Sample records for phototropin lov domain
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Disruption of the LOV-Jalpha helix interaction activates phototropin kinase activity.
Harper, Shannon M; Christie, John M; Gardner, Kevin H
2004-12-28
Light plays a crucial role in activating phototropins, a class of plant photoreceptors that are sensitive to blue and UV-A wavelengths. Previous studies indicated that phototropin uses a bound flavin mononucleotide (FMN) within its light-oxygen-voltage (LOV) domain to generate a protein-flavin covalent bond under illumination. In the C-terminal LOV2 domain of Avena sativa phototropin 1, formation of this bond triggers a conformational change that results in unfolding of a helix external to this domain called Jalpha [Harper, S. M., et al. (2003) Science 301, 1541-1545]. Though the structural effects of illumination were characterized, it was unknown how these changes are coupled to kinase activation. To examine this, we made a series of point mutations along the Jalpha helix to disrupt its interaction with the LOV domain in a manner analogous to light activation. Using NMR spectroscopy and limited proteolysis, we demonstrate that several of these mutations displace the Jalpha helix from the LOV domain independently of illumination. When placed into the full-length phototropin protein, these point mutations display constitutive kinase activation, without illumination of the sample. These results indicate that unfolding of the Jalpha helix is the critical event in regulation of kinase signaling for the phototropin proteins.
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Suetsugu, Noriyuki; Kong, Sam-Geun; Kasahara, Masahiro; Wada, Masamitsu
2013-01-01
Phototropins (phot) are blue light receptor proteins that mediate phototropism and control photomovement responses, such as chloroplast photorelocation movement and stomatal opening. Arabidopsis thaliana has two phototropins, phot1 and phot2. Although both phot1 and phot2 redundantly mediate photomovement responses, phot2 uniquely regulates phototropism and the chloroplast avoidance response under high-intensity blue light. However, compared to that of phot1, the mechanistic basis of phot2 function is poorly understood, and in particular, the importance of the LOV2 domain in phot2 function has not been clearly demonstrated. Indeed, photocycle-deficient LOV2 transgenic lines expressing phot2 in a phot1phot2 mutant background retained phototropism, although with less sensitivity than wild-type plants. We isolated 11 alleles of phot2 mutants and determined the molecular lesion in each allele. We analyzed hypocotyl phototropism, chloroplast photorelocation movement, and leaf flattening in the phot2 mutant and the respective phot1phot2 double mutant plants. We demonstrated that unlike the phot2 null mutant, the phot2-10 mutant, which has the defective phot2 LOV2 domain, retained the phototropic response and had unusual chloroplast movement. Mutants phot2-2 and phot2-6, which have a missense mutation in the kinase activation loop of phot2, had the phot2-null mutant phenotype. Furthermore, we convincingly demonstrated that the commonly used phot2-1 mutant allele is a phot2-null mutant. The analyses of the multiple phot2 mutant alleles provided strong evidence for the importance of both LOV domains and the kinase activation loop of phot2 in phototropism and other phot-dependent responses and also demonstrated that phot2-1 allele is a null mutant.
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A base-catalyzed mechanism for dark state recovery in the Avena sativa phototropin-1 LOV2 domain.
