simply connected spiking neural network which performs a transformation converting two dimensional images to one dimensional temporal patterns suitable for recognition by temporal coding learning and memory networks. The RPN has been developed as a hardware solution linking previously implemented neuromorphic vision and memory structures such as frameless vision sensors and neuromorphic temporal coding spiking neural networks. Working together such systems are potentially capable of delivering end-to-end high-speed, low-power and low-resolution recognition for mobile and autonomous applications where slow, highly sophisticated and power hungry signal processing solutions are ineffective. Key aspects in the proposed approach include utilising the spatial properties of physically embedded neural networks and propagating waves of activity therein for information processing, using dimensional collapse of imagery information into amenable temporal patterns and the use of asynchronous frames for information binding.

  11. Prolonging the postcomplex spike pause speeds eyeblink conditioning.

    Science.gov (United States)

    Maiz, Jaione; Karakossian, Movses H; Pakaprot, Narawut; Robleto, Karla; Thompson, Richard F; Otis, Thomas S

    2012-10-09

    Climbing fiber input to the cerebellum is believed to serve as a teaching signal during associative, cerebellum-dependent forms of motor learning. However, it is not understood how this neural pathway coordinates changes in cerebellar circuitry during learning. Here, we use pharmacological manipulations to prolong the postcomplex spike pause, a component of the climbing fiber signal in Purkinje neurons, and show that these manipulations enhance the rate of learning in classical eyelid conditioning. Our findings elucidate an unappreciated aspect of the climbing fiber teaching signal, and are consistent with a model in which convergent postcomplex spike pauses drive learning-related plasticity in the deep cerebellar nucleus. They also suggest a physiological mechanism that could modulate motor learning rates.

  12. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKES-WAVES ACTIVITY DURING SLEEP

    Directory of Open Access Journals (Sweden)

    E. D. Belousova

    2012-01-01

    Full Text Available The author represents the review and discussion of current scientific literature devoted to epileptic encephalopathy with continuous spikes-waves activity during sleep — the special form of partly reversible age-dependent epileptic encephalopathy, characterized by triad of symptoms: continuous prolonged epileptiform (spike-wave activity on EEG in sleep, epileptic seizures and cognitive disorders. The author describes the aspects of classification, pathogenesis and etiology, prevalence, clinical picture and diagnostics of this disorder, including the peculiar anomalies on EEG. The especial attention is given to approaches to the treatment of epileptic encephalopathy with continuous spikeswaves activity during sleep. Efficacy of valproates, corticosteroid hormones and antiepileptic drugs of other groups is considered. The author represents own experience of treatment this disorder with corticosteroids, scheme of therapy and assessment of efficacy.

  13. Harmonics of Solar Radio Spikes at Metric Wavelengths

    Science.gov (United States)

    Feng, S. W.; Chen, Y.; Li, C. Y.; Wang, B.; Wu, Z.; Kong, X. L.; Du, Q. F.; Zhang, J. R.; Zhao, G. Q.

    2018-03-01

    This paper presents the latest observations from the newly built solar radio spectrograph at the Chashan Solar Observatory. On July 18, 2016, the spectrograph records a solar spike burst event, which has several episodes showing harmonic structures, with the second, third, and fourth harmonics. The lower harmonic radio spike emissions are observed later than the higher harmonic bands, and the temporal delay of the second (third) harmonic relative to the fourth harmonic is about 30 - 40 (10) ms. Based on the electron cyclotron maser emission mechanism, we analyze possible causes of the temporal delay and further infer relevant coronal parameters, such as the magnetic field strength and the electron density at the radio source.

  14. Supervised learning with decision margins in pools of spiking neurons.

    Science.gov (United States)

    Le Mouel, Charlotte; Harris, Kenneth D; Yger, Pierre

    2014-10-01

    Learning to categorise sensory inputs by generalising from a few examples whose category is precisely known is a crucial step for the brain to produce appropriate behavioural responses. At the neuronal level, this may be performed by adaptation of synaptic weights under the influence of a training signal, in order to group spiking patterns impinging on the neuron. Here we describe a framework that allows spiking neurons to perform such "supervised learning", using principles similar to the Support Vector Machine, a well-established and robust classifier. Using a hinge-loss error function, we show that requesting a margin similar to that of the SVM improves performance on linearly non-separable problems. Moreover, we show that using pools of neurons to discriminate categories can also increase the performance by sharing the load among neurons.

  15. A Theory of Material Spike Formation in Flow Separation

    Science.gov (United States)

    Serra, Mattia; Haller, George

    2017-11-01

    We develop a frame-invariant theory of material spike formation during flow separation over a no-slip boundary in two-dimensional flows with arbitrary time dependence. This theory identifies both fixed and moving separation, is effective also over short-time intervals, and admits a rigorous instantaneous limit. Our theory is based on topological properties of material lines, combining objectively stretching- and rotation-based kinematic quantities. The separation profile identified here serves as the theoretical backbone for the material spike from its birth to its fully developed shape, and remains hidden to existing approaches. Finally, our theory can be used to rigorously explain the perception of off-wall separation in unsteady flows, and more importantly, provide the conditions under which such a perception is justified. We illustrate our results in several examples including steady, time-periodic and unsteady analytic velocity fields with flat and curved boundaries, and an experimental dataset.

  16. Binary Associative Memories as a Benchmark for Spiking Neuromorphic Hardware

    Directory of Open Access Journals (Sweden)

    Andreas Stöckel

    2017-08-01

    Full Text Available Large-scale neuromorphic hardware platforms, specialized computer systems for energy efficient simulation of spiking neural networks, are being developed around the world, for example as part of the European Human Brain Project (HBP. Due to conceptual differences, a universal performance analysis of these systems in terms of runtime, accuracy and energy efficiency is non-trivial, yet indispensable for further hard- and software development. In this paper we describe a scalable benchmark based on a spiking neural network implementation of the binary neural associative memory. We treat neuromorphic hardware and software simulators as black-boxes and execute exactly the same network description across all devices. Experiments on the HBP platforms under varying configurations of the associative memory show that the presented method allows to test the quality of the neuron model implementation, and to explain significant deviations from the expected reference output.

  17. Origin of the spike-timing-dependent plasticity rule

    Science.gov (United States)

    Cho, Myoung Won; Choi, M. Y.

    2016-08-01

    A biological synapse changes its efficacy depending on the difference between pre- and post-synaptic spike timings. Formulating spike-timing-dependent interactions in terms of the path integral, we establish a neural-network model, which makes it possible to predict relevant quantities rigorously by means of standard methods in statistical mechanics and field theory. In particular, the biological synaptic plasticity rule is shown to emerge as the optimal form for minimizing the free energy. It is further revealed that maximization of the entropy of neural activities gives rise to the competitive behavior of biological learning. This demonstrates that statistical mechanics helps to understand rigorously key characteristic behaviors of a neural network, thus providing the possibility of physics serving as a useful and relevant framework for probing life.

  18. Spin-orbit torque induced spike-timing dependent plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Sengupta, Abhronil, E-mail: asengup@purdue.edu; Al Azim, Zubair; Fong, Xuanyao; Roy, Kaushik [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States)

    2015-03-02

    Nanoelectronic devices that mimic the functionality of synapses are a crucial requirement for performing cortical simulations of the brain. In this work, we propose a ferromagnet-heavy metal heterostructure that employs spin-orbit torque to implement spike-timing dependent plasticity. The proposed device offers the advantage of decoupled spike transmission and programming current paths, thereby leading to reliable operation during online learning. Possible arrangement of such devices in a crosspoint architecture can pave the way for ultra-dense neural networks. Simulation studies indicate that the device has the potential of achieving pico-Joule level energy consumption (maximum 2 pJ per synaptic event) which is comparable to the energy consumption for synaptic events in biological synapses.

  19. Google Searches for "Cheap Cigarettes" Spike at Tax Increases: Evidence from an Algorithm to Detect Spikes in Time Series Data.

    Science.gov (United States)

    Caputi, Theodore L

    2017-06-22

    Online cigarette dealers have lower prices than brick-and-mortar retailers and advertise tax-free status 1-8. Previous studies show smokers search out these online alternatives at the time of a cigarette tax increase 9-10. However, these studies rely upon researchers' decision to consider a specific date and preclude the possibility that researchers focus on the wrong date. The purpose of this study is to introduce an unbiased methodology to the field of observing search patterns and to use this methodology to determine whether smokers search Google for "cheap cigarettes" at cigarette tax increases and, if so, whether the increased level of searches persists. Publicly available data from Google Trends is used to observe standardized search volumes for the term, "cheap cigarettes." Seasonal Hybrid Extreme Studentized Deviate and E-Divisive with Means tests were performed to observe spikes and mean level shifts in search volume. Of the twelve cigarette tax increases studied, ten showed spikes in searches for "cheap cigarettes" within two weeks of the tax increase. However, the mean level shifts did not occur for any cigarette tax increase. Searches for "cheap cigarettes" spike around the time of a cigarette tax increase, but the mean level of searches does not shift in response to a tax increase. The SHESD and EDM tests are unbiased methodologies that can be used to identify spikes and mean level shifts in time series data without an a priori date to be studied. SHESD and EDM affirm spikes in interest are related to tax increases. Applies improved statistical techniques (SHESD and EDM) to Google search data related to cigarettes, reducing bias and increasing powerContributes to the body of evidence that state and federal tax increases are associated with spikes in searches for cheap cigarettes and may be good dates for increased online health messaging related to tobacco. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research

  20. Archeomagnetic Intensity Spikes: Global or Regional Geomagnetic Field Features?

    Directory of Open Access Journals (Sweden)

    Monika Korte

    2018-03-01

    Full Text Available Variations of the geomagnetic field prior to direct observations are inferred from archeo- and paleomagnetic experiments. Seemingly unusual variations not seen in the present-day and historical field are of particular interest to constrain the full range of core dynamics. Recently, archeomagnetic intensity spikes, characterized by very high field values that appear to be associated with rapid secular variation rates, have been reported from several parts of the world. They were first noted in data from the Levant at around 900 BCE. A recent re-assessment of previous and new Levantine data, involving a rigorous quality assessment, interprets the observations as an extreme local geomagnetic high with at least two intensity spikes between the 11th and 8th centuries BCE. Subsequent reports of similar features from Asia, the Canary Islands and Texas raise the question of whether such features might be common occurrences, or whether they might even be part of a global magnetic field feature. Here we use spherical harmonic modeling to test two hypotheses: firstly, whether the Levantine and other potential spikes might be associated with higher dipole field intensity than shown by existing global field models around 1,000 BCE, and secondly, whether the observations from different parts of the world are compatible with a westward drifting intense flux patch. Our results suggest that the spikes originate from intense flux patches growing and decaying mostly in situ, combined with stronger and more variable dipole moment than shown by previous global field models. Axial dipole variations no more than 60% higher than observed in the present field, probably within the range of normal geodynamo behavior, seem sufficient to explain the observations.

  1. Spiking and LFP activity in PRR during symbolically instructed reaches.

    Science.gov (United States)

    Hwang, Eun Jung; Andersen, Richard A

    2012-02-01

    The spiking activity in the parietal reach region (PRR) represents the spatial goal of an impending reach when the reach is directed toward or away from a visual object. The local field potentials (LFPs) in this region also represent the reach goal when the reach is directed to a visual object. Thus PRR is a candidate area for reading out a patient's intended reach goals for neural prosthetic applications. For natural behaviors, reach goals are not always based on the location of a visual object, e.g., playing the piano following sheet music or moving following verbal directions. So far it has not been directly tested whether and how PRR represents reach goals in such cognitive, nonlocational conditions, and knowing the encoding properties in various task conditions would help in designing a reach goal decoder for prosthetic applications. To address this issue, we examined the macaque PRR under two reach conditions: reach goal determined by the stimulus location (direct) or shape (symbolic). For the same goal, the spiking activity near reach onset was indistinguishable between the two tasks, and thus a reach goal decoder trained with spiking activity in one task performed perfectly in the other. In contrast, the LFP activity at 20-40 Hz showed small but significantly enhanced reach goal tuning in the symbolic task, but its spatial preference remained the same. Consequently, a decoder trained with LFP activity performed worse in the other task than in the same task. These results suggest that LFP decoders in PRR should take into account the task context (e.g., locational vs. nonlocational) to be accurate, while spike decoders can robustly provide reach goal information regardless of the task context in various prosthetic applications.

  2. Simulating large-scale spiking neuronal networks with NEST

    OpenAIRE

    Senk, Johanna; Diesmann, Markus

    2014-01-01

    The Neural Simulation Tool NEST [1, www.nest-simulator.org] is the simulator for spiking neural networkmodels of the HBP that focuses on the dynamics, size and structure of neural systems rather than on theexact morphology of individual neurons. Its simulation kernel is written in C++ and it runs on computinghardware ranging from simple laptops to clusters and supercomputers with thousands of processor cores.The development of NEST is coordinated by the NEST Initiative [www.nest-initiative.or...

  3. Special Electrophysiological Tests: Brain Spiking, EEG Spectral Coherence

    Science.gov (United States)

    1983-01-01

    Mental Sciences 9TIC E-~ MAY (In Press) Handbook of Diagnostic Procedifre, Spectrum Pblications, Jamaica , New York. > This wk was pa -tially supported...likelihood is sufficiently small, then we reject the hypothesis that an EEG record containing N spikes in a time t is a normal record, - ,- - Flor several...significantly from zero, one may concl de that the two signal processes in question are related through ,o linear transformation over the spectral

  4. Stiff fluid spike solutions from Bianchi type V seed solutions

    Science.gov (United States)

    Gregoris, D.; Lim, W. C.; Coley, A. A.

    2017-12-01

    In this paper we expand upon our previous work Coley et al (2016 Class. Quantum Grav. 33 215010) by using the entire family of Bianchi type V stiff fluid solutions as seed solutions of the Stephani transformation. Among the new exact solutions generated, we observe a number of important physical phenomena. The most interesting phenomenon is exact solutions with intersecting spikes. Other interesting phenomena are solutions with saddle states and a close-to-FL epoch.

  5. The cellular RNA helicase UAP56 is required for prevention of double-stranded RNA formation during influenza A virus infection.

    Science.gov (United States)

    Wisskirchen, Christian; Ludersdorfer, Thomas H; Müller, Dominik A; Moritz, Eva; Pavlovic, Jovan

    2011-09-01

    The cellular DEAD box RNA helicase UAP56 plays a pivotal role in the efficient transcription/replication of influenza A virus. UAP56 is recruited by the nucleoprotein (NP) of influenza A viruses, and recent data revealed that the RNA helicase is required for the nuclear export of a subset of spliced and unspliced viral mRNAs. The fact that influenza viruses do not produce detectable amounts of double-stranded RNA (dsRNA) intermediates during transcription/replication suggests the involvement of cellular RNA helicases. Hence, we examined whether the RNA-unwinding activity of UAP56 or its paralog URH49 plays a role in preventing the accumulation of dsRNA during infection. First, our data showed that not only UAP56 but also its paralog URH49 can interact with NPs of avian and human influenza A viruses. The small interfering RNA (siRNA)-mediated depletion of either RNA helicase reduced the transport of M1 and hemagglutinin (HA) mRNAs and, to a lesser extent, NP and NS1 mRNAs into the cytoplasm. Moreover, we found that virus infection of UAP56-depleted cells leads to the rapid accumulation of dsRNA in the perinuclear region. In parallel, we observed a robust virus-mediated activation of dsRNA-dependent protein kinase R (PKR), indicating that the cellular RNA helicase UAP56 may be recruited by influenza virus to prevent dsRNA formation. The accumulation of dsRNA was blocked when actinomycin D or cycloheximide was used to inhibit viral transcription/replication or translation, respectively. In summary, we demonstrate that UAP56 is utilized by influenza A viruses to prevent the formation of dsRNA and, hence, the activation of the innate immune response.

  6. Spike: Artificial intelligence scheduling for Hubble space telescope

    Science.gov (United States)

    Johnston, Mark; Miller, Glenn; Sponsler, Jeff; Vick, Shon; Jackson, Robert

    1990-01-01

    Efficient utilization of spacecraft resources is essential, but the accompanying scheduling problems are often computationally intractable and are difficult to approximate because of the presence of numerous interacting constraints. Artificial intelligence techniques were applied to the scheduling of the NASA/ESA Hubble Space Telescope (HST). This presents a particularly challenging problem since a yearlong observing program can contain some tens of thousands of exposures which are subject to a large number of scientific, operational, spacecraft, and environmental constraints. New techniques were developed for machine reasoning about scheduling constraints and goals, especially in cases where uncertainty is an important scheduling consideration and where resolving conflicts among conflicting preferences is essential. These technique were utilized in a set of workstation based scheduling tools (Spike) for HST. Graphical displays of activities, constraints, and schedules are an important feature of the system. High level scheduling strategies using both rule based and neural network approaches were developed. While the specific constraints implemented are those most relevant to HST, the framework developed is far more general and could easily handle other kinds of scheduling problems. The concept and implementation of the Spike system are described along with some experiments in adapting Spike to other spacecraft scheduling domains.

  7. Stochastic models for spike trains of single neurons

    CERN Document Server

    Sampath, G

    1977-01-01

    1 Some basic neurophysiology 4 The neuron 1. 1 4 1. 1. 1 The axon 7 1. 1. 2 The synapse 9 12 1. 1. 3 The soma 1. 1. 4 The dendrites 13 13 1. 2 Types of neurons 2 Signals in the nervous system 14 2. 1 Action potentials as point events - point processes in the nervous system 15 18 2. 2 Spontaneous activi~ in neurons 3 Stochastic modelling of single neuron spike trains 19 3. 1 Characteristics of a neuron spike train 19 3. 2 The mathematical neuron 23 4 Superposition models 26 4. 1 superposition of renewal processes 26 4. 2 Superposition of stationary point processe- limiting behaviour 34 4. 2. 1 Palm functions 35 4. 2. 2 Asymptotic behaviour of n stationary point processes superposed 36 4. 3 Superposition models of neuron spike trains 37 4. 3. 1 Model 4. 1 39 4. 3. 2 Model 4. 2 - A superposition model with 40 two input channels 40 4. 3. 3 Model 4. 3 4. 4 Discussion 41 43 5 Deletion models 5. 1 Deletion models with 1nd~endent interaction of excitatory and inhibitory sequences 44 VI 5. 1. 1 Model 5. 1 The basic de...

  8. Spiking neural network-based control chart pattern recognition

    Directory of Open Access Journals (Sweden)

    Medhat H.A. Awadalla

    2012-03-01

    Full Text Available Due to an increasing competition in products, consumers have become more critical in choosing products. The quality of products has become more important. Statistical Process Control (SPC is usually used to improve the quality of products. Control charting plays the most important role in SPC. Control charts help to monitor the behavior of the process to determine whether it is stable or not. Unnatural patterns in control charts mean that there are some unnatural causes for variations in SPC. Spiking neural networks (SNNs are the third generation of artificial neural networks that consider time as an important feature for information representation and processing. In this paper, a spiking neural network architecture is proposed to be used for control charts pattern recognition (CCPR. Furthermore, enhancements to the SpikeProp learning algorithm are proposed. These enhancements provide additional learning rules for the synaptic delays, time constants and for the neurons thresholds. Simulated experiments have been conducted and the achieved results show a remarkable improvement in the overall performance compared with artificial neural networks.