Alexandre, Maxime T A; Arents, Jos C; van Grondelle, Rienk; Hellingwerf, Klaas J; Kennis, John T M
2007-03-20
Phototropins are autophosphorylating serine/threonine kinases responsible for blue-light perception in plants; their action gives rise to phototropism, chloroplast relocation, and opening of stomatal guard cells. The kinase domain constitutes the C-terminal part of Avena sativa phototropin 1. The N-terminal part contains two light, oxygen, or voltage (LOV) sensing domains, LOV1 and LOV2; each binds a flavin mononucleotide (FMN) chromophore (lambdamax = 447 nm, termed D447) and forms the light-sensitive domains, of which LOV2 is the principal component. Blue-light absorption produces a covalent adduct between a very conserved nearby cysteine residue and the C(4a) atom of the FMN moiety via the triplet state of the flavin. The covalent adduct thermally decays to regenerate the D447 dark state, with a rate that may vary by several orders of magnitude between different species. We report that the imidazole base can act as a very efficient enhancer of the dark recovery of A. sativa phot1 LOV2 (AsLOV2) and some other well-characterized LOV domains. Imidazole accelerates the thermal decay of AsLOV2 by 3 orders of magnitude in the submolar concentration range, via a base-catalyzed mechanism involving base abstraction of the FMN N(5)-H adduct state and subsequent reprotonation of the reactive cysteine. The LOV2 crystal structure suggests that the imidazole molecules may act from a cavity located in the vicinity of the FMN, explaining its high efficiency, populated through a channel connecting the cavity to the protein surface. Use of pH titration and chemical inactivation by diethyl pyrocarbonate (DEPC) suggests that histidines located at the surface of the LOV domain act as base catalysts via an as yet unidentified H-bond network, operating at a rate of (55 s)-1 at pH 8. In addition, molecular processes other than histidine-mediated base catalysis contibute significantly to the total thermal decay rate of the adduct and operate at a rate constant of (65 s)-1, leading to a
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Oide, Mao; Okajima, Koji; Nakagami, Hirofumi; Kato, Takayuki; Sekiguchi, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi
2018-01-19
Phototropin2 (phot2) is a blue-light (BL) receptor that regulates BL-dependent activities for efficient photosynthesis in plants. phot2 comprises two BL-receiving light-oxygen-voltage-sensing domains (LOV1 and LOV2) and a kinase domain. BL-excited LOV2 is thought to be primarily responsible for the BL-dependent activation of the kinase. However, the molecular mechanisms by which small BL-induced conformational changes in the LOV2 domain are transmitted to the kinase remain unclear. Here, we used full-length wild-type and mutant phot2 proteins from Arabidopsis to study their molecular properties in the dark and under BL irradiation. Phosphorylation assays and absorption measurements indicated that the LOV1 domain assists the thermal relaxation of BL-excited LOV2 and vice versa. Using small-angle X-ray scattering and electron microscopy, we observed that phot2 forms a dimer and has a rod shape with a maximum length of 188 Å and a radius of gyration of 44 Å. Under BL, phot2 displayed large conformational changes that bent the rod shape. By superimposing the crystal structures of the LOV1 dimer, LOV2, and a homology model of the kinase to the observed changes, we inferred that the BL-dependent change consisted of positional shifts of both LOV2 and the kinase relative to LOV1. Furthermore, phot2 mutants lacking the photocycle in LOV1 or LOV2 still exhibited conformational changes under BL, suggesting that LOV1 and LOV2 cooperatively contribute to the conformational changes that activate the kinase. These results suggest that BL-activated LOV1 contributes to the kinase activity of phot2. We discuss the possible intramolecular interactions and signaling mechanisms in phot2. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
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Oide, Mao; Okajima, Koji; Kashojiya, Sachiko; Takayama, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi
2016-09-16
Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent kinase activation. The BL-excited light-oxygen-voltage-sensing domain 2 (LOV2) is primarily responsible for the activation of the kinase domain; however, the molecular mechanism by which conformational changes in LOV2 are transmitted to the kinase domain remains unclear. Here, we investigated BL-induced structural changes of a minimum functional fragment of Arabidopsis phototropin1 composed of LOV2, the kinase domain, and a linker connecting the two domains using small-angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed photoreversible SAXS changes reflected in the radii of gyration of 42.9 Å in the dark and 48.8 Å under BL irradiation. In the dark, the molecular shape reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a twisted arrangement that was 170 Å long, 80 Å wide, and 50 Å thick. The molecular shape under BL became slightly elongated from that in the dark. By fitting the crystal structure of the LOV2 dimer and a homology model of the kinase domain to their inferred shapes, the BL-dependent change could be interpreted as the positional shift in the kinase domain relative to that of the LOV2 dimer. In addition, we found that lysine 475, a functionally important residue, in the N-terminal region of LOV2 plays a critical role in transmitting the structural changes in LOV2 to the kinase domain. The interface between the domains is critical for signaling, suitably changing the structure to activate the kinase in response to conformational changes in the adjoining LOV2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Photochemistry of Arabidopsis phototropin 1 LOV1: transient tetramerization.