  9. Poisson-Like Spiking in Circuits with Probabilistic Synapses

    Science.gov (United States)

    Moreno-Bote, Rubén

    2014-01-01

    Neuronal activity in cortex is variable both spontaneously and during stimulation, and it has the remarkable property that it is Poisson-like over broad ranges of firing rates covering from virtually zero to hundreds of spikes per second. The mechanisms underlying cortical-like spiking variability over such a broad continuum of rates are currently unknown. We show that neuronal networks endowed with probabilistic synaptic transmission, a well-documented source of variability in cortex, robustly generate Poisson-like variability over several orders of magnitude in their firing rate without fine-tuning of the network parameters. Other sources of variability, such as random synaptic delays or spike generation jittering, do not lead to Poisson-like variability at high rates because they cannot be sufficiently amplified by recurrent neuronal networks. We also show that probabilistic synapses predict Fano factor constancy of synaptic conductances. Our results suggest that synaptic noise is a robust and sufficient mechanism for the type of variability found in cortex. PMID:25032705

  10. The Use Of Spikes Protocol In Cancer: An Integrative Review

    Directory of Open Access Journals (Sweden)

    Fernando Henrique de Sousa

    2017-03-01

    Full Text Available This is an integrative review which aimed to evaluate the use of the SPIKES protocol in Oncology. We selected articles published in Medline and CINAHL databases between 2005-2015, in English, with the descriptors defined by the Medical Subject Headings (MeSH:cancer, neoplasms, plus the uncontrolled descriptor: protocol spikes.  Six articles met the inclusion criteria and were analyzed in full, three thematic categories were established: aspects inherent to the health care professional; Aspects related to the patient and aspects related to the protocol. The main effects of the steps of SPIKES protocol can provide the strengthening of ties between health professionals and patients, and ensure the maintenance and quality of this relationship.  The results indicate an important limiting factor for effective doctor-patient relationship, the little training provided to medical professionals communication of bad news, verified by the difficulty reported in this moment through interviews in the analyzed studies.

  11. Economic impact on the Florida economy of energy price spikes

    International Nuclear Information System (INIS)

    Mory, J.F.

    1992-01-01

    A substantial disturbance in oil supplies is likely to generate a large price upsurge and a downturn in the level of economic activity. Each of these two effects diminishes demand by a certain amount. The specific price surge required to reduce demand to the lower level of supply can be calculated with an oil demand function and with empirical estimations of the association between price spikes and declines in economic activity. The first section presents an energy demand model for Florida, which provides the price and income elasticities needed. The second section includes theoretical explanations and empirical estimations of the relationship between price spikes and recessions. Based on historical evidence, it seems that Florida's and the nation's economic systems are very sensitive to oil price surges. As price spikes appear damaging to the economy, it could be expected that reductions in the price of oil are beneficial to the system. That is likely to be the case in the long run, but no empirical evidence of favorable short-term effects of oil price decreases was found. Several possible explanations and theoretical reasons are offered to explain this lack of association. The final section presents estimates of the effect of oil disruptions upon specific industries in Florida and the nation

  12. Efficient Architecture for Spike Sorting in Reconfigurable Hardware

    Science.gov (United States)

    Hwang, Wen-Jyi; Lee, Wei-Hao; Lin, Shiow-Jyu; Lai, Sheng-Ying

    2013-01-01

    This paper presents a novel hardware architecture for fast spike sorting. The architecture is able to perform both the feature extraction and clustering in hardware. The generalized Hebbian algorithm (GHA) and fuzzy C-means (FCM) algorithm are used for feature extraction and clustering, respectively. The employment of GHA allows efficient computation of principal components for subsequent clustering operations. The FCM is able to achieve near optimal clustering for spike sorting. Its performance is insensitive to the selection of initial cluster centers. The hardware implementations of GHA and FCM feature low area costs and high throughput. In the GHA architecture, the computation of different weight vectors share the same circuit for lowering the area costs. Moreover, in the FCM hardware implementation, the usual iterative operations for updating the membership matrix and cluster centroid are merged into one single updating process to evade the large storage requirement. To show the effectiveness of the circuit, the proposed architecture is physically implemented by field programmable gate array (FPGA). It is embedded in a System-on-Chip (SOC) platform for performance measurement. Experimental results show that the proposed architecture is an efficient spike sorting design for attaining high classification correct rate and high speed computation. PMID:24189331

  13. Enhanced polychronisation in a spiking network with metaplasticity

    Directory of Open Access Journals (Sweden)

    Mira eGuise

    2015-02-01

    Full Text Available Computational models of metaplasticity have usually focused on the modeling of single synapses (Shouval et al., 2002. In this paper we study the effect of metaplasticity on network behavior. Our guiding assumption is that the primary purpose of metaplasticity is to regulate synaptic plasticity, by increasing it when input is low and decreasing it when input is high. For our experiments we adopt a model of metaplasticity that demonstrably has this effect for a single synapse; our primary interest is in how metaplasticity thus defined affects network-level phenomena. We focus on a network-level phenomenon called polychronicity, that has a potential role in representation and memory. A network with polychronicity has the ability to produce non-synchronous but precisely timed sequences of neural firing events that can arise from strongly connected groups of neurons called polychronous neural groups (Izhikevich et al., 2004; Izhikevich, 2006a. Polychronous groups (PNGs develop readily when spiking networks are exposed to repeated spatio-temporal stimuli under the influence of spike-timing-dependent plasticity (STDP, but are sensitive to changes in synaptic weight distribution. We use a technique we have recently developed called Response Fingerprinting to show that PNGs formed in the presence of metaplasticity are significantly larger than those with no metaplasticity. A potential mechanism for this enhancement is proposed that links an inherent property of integrator type neurons called spike latency to an increase in the tolerance of PNG neurons to jitter in their inputs.

  14. Efficient Architecture for Spike Sorting in Reconfigurable Hardware

    Directory of Open Access Journals (Sweden)

    Sheng-Ying Lai

    2013-11-01

    Full Text Available This paper presents a novel hardware architecture for fast spike sorting. The architecture is able to perform both the feature extraction and clustering in hardware. The generalized Hebbian algorithm (GHA and fuzzy C-means (FCM algorithm are used for feature extraction and clustering, respectively. The employment of GHA allows efficient computation of principal components for subsequent clustering operations. The FCM is able to achieve near optimal clustering for spike sorting. Its performance is insensitive to the selection of initial cluster centers. The hardware implementations of GHA and FCM feature low area costs and high throughput. In the GHA architecture, the computation of different weight vectors share the same circuit for lowering the area costs. Moreover, in the FCM hardware implementation, the usual iterative operations for updating the membership matrix and cluster centroid are merged into one single updating process to evade the large storage requirement. To show the effectiveness of the circuit, the proposed architecture is physically implemented by field programmable gate array (FPGA. It is embedded in a System-on-Chip (SOC platform for performance measurement. Experimental results show that the proposed architecture is an efficient spike sorting design for attaining high classification correct rate and high speed computation.

  15. A Reinforcement Learning Framework for Spiking Networks with Dynamic Synapses

    Directory of Open Access Journals (Sweden)

    Karim El-Laithy

    2011-01-01

    Full Text Available An integration of both the Hebbian-based and reinforcement learning (RL rules is presented for dynamic synapses. The proposed framework permits the Hebbian rule to update the hidden synaptic model parameters regulating the synaptic response rather than the synaptic weights. This is performed using both the value and the sign of the temporal difference in the reward signal after each trial. Applying this framework, a spiking network with spike-timing-dependent synapses is tested to learn the exclusive-OR computation on a temporally coded basis. Reward values are calculated with the distance between the output spike train of the network and a reference target one. Results show that the network is able to capture the required dynamics and that the proposed framework can reveal indeed an integrated version of Hebbian and RL. The proposed framework is tractable and less computationally expensive. The framework is applicable to a wide class of synaptic models and is not restricted to the used neural representation. This generality, along with the reported results, supports adopting the introduced approach to benefit from the biologically plausible synaptic models in a wide range of intuitive signal processing.

  16. Linking structure and activity in nonlinear spiking networks.

    Directory of Open Access Journals (Sweden)

    Gabriel Koch Ocker

    2017-06-01

    Full Text Available Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks' spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities-including those of different cell types-combine with connectivity to shape population activity and function.

  17. How adaptation shapes spike rate oscillations in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Moritz eAugustin

    2013-02-01

    Full Text Available Neural mass signals from in-vivo recordings often show oscillations with frequencies ranging from <1 Hz to 100 Hz. Fast rhythmic activity in the beta and gamma range can be generated by network based mechanisms such as recurrent synaptic excitation-inhibition loops. Slower oscillations might instead depend on neuronal adaptation currents whose timescales range from tens of milliseconds to seconds. Here we investigate how the dynamics of such adaptation currents contribute to spike rate oscillations and resonance properties in recurrent networks of excitatory and inhibitory neurons. Based on a network of sparsely coupled spiking model neurons with two types of adaptation current and conductance based synapses with heterogeneous strengths and delays we use a mean-field approach to analyze oscillatory network activity. For constant external input, we find that spike-triggered adaptation currents provide a mechanism to generate slow oscillations over a wide range of adaptation timescales as long as recurrent synaptic excitation is sufficiently strong. Faster rhythms occur when recurrent inhibition is slower than excitation and oscillation frequency increases with the strength of inhibition. Adaptation facilitates such network based oscillations for fast synaptic inhibition and leads to decreased frequencies. For oscillatory external input, adaptation currents amplify a narrow band of frequencies and cause phase advances for low frequencies in addition to phase delays at higher frequencies. Our results therefore identify the different key roles of neuronal adaptation dynamics for rhythmogenesis and selective signal propagation in recurrent networks.

  18. Spike latency and response properties of an excitable micropillar laser

    Science.gov (United States)

    Selmi, F.; Braive, R.; Beaudoin, G.; Sagnes, I.; Kuszelewicz, R.; Erneux, T.; Barbay, S.

    2016-10-01

    We present experimental measurements concerning the response of an excitable micropillar laser with saturable absorber to incoherent as well as coherent perturbations. The excitable response is similar to the behavior of spiking neurons but with much faster time scales. It is accompanied by a subnanosecond nonlinear delay that is measured for different bias pump values. This mechanism provides a natural scheme for encoding the strength of an ultrafast stimulus in the response delay of excitable spikes (temporal coding). Moreover, we demonstrate coherent and incoherent perturbations techniques applied to the micropillar with perturbation thresholds in the range of a few femtojoules. Responses to coherent perturbations assess the cascadability of the system. We discuss the physical origin of the responses to single and double perturbations with the help of numerical simulations of the Yamada model and, in particular, unveil possibilities to control the relative refractory period that we recently evidenced in this system. Experimental measurements are compared to both numerical simulations of the Yamada model and analytic expressions obtained in the framework of singular perturbation techniques. This system is thus a good candidate to perform photonic spike processing tasks in the framework of novel neuroinspired computing systems.

  19. Fast convergence of spike sequences to periodic patterns in recurrent networks

    International Nuclear Information System (INIS)

    Jin, Dezhe Z.

    2002-01-01

    The dynamical attractors are thought to underlie many biological functions of recurrent neural networks. Here we show that stable periodic spike sequences with precise timings are the attractors of the spiking dynamics of recurrent neural networks with global inhibition. Almost all spike sequences converge within a finite number of transient spikes to these attractors. The convergence is fast, especially when the global inhibition is strong. These results support the possibility that precise spatiotemporal sequences of spikes are useful for information encoding and processing in biological neural networks

  20. Controllable spiking patterns in long-wavelength vertical cavity surface emitting lasers for neuromorphic photonics systems

    Energy Technology Data Exchange (ETDEWEB)

    Hurtado, Antonio, E-mail: antonio.hurtado@strath.ac.uk [Institute of Photonics, SUPA Department of Physics, University of Strathclyde, TIC Centre, 99 George Street, Glasgow G1 1RD (United Kingdom); Javaloyes, Julien [Departament de Fisica, Universitat de les Illes Balears, c/Valldemossa km 7.5, 07122 Mallorca (Spain)

    2015-12-14

    Multiple controllable spiking patterns are achieved in a 1310 nm Vertical-Cavity Surface Emitting Laser (VCSEL) in response to induced perturbations and for two different cases of polarized optical injection, namely, parallel and orthogonal. Furthermore, reproducible spiking responses are demonstrated experimentally at sub-nanosecond speed resolution and with a controlled number of spikes fired. This work opens therefore exciting research avenues for the use of VCSELs in ultrafast neuromorphic photonic systems for non-traditional computing applications, such as all-optical binary-to-spiking format conversion and spiking information encoding.

  1. Detecting spikes of wheat plants using neural networks with Laws texture energy.

    Science.gov (United States)

    Qiongyan, Li; Cai, Jinhai; Berger, Bettina; Okamoto, Mamoru; Miklavcic, Stanley J

    2017-01-01

    The spike of a cereal plant is the grain-bearing organ whose physical characteristics are proxy measures of grain yield. The ability to detect and characterise spikes from 2D images of cereal plants, such as wheat, therefore provides vital information on tiller number and yield potential. We have developed a novel spike detection method for wheat plants involving, firstly, an improved colour index method for plant segmentation and, secondly, a neural network-based method using Laws texture energy for spike detection. The spike detection step was further improved by removing noise using an area and height threshold. The evaluation results showed an accuracy of over 80% in identification of spikes. In the proposed method we also measure the area of individual spikes as well as all spikes of individual plants under different experimental conditions. The correlation between the final average grain yield and spike area is also discussed in this paper. Our highly accurate yield trait phenotyping method for spike number counting and spike area estimation, is useful and reliable not only for grain yield estimation but also for detecting and quantifying subtle phenotypic variations arising from genetic or environmental differences.

  2. Involvement of specialized DNA polymerases Pol II, Pol IV and DnaE2 in DNA replication in the absence of Pol I in Pseudomonas putida

    International Nuclear Information System (INIS)

    Sidorenko, Julia; Jatsenko, Tatjana; Saumaa, Signe; Teras, Riho; Tark-Dame, Mariliis; Horak, Rita; Kivisaar, Maia

    2011-01-01

    The majority of bacteria possess a different set of specialized DNA polymerases than those identified in the most common model organism Escherichia coli. Here, we have studied the ability of specialized DNA polymerases to substitute Pol I in DNA replication in Pseudomonas putida. Our results revealed that P. putida Pol I-deficient cells have severe growth defects in LB medium, which is accompanied by filamentous cell morphology. However, growth of Pol I-deficient bacteria on solid rich medium can be restored by reduction of reactive oxygen species in cells. Also, mutants with improved growth emerge rapidly. Similarly to the initial Pol I-deficient P. putida, its adapted derivatives express a moderate mutator phenotype, which indicates that DNA replication carried out in the absence of Pol I is erroneous both in the original Pol I-deficient bacteria and the adapted derivatives. Analysis of the spectra of spontaneous Rif r mutations in P. putida strains lacking different DNA polymerases revealed that the presence of specialized DNA polymerases Pol II and Pol IV influences the frequency of certain base substitutions in Pol I-proficient and Pol I-deficient backgrounds in opposite ways. Involvement of another specialized DNA polymerase DnaE2 in DNA replication in Pol I-deficient bacteria is stimulated by UV irradiation of bacteria, implying that DnaE2-provided translesion synthesis partially substitutes the absence of Pol I in cells containing heavily damaged DNA.

  3. Involvement of specialized DNA polymerases Pol II, Pol IV and DnaE2 in DNA replication in the absence of Pol I in Pseudomonas putida

    Energy Technology Data Exchange (ETDEWEB)

    Sidorenko, Julia; Jatsenko, Tatjana; Saumaa, Signe; Teras, Riho; Tark-Dame, Mariliis; Horak, Rita [Department of Genetics, Institute of Molecular and Cell Biology, Tartu University and Estonian Biocentre, 23 Riia Street, 51010 Tartu (Estonia); Kivisaar, Maia, E-mail: maiak@ebc.ee [Department of Genetics, Institute of Molecular and Cell Biology, Tartu University and Estonian Biocentre, 23 Riia Street, 51010 Tartu (Estonia)

    2011-09-01

    The majority of bacteria possess a different set of specialized DNA polymerases than those identified in the most common model organism Escherichia coli. Here, we have studied the ability of specialized DNA polymerases to substitute Pol I in DNA replication in Pseudomonas putida. Our results revealed that P. putida Pol I-deficient cells have severe growth defects in LB medium, which is accompanied by filamentous cell morphology. However, growth of Pol I-deficient bacteria on solid rich medium can be restored by reduction of reactive oxygen species in cells. Also, mutants with improved growth emerge rapidly. Similarly to the initial Pol I-deficient P. putida, its adapted derivatives express a moderate mutator phenotype, which indicates that DNA replication carried out in the absence of Pol I is erroneous both in the original Pol I-deficient bacteria and the adapted derivatives. Analysis of the spectra of spontaneous Rif{sup r} mutations in P. putida strains lacking different DNA polymerases revealed that the presence of specialized DNA polymerases Pol II and Pol IV influences the frequency of certain base substitutions in Pol I-proficient and Pol I-deficient backgrounds in opposite ways. Involvement of another specialized DNA polymerase DnaE2 in DNA replication in Pol I-deficient bacteria is stimulated by UV irradiation of bacteria, implying that DnaE2-provided translesion synthesis partially substitutes the absence of Pol I in cells containing heavily damaged DNA.

  4. A stimulus-dependent spike threshold is an optimal neural coder

    Directory of Open Access Journals (Sweden)

    Douglas L Jones

    2015-06-01

    Full Text Available A neural code based on sequences of spikes can consume a significant portion of the brain’s energy budget. Thus, energy considerations would dictate that spiking activity be kept as low as possible. However, a high spike-rate improves the coding and representation of signals in spike trains, particularly in sensory systems. These are competing demands, and selective pressure has presumably worked to optimize coding by apportioning a minimum number of spikes so as to maximize coding fidelity. The mechanisms by which a neuron generates spikes while maintaining a fidelity criterion are not known. Here, we show that a signal-dependent neural threshold, similar to a dynamic or adapting threshold, optimizes the trade-off between spike generation (encoding and fidelity (decoding. The threshold mimics a post-synaptic membrane (a low-pass filter and serves as an internal decoder. Further, it sets the average firing rate (the energy constraint. The decoding process provides an internal copy of the coding error to the spike-generator which emits a spike when the error equals or exceeds a spike threshold. When optimized, the trade-off leads to a deterministic spike firing-rule that generates optimally timed spikes so as to maximize fidelity. The optimal coder is derived in closed-form in the limit of high spike-rates, when the signal can be approximated as a piece-wise constant signal. The predicted spike-times are close to those obtained experimentally in the primary electrosensory afferent neurons of weakly electric fish (Apteronotus leptorhynchus and pyramidal neurons from the somatosensory cortex of the rat. We suggest that KCNQ/Kv7 channels (underlying the M-current are good candidates for the decoder. They are widely coupled to metabolic processes and do not inactivate. We conclude that the neural threshold is optimized to generate an energy-efficient and high-fidelity neural code.

  5. GABA(B) receptors inhibit backpropagating dendritic spikes in hippocampal CA1 pyramidal cells in vivo.

    Science.gov (United States)

    Leung, L Stan; Peloquin, Pascal

    2006-01-01

    Spike backpropagation has been proposed to enhance dendritic depolarization and synaptic plasticity. However, relatively little is known about the inhibitory control of spike backpropagation in vivo. In this study, the backpropagation of the antidromic spike into the dendrites of CA1 pyramidal cells was studied by extracellular recording in urethane-anesthetized rats. The population antidromic spike (pAS) in CA1 following stimulation of the alveus was recorded simultaneously with a 16-channel silicon probe and analyzed as current source density (CSD). The pAS current sink was shown to sequentially invade the soma and then the apical and basal dendrites. When the pAS was preceded sinks were reduced and delayed. Dendritic spike suppression was large after a high-intensity CA3 conditioning stimulus that evoked a population spike, small after a low-intensity CA3 conditioning stimulus, and weak after conditioning by another pAS. The late (150-400 ms latency) inhibition of the backpropagating pAS at the apical and basal dendrites was partially relieved by a GABA(B) receptor antagonist, CGP35348 or CGP56999A, given intracerebroventricularly (icv). CGP35348 icv also decreased the latency of the antidromic spike sinks at all depths. A compartment cable model of a CA1 pyramidal cell with excitable dendrites, combined with a model of extracellular potential generation, confirms that GABA(B) receptor activation delays a backpropagating spike and blocks distal dendritic spikes. GABA(B) receptor-mediated conductance increase and hyperpolarization, amplified by removing dendritic I(A) inactivation, contribute to conditioned dendritic spike suppression. In addition, the model shows that slow Na(+) channel inactivation also participates in conditioned spike suppression, which may partly explain the small dendritic spike suppression after conditioning with a weak orthodromic stimulus or another antidromic spike. Thus, both theory and experiment confirm an important role of the GABA

  6. The Caenorhabditis elegans WRN helicase promotes double-strand DNA break repair by mediating end resection and checkpoint activation.

    Science.gov (United States)

    Ryu, Jin-Sun; Koo, Hyeon-Sook

    2017-07-01

    The protein associated with Werner syndrome (WRN), is involved in DNA repair, checkpoint activation, and telomere maintenance. To better understand the involvement of WRN in double-strand DNA break (DSB) repair, we analyzed the combinatorial role of WRN-1, the Caenorhabditis elegans WRN helicase, in conjunction with EXO-1 and DNA-2 nucleases. We found that WRN-1 cooperates with DNA-2 to resect DSB ends in a pathway acting in parallel to EXO-1. The wrn-1 mutants show an aberrant accumulation of replication protein A (RPA) and RAD-51, and the same pattern of accumulation is also observed in checkpoint-defective strains. We conclude that WRN-1 plays a conserved role in the resection of DSB ends and mediates checkpoint signaling, thereby influencing levels of RPA and RAD-51. © 2017 Federation of European Biochemical Societies.

  7. HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

    Science.gov (United States)

    Fiorini, Francesca; Robin, Jean-Philippe; Kanaan, Joanne; Borowiak, Malgorzata; Croquette, Vincent; Le Hir, Hervé; Jalinot, Pierre; Mocquet, Vincent

    2018-01-30

    Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

  8. Molecular architecture of the recombinant human MCM2-7 helicase in complex with nucleotides and DNA

    DEFF Research Database (Denmark)

    Boskovic, Jasminka; Bragado-Nilsson, Elisabeth; Saligram Prabhakar, Bhargav

    2016-01-01

    DNA replication is a key biological process that involves different protein complexes whose assembly is rigorously regulated in a successive order. One of these complexes is a replicative hexameric helicase, the MCM complex, which is essential for the initiation and elongation phases of replication....... After the assembly of a double heterohexameric MCM2-7 complex at replication origins in G1, the 2 heterohexamers separate from each other and associate with Cdc45 and GINS proteins in a CMG complex that is capable of unwinding dsDNA during S phase. Here, we have reconstituted and characterized...... the purified human MCM2-7 (hMCM2-7) hexameric complex by co-expression of its 6 different subunits in insect cells. The conformational variability of the complex has been analyzed by single particle electron microscopy in the presence of different nucleotide analogs and DNA. The interaction with nucleotide...

  9. A review on architecture of the gag-pol ribosomal frameshifting RNA in human immunodeficiency virus: a variability survey of virus genotypes.

    Science.gov (United States)

    Qiao, Qi; Yan, Yanhua; Guo, Jinmei; Du, Shuqiang; Zhang, Jiangtao; Jia, Ruyue; Ren, Haimin; Qiao, Yuanbiao; Li, Qingshan

    2017-06-01

    Programmed '-1' ribosomal frameshifting is necessary for expressing the pol gene overlapped from a gag of human immunodeficiency virus. A viral RNA structure that requires base pairing across the overlapping sequence region suggests a mechanism of regulating ribosome and helicase traffic during expression. To get precise roles of an element around the frameshift site, a review on architecture of the frameshifting RNA is performed in combination of reported information with augments of a representative set of 19 viral samples. In spite of a different length for the viral RNAs, a canonical comparison on the element sequence allocation is performed for viewing variability associations between virus genotypes. Additionally, recent and historical insights recognized in frameshifting regulation are looked back as for indel and single nucleotide polymorphism of RNA. As specially noted, structural changes at a frameshift site, the spacer sequence, and a three-helix junction element, as well as two Watson-Crick base pairs near a bulge and a C-G pair close a loop, are the most vital strategies for the virus frameshifting regulations. All of structural changes, which are dependent upon specific sequence variations, facilitate an elucidation about the RNA element conformation-dependent mechanism for frameshifting. These facts on disrupting base pair interactions also allow solving the problem of competition between ribosome and helicase on a same RNA template, common to single-stranded RNA viruses. In a broad perspective, each new insight of frameshifting regulation in the competition systems introduced by the RNA element construct changes will offer a compelling target for antiviral therapy.

  10. Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production.

    Science.gov (United States)

    Zhou, Yanrong; Wu, Wei; Xie, Lilan; Wang, Dang; Ke, Qiyun; Hou, Zhenzhen; Wu, Xiaoli; Fang, Ying; Chen, Huanchun; Xiao, Shaobo; Fang, Liurong

    2017-01-01

    Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus (CoV) of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN) production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro . However, the underlying mechanism(s) remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14) was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA) significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG) expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins.

  11. Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production

    Directory of Open Access Journals (Sweden)

    Yanrong Zhou

    2017-08-01

    Full Text Available Transmissible gastroenteritis virus (TGEV, an enteropathogenic coronavirus (CoV of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro. However, the underlying mechanism(s remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3 and nuclear factor-kappaB (NF-κB in porcine kidney (PK-15 cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14 was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins.

  12. Sensing and control of bluetongue virus infection in epithelial cells via RIG-I and MDA5 helicases.

    Science.gov (United States)

    Chauveau, Emilie; Doceul, Virginie; Lara, Estelle; Adam, Micheline; Breard, Emmanuel; Sailleau, Corinne; Viarouge, Cyril; Desprat, Alexandra; Meyer, Gilles; Schwartz-Cornil, Isabelle; Ruscanu, Suzana; Charley, Bernard; Zientara, Stéphan; Vitour, Damien

    2012-11-01

    Bluetongue virus (BTV), an arthropod-borne member of the Reoviridae family, is a double-stranded RNA virus that causes an economically important livestock disease that has spread across Europe in recent decades. Production of type I interferon (alpha/beta interferon [IFN-α/β]) has been reported in vivo and in vitro upon BTV infection. However, the cellular sensors and signaling pathways involved in this process remain unknown. Here we studied the mechanisms responsible for the production of IFN-β in response to BTV serotype 8. Upon BTV infection of A549 cells, expression of IFN-β and other proinflammatory cytokines was strongly induced at both the protein and mRNA levels. This response appeared to be dependent on virus replication, since exposure to UV-inactivated virus failed to induce IFN-β. We also demonstrated that BTV infection activated the transcription factors IFN regulatory factor 3 and nuclear factor κB. We investigated the role of several pattern recognition receptors in this response and showed that expression of IFN-β was greatly reduced after small-interfering-RNA-mediated knockdown of the RNA helicase encoded by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated gene 5 (MDA5). In contrast, silencing of MyD88, Toll-like receptor 3, or the recently described DexD/H-box helicase DDX1 sensor had no or a weak effect on IFN-β induction, suggesting that the RIG-I-like receptor pathway is specifically engaged for BTV sensing. Moreover, we also showed that overexpression of either RIG-I or MDA5 impaired BTV expression in infected A549 cells. Overall, this indicates that RIG-I and MDA5 can both contribute to the recognition and control of BTV infection.

  13. In the Crosshair: Astrometric Exoplanet Detection with WFIRST's Diffraction Spikes

    Science.gov (United States)

    Melchior, Peter; Spergel, David; Lanz, Arianna

    2018-02-01

    WFIRST will conduct a coronagraphic program that characterizes the atmospheres of planets around bright nearby stars. When observed with the WFIRST Wide Field Camera, these stars will saturate the detector and produce very strong diffraction spikes. In this paper, we forecast the astrometric precision that WFIRST can achieve by centering on the diffraction spikes of highly saturated stars. This measurement principle is strongly facilitated by the WFIRST H4RG detectors, which confine excess charges within the potential well of saturated pixels. By adopting a simplified analytical model of the diffraction spike caused by a single support strut obscuring the telescope aperture, integrated over the WFIRST pixel size, we predict the performance of this approach with the Fisher-matrix formalism. We discuss the validity of the model and find that 10 μ {as} astrometric precision is achievable with a single 100 s exposure of an {R}{AB}=6 or a {J}{AB}=5 star. We discuss observational limitations from the optical distortion correction and pixel-level artifacts, which need to be calibrated at the level of 10{--}20 μ {as} so as to not dominate the error budget. To suppress those systematics, we suggest a series of short exposures, dithered by at least several hundred pixels, to reach an effective per-visit astrometric precision better than 10 μ {as}. If this can be achieved, a dedicated WFIRST GO program will be able to detect Earth-mass exoplanets with orbital periods of ≳ 1 {year} around stars within a few pc as well as Neptune-like planets with shorter periods or around more massive or distant stars. Such a program will also enable mass measurements of many anticipated direct-imaging exoplanet targets of the WFIRST coronagraph and a “starshade” occulter.

  14. Systematic regional variations in Purkinje cell spiking patterns.

    Directory of Open Access Journals (Sweden)

    Jianqiang Xiao

    Full Text Available In contrast to the uniform anatomy of the cerebellar cortex, molecular and physiological studies indicate that significant differences exist between cortical regions, suggesting that the spiking activity of Purkinje cells (PCs in different regions could also show distinct characteristics. To investigate this possibility we obtained extracellular recordings from PCs in different zebrin bands in crus IIa and vermis lobules VIII and IX in anesthetized rats in order to compare PC firing characteristics between zebrin positive (Z+ and negative (Z- bands. In addition, we analyzed recordings from PCs in the A2 and C1 zones of several lobules in the posterior lobe, which largely contain Z+ and Z- PCs, respectively. In both datasets significant differences in simple spike (SS activity were observed between cortical regions. Specifically, Z- and C1 PCs had higher SS firing rates than Z+ and A2 PCs, respectively. The irregularity of SS firing (as assessed by measures of interspike interval distribution was greater in Z+ bands in both absolute and relative terms. The results regarding systematic variations in complex spike (CS activity were less consistent, suggesting that while real differences can exist, they may be sensitive to other factors than the cortical location of the PC. However, differences in the interactions between SSs and CSs, including the post-CS pause in SSs and post-pause modulation of SSs, were also consistently observed between bands. Similar, though less strong trends were observed in the zonal recordings. These systematic variations in spontaneous firing characteristics of PCs between zebrin bands in vivo, raises the possibility that fundamental differences in information encoding exist between cerebellar cortical regions.

  15. Spike-timing dependent plasticity in the striatum

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    2010-06-01

    Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

  16. From spiking neuron models to linear-nonlinear models.

    Directory of Open Access Journals (Sweden)

    Srdjan Ostojic

    Full Text Available Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF, exponential integrate-and-fire (EIF and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.

  17. Acciones políticas con las que resisten la cultura política tradicional

    Directory of Open Access Journals (Sweden)

    Catalina María Tabares Ochoa

    2013-01-01

    Full Text Available El artículo presenta resultados de la investigación Jóvenes, formación política y participación democrática, cuyo objetivo principal fue identificar los discursos con los cuales los jóvenes reconfiguran la política. La metodología implementada fue la reflexividad dialógica basada en observaciones participantes, talleres de la memoria y entrevistas semiestructuradas, realizadas con jóvenes de Medellín articulados a colectivos artísticos, ecologistas, vegetarianistas, feministas y antimilitaristas. El texto se compone de tres partes: la primera, denominada contextos investigativos, ubica el problema de investigación y el referente teórico de la cultura política en su dimensión interpretativa en la Ciencia Política; la segunda, describe la imagen que del sistema político tienen los jóvenes, para finalmente mostrar cómo con sus acciones debaten y recrean espacios de socialización política como la familia, la iglesia, la escuela, los medios de comunicación y la calle, dotándolos de nuevos sentidos y significados políticos.

  18. Agendamento de Políticas Públicas

    Directory of Open Access Journals (Sweden)

    Rosane Rosa

    2011-07-01

    Full Text Available Aborda-se o conceito de advocacy e contra-agendamento como uma forma de a Sociedade Civil incluir suas causas na mídia, objetivando a tematização e a possibilidade de transformar-se em política pública. Analisa-se a reportagem “Uma conquista longe das ruas”; resultado de um agendamento compartilhado e que, em muitos aspectos, serve de referência para cobertura de políticas públicas sociais.

  19. Políticas y ambiente

    Directory of Open Access Journals (Sweden)

    Nicolás Cuvi

    2013-10-01

    Full Text Available La presente edición de Letras Verdes está dedicada al amplio tema de las interacciones entre las políticas y el ambiente. Las preguntas que planteamos tenían como fin convocar a reflexiones tanto sobre los cambios discursivos en las políticas ambientales en América Latina, como sobre los impactos materiales que éstas han tenido, al suscitar (o no procesos de transformación en la relación que mantenemos con nuestro entorno.

  20. Codeine-spiked beer in a date rape case?

    Science.gov (United States)

    Havig, Stine Marie; Wiik, Elisabeth; Karinen, Ritva; Brochmann, Gerd Wenche; Vevelstad, Merete

    2016-11-01

    A case of suspected drug-facilitated sexual assault, involving codeine and acetaminophen, possibly mixed in beer, was recently addressed at the Norwegian Institute of Public Health. To examine the case, a small study was performed, spiking beer with preparations containing codeine and acetaminophen and observing the concentrations, appearance, and taste of the solutions. The study revealed the majority of the preparations to be quickly soluble in beer, achieving high concentrations, but at the expense of strong taste and drastic visible changes in the beer.

  1. Self-organization of spiking neurons using action potential timing.

    Science.gov (United States)

    Ruf, B; Schmitt, M

    1998-01-01

    We propose a mechanism for unsupervised learning in networks of spiking neurons which is based on the timing of single firing events. Our results show that a topology preserving behavior quite similar to that of Kohonen's self-organizing map can be achieved using temporal coding. In contrast to previous approaches, which use rate coding, the winner among competing neurons can be determined fast and locally. Our model is a further step toward a more realistic description of unsupervised learning in biological neural systems. Furthermore, it may provide a basis for fast implementations in pulsed VLSI (very large scale integration).

  2. First-spike latency in the presence of spontaneous activity

    Czech Academy of Sciences Publication Activity Database

    Pawlas, Z.; Klebanov, L. B.; Beneš, V.; Prokešová, M.; Popelář, Jiří; Lánský, Petr

    2010-01-01

    Roč. 22, č. 7 (2010), s. 1675-1693 ISSN 0899-7667 R&D Projects: GA ČR(CZ) GA309/07/1336; GA MŠk(CZ) LC554 Grant - others:GA AVCR(CZ) IAA101120604; GA ČR(CZ) GP201/08/P100 Program:IA Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z50110509 Keywords : spike trans * inferior colliculus * response latency Subject RIV: FH - Neurology Impact factor: 2.290, year: 2010

  3. On the Non-Learnability of a Single Spiking Neuron

    Czech Academy of Sciences Publication Activity Database

    Šíma, Jiří; Sgall, Jiří

    2005-01-01

    Roč. 17, č. 12 (2005), s. 2635-2647 ISSN 0899-7667 R&D Projects: GA ČR GA201/02/1456; GA AV ČR 1ET100300517; GA MŠk LN00A056; GA MŠk(CZ) 1M0545 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z10190503 Keywords : spiking neuron * consistency problem * NP-completness * PAC model * robust learning * representation problem Subject RIV: BA - General Mathematics Impact factor: 2.591, year: 2005

  4. Propagation of epileptic spikes reconstructed from spatiotemporal magnetoencephalographic and electroencephalographic source analysis.

    Science.gov (United States)

    Tanaka, Naoaki; Hämäläinen, Matti S; Ahlfors, Seppo P; Liu, Hesheng; Madsen, Joseph R; Bourgeois, Blaise F; Lee, Jong Woo; Dworetzky, Barbara A; Belliveau, John W; Stufflebeam, Steven M

    2010-03-01

    The purpose of this study is to assess the accuracy of spatiotemporal source analysis of magnetoencephalography (MEG) and scalp electroencephalography (EEG) for representing the propagation of frontotemporal spikes in patients with partial epilepsy. This study focuses on frontotemporal spikes, which are typically characterized by a preceding anterior temporal peak followed by an ipsilateral inferior frontal peak. Ten patients with frontotemporal spikes on MEG/EEG were studied. We analyzed the propagation of temporal to frontal epileptic spikes on both MEG and EEG independently by using a cortically constrained minimum norm estimate (MNE). Spatiotemporal source distribution of each spike was obtained on the cortical surface derived from the patient's MRI. All patients underwent an extraoperative intracranial EEG (IEEG) recording covering temporal and frontal lobes after presurgical evaluation. We extracted source waveforms of MEG and EEG from the source distribution of interictal spikes at the sites corresponding to the location of intracranial electrodes. The time differences of the ipsilateral temporal and frontal peaks as obtained by MEG, EEG and IEEG were statistically compared in each patient. In all patients, MEG and IEEG showed similar time differences between temporal and frontal peaks. The time differences of EEG spikes were significantly smaller than those of IEEG in nine of ten patients. Spatiotemporal analysis of MEG spikes models the time course of frontotemporal spikes as observed on IEEG more adequately than EEG in our patients. Spatiotemporal source analysis may be useful for planning epilepsy surgery, by predicting the pattern of IEEG spikes. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  5. Changes in Purkinje Cell Simple Spike Encoding of Reach Kinematics during Adaption to a Mechanical Perturbation

    Science.gov (United States)

    Hewitt, Angela L.; Popa, Laurentiu S.

    2015-01-01

    The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. PMID:25609626

  6. Routes to Chaos Induced by a Discontinuous Resetting Process in a Hybrid Spiking Neuron Model.

    Science.gov (United States)

    Nobukawa, Sou; Nishimura, Haruhiko; Yamanishi, Teruya

    2018-01-10

    Several hybrid spiking neuron models combining continuous spike generation mechanisms and discontinuous resetting processes following spiking have been proposed. The Izhikevich neuron model, for example, can reproduce many spiking patterns. This model clearly possesses various types of bifurcations and routes to chaos under the effect of a state-dependent jump in the resetting process. In this study, we focus further on the relation between chaotic behaviour and the state-dependent jump, approaching the subject by comparing spiking neuron model versions with and without the resetting process. We first adopt a continuous two-dimensional spiking neuron model in which the orbit in the spiking state does not exhibit divergent behaviour. We then insert the resetting process into the model. An evaluation using the Lyapunov exponent with a saltation matrix and a characteristic multiplier of the Poincar'e map reveals that two types of chaotic behaviour (i.e. bursting chaotic spikes and near-period-two chaotic spikes) are induced by the resetting process. In addition, we confirm that this chaotic bursting state is generated from the periodic spiking state because of the slow- and fast-scale dynamics that arise when jumping to the hyperpolarization and depolarization regions, respectively.

  7. Combining abilities for spike traits in a diallel cross of barley

    Directory of Open Access Journals (Sweden)

    Milomirka Madić

    2014-03-01

    Full Text Available Five two-row winter barley (Hordeum vulgare L. cultivars divergent in spike traits were crossed in all possible combinations excluding reciprocals to produce 10 F1 and F2 hybrids for analysis of combining abilities. The analysis of variance of combining abilities showed significant differences for GCA and SCA in F1 hybrids and F2 generation, suggesting additive and non-additive gene action. The GCA/SCA ratio in F1 and F2 indicated the prevalence of the additive component of genetic variance for spike length, grain weight per spike and spike harvest index. By contrast, the SCA variance for grain weight per spike was higher than the GCA variance, indicating the dominance of non-additive gene action. Good GCAs were found in parents having high values for spike length (Djerdap, NS-293, grain number per spike (Vada, Jagodinac, grain weight per spike (Vada, NS-293 and spike harvest index (Djerdap, Jagodinac. None of the parents had good GCA for all traits, suggesting a potential increase in combining abilities for spike traits. The best SCA were obtained mostly from crosses between parents having high x low, high x high or average x low GCA values. Parents having high GCA values may be used to produce improved lines in hybridisation programmes. Combinations with high SCA values may yield good segregating lines in further selection programmes.