Nakasone, Yusuke; Zikihara, Kazunori; Tokutomi, Satoru; Terazima, Masahide
2013-07-01
The photochemical reaction of the LOV1 (light-oxygen-voltage 1) domain of phototropin 1 from Arabidopsis thaliana was investigated by the time-resolved transient grating method. As with other LOV domains, an absorption spectral change associated with an adduct formation between its chromophore (flavin mononucleotide) and a cysteine residue was observed with a time constant of 1.1 μs. After this reaction, a significant diffusion coefficient (D) change (D of the reactant = 8.2 × 10(-11) m(2) s(-1), and D of the photoproduct = 6.4 × 10(-11) m(2) s(-1)) was observed with a time constant of 14 ms at a protein concentration of 270 μM. From the D value of the ground state and the peak position in size exclusion chromatography, we have confirmed that the phot1LOV1 domain exists as a dimer in the dark. The D-value and the concentration dependence of the rate indicated that the phot1LOV1 domain associates to form a tetramer (dimerization of the dimer) upon photoexcitation. We also found that the chromophore is released from the binding pocket of the LOV domain when it absorbs two photons within a pulse duration, which occurs in addition to the normal photocycle reaction. On the basis of these results, we discuss the molecular mechanism of the light dependent role of the phot1LOV1 domain.
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Okajima, Koji; Aihara, Yusuke; Takayama, Yuki; Nakajima, Mihoko; Kashojiya, Sachiko; Hikima, Takaaki; Oroguchi, Tomotaka; Kobayashi, Amane; Sekiguchi, Yuki; Yamamoto, Masaki; Suzuki, Tomomi; Nagatani, Akira; Nakasako, Masayoshi; Tokutomi, Satoru
2014-01-03
Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that undergoes a cyclic photoreaction upon BL excitation via a signaling state in which the inhibition of the kinase activity by LOV2 is negated. To understand the molecular mechanism underlying the BL-dependent activation of the kinase, the photochemistry, kinase activity, and molecular structure were studied with the phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C. reinhardtii phot showed cyclic photoreaction characteristics with the activation of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the photosensitivity of the kinase activation, which was well explained by the fact that the signaling state lasted for a shorter period of time compared with that of the phot. Small angle x-ray scattering revealed monomeric forms of the proteins in solution and detected BL-dependent conformational changes, suggesting an extension of the global molecular shapes of both samples. Constructed molecular model of full-length phot based on the small angle x-ray scattering data proved the arrangement of LOV1, LOV2, and KD for the first time that showed a tandem arrangement both in the dark and under BL irradiation. The models suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation. This finding demonstrates that LOV1 may interact with LOV2 and modify the photosensitivity of the kinase activation through alteration of the duration of the signaling state in LOV2.
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A conserved glutamine plays a central role in LOV domain signal transmission and duration
Nash, Abigail I.; Ko, Wen-Huang; Harper, Shannon M.; Gardner, Kevin H.
2009-01-01
Light is a key stimulus for plant biological functions, several of which are controlled by light-activated kinases known as phototropins, a group of kinases that contain two light-sensing domains (LOV, Light-Oxygen-Voltage domains) and a C-terminal serine/threonine kinase domain. The second sensory domain, LOV2, plays a key role in regulating kinase enzymatic activity via the photochemical formation of a covalent adduct between a LOV2 cysteine residue and an internally-bound flavin mononucleotide (FMN) chromophore. Subsequent conformational changes in LOV2 lead to the unfolding of a peripheral Jα helix, and ultimately, phototropin kinase activation. To date, the mechanism coupling bond formation and helix dissociation has remained unclear. Previous studies found that a conserved glutamine residue (Q513 in the Avena sativa phototropin 1 LOV2 (AsLOV2) domain) switches its hydrogen-bonding pattern with FMN upon light stimulation. Located in the immediate vicinity of the FMN binding site, this Gln residue is provided by the Iβ strand that interacts with the Jα helix, suggesting a route for signal propagation from the core of the LOV domain to its peripheral Jα helix. To test whether Q513 plays a key role in tuning the photochemical and transduction properties of AsLOV2, we designed two point mutations, Q513L and Q513N, and monitored the effects on the chromophore and protein using a combination of UV-visible absorbance and circular dichroism spectroscopy, limited proteolysis, and solution NMR. The results show that these mutations significantly dampen the changes between the dark and lit state AsLOV2 structures, leaving the protein in a pseudo-dark state (Q513L) or a pseudo-lit state (Q513N) conformation. Further, both mutations changed the photochemical properties of this receptor, particularly the lifetime of the photoexcited signaling states. Together, these data establish that this residue plays a central role in both spectral tuning and signal propagation from
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Designing photoswitchable peptides using the AsLOV2 domain.