  8. An online supervised learning method based on gradient descent for spiking neurons.

    Science.gov (United States)

    Xu, Yan; Yang, Jing; Zhong, Shuiming

    2017-09-01

    The purpose of supervised learning with temporal encoding for spiking neurons is to make the neurons emit a specific spike train encoded by precise firing times of spikes. The gradient-descent-based (GDB) learning methods are widely used and verified in the current research. Although the existing GDB multi-spike learning (or spike sequence learning) methods have good performance, they work in an offline manner and still have some limitations. This paper proposes an online GDB spike sequence learning method for spiking neurons that is based on the online adjustment mechanism of real biological neuron synapses. The method constructs error function and calculates the adjustment of synaptic weights as soon as the neurons emit a spike during their running process. We analyze and synthesize desired and actual output spikes to select appropriate input spikes in the calculation of weight adjustment in this paper. The experimental results show that our method obviously improves learning performance compared with the offline learning manner and has certain advantage on learning accuracy compared with other learning methods. Stronger learning ability determines that the method has large pattern storage capacity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A matched-filter algorithm to detect amperometric spikes resulting from quantal secretion.

    Science.gov (United States)

    Balaji Ramachandran, Supriya; Gillis, Kevin D

    2018-01-01

    Electrochemical microelectrodes located immediately adjacent to the cell surface can detect spikes of amperometric current during exocytosis as the transmitter released from a single vesicle is oxidized on the electrode surface. Automated techniques to detect spikes are needed in order to quantify the spike rate as a measure of the rate of exocytosis. We have developed a Matched Filter (MF) detection algorithm that scans the data set with a library of prototype spike templates while performing a least-squares fit to determine the amplitude and standard error. The ratio of the fit amplitude to the standard error constitutes a criterion score that is assigned for each time point and for each template. A spike is detected when the criterion score exceeds a threshold and the highest-scoring template and the time of peak score is identified. The search for the next spike commences only after the score falls below a second, lower threshold to reduce false positives. The approach was extended to detect spikes with double-exponential decays with the sum of two templates. Receiver Operating Characteristic plots (ROCs) demonstrate that the algorithm detects >95% of manually identified spikes with a false-positive rate of ∼2%. ROCs demonstrate that the MF algorithm performs better than algorithms that detect spikes based on a derivative-threshold approach. The MF approach performs well and leads into approaches to identify spike parameters. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Impact of substance P on the correlation of spike train evoked by electro acupuncture

    International Nuclear Information System (INIS)

    Jin, Chen; Zhang, Xuan; Wang, Jiang; Guo, Yi; Zhao, Xue; Guo, Yong-Ming

    2016-01-01

    Highlights: • We analyze spike trains induced by EA before and after inhibiting SP in PC6 area. • Inhibiting SP leads to an increase of spiking rate of median nerve. • SP may modulate membrane potential to affect the spiking rate. • SP has an influence on long-range correlation of spike train evoked by EA. • SP play an important role in EA-induced neural spiking and encoding. - Abstract: Substance P (SP) participates in the neural signal transmission evoked by electro-acupuncture (EA). This paper investigates the impact of SP on the correlation of spike train in the median nerve evoked by EA at 'Neiguan' acupoint (PC6). It shows that the spiking rate and interspike interval (ISI) distribution change obviously after inhibiting SP. This variation of spiking activity indicates that SP affects the temporal structure of spike train through modulating the action potential on median nerve filaments. Furtherly, the correlation coefficient and scaling exponent are considered to measure the correlation of spike train. Scaled Windowed Variance (SWV) method is applied to calculate scaling exponent which quantifies the long-range correlation of the neural electrical signals. It is found that the correlation coefficients of ISI increase after inhibiting SP released. In addition, the scaling exponents of neuronal spike train have significant differences between before and after inhibiting SP. These findings demonstrate that SP has an influence on the long-range correlation of spike train. Our results indicate that SP may play an important role in EA-induced neural spiking and encoding.

  11. Characterization of Mycobacterium smegmatis PolD2 and PolD1 as RNA/DNA polymerases homologous to the POL domain of bacterial DNA ligase D.

    Science.gov (United States)

    Zhu, Hui; Bhattarai, Hitesh; Yan, Han-Guang; Shuman, Stewart; Glickman, Michael S

    2012-12-21

    Mycobacteria exploit nonhomologous end-joining (NHEJ) to repair DNA double-strand breaks. The core NHEJ machinery comprises the homodimeric DNA end-binding protein Ku and DNA ligase D (LigD), a modular enzyme composed of a C-terminal ATP-dependent ligase domain (LIG), a central 3'-phosphoesterase domain (PE), and an N-terminal polymerase domain (POL). LigD POL is proficient at adding templated and nontemplated deoxynucleotides and ribonucleotides to DNA ends in vitro and is the catalyst in vivo of unfaithful NHEJ events involving nontemplated single-nucleotide additions to blunt DSB ends. Here, we identify two mycobacterial proteins, PolD1 and PolD2, as stand-alone homologues of the LigD POL domain. Biochemical characterization of PolD1 and PolD2 shows that they resemble LigD POL in their monomeric quaternary structures, their ability to add templated and nontemplated nucleotides to primer-templates and blunt ends, and their preference for rNTPs versus dNTPs. Deletion of polD1, polD2, or both from a Mycobacterium smegmatis strain carrying an inactivating mutation in LigD POL failed to reveal a role for PolD1 or PolD2 in templated nucleotide additions during NHEJ of 5'-overhang DSBs or in clastogen resistance. Whereas our results document the existence and characteristics of new stand-alone members of the LigD POL family of RNA/DNA polymerases, they imply that other polymerases can perform fill-in synthesis during mycobacterial NHEJ.

  12. Effect of heavy metals on pH buffering capacity and solubility of Ca, Mg, K, and P in non-spiked and heavy metal-spiked soils.

    Science.gov (United States)

    Najafi, Sarvenaz; Jalali, Mohsen

    2016-06-01

    In many parts of the world, soil acidification and heavy metal contamination has become a serious concern due to the adverse effects on chemical properties of soil and crop yield. The aim of this study was to investigate the effect of pH (in the range of 1 to 3 units above and below the native pH of soils) on calcium (Ca), magnesium (Mg), potassium (K), and phosphorus (P) solubility in non-spiked and heavy metal-spiked soil samples. Spiked samples were prepared by cadmium (Cd), copper (Cu), nickel (Ni), and zinc (Zn) as chloride salts and incubating soils for 40 days. The pH buffering capacity (pHBC) of each sample was determined by plotting the amount of H(+) or OH(-) added (mmol kg(-1)) versus the related pH value. The pHBC of soils ranged from 47.1 to 1302.5 mmol kg(-1) for non-spiked samples and from 45.0 to 1187.4 mmol kg(-1) for spiked soil samples. The pHBC values were higher in soil 2 (non-spiked and spiked) which had higher calcium carbonate content. The results indicated the presence of heavy metals in soils generally decreased the solution pH and pHBC values in spiked samples. In general, solubility of Ca, Mg, and K decreased with increasing equilibrium pH of non-spiked and spiked soil samples. In the case of P, increasing the pH to about 7, decreased the solubility in all soils but further increase of pH from 7, enhanced P solubility. The solubility trends and values for Ca, Mg, and K did not differed significantly in non-spiked and spiked samples. But in the case of P, a reduction in solubility was observed in heavy metal-spiked soils. The information obtained in this study can be useful to make better estimation of the effects of soil pollutants on anion and cation solubility from agricultural and environmental viewpoints.

  13. Theory of input spike auto- and cross-correlations and their effect on the response of spiking neurons.

    Science.gov (United States)

    Moreno-Bote, Rubén; Renart, Alfonso; Parga, Néstor

    2008-07-01

    Spike correlations between neurons are ubiquitous in the cortex, but their role is not understood. Here we describe the firing response of a leaky integrate-and-fire neuron (LIF) when it receives a temporarily correlated input generated by presynaptic correlated neuronal populations. Input correlations are characterized in terms of the firing rates, Fano factors, correlation coefficients, and correlation timescale of the neurons driving the target neuron. We show that the sum of the presynaptic spike trains cannot be well described by a Poisson process. In fact, the total input current has a nontrivial two-point correlation function described by two main parameters: the correlation timescale (how precise the input correlations are in time) and the correlation magnitude (how strong they are). Therefore, the total current generated by the input spike trains is not well described by a white noise gaussian process. Instead, we model the total current as a colored gaussian process with the same mean and two-point correlation function, leading to the formulation of the problem in terms of a Fokker-Planck equation. Solutions of the output firing rate are found in the limit of short and long correlation timescales. The solutions described here expand and improve on our previous results (Moreno, de la Rocha, Renart, & Parga, 2002) by presenting new analytical expressions for the output firing rate for general IF neurons, extending the validity of the results for arbitrarily large correlation magnitude, and by describing the differential effect of correlations on the mean-driven or noise-dominated firing regimes. Also the details of this novel formalism are given here for the first time. We employ numerical simulations to confirm the analytical solutions and study the firing response to sudden changes in the input correlations. We expect this formalism to be useful for the study of correlations in neuronal networks and their role in neural processing and information

  14. Spike timing analysis in neural networks with unsupervised synaptic plasticity

    Science.gov (United States)

    Mizusaki, B. E. P.; Agnes, E. J.; Brunnet, L. G.; Erichsen, R., Jr.

    2013-01-01

    The synaptic plasticity rules that sculpt a neural network architecture are key elements to understand cortical processing, as they may explain the emergence of stable, functional activity, while avoiding runaway excitation. For an associative memory framework, they should be built in a way as to enable the network to reproduce a robust spatio-temporal trajectory in response to an external stimulus. Still, how these rules may be implemented in recurrent networks and the way they relate to their capacity of pattern recognition remains unclear. We studied the effects of three phenomenological unsupervised rules in sparsely connected recurrent networks for associative memory: spike-timing-dependent-plasticity, short-term-plasticity and an homeostatic scaling. The system stability is monitored during the learning process of the network, as the mean firing rate converges to a value determined by the homeostatic scaling. Afterwards, it is possible to measure the recovery efficiency of the activity following each initial stimulus. This is evaluated by a measure of the correlation between spike fire timings, and we analysed the full memory separation capacity and limitations of this system.

  15. Approximate, computationally efficient online learning in Bayesian spiking neurons.

    Science.gov (United States)

    Kuhlmann, Levin; Hauser-Raspe, Michael; Manton, Jonathan H; Grayden, David B; Tapson, Jonathan; van Schaik, André

    2014-03-01

    Bayesian spiking neurons (BSNs) provide a probabilistic interpretation of how neurons perform inference and learning. Online learning in BSNs typically involves parameter estimation based on maximum-likelihood expectation-maximization (ML-EM) which is computationally slow and limits the potential of studying networks of BSNs. An online learning algorithm, fast learning (FL), is presented that is more computationally efficient than the benchmark ML-EM for a fixed number of time steps as the number of inputs to a BSN increases (e.g., 16.5 times faster run times for 20 inputs). Although ML-EM appears to converge 2.0 to 3.6 times faster than FL, the computational cost of ML-EM means that ML-EM takes longer to simulate to convergence than FL. FL also provides reasonable convergence performance that is robust to initialization of parameter estimates that are far from the true parameter values. However, parameter estimation depends on the range of true parameter values. Nevertheless, for a physiologically meaningful range of parameter values, FL gives very good average estimation accuracy, despite its approximate nature. The FL algorithm therefore provides an efficient tool, complementary to ML-EM, for exploring BSN networks in more detail in order to better understand their biological relevance. Moreover, the simplicity of the FL algorithm means it can be easily implemented in neuromorphic VLSI such that one can take advantage of the energy-efficient spike coding of BSNs.

  16. Spiked natural matrix materials as quality assessment samples

    International Nuclear Information System (INIS)

    Feiner, M.S.; Sanderson, C.G.

    1988-01-01

    The Environmental Measurements Laboratory has conducted the Quality Assessment Program since 1976 to evaluate the quality of the environmental radioactivity data, which is reported to the Department of Energy by as many as 42 commercial contractors involved in nuclear work. In this program, matrix materials of known radionuclide concentrations are distributed routinely to the contractors and the reported results are compared. The five matrices used are: soil, vegetation, animal tissue, water and filter paper. Environmental soil, vegetation and animal tissue are used, but the water and filter paper samples are prepared by spiking with known amounts of standard solutions traceable to the National Bureau of Standards. A summary of results is given to illustrate the successful operation of the program. Because of the difficulty and high cost of collecting large samples of natural matrix material and to increase the versatility of the program, an attempt was recently made to prepare the soil, vegetation and animal tissue samples with spiked solutions. A description of the preparation of these reference samples and the results of analyses are presented along with a discussion of the pitfalls and advantages of this approach. 19 refs.; 6 tabs

  17. Fuel switching? Demand destruction? Gas market responses to price spikes

    International Nuclear Information System (INIS)

    Lippe, D.

    2004-01-01

    This presentation defined fuel switching and addressed the issue regarding which consumers have the capability to switch fuels. In response to short term price aberrations, consumers with fuel switching capabilities reduce their use of one fuel and increase consumption of an alternative fuel. For example, natural gas consumption by some consumers declines in response to price spikes relative to prices of alternative fuels. This presentation also addressed the issue of differentiating between fuel switching and demand destruction. It also demonstrated how to compare gas prices versus alternative fuel prices and how to determine when consumers will likely switch fuels. Price spikes have implications for long term trends in natural gas demand, supply/demand balances and prices. The power generating sector represents a particular class of gas consumers that reduce operating rates of gas fired plants and increase operating rates of other plants. Some gas consumers even shut down plants until gas prices declines and relative economies improve. Some practical considerations for fuel switching include storage tank capacity, domestic refinery production, winter heating season, and decline in working gas storage. tabs., figs

  18. SWAT: a spiking neural network training algorithm for classification problems.

    Science.gov (United States)

    Wade, John J; McDaid, Liam J; Santos, Jose A; Sayers, Heather M

    2010-11-01

    This paper presents a synaptic weight association training (SWAT) algorithm for spiking neural networks (SNNs). SWAT merges the Bienenstock-Cooper-Munro (BCM) learning rule with spike timing dependent plasticity (STDP). The STDP/BCM rule yields a unimodal weight distribution where the height of the plasticity window associated with STDP is modulated causing stability after a period of training. The SNN uses a single training neuron in the training phase where data associated with all classes is passed to this neuron. The rule then maps weights to the classifying output neurons to reflect similarities in the data across the classes. The SNN also includes both excitatory and inhibitory facilitating synapses which create a frequency routing capability allowing the information presented to the network to be routed to different hidden layer neurons. A variable neuron threshold level simulates the refractory period. SWAT is initially benchmarked against the nonlinearly separable Iris and Wisconsin Breast Cancer datasets. Results presented show that the proposed training algorithm exhibits a convergence accuracy of 95.5% and 96.2% for the Iris and Wisconsin training sets, respectively, and 95.3% and 96.7% for the testing sets, noise experiments show that SWAT has a good generalization capability. SWAT is also benchmarked using an isolated digit automatic speech recognition (ASR) system where a subset of the TI46 speech corpus is used. Results show that with SWAT as the classifier, the ASR system provides an accuracy of 98.875% for training and 95.25% for testing.

  19. Macroscopic phase-resetting curves for spiking neural networks

    Science.gov (United States)

    Dumont, Grégory; Ermentrout, G. Bard; Gutkin, Boris

    2017-10-01

    The study of brain rhythms is an open-ended, and challenging, subject of interest in neuroscience. One of the best tools for the understanding of oscillations at the single neuron level is the phase-resetting curve (PRC). Synchronization in networks of neurons, effects of noise on the rhythms, effects of transient stimuli on the ongoing rhythmic activity, and many other features can be understood by the PRC. However, most macroscopic brain rhythms are generated by large populations of neurons, and so far it has been unclear how the PRC formulation can be extended to these more common rhythms. In this paper, we describe a framework to determine a macroscopic PRC (mPRC) for a network of spiking excitatory and inhibitory neurons that generate a macroscopic rhythm. We take advantage of a thermodynamic approach combined with a reduction method to simplify the network description to a small number of ordinary differential equations. From this simplified but exact reduction, we can compute the mPRC via the standard adjoint method. Our theoretical findings are illustrated with and supported by numerical simulations of the full spiking network. Notably our mPRC framework allows us to predict the difference between effects of transient inputs to the excitatory versus the inhibitory neurons in the network.

  20. Spike neural models (part I: The Hodgkin-Huxley model

    Directory of Open Access Journals (Sweden)

    Johnson, Melissa G.

    2017-05-01

    Full Text Available Artificial neural networks, or ANNs, have grown a lot since their inception back in the 1940s. But no matter the changes, one of the most important components of neural networks is still the node, which represents the neuron. Within spiking neural networks, the node is especially important because it contains the functions and properties of neurons that are necessary for their network. One important aspect of neurons is the ionic flow which produces action potentials, or spikes. Forces of diffusion and electrostatic pressure work together with the physical properties of the cell to move ions around changing the cell membrane potential which ultimately produces the action potential. This tutorial reviews the Hodkgin-Huxley model and shows how it simulates the ionic flow of the giant squid axon via four differential equations. The model is implemented in Matlab using Euler's Method to approximate the differential equations. By using Euler's method, an extra parameter is created, the time step. This new parameter needs to be carefully considered or the results of the node may be impaired.

  1. Information filtering by synchronous spikes in a neural population.

    Science.gov (United States)

    Sharafi, Nahal; Benda, Jan; Lindner, Benjamin

    2013-04-01

    Information about time-dependent sensory stimuli is encoded by the spike trains of neurons. Here we consider a population of uncoupled but noisy neurons (each subject to some intrinsic noise) that are driven by a common broadband signal. We ask specifically how much information is encoded in the synchronous activity of the population and how this information transfer is distributed with respect to frequency bands. In order to obtain some insight into the mechanism of information filtering effects found previously in the literature, we develop a mathematical framework to calculate the coherence of the synchronous output with the common stimulus for populations of simple neuron models. Within this frame, the synchronous activity is treated as the product of filtered versions of the spike trains of a subset of neurons. We compare our results for the simple cases of (1) a Poisson neuron with a rate modulation and (2) an LIF neuron with intrinsic white current noise and a current stimulus. For the Poisson neuron, formulas are particularly simple but show only a low-pass behavior of the coherence of synchronous activity. For the LIF model, in contrast, the coherence function of the synchronous activity shows a clear peak at high frequencies, comparable to recent experimental findings. We uncover the mechanism for this shift in the maximum of the coherence and discuss some biological implications of our findings.

  2. Dynamics of Monoterpene Formation in Spike Lavender Plants

    Science.gov (United States)

    Kutzner, Erika; Huber, Claudia; Segura, Juan; Arrillaga, Isabel

    2017-01-01

    The metabolic cross-talk between the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways was analyzed in spike lavender (Lavandula latifolia Med) on the basis of 13CO2-labelling experiments using wildtype and transgenic plants overexpressing the 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the first and key enzyme of the MVA pathway. The plants were labelled in the presence of 13CO2 in a gas chamber for controlled pulse and chase periods of time. GC/MS and NMR analysis of 1,8-cineole and camphor, the major monoterpenes present in their essential oil, indicated that the C5-precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) of both monoterpenes are predominantly biosynthesized via the MEP pathway. Surprisingly, overexpression of HMGR did not have significant impact upon the crosstalk between the MVA and MEP pathways indicating that the MEP route is the preferred pathway for the synthesis of C5 monoterpene precursors in spike lavender. PMID:29257083

  3. Spike-Based Bayesian-Hebbian Learning of Temporal Sequences.

    Directory of Open Access Journals (Sweden)

    Philip J Tully

    2016-05-01

    Full Text Available Many cognitive and motor functions are enabled by the temporal representation and processing of stimuli, but it remains an open issue how neocortical microcircuits can reliably encode and replay such sequences of information. To better understand this, a modular attractor memory network is proposed in which meta-stable sequential attractor transitions are learned through changes to synaptic weights and intrinsic excitabilities via the spike-based Bayesian Confidence Propagation Neural Network (BCPNN learning rule. We find that the formation of distributed memories, embodied by increased periods of firing in pools of excitatory neurons, together with asymmetrical associations between these distinct network states, can be acquired through plasticity. The model's feasibility is demonstrated using simulations of adaptive exponential integrate-and-fire model neurons (AdEx. We show that the learning and speed of sequence replay depends on a confluence of biophysically relevant parameters including stimulus duration, level of background noise, ratio of synaptic currents, and strengths of short-term depression and adaptation. Moreover, sequence elements are shown to flexibly participate multiple times in the sequence, suggesting that spiking attractor networks of this type can support an efficient combinatorial code. The model provides a principled approach towards understanding how multiple interacting plasticity mechanisms can coordinate hetero-associative learning in unison.

  4. Automatic detection of interictal spikes using data mining models.

    Science.gov (United States)

    Valenti, Pablo; Cazamajou, Enrique; Scarpettini, Marcelo; Aizemberg, Ariel; Silva, Walter; Kochen, Silvia

    2006-01-15

    A prospective candidate for epilepsy surgery is studied both the ictal and interictal spikes (IS) to determine the localization of the epileptogenic zone. In this work, data mining (DM) classification techniques were utilized to build an automatic detection model. The selected DM algorithms are: Decision Trees (J 4.8), and Statistical Bayesian Classifier (naïve model). The main objective was the detection of IS, isolating them from the EEG's base activity. On the other hand, DM has an attractive advantage in such applications, in that the recognition of epileptic discharges does not need a clear definition of spike morphology. Furthermore, previously 'unseen' patterns could be recognized by the DM with proper 'training'. The results obtained showed that the efficacy of the selected DM algorithms is comparable to the current visual analysis used by the experts. Moreover, DM is faster than the time required for the visual analysis of the EEG. So this tool can assist the experts by facilitating the analysis of a patient's information, and reducing the time and effort required in the process.

  5. Hg stable isotope analysis by the double-spike method.

    Science.gov (United States)

    Mead, Chris; Johnson, Thomas M

    2010-06-01

    Recent publications suggest great potential for analysis of Hg stable isotope abundances to elucidate sources and/or chemical processes that control the environmental impact of mercury. We have developed a new MC-ICP-MS method for analysis of mercury isotope ratios using the double-spike approach, in which a solution containing enriched (196)Hg and (204)Hg is mixed with samples and provides a means to correct for instrumental mass bias and most isotopic fractionation that may occur during sample preparation and introduction into the instrument. Large amounts of isotopic fractionation induced by sample preparation and introduction into the instrument (e.g., by batch reactors) are corrected for. This may greatly enhance various Hg pre-concentration methods by correcting for minor fractionation that may occur during preparation and removing the need to demonstrate 100% recovery. Current precision, when ratios are normalized to the daily average, is 0.06 per thousand, 0.06 per thousand, 0.05 per thousand, and 0.05 per thousand (2sigma) for (202)Hg/(198)Hg, (201)Hg/(198)Hg, (200)Hg/(198)Hg, and (199)Hg/(198)Hg, respectively. This is slightly better than previously published methods. Additionally, this precision was attained despite the presence of large amounts of other Hg isotopes (e.g., 5.0% atom percent (198)Hg) in the spike solution; substantially better precision could be achieved if purer (196)Hg were used.

  6. Subjetividad política: intersectaciones afrodescendientes

    Directory of Open Access Journals (Sweden)

    Adriana Arroyo-Ortega

    2017-01-01

    Full Text Available En el presente artículo recogemos algunos hallazgos sobre la subjetividad política tomados de una investigación doctoral que se encuentra en curso y que explora la narración de una mujer joven afrodescendiente que, en su acción en un colectivo de la ciudad de Medellín, interroga las prácticas cotidianas de exclusión y precisa los intereses que en su lugar de ubicación ha venido desarrollando. En un primer momento, avanzamos sobre la subjetividad política mediante la reflexión que algunos investigadores e investigadoras han realizado al respecto en relación con lo expresado por esta mujer joven en su acción política, articulado posteriormente con una profundización sobre las implicaciones de la expansión de la subjetividad política de las mujeres jóvenes afrodescendientes, para finalizar con unas líneas conclusivas.

  7. Ingeniero, político, economista, inventor

    Directory of Open Access Journals (Sweden)

    Jimena Montaña Cuéllar

    2001-01-01

    Full Text Available Técnica y utopía. Biografía intelectual y política de Alejandro López, 1876-1940. Alberto Mayor Mora. Fondo Editorial Universidad Eafit, colección Cielos de Arena, Medellín, 2001, 621 págs., il.

  8. El marketing político

    Directory of Open Access Journals (Sweden)

    Alvaro H. Cifuentes G.

    2015-04-01

    Full Text Available RESUMEN Si un candidato desea ser elegido, las técnicas de marketing aplicadas a la política, le son imprescindibles. El marketing político (Politing es el análisis  metódico de los diferentes segmentos que integran el ámbito político de una sociedad y de los factores que puedan modificarlos. Se aplican al candidato, a los votantes, al análisis de la publicidad política, a los simpatizantes, a desconocedores  del partido y a los indecisos. Los candidatos colombianos lo están aplicando, y compañías nuestras exportan servicios  de asesoría de países suramericanos.Promocionar  un candidato implica estructurar una compañía tal como una empresa, aplicando técnicas de ventas, de fijación de cuotas y de planeación estratégica.

  9. Reduction of the fast electrons preheating by changing the spike launch time in shock ignition approach

    Science.gov (United States)

    Jafar Jafari, Mohammad; Farahbod, Amir Hossein; Rezaei, Somayeh

    2016-01-01

    Target characteristic parameters in shock ignition approach before launching the spike pulse are studied using a 1-D hydrodynamic simulation code. By delaying the spike launch time, the shell areal density, ρR, is increased. The enhanced shell areal density prevents the hot electrons preheating of main fuel which in turn is generated from the intense laser plasma interaction with corona. To consider the effect of the spike launch time on the target performance, the target gain for a wide range of spike powers and launch times are computed. It is noticed that for HiPER reference target, few tenth nanoseconds displacement of spike launch time increases the areal density, ρR, value up to 30-70 percent. Furthermore, by choosing an appropriate spike energy and peak power, the optimum target gain is achieved in which the total driver energy is reduced.

  10. Principal cell spiking, postsynaptic excitation, and oxygen consumption in the rat cerebellar cortex

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Piilgaard, Henning; Gjedde, Albert

    2009-01-01

    . In contrast, PC spiking was largely responsible for the increase in CMRO2 when ongoing neuronal activity was increased by gamma-aminobutyric acid type A receptor blockade. In this case, CMRO2 increased equally during PC spiking with excitatory synaptic activity as during PC pacemaker spiking without......One contention within the field of neuroimaging concerns the character of the depicted activity: Does it represent neuronal action potential generation (i.e., spiking) or postsynaptic excitation? This question is related to the metabolic costs of different aspects of neurosignaling. The cerebellar...... cortex is well suited for addressing this problem because synaptic input to and spiking of the principal cell, the Purkinje cell (PC), are spatially segregated. Also, PCs are pacemakers, able to generate spikes endogenously. We examined the contributions to cerebellar cortical oxygen consumption (CMRO2...

  11. On the Spike Train Variability Characterized by Variance-to-Mean Power Relationship.

    Science.gov (United States)

    Koyama, Shinsuke

    2015-07-01

    We propose a statistical method for modeling the non-Poisson variability of spike trains observed in a wide range of brain regions. Central to our approach is the assumption that the variance and the mean of interspike intervals are related by a power function characterized by two parameters: the scale factor and exponent. It is shown that this single assumption allows the variability of spike trains to have an arbitrary scale and various dependencies on the firing rate in the spike count statistics, as well as in the interval statistics, depending on the two parameters of the power function. We also propose a statistical model for spike trains that exhibits the variance-to-mean power relationship. Based on this, a maximum likelihood method is developed for inferring the parameters from rate-modulated spike trains. The proposed method is illustrated on simulated and experimental spike trains.

  12. Oposición política

    OpenAIRE

    Betancourt, Sergio Raimundo; Centeno, Daniel Félix; Luconi, Leonardo Martín; Viadana, Alejandro Daniel

    1991-01-01

    Fil: Betancourt, Sergio Raimundo. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales Fil: Centeno, Daniel Félix. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales Fil: Luconi, Leonardo Martín . Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales Fil: Viadana, Alejandro Daniel. Univer...

  13. Cloning and expression of NS3 helicase fragment of hepatitis C virus and the study of its immunoreactivity in HCV infected patients

    Directory of Open Access Journals (Sweden)

    Mahrou Sadri

    2015-02-01

    Full Text Available Objective(s: Hepatitis C is a major cause of liver failure worldwide. Current therapies applied for this disease are not fully effective and produce side effects in most cases. Non-structural protein 3 helicase (NS3 of HCV is one of the key enzymes in viral replication and infection. Therefore, this region is a promising target to design new drugs and therapies against HCV infection. The aim of this study was cloning and expression of HCV NS3 helicase fragment in Escherichia coli BL21 (DE3 using pET102/D-TOPO expression vector and studying immunoreactivity of the expressed antigen in Iranian infected with hepatitis C. Materials and Methods: The viral RNA was extracted from the serum of HCV infected patient. The NS3 helicase region was amplified by RT-PCR. The PCR product was directionally cloned into the expression vector pET102/D-TOPO and transformed into the BL21 strain of E. coli (DE3. The transformed bacteria were then induced by adding 1mM isopropyl-β-D-thiogalactopyranoside (IPTG into the culture medium to enhance the protein expression. SDS-PAGE and western blotting were carried out to identify the protein under investigation, and finally purified recombinant fusion protein was used as the antigen for ELISA method. Results: Theinsertion of theDNA fragment of the NS3 regioninto the expression vectorwas further confirmed by PCR and sequencing. SDS-PAGE analysis showed the successful expression of the recombinant protein of interest. Furthermore, immunoreactivity of fusion NS3 helicase was confirmed by ELISA and western blotting. Conclusion: It seems that this recombinant protein could be a useful source of antigen for future studies on HCV diagnosis and therapy.

  14. Mechanism and stoichiometry of interaction of DnaG primase with DnaB helicase of Escherichia coli in RNA primer synthesis.

    Science.gov (United States)

    Mitkova, Atanaska V; Khopde, Sujata M; Biswas, Subhasis B

    2003-12-26

    Initiation and synthesis of RNA primers in the lagging strand of the replication fork in Escherichia coli requires the replicative DnaB helicase and the DNA primase, the DnaG gene product. In addition, the physical interaction between these two replication enzymes appears to play a role in the initiation of chromosomal DNA replication. In vitro, DnaB helicase stimulates primase to synthesize primers on single-stranded (ss) oligonucleotide templates. Earlier studies hypothesized that multiple primase molecules interact with each DnaB hexamer and single-stranded DNA. We have examined this hypothesis and determined the exact stoichiometry of primase to DnaB hexamer. We have also demonstrated that ssDNA binding activity of the DnaB helicase is necessary for directing the primase to the initiator trinucleotide and synthesis of 11-20-nucleotide long primers. Although, association of these two enzymes determines the extent and rate of synthesis of the RNA primers in vitro, direct evidence of the formation of primase-DnaB complex has remained elusive in E. coli due to the transient nature of their interaction. Therefore, we stabilized this complex using a chemical cross-linker and carried out a stoichiometric analysis of this complex by gel filtration. This allowed us to demonstrate that the primase-helicase complex of E. coli is comprised of three molecules of primase bound to one DnaB hexamer. Fluorescence anisotropy studies of the interaction of DnaB with primase, labeled with the fluorescent probe Ru(bipy)3, and Scatchard analysis further supported this conclusion. The addition of DnaC protein, leading to the formation of the DnaB-DnaC complex, to the simple priming system resulted in the synthesis of shorter primers. Therefore, interactions of the DnaB-primase complex with other replication factors might be critical for determining the physiological length of the RNA primers in vivo and the overall kinetics of primer synthesis.

  15. SPAN: spike pattern association neuron for learning spatio-temporal sequences

    OpenAIRE

    Mohemmed, A; Schliebs, S; Matsuda, S; Kasabov, N

    2012-01-01

    Spiking Neural Networks (SNN) were shown to be suitable tools for the processing of spatio-temporal information. However, due to their inherent complexity, the formulation of efficient supervised learning algorithms for SNN is difficult and remains an important problem in the research area. This article presents SPAN — a spiking neuron that is able to learn associations of arbitrary spike trains in a supervised fashion allowing the processing of spatio-temporal information encoded in the prec...

  16. Spike Pattern Structure Influences Efficacy Variability under STDP and Synaptic Homeostasis

    OpenAIRE

    Bi, Zedong; Zhou, Changsong; Zhou, Hai-Jun

    2015-01-01

    In neural systems, synaptic plasticity is usually driven by spike trains. Due to the inherent noises of neurons, synapses and networks, spike trains typically exhibit externally uncontrollable variability such as spatial heterogeneity and temporal stochasticity, resulting in variability of synapses, which we call efficacy variability. Spike patterns with the same population rate but inducing different efficacy variability may result in neuronal networks with sharply different structures and f...

  17. The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells.

    Science.gov (United States)

    Liu, Ying; Lu, Ning; Yuan, Bin; Weng, Leiyun; Wang, Feng; Liu, Yong-Jun; Zhang, Zhiqiang

    2014-01-01

    In eukaryotes, there are at least 60 members of the DExD/H helicase family, many of which are able to sense viral nucleic acids. By screening all known family members, we identified the helicase DHX33 as a novel double-stranded RNA (dsRNA) sensor in myeloid dendritic cells (mDCs). The knockdown of DHX33 using small heteroduplex RNA (shRNA) blocked the ability of mDCs to produce type I interferon (IFN) in response to poly I:C and reovirus. The HELICc domain of DHX33 was shown to bind poly I:C. The interaction between DHX33 and IPS-1 is mediated by the HELICc region of DHX33 and the C-terminal domain of IPS-1 (also referred to MAVS and VISA). The inhibition of DHX33 expression by RNA interference blocked the poly I:C-induced activation of MAP kinases, NF-κB and IRF3. The interaction between the helicase DHX33 and IPS-1 was independent of RIG-I/MDA5 and may be a novel pathway for sensing poly I:C and RNA viruses in mDCs.

  18. Trayectorias de vida, trayectorias políticas: ejercicios situados de política encarnada

    Directory of Open Access Journals (Sweden)

    Gabriela Montiel

    2016-08-01

    Full Text Available rayectorias de vida, trayectorias políticas: ejercicios situados de una política encarnada, es una invitación a repensar la política y lo político ubicando como pauta de enunciación los cuerpos. Corporalidades que no se configuran a solas, sino que son atravesadas constantemente por discursos de poder (orden, alimentación, belleza, deseo, movilidad, agencia, subordinación, represión. Esta tesis la fuimos tejiendo mediante la narrativa de vida de la mano del Método Biográfico (Sautu, 2004, la propuesta de investigación feminista del Conocimiento Situado (Haraway, 1989 y en cuanto al cuerpo teórico para el análisis concretamente la línea de reflexión desde los Feminismos decoloniales en relación a las identidades políticas y movimientos sociales (Flórez, 2010 y el Transfeminismo (Álvarez Castillo, 2014; Preciado, 2013; Solá, 2013; Sentamans, 2013. ¿Qué implica encarnar la política? Responder a esta pregunta es el objetivo a lo largo de este diálogo entre tres compañeras artistas y mi persona, posicionando este cuerpo situado como principal pauta de enunciación.

  19. Exploration of the Use of Spiking Detectors to Solve GNC Problems

    Data.gov (United States)

    National Aeronautics and Space Administration — This task is evaluating spiking sensor technology for Guidance, Navigation and Control applications, which includes detailed study, analysis and test for...

  20. Voltage-spike analysis for a free-running parallel inverter

    Science.gov (United States)

    Lee, F. C. Y.; Wilson, T. G.

    1974-01-01

    Unwanted and sometimes damaging high-amplitude voltage spikes occur during each half cycle in many transistor saturable-core inverters at the moment when the core saturates and the transistors switch. The analysis shows that spikes are an intrinsic characteristic of certain types of inverters even with negligible leakage inductance and purely resistive load. The small but unavoidable after-saturation inductance of the saturable-core transformer plays an essential role in creating these undesired thigh-voltage spikes. State-plane analysis provides insight into the complex interaction between core and transistors, and shows the circuit parameters upon which the magnitude of these spikes depends.

  1. Multineuron spike train analysis with R-convolution linear combination kernel.

    Science.gov (United States)

    Tezuka, Taro

    2018-06-01

    A spike train kernel provides an effective way of decoding information represented by a spike train. Some spike train kernels have been extended to multineuron spike trains, which are simultaneously recorded spike trains obtained from multiple neurons. However, most of these multineuron extensions were carried out in a kernel-specific manner. In this paper, a general framework is proposed for extending any single-neuron spike train kernel to multineuron spike trains, based on the R-convolution kernel. Special subclasses of the proposed R-convolution linear combination kernel are explored. These subclasses have a smaller number of parameters and make optimization tractable when the size of data is limited. The proposed kernel was evaluated using Gaussian process regression for multineuron spike trains recorded from an animal brain. It was compared with the sum kernel and the population Spikernel, which are existing ways of decoding multineuron spike trains using kernels. The results showed that the proposed approach performs better than these kernels and also other commonly used neural decoding methods. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Spike frequency adaptation is a possible mechanism for control of attractor preference in auto-associative neural networks

    Science.gov (United States)

    Roach, James; Sander, Leonard; Zochowski, Michal

    Auto-associative memory is the ability to retrieve a pattern from a small fraction of the pattern and is an important function of neural networks. Within this context, memories that are stored within the synaptic strengths of networks act as dynamical attractors for network firing patterns. In networks with many encoded memories, some attractors will be stronger than others. This presents the problem of how networks switch between attractors depending on the situation. We suggest that regulation of neuronal spike-frequency adaptation (SFA) provides a universal mechanism for network-wide attractor selectivity. Here we demonstrate in a Hopfield type attractor network that neurons minimal SFA will reliably activate in the pattern corresponding to a local attractor and that a moderate increase in SFA leads to the network to converge to the strongest attractor state. Furthermore, we show that on long time scales SFA allows for temporal sequences of activation to emerge. Finally, using a model of cholinergic modulation within the cortex we argue that dynamic regulation of attractor preference by SFA could be critical for the role of acetylcholine in attention or for arousal states in general. This work was supported by: NSF Graduate Research Fellowship Program under Grant No. DGE 1256260 (JPR), NSF CMMI 1029388 (MRZ) and NSF PoLS 1058034 (MRZ & LMS).

  3. The overexpression of Twinkle helicase ameliorates the progression of cardiac fibrosis and heart failure in pressure overload model in mice.