Lungu, Oana I; Hallett, Ryan A; Choi, Eun Jung; Aiken, Mary J; Hahn, Klaus M; Kuhlman, Brian
2012-04-20
Photocontrol of functional peptides is a powerful tool for spatial and temporal control of cell signaling events. We show that the genetically encoded light-sensitive LOV2 domain of Avena Sativa phototropin 1 (AsLOV2) can be used to reversibly photomodulate the affinity of peptides for their binding partners. Sequence analysis and molecular modeling were used to embed two peptides into the Jα helix of the AsLOV2 domain while maintaining AsLOV2 structure in the dark but allowing for binding to effector proteins when the Jα helix unfolds in the light. Caged versions of the ipaA and SsrA peptides, LOV-ipaA and LOV-SsrA, bind their targets with 49- and 8-fold enhanced affinity in the light, respectively. These switches can be used as general tools for light-dependent colocalization, which we demonstrate with photo-activable gene transcription in yeast. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Phototropin and light-signaling in phototropism.
Kimura, Mitsuhiro; Kagawa, Takatoshi
2006-10-01
Blue-light-induced phototropism in higher plants is regulated by phototropin, which is a photoreceptor kinase that contains a flavin mononucleotide (FMN). Recently, it was found that this kinase is inhibited by the binding of the LOV2 (light-oxygen-voltage2) domain in the dark but that its activity is increased in the light by the release of the LOV2 domain. Phototropin-associated proteins have been identified, although the proteins that are phosphorylated by phototropin are still unknown. The asymmetrical auxin distribution caused by unilateral irradiation suggests that differential growth is induced by a difference in auxin-regulated gene expression between the shaded and illuminated sides of plant organs. Transcription-related factors, such as NPH4/ARF7, MSG2/IAA19 and SCF(TIR1), play key roles in this process.
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Trippens, Jessica; Greiner, Andre; Schellwat, Jana; Neukam, Martin; Rottmann, Theresa; Lu, Yinghong; Kateriya, Suneel; Hegemann, Peter; Kreimer, Georg
2012-01-01
The eyespot of Chlamydomonas reinhardtii is a light-sensitive organelle important for phototactic orientation of the alga. Here, we found that eyespot size is strain specific and downregulated in light. In a strain in which the blue light photoreceptor phototropin was deleted by homologous recombination, the light regulation of the eyespot size was affected. We restored this dysfunction in different phototropin complementation experiments. Complementation with the phototropin kinase fragment reduced the eyespot size, independent of light. Interestingly, overexpression of the N-terminal light, oxygen or voltage sensing domains (LOV1+LOV2) alone also affected eyespot size and phototaxis, suggesting that aside from activation of the kinase domain, they fulfill an independent signaling function in the cell. Moreover, phototropin is involved in adjusting the level of channelrhodopsin-1, the dominant primary receptor for phototaxis within the eyespot. Both the level of channelrhodopsin-1 at the onset of illumination and its steady state level during the light period are downregulated by phototropin, whereas the level of channelrhodopsin-2 is not significantly altered. Furthermore, a light intensity–dependent formation of a C-terminal truncated phototropin form was observed. We propose that phototropin is a light regulator of phototaxis that desensitizes the eyespot when blue light intensities increase. PMID:23204408
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Engineering and Application of LOV2-based Photoswitches
Zimmerman, Seth Parker; Kuhlman, Brian; Yumerefendi, Hayretin
2017-01-01
Cellular optogenetic switches, a novel class of biological tools, have improved our understanding of biological phenomena that were previously intractable. While the design and engineering of these proteins has historically varied they are all based on borrowed elements from plant and bacterial photoreceptors. In general terms, each of the optogenetic switches designed to date exploits the endogenous light induced change in photoreceptor conformation while repurposing its effect to target a different biological phenomena. We focus on the well-characterized Light Oxygen Voltage 2 (LOV2) domain from Avena sativa phototropin 1 as our cornerstone for design. While the function of the LOV2 domain in the context of the phototropin protein is not fully elucidated, its thorough biophysical characterization as an isolated domain has created a strong foundation for engineering of photoswitches. In this chapter, we examine the biophysical characteristics of the LOV2 domain that may be exploited to produce an optogenetic protein and summarize previous design efforts to provide guidelines for an effective design. Furthermore, we provide protocols for assays including fluorescent polarization, phage display, and microscopy that are optimized for validating, improving, and using newly designed photoswitches. PMID:27586333
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Losi, Aba; Ternelli, Elena; Gärtner, Wolfgang
2004-01-01
The Bacillus subtilis protein YtvA, related to plant phototropins (phot), binds flavin mononucleotide (FMN) within the N-terminal light, oxygen and voltage (LOV) domain. The blue light-triggered photocycle of YtvA and phot involves the reversible formation of a covalent photoadduct between FMN and a cysteine (cys) residue. YtvA contains a single tryptophan, W103, localized on the LOV domain and conserved in all phot-LOV domains. In this study, we show that the fluorescence parameters of W103 in YtvA-LOV are markedly different from those observed in the full-length YtvA. The fluorescence quantum yields are ca 0.03 and 0.08, respectively. In YtvA-LOV, the maximum is redshifted (ca 345 vs 335 nm) and the average fluorescence lifetime shorter (2.7 vs 4.7 ns). These data indicate that W103 is located in a site of tight contact between the two domains of YtvA. In the FMN-cys adduct, selective excitation of W103 at 295 nm results in minimal changes of the fluorescence parameters with respect to the dark state. On 280 nm excitation, however, there is a detectable decrease in the fluorescence emitted from tyrosines, with concomitant increase in W103 fluorescence. This effect is reversible in the dark and might arise from a light-regulated energy transfer process from a yet unidentified tyrosine to W103.
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Song, S-H; Dick, B; Zirak, P; Penzkofer, A; Schiereis, T; Hegemann, P
2005-10-03
An absorption and emission spectroscopic characterisation of the combined wild-type LOV1-LOV2 domain string (abbreviated LOV1/2) of phot from the green alga Chlamydomonas reinhardtii is carried out at pH 8. A LOV1/2-MBP fusion protein (MBP=maltose binding protein) and LOV1/2 with a His-tag at the C-terminus (LOV1/2-His) expressed in an Escherichia coli strain are investigated. Blue-light photo-excitation generates a non-fluorescent intermediate photoproduct (flavin-C(4a)-cysteinyl adduct with absorption peak at 390 nm). The photo-cycle dynamics is studied by dark-state absorption and fluorescence measurement, by following the temporal absorption and emission changes under blue and violet light exposure, and by measuring the temporal absorption and fluorescence recovery after light exposure. The fluorescence quantum yield, phi(F), of the dark adapted samples is phi(F)(LOV1/2-His) approximately 0.15 and phi(F)(LOV1/2-MBP) approximately 0.17. A bi-exponential absorption recovery after light exposure with a fast (in the several 10-s range) and a slow component (in the near 10-min range) are resolved. The quantum yield of photo-adduct formation, phi(Ad), is extracted from excitation intensity dependent absorption measurements. It decreases somewhat with rising excitation intensity. The behaviour of the combined wildtype LOV1-LOV2 double domains is compared with the behaviour of the separate LOV1 and LOV2 domains.
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Kinetics of the LOV domain of ZEITLUPE determine its circadian function in Arabidopsis
Pudasaini, Ashutosh; Shim, Jae Sung; Song, Young Hun; Shi, Hua; Kiba, Takatoshi; Somers, David E; Imaizumi, Takato; Zoltowski, Brian D
2017-01-01
A LOV (Light, Oxygen, or Voltage) domain containing blue-light photoreceptor ZEITLUPE (ZTL) directs circadian timing by degrading clock proteins in plants. Functions hinge upon allosteric differences coupled to the ZTL photocycle; however, structural and kinetic information was unavailable. Herein, we tune the ZTL photocycle over two orders of magnitude. These variants reveal that ZTL complexes with targets independent of light, but dictates enhanced protein degradation in the dark. In vivo experiments definitively show photocycle kinetics dictate the rate of clock component degradation, thereby impacting circadian period. Structural studies demonstrate that photocycle dependent activation of ZTL depends on an unusual dark-state conformation of ZTL. Crystal structures of ZTL LOV domain confirm delineation of structural and kinetic mechanisms and identify an evolutionarily selected allosteric hinge differentiating modes of PAS/LOV signal transduction. The combined biochemical, genetic and structural studies provide new mechanisms indicating how PAS/LOV proteins integrate environmental variables in complex networks. DOI: http://dx.doi.org/10.7554/eLife.21646.001 PMID:28244872
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Kanegae, Takeshi; Kimura, Izumi
2015-08-01
In the fern Adiantum capillus-veneris, the phototropic response of the protonemal cells is induced by blue light and partially inhibited by subsequent irradiation with far-red light. This observation strongly suggests the existence of a phytochrome that mediates this blue/far-red reversible response; however, the phytochrome responsible for this response has not been identified. PHY3/NEO1, one of the three phytochrome genes identified in Adiantum, encodes a chimeric photoreceptor composed of both a phytochrome and a phototropin domain. It was demonstrated that phy3 mediates the red light-dependent phototropic response of Adiantum, and that phy3 potentially functions as a phototropin. These findings suggest that phy3 is the phytochrome that mediates the blue/far-red response in Adiantum protonemata. In the present study, we expressed Adiantum phy3 in a phot1 phot2 phototropin-deficient Arabidopsis line, and investigated the ability of phy3 to induce phototropic responses under various light conditions. Blue light irradiation clearly induced a phototropic response in the phy3-expressing transgenic seedlings, and this effect was fully inhibited by simultaneous irradiation with far-red light. In addition, experiments using amino acid-substituted phy3 indicated that FMN-cysteinyl adduct formation in the light, oxygen, voltage (LOV) domain was not necessary for the induction of blue light-dependent phototropism by phy3. We thus demonstrate that phy3 is the phytochrome that mediates the blue/far-red reversible phototropic response in Adiantum. Furthermore, our results imply that phy3 can function as a phototropin, but that it acts principally as a phytochrome that mediates both the red/far-red and blue/far-red light responses. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.