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    Full Text Available Myocardial mitochondrial DNA (mtDNA copy number decreases in heart failure. In post-myocardial infarction mice, increasing mtDNA copy number by overexpressing mitochondrial transcription factor attenuates mtDNA deficiency and ameliorates pathological remodeling thereby markedly improving survival. However, the functional significance of increased mtDNA copy number in hypertensive heart disease remains unknown. We addressed this question using transgenic mice that overexpress Twinkle helicase (Twinkle; Tg, the mtDNA helicase, and examined whether Twinkle overexpression protects the heart from left ventricular (LV remodeling and failure after pressure overload created by transverse aortic constriction (TAC. Twinkle overexpression increased mtDNA copy number by 2.2 ± 0.1-fold. Heart weight, LV diastolic volume and wall thickness were comparable between Tg and wild type littermates (WT at 28 days after TAC operation. LV end-diastolic pressure increased in WT after TAC (8.6 ± 2.8 mmHg, and this increase was attenuated in Tg (4.6 ± 2.6 mmHg. Impaired LV fractional shortening after TAC operation was also suppressed in Tg, as measured by echocardiography (WT: 16.2 ± 7.2% vs Tg: 20.7 ± 6.2%. These LV functional improvements were accompanied by a decrease in interstitial fibrosis (WT: 10.6 ± 1.1% vs Tg: 3.0 ± 0.6%. In in vitro studies, overexpressing Twinkle using an adenovirus vector in cultured cardiac fibroblasts significantly suppressed mRNA of collagen 1a, collagen 3a and connective tissue growth factor, and angiotensin II-induced transforming growth factor β1 expression. The findings suggest that Twinkle overexpression prevents LV function deterioration. In conclusion, Twinkle overexpression increases mtDNA copy number and ameliorates the progression of LV fibrosis and heart failure in a mouse pressure overload model. Increasing mtDNA copy number by Twinkle overexpression could be a novel therapeutic strategy for hypertensive heart disease.

  4. Non-Euclidean properties of spike train metric spaces.

    Science.gov (United States)

    Aronov, Dmitriy; Victor, Jonathan D

    2004-06-01

    Quantifying the dissimilarity (or distance) between two sequences is essential to the study of action potential (spike) trains in neuroscience and genetic sequences in molecular biology. In neuroscience, traditional methods for sequence comparisons rely on techniques appropriate for multivariate data, which typically assume that the space of sequences is intrinsically Euclidean. More recently, metrics that do not make this assumption have been introduced for comparison of neural activity patterns. These metrics have a formal resemblance to those used in the comparison of genetic sequences. Yet the relationship between such metrics and the traditional Euclidean distances has remained unclear. We show, both analytically and computationally, that the geometries associated with metric spaces of event sequences are intrinsically non-Euclidean. Our results demonstrate that metric spaces enrich the study of neural activity patterns, since accounting for perceptual spaces requires a non-Euclidean geometry.

  5. Variational and perturbative schemes for a spiked harmonic oscillator

    International Nuclear Information System (INIS)

    Aguilera-Navarro, V.C.; Estevez, G.A.; Guardiola, R.

    1989-01-01

    A variational analysis of the spiked harmonic-oscillator Hamiltonian operator -d 2 /dx 2 + x 2 + l(l+1)/x 2 + λ |x| -α , where α is a real positive parameter, is reported in this work. The formalism makes use of the functional space spanned by the solutions of the Schroedinger equation for the linear harmonic-oscillator Hamiltonian supplemented by a Dirichlet boundary condition, and a standard procedure for diagonalizing symmetric matrices. The eigenvalues obtained by increasing the dimension of the basis set provides accurate approximations for the ground-state energy of the model system, valid for positive and relatively large values of the coupling parameter λ. Additionally, a large-coupling pertubative-expansion is carried out and the contributions up to fourth order to the ground-state energy are explicitly evaluated. Numerical results are compared for the special case α=5/2. (author) [pt

  6. A Model of Fast Hebbian Spike Latency Normalization

    Directory of Open Access Journals (Sweden)

    Hafsteinn Einarsson

    2017-05-01

    Full Text Available Hebbian changes of excitatory synapses are driven by and enhance correlations between pre- and postsynaptic neuronal activations, forming a positive feedback loop that can lead to instability in simulated neural networks. Because Hebbian learning may occur on time scales of seconds to minutes, it is conjectured that some form of fast stabilization of neural firing is necessary to avoid runaway of excitation, but both the theoretical underpinning and the biological implementation for such homeostatic mechanism are to be fully investigated. Supported by analytical and computational arguments, we show that a Hebbian spike-timing-dependent metaplasticity rule, accounts for inherently-stable, quick tuning of the total input weight of a single neuron in the general scenario of asynchronous neural firing characterized by UP and DOWN states of activity.

  7. Brian: a simulator for spiking neural networks in Python

    Directory of Open Access Journals (Sweden)

    Dan F M Goodman

    2008-11-01

    Full Text Available Brian is a new simulator for spiking neural networks, written in Python (http://brian.di.ens.fr. It is an intuitive and highly flexible tool for rapidly developing new models, especially networks of single-compartment neurons. In addition to using standard types of neuron models, users can define models by writing arbitrary differential equations in ordinary mathematical notation. Python scientific libraries can also be used for defining models and analysing data. Vectorisation techniques allow efficient simulations despite the overheads of an interpreted language. Brian will be especially valuable for working on non-standard neuron models not easily covered by existing software, and as an alternative to using Matlab or C for simulations. With its easy and intuitive syntax, Brian is also very well suited for teaching computational neuroscience.

  8. Spike-Based Bayesian-Hebbian Learning of Temporal Sequences

    DEFF Research Database (Denmark)

    Tully, Philip J; Lindén, Henrik; Hennig, Matthias H

    2016-01-01

    and speed of sequence replay depends on a confluence of biophysically relevant parameters including stimulus duration, level of background noise, ratio of synaptic currents, and strengths of short-term depression and adaptation. Moreover, sequence elements are shown to flexibly participate multiple times......Many cognitive and motor functions are enabled by the temporal representation and processing of stimuli, but it remains an open issue how neocortical microcircuits can reliably encode and replay such sequences of information. To better understand this, a modular attractor memory network is proposed...... in which meta-stable sequential attractor transitions are learned through changes to synaptic weights and intrinsic excitabilities via the spike-based Bayesian Confidence Propagation Neural Network (BCPNN) learning rule. We find that the formation of distributed memories, embodied by increased periods...

  9. A self-resetting spiking phase-change neuron.

    Science.gov (United States)

    Cobley, R A; Hayat, H; Wright, C D

    2018-05-11

    Neuromorphic, or brain-inspired, computing applications of phase-change devices have to date concentrated primarily on the implementation of phase-change synapses. However, the so-called accumulation mode of operation inherent in phase-change materials and devices can also be used to mimic the integrative properties of a biological neuron. Here we demonstrate, using physical modelling of nanoscale devices and SPICE modelling of associated circuits, that a single phase-change memory cell integrated into a comparator type circuit can deliver a basic hardware mimic of an integrate-and-fire spiking neuron with self-resetting capabilities. Such phase-change neurons, in combination with phase-change synapses, can potentially open a new route for the realisation of all-phase-change neuromorphic computing.

  10. Double spike with isotope pattern deconvolution for mercury speciation

    International Nuclear Information System (INIS)

    Castillo, A.; Rodriguez-Gonzalez, P.; Centineo, G.; Roig-Navarro, A.F.; Garcia Alonso, J.I.

    2009-01-01

    Full text: A double-spiking approach, based on an isotope pattern deconvolution numerical methodology, has been developed and applied for the accurate and simultaneous determination of inorganic mercury (IHg) and methylmercury (MeHg). Isotopically enriched mercury species ( 199 IHg and 201 MeHg) are added before sample preparation to quantify the extent of methylation and demethylation processes. Focused microwave digestion was evaluated to perform the quantitative extraction of such compounds from solid matrices of environmental interest. Satisfactory results were obtained in different certificated reference materials (dogfish liver DOLT-4 and tuna fish CRM-464) both by using GC-ICPMS and GC-MS, demonstrating the suitability of the proposed analytical method. (author)

  11. A simultaneous comparison of acupuncture needle and insulated needle sphenoidal electrodes for detection of anterior temporal spikes.

    Science.gov (United States)

    Chu, N S

    1992-01-01

    Uninsulated acupuncture needles have been used as sphenoidal electrodes, but the issue of insulation has not been adequately addressed. In this report, acupuncture needles and insulated needle sphenoidal electrodes were simultaneously used to compare the rate of spike detection, spike amplitude and distribution of maximal spikes from eight spike foci in seven patients with temporal lobe epilepsy. When compared to the insulated needle electrode, the acupuncture needle electrode was equally effective in spike detection, but spike amplitudes tended to be smaller and maximal spikes were less frequently encountered. Thus, insulation has an influence on the spikes recorded by the acupuncture needle sphenoidal electrode. However, the overall effect appears to be not sufficiently different from the insulated needle electrode for the purpose of detecting anterior temporal spikes in outpatient EEG recordings for the diagnosis of temporal lobe epilepsy.

  12. The RNA Helicase DeaD Stimulates ExsA Translation To Promote Expression of the Pseudomonas aeruginosa Type III Secretion System

    Science.gov (United States)

    Intile, Peter J.; Balzer, Grant J.; Wolfgang, Matthew C.

    2015-01-01

    ABSTRACT The Pseudomonas aeruginosa type III secretion system (T3SS) is a primary virulence factor important for phagocytic avoidance, disruption of host cell signaling, and host cell cytotoxicity. ExsA is the master regulator of T3SS transcription. The expression, synthesis, and activity of ExsA is tightly regulated by both intrinsic and extrinsic factors. Intrinsic regulation consists of the well-characterized ExsECDA partner-switching cascade, while extrinsic factors include global regulators that alter exsA transcription and/or translation. To identify novel extrinsic regulators of ExsA, we conducted a transposon mutagenesis screen in the absence of intrinsic control. Transposon disruptions within gene PA2840, which encodes a homolog of the Escherichia coli RNA-helicase DeaD, significantly reduced T3SS gene expression. Recent studies indicate that E. coli DeaD can promote translation by relieving inhibitory secondary structures within target mRNAs. We report here that PA2840, renamed DeaD, stimulates ExsA synthesis at the posttranscriptional level. Genetic experiments demonstrate that the activity of an exsA translational fusion is reduced in a deaD mutant. In addition, exsA expression in trans fails to restore T3SS gene expression in a deaD mutant. We hypothesized that DeaD relaxes mRNA secondary structure to promote exsA translation and found that altering the mRNA sequence of exsA or the native exsA Shine-Dalgarno sequence relieved the requirement for DeaD in vivo. Finally, we show that purified DeaD promotes ExsA synthesis using in vitro translation assays. Together, these data reveal a novel regulatory mechanism for P. aeruginosa DeaD and add to the complexity of global regulation of T3SS. IMPORTANCE Although members of the DEAD box family of RNA helicases are appreciated for their roles in mRNA degradation and ribosome biogenesis, an additional role in gene regulation is now emerging in bacteria. By relaxing secondary structures in mRNAs, DEAD box

  13. Unwinding after high salinity stress: Pea DNA helicase 45 over- expression in tobacco confers high salinity tolerance without affecting yield (abstract)

    International Nuclear Information System (INIS)

    Tuteja, N.

    2005-01-01

    Soil salinity is an increasing threat for agriculture and is a major factor in reducing plant productivity; therefore, it is necessary to obtain salinity-tolerant varieties. A typical characteristic of soil salinity is the induction of multiple stress- inducible genes. Some of the genes encoding osmolytes, ion channels or enzymes are able to confer salinity-tolerant phenotypes when transferred to sensitive plants. As salinity stress affects the cellular gene-expression machinery, it is evident that molecules involved in nucleic acid processing including helicases, are likely to be affected as well. DNA helicases unwind duplex DNA and are involved in replication, repair, recombination and transcription while RNA helicases unfold the secondary structures in RNA and are involved in transcription, ribosome biogenesis and translation initiation. We have earlier reported the isolation of a pea DNA helicase 45 (PDH45) that exhibits striking homology with eIF-4A (Plant J. 24:219-230,2000). Here we report that PDH45 mRNA is induced in pea seedlings in response to high salt and its over- expression driven by a constitutive CAMV-355-promoter in tobacco plants confers salinity tolerance, thus suggesting a new pathway for manipulating stress tolerance in crop plants. The T0 transgenic plants showed high-levels of PDH45 protein in normal and stress conditions, as compared to wild type (WT) plants. The T0 transgenics also showed tolerance to high salinity as tested by a leaf disc senescence assay. The T1 transgenics were able to grow to maturity and set normal viable seeds under continuous salinity stress, without any reduction in plant yield, in terms of seed weight. Measurement of Na/sup +/ ions in different parts of the plant showed higher accumulation in the old leaves and negligible in seeds of T1 transgenic lines as compared with the WT plants. The possible mechanism of salinity tolerance will be discussed. Over-expression of PDH45 provides a possible example of the

  14. Adaptive robotic control driven by a versatile spiking cerebellar network.

    Directory of Open Access Journals (Sweden)

    Claudia Casellato

    Full Text Available The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning, a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions.

  15. Spike-timing dependent plasticity and the cognitive map

    Directory of Open Access Journals (Sweden)

    Daniel eBush

    2010-10-01

    Full Text Available Since the discovery of place cells – single pyramidal neurons that encode spatial location – it has been hypothesised that the hippocampus may act as a cognitive map of known environments. This putative function has been extensively modelled using auto-associative networks, which utilise rate-coded synaptic plasticity rules in order to generate strong bi-directional connections between concurrently active place cells that encode for neighbouring place fields. However, empirical studies using hippocampal cultures have demonstrated that the magnitude and direction of changes in synaptic strength can also be dictated by the relative timing of pre- and post- synaptic firing according to a spike-timing dependent plasticity (STDP rule. Furthermore, electrophysiology studies have identified persistent ‘theta-coded’ temporal correlations in place cell activity in vivo, characterised by phase precession of firing as the corresponding place field is traversed. It is not yet clear if STDP and theta-coded neural dynamics are compatible with cognitive map theory and previous rate-coded models of spatial learning in the hippocampus. Here, we demonstrate that an STDP rule based on empirical data obtained from the hippocampus can mediate rate-coded Hebbian learning when pre- and post- synaptic activity is stochastic and has no persistent sequence bias. We subsequently demonstrate that a spiking recurrent neural network that utilises this STDP rule, alongside theta-coded neural activity, allows the rapid development of a cognitive map during directed or random exploration of an environment of overlapping place fields. Hence, we establish that STDP and phase precession are compatible with rate-coded models of cognitive map development.

  16. Analog Memristive Synapse in Spiking Networks Implementing Unsupervised Learning

    Science.gov (United States)

    Covi, Erika; Brivio, Stefano; Serb, Alexander; Prodromakis, Themis; Fanciulli, Marco; Spiga, Sabina

    2016-01-01

    Emerging brain-inspired architectures call for devices that can emulate the functionality of biological synapses in order to implement new efficient computational schemes able to solve ill-posed problems. Various devices and solutions are still under investigation and, in this respect, a challenge is opened to the researchers in the field. Indeed, the optimal candidate is a device able to reproduce the complete functionality of a synapse, i.e., the typical synaptic process underlying learning in biological systems (activity-dependent synaptic plasticity). This implies a device able to change its resistance (synaptic strength, or weight) upon proper electrical stimuli (synaptic activity) and showing several stable resistive states throughout its dynamic range (analog behavior). Moreover, it should be able to perform spike timing dependent plasticity (STDP), an associative homosynaptic plasticity learning rule based on the delay time between the two firing neurons the synapse is connected to. This rule is a fundamental learning protocol in state-of-art networks, because it allows unsupervised learning. Notwithstanding this fact, STDP-based unsupervised learning has been proposed several times mainly for binary synapses rather than multilevel synapses composed of many binary memristors. This paper proposes an HfO2-based analog memristor as a synaptic element which performs STDP within a small spiking neuromorphic network operating unsupervised learning for character recognition. The trained network is able to recognize five characters even in case incomplete or noisy images are displayed and it is robust to a device-to-device variability of up to ±30%. PMID:27826226

  17. Relationship of Sphincter of Oddi Spike Bursts to Gastrointestinal Myoelectric Activity in Conscious Opossums

    Science.gov (United States)

    Honda, Ryuichi; Toouli, James; Dodds, Wylie J.; Sarna, Sushil; Hogan, Walter J.; Itoh, Zen

    1982-01-01

    The oppossum sphincter of Oddi (SO) exhibits peristaltic spike bursts with accompanying contraction waves that originate proximally in the sphincter of Oddi and propagate toward the duodenum. In this study we recorded myoelectrical activity of the opossum SO and upper gastrointestinal tract in six conscious animals using chronically implanted electrodes. Biopolar electrodes were implanted in the gastric antrum, duodenum, SO segment, jejunum, and ileum. During fasting the frequency of SO spike bursts, scored as number per minute, showed a cyclic pattern consisting of four phases (A to D). Phase A had a low spike burst frequency of ∼2/min that lasted ∼20 min. In phase B, the spike burst frequency increased progressively during a 40-45 min interval culminating in a short interval of phase C activity characterized by a maximal spike burst frequency of ∼5/min. During phase D, the spike bursts decreased over 15 min to merge with the low frequency of phase A and the cycle repeated. Cycle length of the interdigestive SO cycle, 87±11 SD min, was virtually identical with that of the interdigestive migrating myoelectric complex (MMC) of the upper gastrointestinal tract. The onset of phase C activity in the SO began 1-2 min before phase III of the MMC activity in the duodenum. Feeding abolished the cyclic pattern of spike burst activity in the SO as well as in the upper gastrointestinal tract. After feeding the SO spike bursts occurred at a frequency of 5-6/min for at least 3 h. We conclude that: (a) During fasting, the oppossum SO exhibits cyclic changes in its spike burst frequency; (b) Maximal spike burst frequency of the SO occurs virtually concurrent with passage of phase III MMC activity through the duodenum and; (c) Feeding abolishes the interdigestive cyclic spike burst pattern of the SO as well as that of the gastrointestinal tract. PMID:7076847

  18. Extracting information in spike time patterns with wavelets and information theory.

    Science.gov (United States)

    Lopes-dos-Santos, Vítor; Panzeri, Stefano; Kayser, Christoph; Diamond, Mathew E; Quian Quiroga, Rodrigo

    2015-02-01

    We present a new method to assess the information carried by temporal patterns in spike trains. The method first performs a wavelet decomposition of the spike trains, then uses Shannon information to select a subset of coefficients carrying information, and finally assesses timing information in terms of decoding performance: the ability to identify the presented stimuli from spike train patterns. We show that the method allows: 1) a robust assessment of the information carried by spike time patterns even when this is distributed across multiple time scales and time points; 2) an effective denoising of the raster plots that improves the estimate of stimulus tuning of spike trains; and 3) an assessment of the information carried by temporally coordinated spikes across neurons. Using simulated data, we demonstrate that the Wavelet-Information (WI) method performs better and is more robust to spike time-jitter, background noise, and sample size than well-established approaches, such as principal component analysis, direct estimates of information from digitized spike trains, or a metric-based method. Furthermore, when applied to real spike trains from monkey auditory cortex and from rat barrel cortex, the WI method allows extracting larger amounts of spike timing information. Importantly, the fact that the WI method incorporates multiple time scales makes it robust to the choice of partly arbitrary parameters such as temporal resolution, response window length, number of response features considered, and the number of available trials. These results highlight the potential of the proposed method for accurate and objective assessments of how spike timing encodes information. Copyright © 2015 the American Physiological Society.

  19. Channel noise effects on first spike latency of a stochastic Hodgkin-Huxley neuron

    Science.gov (United States)

    Maisel, Brenton; Lindenberg, Katja

    2017-02-01

    While it is widely accepted that information is encoded in neurons via action potentials or spikes, it is far less understood what specific features of spiking contain encoded information. Experimental evidence has suggested that the timing of the first spike may be an energy-efficient coding mechanism that contains more neural information than subsequent spikes. Therefore, the biophysical features of neurons that underlie response latency are of considerable interest. Here we examine the effects of channel noise on the first spike latency of a Hodgkin-Huxley neuron receiving random input from many other neurons. Because the principal feature of a Hodgkin-Huxley neuron is the stochastic opening and closing of channels, the fluctuations in the number of open channels lead to fluctuations in the membrane voltage and modify the timing of the first spike. Our results show that when a neuron has a larger number of channels, (i) the occurrence of the first spike is delayed and (ii) the variation in the first spike timing is greater. We also show that the mean, median, and interquartile range of first spike latency can be accurately predicted from a simple linear regression by knowing only the number of channels in the neuron and the rate at which presynaptic neurons fire, but the standard deviation (i.e., neuronal jitter) cannot be predicted using only this information. We then compare our results to another commonly used stochastic Hodgkin-Huxley model and show that the more commonly used model overstates the first spike latency but can predict the standard deviation of first spike latencies accurately. We end by suggesting a more suitable definition for the neuronal jitter based upon our simulations and comparison of the two models.

  20. Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

    Directory of Open Access Journals (Sweden)

    Christian Albers

    Full Text Available Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP. Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious and strong (teacher spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

  1. Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

    Science.gov (United States)

    Albers, Christian; Westkott, Maren; Pawelzik, Klaus

    2016-01-01

    Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

  2. EFFECTS OF DIFFERENT GROWING CONDITIONS ON THE MORPHOLOGICAL FEATURES OF THE SPIKE OF HEXAPLOID TRITICALE

    Directory of Open Access Journals (Sweden)

    K. U. Kurkiev

    2016-01-01

    Full Text Available Aim. The aim is to study the effect of different environmental conditions on the morphological traits of the spike of hexaploid triticale varieties.Methods. We analyzed 507 samples of triticale of various eco-geographical origins, in different years of study and at different seeding times. To investigate the influence of environmental conditions on the phenotypic expression of the studied traits we held a comparative analysis of the spike of two years and, in addition, of spring triticale during winter and spring crops. Analysis on the features was carried out on the main spikes. We studied the following morphological characteristics of the spike: length, number of spikelets and density.Results and discussion. The study of differences in individual variety samples showed that more than 60% triticale samples had significant differences in the length of the spike, depending on the weather conditions of the year – with the winter crops number of spikelets per spike was significantly higher than with the spring crops. A comparative analysis of the impact of the weather conditions of the year on triticale showed that significant differences in the density of the spike were observed in less than 30%.Conclusion. Study of the influence of conditions of the year and sowing dates on the main features of the spike of triticale showed that the density of the spike is the least affected by the external environment. The length of the spikes and the number of spikelets per spike differed significantly when growing in a various conditions.

  3. Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity

    Science.gov (United States)

    Albers, Christian; Westkott, Maren; Pawelzik, Klaus

    2016-01-01

    Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns. PMID:26900845

  4. Amor y política.

    OpenAIRE

    Hernando Bernal.

    1998-01-01

    Este trabajo pretende hacer una serie de consideraciones que apuntan sobre todo a extraer una definición de lo que es «la política» para el psicoanálisis a partir de una observación que hace Jacques Alain Miller en su texto Lógicas de la vida amorosa sobre cómo Freud introduce una «teoría política» a partir de su texto Psicología de las masas y análisis del yo.En dicho texto Freud hace ver el poder ordenador y apaciguador del amor) significante amo) en la medida en que una masa no es más que ...

  5. Neuro-Inspired Spike-Based Motion: From Dynamic Vision Sensor to Robot Motor Open-Loop Control through Spike-VITE

    Directory of Open Access Journals (Sweden)

    Fernando Perez-Peña

    2013-11-01

    Full Text Available In this paper we present a complete spike-based architecture: from a Dynamic Vision Sensor (retina to a stereo head robotic platform. The aim of this research is to reproduce intended movements performed by humans taking into account as many features as possible from the biological point of view. This paper fills the gap between current spike silicon sensors and robotic actuators by applying a spike processing strategy to the data flows in real time. The architecture is divided into layers: the retina, visual information processing, the trajectory generator layer which uses a neuroinspired algorithm (SVITE that can be replicated into as many times as DoF the robot has; and finally the actuation layer to supply the spikes to the robot (using PFM. All the layers do their tasks in a spike-processing mode, and they communicate each other through the neuro-inspired AER protocol. The open-loop controller is implemented on FPGA using AER interfaces developed by RTC Lab. Experimental results reveal the viability of this spike-based controller. Two main advantages are: low hardware resources (2% of a Xilinx Spartan 6 and power requirements (3.4 W to control a robot with a high number of DoF (up to 100 for a Xilinx Spartan 6. It also evidences the suitable use of AER as a communication protocol between processing and actuation.

  6. Hans Kelsen: pensador político

    Directory of Open Access Journals (Sweden)

    Sara Lagi

    2011-01-01

    Full Text Available Hasta la publicación de Sobre la esencia y el valor de la democracia, Hans Kelsen era solo conocido como experto en derecho público. El valor de este artículo de Lagi radica en rescatar de la obra kelseniana un aspecto casi por completo olvidado por la crítica, a saber, sus análisis sobre el significado y las características de la democracia parlamentaria en los Estados modernos. Se aborda la cuestión no solo desde el debate teórico sino también desde su contexto histórico¿político. La teoría política de Kelsen es considerada una parte integral de su doctrina central, presentada en Teoría pura del derecho, su obra más conspicua. Un análisis del trabajo sobre la esencia y el valor de la democracia nos restituye la imagen de un Kelsen como original pensador político. Se analizan las dos ediciones de Sobre la esencia y el valor de la democracia (1920¿1929 con estos propósitos: comprender por qué decidió dedicarse a la teoría de la democracia un teórico que rigurosamente defendió la separación de la esfera jurídica respecto de la historia, la filosofía y la política; y por qué no se limitó a explicar la esencia de la democracia sino que decidió concentrarse en clarificar qué se entiende por valor de la democracia.

  7. Learning of spiking networks with different forms of long-term synaptic plasticity

    International Nuclear Information System (INIS)

    Vlasov, D.S.; Sboev, A.G.; Serenko, A.V.; Rybka, R.B.; Moloshnikov, I.A.

    2016-01-01

    The possibility of modeling the learning process based on different forms of spike timing-dependent plasticity (STDP) has been studied. It has been shown that the learnability depends on the choice of the spike pairing scheme in the STDP rule and the type of the input signal used during learning [ru

  8. The coronavirus spike protein : mechanisms of membrane fusion and virion incorporation

    NARCIS (Netherlands)

    Bosch, B.J.

    2004-01-01

    The coronavirus spike protein is a membrane-anchored glycoprotein responsible for virus-cell attachment and membrane fusion, prerequisites for a successful virus infection. In this thesis, two aspects are described regarding the molecular biology of the coronavirus spike protein: its membrane fusion

  9. Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex.

    Directory of Open Access Journals (Sweden)

    Laureline Logiaco

    2015-08-01

    Full Text Available The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70-200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys' behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators.

  10. Characterizing neural activities evoked by manual acupuncture through spiking irregularity measures

    International Nuclear Information System (INIS)

    Xue Ming; Wang Jiang; Deng Bin; Wei Xi-Le; Yu Hai-Tao; Chen Ying-Yuan

    2013-01-01

    The neural system characterizes information in external stimulations by different spiking patterns. In order to examine how neural spiking patterns are related to acupuncture manipulations, experiments are designed in such a way that different types of manual acupuncture (MA) manipulations are taken at the ‘Zusanli’ point of experimental rats, and the induced electrical signals in the spinal dorsal root ganglion are detected and recorded. The interspike interval (ISI) statistical histogram is fitted by the gamma distribution, which has two parameters: one is the time-dependent firing rate and the other is a shape parameter characterizing the spiking irregularities. The shape parameter is the measure of spiking irregularities and can be used to identify the type of MA manipulations. The coefficient of variation is mostly used to measure the spike time irregularity, but it overestimates the irregularity in the case of pronounced firing rate changes. However, experiments show that each acupuncture manipulation will lead to changes in the firing rate. So we combine four relatively rate-independent measures to study the irregularity of spike trains evoked by different types of MA manipulations. Results suggest that the MA manipulations possess unique spiking statistics and characteristics and can be distinguished according to the spiking irregularity measures. These studies have offered new insights into the coding processes and information transfer of acupuncture. (interdisciplinary physics and related areas of science and technology)

  11. Reconstruction of audio waveforms from spike trains of artificial cochlea models

    Science.gov (United States)

    Zai, Anja T.; Bhargava, Saurabh; Mesgarani, Nima; Liu, Shih-Chii

    2015-01-01

    Spiking cochlea models describe the analog processing and spike generation process within the biological cochlea. Reconstructing the audio input from the artificial cochlea spikes is therefore useful for understanding the fidelity of the information preserved in the spikes. The reconstruction process is challenging particularly for spikes from the mixed signal (analog/digital) integrated circuit (IC) cochleas because of multiple non-linearities in the model and the additional variance caused by random transistor mismatch. This work proposes an offline method for reconstructing the audio input from spike responses of both a particular spike-based hardware model called the AEREAR2 cochlea and an equivalent software cochlea model. This method was previously used to reconstruct the auditory stimulus based on the peri-stimulus histogram of spike responses recorded in the ferret auditory cortex. The reconstructed audio from the hardware cochlea is evaluated against an analogous software model using objective measures of speech quality and intelligibility; and further tested in a word recognition task. The reconstructed audio under low signal-to-noise (SNR) conditions (SNR < –5 dB) gives a better classification performance than the original SNR input in this word recognition task. PMID:26528113

  12. Spike sorting of heterogeneous neuron types by multimodality-weighted PCA and explicit robust variational Bayes

    Directory of Open Access Journals (Sweden)

    Takashi eTakekawa

    2012-03-01

    Full Text Available This study introduces a new spike sorting method that classifies spike waveforms from multiunit recordings into spike trains of individual neurons. In particular, we develop a method to sort a spike mixture generated by a heterogeneous neural population. Such a spike sorting has a significant practical value, but was previously difficult. The method combines a feature extraction method, which we may term multimodality-weighted principal component analysis (mPCA, and a clustering method by variational Bayes for Student’s t mixture model (SVB. The performance of the proposed method was compared with that of other conventional methods for simulated and experimental data sets. We found that the mPCA efficiently extracts highly informative features as clusters clearly separable in a relatively low-dimensional feature space. The SVB was implemented explicitly without relying on Maximum-A-Posterior (MAP inference for the degree of freedom parameters. The explicit SVB is faster than the conventional SVB derived with MAP inference and works more reliably over various data sets that include spiking patterns difficult to sort. For instance, spikes of a single bursting neuron may be separated incorrectly into multiple clusters, whereas those of a sparsely firing neuron tend to be merged into clusters for other neurons. Our method showed significantly improved performance in spike sorting of these difficult neurons. A parallelized implementation of the proposed algorithm (EToS version 3 is available as open-source code at http://etos.sourceforge.net/.

  13. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

    DEFF Research Database (Denmark)

    Lemke, Johannes R; Lal, Dennis; Reinthaler, Eva M

    2013-01-01

    Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic enc...

  14. Conduction Delay Learning Model for Unsupervised and Supervised Classification of Spatio-Temporal Spike Patterns.

    Science.gov (United States)

    Matsubara, Takashi

    2017-01-01

    Precise spike timing is considered to play a fundamental role in communications and signal processing in biological neural networks. Understanding the mechanism of spike timing adjustment would deepen our understanding of biological systems and enable advanced engineering applications such as efficient computational architectures. However, the biological mechanisms that adjust and maintain spike timing remain unclear. Existing algorithms adopt a supervised approach, which adjusts the axonal conduction delay and synaptic efficacy until the spike timings approximate the desired timings. This study proposes a spike timing-dependent learning model that adjusts the axonal conduction delay and synaptic efficacy in both unsupervised and supervised manners. The proposed learning algorithm approximates the Expectation-Maximization algorithm, and classifies the input data encoded into spatio-temporal spike patterns. Even in the supervised classification, the algorithm requires no external spikes indicating the desired spike timings unlike existing algorithms. Furthermore, because the algorithm is consistent with biological models and hypotheses found in existing biological studies, it could capture the mechanism underlying biological delay learning.

  15. Reconstruction of audio waveforms from spike trains of artificial cochlea models

    Directory of Open Access Journals (Sweden)

    Anja eZai

    2015-10-01

    Full Text Available Spiking cochlea models describe the analog processing and spike generation process within the biological cochlea. Reconstructing the audio input from the artificial cochlea spikes is therefore useful for understanding the fidelity of the information preserved in the spikes. The reconstruction process is challenging particularly for spikes from the mixed signal (analog/digital integrated circuit (IC cochleas because of multiple nonlinearities in the model and the additional variance caused by random transistor mismatch. This work proposes an offline method for reconstructing the audio input from spike responses of both a particular spike-based hardware model called the AEREAR2 cochlea and an equivalent software cochlea model. This method was previously used to reconstruct the auditory stimulus based on the peri-stimulus histogram of spike responses recorded in the ferret auditory cortex. The reconstructed audio from the hardware cochlea is evaluated against an analogous software model using objective measures of speech quality and intelligibility; and further tested in a word recognition task. The reconstructed audio under low signal-to-noise (SNR conditions (SNR < -5 dB gives a better classification performance than the original SNR input in this word recognition task.

  16. Ictal source imaging and electroclinical correlation in self-limited epilepsy with centrotemporal spikes

    DEFF Research Database (Denmark)

    Alving, Jørgen; Fabricius, Martin; Rosenzweig, Ivana

    2017-01-01

    PURPOSE: To elucidate the localization of ictal EEG activity, and correlate it to semiological features in self-limited epilepsy with centrotemporal spikes (formerly called "benign epilepsy with centrotemporal spikes"). METHODS: We have performed ictal electric source imaging, and we analysed...

  17. New explicit spike solution -- non-local component of the generalized Mixmaster attractor

    OpenAIRE

    Lim, Woei Chet

    2007-01-01

    By applying a standard solution-generating transformation to an arbitrary vacuum Bianchi type II solution, one generates a new solution with spikes commonly observed in numerical simulations. It is conjectured that the spike solution is part of the generalized Mixmaster attractor.

  18. Remifentanil-induced spike activity as a diagnostic tool in epilepsy surgery

    DEFF Research Database (Denmark)

    Grønlykke, L; Knudsen, M L; Høgenhaven, H

    2008-01-01

    To assess the value of remifentanil in intraoperative evaluation of spike activity in patients undergoing surgery for mesial temporal lobe epilepsy (MTLE).......To assess the value of remifentanil in intraoperative evaluation of spike activity in patients undergoing surgery for mesial temporal lobe epilepsy (MTLE)....

  19. Regulation of granule cell excitability by a low-threshold calcium spike in turtle olfactory bulb

    DEFF Research Database (Denmark)

    Pinato, Giulietta; Midtgaard, Jens

    2003-01-01

    Granule cells excitability in the turtle olfactory bulb was analyzed using whole cell recordings in current- and voltage-clamp mode. Low-threshold spikes (LTSs) were evoked at potentials that are subthreshold for Na spikes in normal medium. The LTSs were evoked from rest, but hyperpolarization...

  20. VARIABILITY OF NUMBER OF KERNELS PER SPIKE IN WHEAT CULTIVARS (Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Desimir KNEZEVIC

    2012-09-01

    Full Text Available In this paper was analyzed number of kernels per spike in 20 genetically divergent wheat cultivars originated from different breeding centers in Serbia. Investigation conducted during two seasons which characterized different climatic condition. For analysis used samples of 60 wheat plants (20 plants in 3 replications which were harvested in full maturity stage. The differences in average values for number of kernels per spike in studied cultivars were determined. The variability of number of kernels per spike was established. In average, number of kernels per spike for all cultivars was higher in second year 72.22 than in first experimental year 68.73. The highest number of kernels/spike in both year expressed Tanjugovka cultivar and the lowest Yugoslavia cultivar. Average value of coefficientvariation for all cultivars varied from 14.19 in first year to 12.92 in second year. Average number of kernels per spike for both year of growing, varied from 54.56 in cultivar Yugoslavia to 77.83 in cultivar Tanjugovka. Significant differences for number of kernels/spike were found among cultivars in both years as well between years. Heritability in wide sense for number of kernels/spike was 79.13%.

  1. Spike detection from noisy neural data in linear-probe recordings.

    Science.gov (United States)

    Takekawa, Takashi; Ota, Keisuke; Murayama, Masanori; Fukai, Tomoki

    2014-06-01

    Simultaneous recordings of multiple neuron activities with multi-channel extracellular electrodes are widely used for studying information processing by the brain's neural circuits. In this method, the recorded signals containing the spike events of a number of adjacent or distant neurons must be correctly sorted into spike trains of individual neurons, and a variety of methods have been proposed for this spike sorting. However, spike sorting is computationally difficult because the recorded signals are often contaminated by biological noise. Here, we propose a novel method for spike detection, which is the first stage of spike sorting and hence crucially determines overall sorting performance. Our method utilizes a model of extracellular recording data that takes into account variations in spike waveforms, such as the widths and amplitudes of spikes, by detecting the peaks of band-pass-filtered data. We show that the new method significantly improves the cost-performance of multi-channel electrode recordings by increasing the number of cleanly sorted neurons. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Conduction Delay Learning Model for Unsupervised and Supervised Classification of Spatio-Temporal Spike Patterns

    Directory of Open Access Journals (Sweden)

    Takashi Matsubara

    2017-11-01

    Full Text Available Precise spike timing is considered to play a fundamental role in communications and signal processing in biological neural networks. Understanding the mechanism of spike timing adjustment would deepen our understanding of biological systems and enable advanced engineering applications such as efficient computational architectures. However, the biological mechanisms that adjust and maintain spike timing remain unclear. Existing algorithms adopt a supervised approach, which adjusts the axonal conduction delay and synaptic efficacy until the spike timings approximate the desired timings. This study proposes a spike timing-dependent learning model that adjusts the axonal conduction delay and synaptic efficacy in both unsupervised and supervised manners. The proposed learning algorithm approximates the Expectation-Maximization algorithm, and classifies the input data encoded into spatio-temporal spike patterns. Even in the supervised classification, the algorithm requires no external spikes indicating the desired spike timings unlike existing algorithms. Furthermore, because the algorithm is consistent with biological models and hypotheses found in existing biological studies, it could capture the mechanism underlying biological delay learning.

  3. Neuronal Networks in Children with Continuous Spikes and Waves during Slow Sleep

    Science.gov (United States)

    Siniatchkin, Michael; Groening, Kristina; Moehring, Jan; Moeller, Friederike; Boor, Rainer; Brodbeck, Verena; Michel, Christoph M.; Rodionov, Roman; Lemieux, Louis; Stephani, Ulrich

    2010-01-01

    Epileptic encephalopathy with continuous spikes and waves during slow sleep is an age-related disorder characterized by the presence of interictal epileptiform discharges during at least greater than 85% of sleep and cognitive deficits associated with this electroencephalography pattern. The pathophysiological mechanisms of continuous spikes and…

  4. Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

    The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate......+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle....

  5. Novela policiaca, novela política

    Directory of Open Access Journals (Sweden)

    José Colmeiro

    2015-10-01

    Full Text Available Uno de los aspectos más significativos de la evolución de la novela policiaca en España en la última parte del siglo XX ha sido su transformación en un género político, utilizado a menudo como instrumento de observación social y crítica cultural, así como un espacio de resistencia política y subversión ideológica del statu quo por parte de muchos escritores españoles, durante y después del régimen de Franco. La novela negra ha tendido a ofrecer una visión desestabilizadora del crimen en la sociedad, exponiendo los aspectos represivos, el castigo y el control social, centrándose en poner de manifiesto las causas sociales y políticas subyacentes de la delincuencia. En los últimos años, particularmente con la aparición de un número de escritoras de novela negra y de una mayor sensibilidad hacia planteamientos no heteronormativos, el género ha servido también como espacio de exploración, crítica y subversión de los valores patriarcales y del masculinismo característico de los modelos clásicos, como una nueva forma de autocuestionamiento genérico.