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Kashojiya, Sachiko; Okajima, Koji; Shimada, Takashi; Tokutomi, Satoru
2015-01-01
Phototropin (phot) is a blue light (BL) receptor in plants and is involved in phototropism, chloroplast movement, stomata opening, etc. A phot molecule has two photo-receptive domains named LOV (Light-Oxygen-Voltage) 1 and 2 in its N-terminal region and a serine/threonine kinase (STK) in its C-terminal region. STK activity is regulated mainly by LOV2, which has a cyclic photoreaction, including the transient formation of a flavin mononucleotide (FMN)-cysteinyl adduct (S390). One of the key events for the propagation of the BL signal from LOV2 to STK is conformational changes in a Jα-helix residing downstream of the LOV2 C-terminus. In contrast, we focused on the role of the A'α-helix, which is located upstream of the LOV2 N-terminus and interacts with the Jα-helix. Using LOV2-STK polypeptides from Arabidopsis thaliana phot1, we found that truncation of the A'α-helix and amino acid substitutions at Glu474 and Lys475 in the gap between the A'α and the Aβ strand of LOV2 (A'α/Aβ gap) to Ala impaired the BL-induced activation of the STK, although they did not affect S390 formation. Trypsin digested the LOV2-STK at Lys603 and Lys475 in a light-dependent manner indicating BL-induced structural changes in both the Jα-helix and the gap. The digestion at Lys603 is faster than at Lys475. These BL-induced structural changes were observed with the Glu474Ala and the Lys475Ala substitutes, indicating that the BL signal reached the Jα-helix as well as the A'α/Aβ gap but could not activate STK. The amino acid residues, Glu474 and Lys475, in the gap are conserved among the phots of higher plants and may act as a joint to connect the structural changes in the Jα-helix with the activation of STK.
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Heintz, Udo; Schlichting, Ilme
2016-01-01
The design of synthetic optogenetic tools that allow precise spatiotemporal control of biological processes previously inaccessible to optogenetic control has developed rapidly over the last years. Rational design of such tools requires detailed knowledge of allosteric light signaling in natural photoreceptors. To understand allosteric communication between sensor and effector domains, characterization of all relevant signaling states is required. Here, we describe the mechanism of light-dependent DNA binding of the light-oxygen-voltage (LOV) transcription factor Aureochrome 1a from Phaeodactylum tricornutum (PtAu1a) and present crystal structures of a dark state LOV monomer and a fully light-adapted LOV dimer. In combination with hydrogen/deuterium-exchange, solution scattering data and DNA-binding experiments, our studies reveal a light-sensitive interaction between the LOV and basic region leucine zipper DNA-binding domain that together with LOV dimerization results in modulation of the DNA affinity of PtAu1a. We discuss the implications of these results for the design of synthetic LOV-based photosensors with application in optogenetics. DOI: http://dx.doi.org/10.7554/eLife.11860.001 PMID:26754770
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Suetsugu, Noriyuki; Kagawa, Takatoshi; Wada, Masamitsu
2005-01-01
The ambient-light conditions mediate chloroplast relocation in plant cells. Under the low-light conditions, chloroplasts accumulate in the light (accumulation response), while under the high-light conditions, they avoid the light (avoidance response). In Arabidopsis (Arabidopsis thaliana), the accumulation response is mediated by two blue-light receptors, termed phototropins (phot1 and phot2) that act redundantly, and the avoidance response is mediated by phot2 alone. A mutant, J-domain protein required for chloroplast accumulation response 1 (jac1), lacks the accumulation response under weak blue light but shows a normal avoidance response under strong blue light. In dark-adapted wild-type cells, chloroplasts accumulate on the bottom of cells. Both the jac1 and phot2 mutants are defective in this chloroplast movement in darkness. Positional cloning of JAC1 reveals that this gene encodes a J-domain protein, resembling clathrin-uncoating factor auxilin at its C terminus. The amounts of JAC1 transcripts and JAC1 proteins are not regulated by light and by phototropins. A green fluorescent protein-JAC1 fusion protein showed a similar localization pattern to green fluorescent protein alone in a transient expression assay using Arabidopsis mesophyll cells and onion (Allium cepa) epidermal cells, suggesting that the JAC1 protein may be a soluble cytosolic protein. Together, these results suggest that JAC1 is an essential component of phototropin-mediated chloroplast movement. PMID:16113208