  6. The RNA Helicase DHX34 Activates NMD by Promoting a Transition from the Surveillance to the Decay-Inducing Complex

    Directory of Open Access Journals (Sweden)

    Nele Hug

    2014-09-01

    Full Text Available Nonsense-mediated decay (NMD is a surveillance mechanism that degrades aberrant mRNAs. A complex comprising SMG1, UPF1, and the translation termination factors eRF1 and eRF3 (SURF is assembled in the vicinity of a premature termination codon. Subsequently, an interaction with UPF2, UPF3b, and the exon junction complex induces the formation of the decay-inducing complex (DECID and triggers NMD. We previously identified the RNA helicase DHX34 as an NMD factor in C. elegans and in vertebrates. Here, we investigate the mechanism by which DHX34 activates NMD in human cells. We show that DHX34 is recruited to the SURF complex via its preferential interaction with hypophosphorylated UPF1. A series of molecular transitions induced by DHX34 include enhanced recruitment of UPF2, increased UPF1 phosphorylation, and dissociation of eRF3 from UPF1. Thus, DHX34 promotes mRNP remodeling and triggers the conversion from the SURF complex to the DECID complex resulting in NMD activation.

  7. The structure and function of an RNA polymerase interaction domain in the PcrA/UvrD helicase.

    Science.gov (United States)

    Sanders, Kelly; Lin, Chia-Liang; Smith, Abigail J; Cronin, Nora; Fisher, Gemma; Eftychidis, Vasileios; McGlynn, Peter; Savery, Nigel J; Wigley, Dale B; Dillingham, Mark S

    2017-04-20

    The PcrA/UvrD helicase functions in multiple pathways that promote bacterial genome stability including the suppression of conflicts between replication and transcription and facilitating the repair of transcribed DNA. The reported ability of PcrA/UvrD to bind and backtrack RNA polymerase (1,2) might be relevant to these functions, but the structural basis for this activity is poorly understood. In this work, we define a minimal RNA polymerase interaction domain in PcrA, and report its crystal structure at 1.5 Å resolution. The domain adopts a Tudor-like fold that is similar to other RNA polymerase interaction domains, including that of the prototype transcription-repair coupling factor Mfd. Removal or mutation of the interaction domain reduces the ability of PcrA/UvrD to interact with and to remodel RNA polymerase complexes in vitro. The implications of this work for our understanding of the role of PcrA/UvrD at the interface of DNA replication, transcription and repair are discussed. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Incorporation into the prereplicative complex activates the Mcm2–7 helicase for Cdc7–Dbf4 phosphorylation

    Science.gov (United States)

    Francis, Laura I.; Randell, John C.W.; Takara, Thomas J.; Uchima, Lilen; Bell, Stephen P.

    2009-01-01

    The essential S-phase kinase Cdc7–Dbf4 acts at eukaryotic origins of replication to trigger a cascade of protein associations that activate the Mcm2–7 replicative helicase. Also known as Dbf4-dependent kinase (DDK), this kinase preferentially targets chromatin-associated Mcm2–7 complexes that are assembled on the DNA during prereplicative complex (pre-RC) formation. Here we address the mechanisms that control the specificity of DDK action. We show that incorporation of Mcm2–7 into the pre-RC increased the level and changes the specificity of DDK phosphorylation of this complex. In the context of the pre-RC, DDK preferentially targets a conformationally distinct subpopulation of Mcm2–7 complexes that is tightly linked to the origin DNA. This targeting requires DDK to tightly associate with Mcm2–7 complexes in a Dbf4-dependent manner. Importantly, we find that DDK association with and phosphorylation of origin-linked Mcm2–7 complexes require prior phosphorylation of the pre-RC. Our findings provide insights into the mechanisms that ensure that DDK action is spatially and temporally restricted to the origin-bound Mcm2–7 complexes that will drive replication fork movement during S phase and suggest new mechanisms to regulate origin activity. PMID:19270162

  9. DNA unwinding by ASCC3 helicase is coupled to ALKBH3 dependent DNA alkylation repair and cancer cell proliferation

    Science.gov (United States)

    Dango, Sebastian; Mosammaparast, Nima; Sowa, Mathew E.; Xiong, Li-Jun; Wu, Feizhen; Park, Keyjung; Rubin, Mark; Gygi, Steve; Harper, J. Wade; Shi, Yang

    2011-01-01

    Summary Demethylation by the AlkB dioxygenases represents an important mechanism for repair of N-alkylated nucleotides. However, little is known about their functions in mammalian cells. We report the purification of the ALKBH3 complex and demonstrate its association with the Activating Signal Co-integrator Complex (ASCC). ALKBH3 is overexpressed in various cancers, and both ALKBH3 and ASCC are important for alkylation damage resistance in these tumor cell lines. ASCC3, the largest subunit of ASCC, encodes a 3′-5′ DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. In cell lines that are dependent on ALKBH3 and ASCC3 for alkylation damage resistance, loss of ALKBH3 or ASCC3 leads to increased 3-methylcytosine and reduced cell proliferation, which correlates with pH2A.X and 53BP1 foci formation. Our data provide a molecular mechanism by which ALKBH3 collaborates with ASCC to maintain genomic integrity in a cell type specific manner. PMID:22055184

  10. Development of Reverse Transcription Thermostable Helicase-Dependent DNA Amplification for the Detection of Tomato Spotted Wilt Virus.

    Science.gov (United States)

    Wu, Xinghai; Chen, Chanfa; Xiao, Xizhi; Deng, Ming Jun

    2016-11-01

    A protocol for the reverse transcription-helicase-dependent amplification (RT-HDA) of isothermal DNA was developed for the detection of tomato spotted wilt virus (TSWV). Specific primers, which were based on the highly conserved region of the N gene sequence in TSWV, were used for the amplification of virus's RNA. The LOD of RT-HDA, reverse transcriptase-loop-mediated isothermal amplification (RT-LAMP), and reverse transcriptase-polymerase chain reaction (RT-PCR) assays were conducted using 10-fold serial dilution of RNA eluates. TSWV sensitivity in RT-HDA and RT-LAMP was 4 pg RNA compared with 40 pg RNA in RT-PCR. The specificity of RT-HDA for TSWV was high, showing no cross-reactivity with other tomato and Tospovirus viruses including cucumber mosaic virus (CMV), tomato black ring virus (TBRV), tomato mosaic virus (ToMV), or impatiens necrotic spot virus (INSV). The RT-HDA method is effective for the detection of TSWV in plant samples and is a potential tool for early and rapid detection of TSWV.

  11. Characterization of papillomavirus E1 helicase mutants defective for interaction with the SUMO-conjugating enzyme Ubc9

    International Nuclear Information System (INIS)

    Fradet-Turcotte, Amelie; Brault, Karine; Titolo, Steve; Howley, Peter M.; Archambault, Jacques

    2009-01-01

    The E1 helicase from BPV and HPV16 interacts with Ubc9 to facilitate viral genome replication. We report that HPV11 E1 also interacts with Ubc9 in vitro and in the yeast two-hybrid system. Residues in E1 involved in oligomerization (353-435) were sufficient for binding to Ubc9 in vitro, but the origin-binding and ATPase domains were additionally required in yeast. Nuclear accumulation of BPV E1 was shown previously to depend on its interaction with Ubc9 and sumoylation on lysine 514. In contrast, HPV11 and HPV16 E1 mutants defective for Ubc9 binding remained nuclear even when the SUMO pathway was inhibited. Furthermore, we found that K514 in BPV E1 and the analogous K559 in HPV11 E1 are not essential for nuclear accumulation of E1. These results suggest that the interaction of E1 with Ubc9 is not essential for its nuclear accumulation but, rather, depends on its oligomerization and binding to DNA and ATP.

  12. Structure based modification of Bluetongue virus helicase protein VP6 to produce a viable VP6-truncated BTV

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Eiko [Microbiology and Immunology, Division of Animal Science, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe-City 657-8501 (Japan); Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT (United Kingdom); Leon, Esther; Matthews, Steve J. [Division of Molecular Biosciences, Centre for Structural Biology, Imperial College London, South Kensington, London SW7 2AZ (United Kingdom); Roy, Polly, E-mail: polly.roy@lshtm.ac.uk [Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT (United Kingdom)

    2014-09-05

    Highlights: • NMR analysis on BTV VP6 reveals two large loop regions. • The loss of a loop (aa 34–130) does not affect the overall fold of the protein. • A region of VP6 (aa 34–92) is not required for BTV replication. • A region of VP6 (aa 93–130) plays an essential role in the virus replication. - Abstract: Bluetongue virus core protein VP6 is an ATP hydrolysis dependent RNA helicase. However, despite much study, the precise role of VP6 within the viral capsid and its structure remain unclear. To investigate the requirement of VP6 in BTV replication, we initiated a structural and biological study. Multinuclear nuclear magnetic resonance spectra were assigned on his-tagged full-length VP6 (329 amino acid residues) as well as several truncated VP6 variants. The analysis revealed a large structured domain with two large loop regions that exhibit significant conformational exchange. One of the loops (amino acid position 34–130) could be removed without affecting the overall fold of the protein. Moreover, using a BTV reverse genetics system, it was possible to demonstrate that the VP6-truncated BTV was viable in BHK cells in the absence of any helper VP6 protein, suggesting that a large portion of this loop region is not absolutely required for BTV replication.

  13. Helicase-Dependent Isothermal Amplification of DNA and RNA by Using Self-Avoiding Molecular Recognition Systems.

    Science.gov (United States)

    Yang, Zunyi; McLendon, Chris; Hutter, Daniel; Bradley, Kevin M; Hoshika, Shuichi; Frye, Carole B; Benner, Steven A

    2015-06-15

    Assays that detect DNA or RNA (xNA) are highly sensitive, as small amounts of xNA can be amplified by PCR. Unfortunately, PCR is inconvenient in low-resource environments, and requires equipment and power that might not be available in these environments. Isothermal procedures, which avoid thermal cycling, are often confounded by primer dimers, off-target priming, and other artifacts. Here, we show how a "self avoiding molecular recognition system" (SAMRS) eliminates these artifacts and gives clean amplicons in a helicase-dependent isothermal amplification (SAMRS-HDA). We also show that incorporating SAMRS into the 3'-ends of primers facilitates the design and screening of primers for HDA assays. Finally, we show that SAMRS-HDA can be twofold multiplexed, difficult to achieve with HDA using standard primers. Thus, SAMRS-HDA is a more versatile approach than standard HDA, with a broader applicability for xNA-targeted diagnostics and research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. To sort or not to sort: the impact of spike-sorting on neural decoding performance

    Science.gov (United States)

    Todorova, Sonia; Sadtler, Patrick; Batista, Aaron; Chase, Steven; Ventura, Valérie

    2014-10-01

    Objective. Brain-computer interfaces (BCIs) are a promising technology for restoring motor ability to paralyzed patients. Spiking-based BCIs have successfully been used in clinical trials to control multi-degree-of-freedom robotic devices. Current implementations of these devices require a lengthy spike-sorting step, which is an obstacle to moving this technology from the lab to the clinic. A viable alternative is to avoid spike-sorting, treating all threshold crossings of the voltage waveform on an electrode as coming from one putative neuron. It is not known, however, how much decoding information might be lost by ignoring spike identity. Approach. We present a full analysis of the effects of spike-sorting schemes on decoding performance. Specifically, we compare how well two common decoders, the optimal linear estimator and the Kalman filter, reconstruct the arm movements of non-human primates performing reaching tasks, when receiving input from various sorting schemes. The schemes we tested included: using threshold crossings without spike-sorting; expert-sorting discarding the noise; expert-sorting, including the noise as if it were another neuron; and automatic spike-sorting using waveform features. We also decoded from a joint statistical model for the waveforms and tuning curves, which does not involve an explicit spike-sorting step. Main results. Discarding the threshold crossings that cannot be assigned to neurons degrades decoding: no spikes should be discarded. Decoding based on spike-sorted units outperforms decoding based on electrodes voltage crossings: spike-sorting is useful. The four waveform based spike-sorting methods tested here yield similar decoding efficiencies: a fast and simple method is competitive. Decoding using the joint waveform and tuning model shows promise but is not consistently superior. Significance. Our results indicate that simple automated spike-sorting performs as well as the more computationally or manually intensive

  15. No bacterial growth found in spiked intravenous fluids over an 8-hour period.

    Science.gov (United States)

    Haas, Richard E; Beitz, Edwin; Reed, Amy; Burtnett, Howard; Lowe, Jason; Crist, Arthur E; Stierer, Kevin A; Birenberg, Allan M

    2017-04-01

    Protocol changes prompted by the Joint Commission mandating intravenous (IV) fluid bags to be used within 1 hour of spiking because of possible bacterial contamination have sparked clinical and economic concerns. This study investigated the degree of bacterial growth in which samples were obtained from spiked IV fluid bags at the time of spiking and 1, 2, 4, and 8 hours after spiking. No bacterial growth occurred in any of the 80 bags of Lactated Ringer's (LR) IV solutions sampled. This study demonstrated that LR IV bags do not support any bacterial growth for up to 8 hours after spiking. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Analysis and solution of current spike occurred in dynamic compensation of self-powered neutron detectors

    International Nuclear Information System (INIS)

    Peng, Xingjie; Li, Qing; Wang, Kan

    2017-01-01

    Highlights: • The current spike problem is observed in the dynamic compensation process of SPNDs. • The current spike is caused by unphysical current change due to range switching. • Modification on the compensation algorithm is introduced to deal with current spike. - Abstract: Dynamic compensation methods are required to improve the response speed of the Self-Powered Neutron Detectors (SPNDs) and make it possible to apply the SPNDs for core monitoring and surveillance. During the experimental test of the compensation method based on linear matrix inequality (LMI), spikes are observed in the compensated SPND current. After analyzing the measurement data, the cause is fixed on the unphysical change of the uncompensated SPND current due to range switching. Then some modifications on the dynamic compensation algorithms are proposed to solve the current spike problem.

  17. Approach for domestic preparation of standard material (LSD spike) for isotope dilution mass spectrometry

    International Nuclear Information System (INIS)

    Ishikawa, Fumitaka; Sumi, Mika; Chiba, Masahiko; Suzuki, Toru; Abe, Tomoyuki; Kuno, Yusuke

    2008-01-01

    The accountancy analysis of the nuclear fuel material at Plutonium Fuel Development Center of JAEA is performed by isotope dilution mass spectrometry (IDMS; Isotope Dilution Mass Spectrometry). IDMS requires the standard material called LSD spike (Large Size Dried spike) which is indispensable for the accountancy in the facilities where the nuclear fuel materials are handled. Although the LSD spike and Pu source material have been supplied from foreign countries, the transportation for such materials has been getting more difficult recently. This difficulty may affect the operation of nuclear facilities in the future. Therefore, research and development of the domestic LSD spike and base material has been performed at JAEA. Certification for such standard nuclear materials including spikes produced in Japan is being studied. This report presents the current status and the future plan for the technological development. (author)

  18. Voltage spikes in Nb3Sn and NbTi strands

    Energy Technology Data Exchange (ETDEWEB)

    Bordini, B.; Ambrosio, G.; Barzi, E.; Carcagno, R.; Feher, S.; Kashikhin, V.V.; Lamm, M.J.; Orris, D.; Tartaglia, M.; Tompkins, J.C.; Turrioni, D.; Yamada, R.; Zlobin,; /Fermilab

    2005-09-01

    As part of the High Field Magnet program at Fermilab several NbTi and Nb{sub 3}Sn strands were tested with particular emphasis on the study of voltage spikes and their relationship to superconductor instabilities. The voltage spikes were detected under various experimental conditions using voltage-current (V-I) and voltage-field (V-H) methods. Two types of spikes, designated ''magnetization'' and ''transport current'' spikes, have been identified. Their origin is most likely related to magnetization flux jump and transport current redistribution, respectively. Many of the signals observed appear to be a combination of these two types of spikes; the combination of these two instability mechanisms should play a dominant role in determining the minimum quench current.

  19. Input-output relation and energy efficiency in the neuron with different spike threshold dynamics

    Directory of Open Access Journals (Sweden)

    Guo-Sheng eYi

    2015-05-01

    Full Text Available Neuron encodes and transmits information through generating sequences of output spikes, which is a high energy-consuming process. The spike is initiated when membrane depolarization reaches a threshold voltage. In many neurons, threshold is dynamic and depends on the rate of membrane depolarization (dV/dt preceding a spike. Identifying the metabolic energy involved in neural coding and their relationship to threshold dynamic is critical to understanding neuronal function and evolution. Here, we use a modified Morris-Lecar model to investigate neuronal input-output property and energy efficiency associated with different spike threshold dynamics. We find that the neurons with dynamic threshold sensitive to dV/dt generate discontinuous frequency-current curve and type II phase response curve (PRC through Hopf bifurcation, and weak noise could prohibit spiking when bifurcation just occurs. The threshold that is insensitive to dV/dt, instead, results in a continuous frequency-current curve, a type I PRC and a saddle-node on invariant circle bifurcation, and simultaneously weak noise cannot inhibit spiking. It is also shown that the bifurcation, frequency-current curve and PRC type associated with different threshold dynamics arise from the distinct subthreshold interactions of membrane currents. Further, we observe that the energy consumption of the neuron is related to its firing characteristics. The depolarization of spike threshold improves neuronal energy efficiency by reducing the overlap of Na+ and K+ currents during an action potential. The high energy efficiency is achieved at more depolarized spike threshold and high stimulus current. These results provide a fundamental biophysical connection that links spike threshold dynamics, input-output relation, energetics and spike initiation, which could contribute to uncover neural encoding mechanism.

  20. Intracellular calcium spikes in rat suprachiasmatic nucleus neurons induced by BAPTA-based calcium dyes.

    Directory of Open Access Journals (Sweden)

    Jin Hee Hong

    Full Text Available BACKGROUND: Circadian rhythms in spontaneous action potential (AP firing frequencies and in cytosolic free calcium concentrations have been reported for mammalian circadian pacemaker neurons located within the hypothalamic suprachiasmatic nucleus (SCN. Also reported is the existence of "Ca(2+ spikes" (i.e., [Ca(2+](c transients having a bandwidth of 10 approximately 100 seconds in SCN neurons, but it is unclear if these SCN Ca(2+ spikes are related to the slow circadian rhythms. METHODOLOGY/PRINCIPAL FINDINGS: We addressed this issue based on a Ca(2+ indicator dye (fluo-4 and a protein Ca(2+ sensor (yellow cameleon. Using fluo-4 AM dye, we found spontaneous Ca(2+ spikes in 18% of rat SCN cells in acute brain slices, but the Ca(2+ spiking frequencies showed no day/night variation. We repeated the same experiments with rat (and mouse SCN slice cultures that expressed yellow cameleon genes for a number of different circadian phases and, surprisingly, spontaneous Ca(2+ spike was barely observed (<3%. When fluo-4 AM or BAPTA-AM was loaded in addition to the cameleon-expressing SCN cultures, however, the number of cells exhibiting Ca(2+ spikes was increased to 13 approximately 14%. CONCLUSIONS/SIGNIFICANCE: Despite our extensive set of experiments, no evidence of a circadian rhythm was found in the spontaneous Ca(2+ spiking activity of SCN. Furthermore, our study strongly suggests that the spontaneous Ca(2+ spiking activity is caused by the Ca(2+ chelating effect of the BAPTA-based fluo-4 dye. Therefore, this induced activity seems irrelevant to the intrinsic circadian rhythm of [Ca(2+](c in SCN neurons. The problems with BAPTA based dyes are widely known and our study provides a clear case for concern, in particular, for SCN Ca(2+ spikes. On the other hand, our study neither invalidates the use of these dyes as a whole, nor undermines the potential role of SCN Ca(2+ spikes in the function of SCN.