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Moriconi, Victoria; Sellaro, Romina; Ayub, Nicolás; Soto, Gabriela; Rugnone, Matías; Shah, Rashmi; Pathak, Gopal P; Gärtner, Wolfgang; Casal, Jorge J
2013-10-01
In Arabidopsis thaliana, light signals modulate the defences against bacteria. Here we show that light perceived by the LOV domain-regulated two-component system (Pst-Lov) of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) modulates virulence against A. thaliana. Bioinformatic analysis and the existence of an episomal circular intermediate indicate that the locus encoding Pst-Lov is present in an active genomic island acquired by horizontal transfer. Strains mutated at Pst-Lov showed enhanced growth on minimal medium and in leaves of A. thaliana exposed to light, but not in leaves incubated in darkness or buried in the soil. Pst-Lov repressed the expression of principal and alternative sigma factor genes and their downstream targets linked to bacterial growth, virulence and quorum sensing, in a strictly light-dependent manner. We propose that the function of Pst-Lov is to distinguish between soil (dark) and leaf (light) environments, attenuating the damage caused to host tissues while releasing growth out of the host. Therefore, in addition to its direct actions via photosynthesis and plant sensory receptors, light may affect plants indirectly via the sensory receptors of bacterial pathogens. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.
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Rani, Raj; Jentzsch, Katrin; Lecher, Justin; Hartmann, Rudolf; Willbold, Dieter; Jaeger, Karl-Erich; Krauss, Ulrich
2013-07-02
In bacteria and fungi, various light, oxygen, voltage (LOV) sensory systems that lack a fused effector domain but instead contain only short N- and C-terminal extensions flanking the LOV core exist. In the prokaryotic kingdom, this so-called "short" LOV protein family represents the third largest LOV photoreceptor family. This observation prompted us to study their distribution and phylogeny as well as their photochemical and structural properties in more detail. We recently described the slow and fast reverting "short" LOV proteins PpSB1-LOV and PpSB2-LOV from Pseudomonas putida KT2440 whose adduct state lifetimes varied by 3 orders of magnitude [Jentzsch, K., Wirtz, A., Circolone, F., Drepper, T., Losi, A., Gärtner, W., Jaeger, K. E., and Krauss, U. (2009) Biochemistry 48, 10321-10333]. We now present evidence of the conservation of similar fast and slow-reverting "short" LOV proteins in different Pseudomonas species. Truncation studies conducted with PpSB1-LOV and PpSB2-LOV suggested that the short N- and C-terminal extensions outside of the LOV core domain are essential for the structural integrity and folding of the two proteins. While circular dichroism and solution nuclear magnetic resonance experiments verify that the two short C-terminal extensions of PpSB1-LOV and PpSB2-LOV form independently folding helical structures in solution, bioinformatic analyses imply the formation of coiled coils of the respective structural elements in the context of the dimeric full-length proteins. Given their prototypic architecture, conserved in most more complex LOV photoreceptor systems, "short" LOV proteins could represent ideally suited building blocks for the design of genetically encoded photoswitches (i.e., LOV-based optogenetic tools).
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Zoltowski, Brian D.; Nash, Abigail I.; Gardner, Kevin H.
2011-01-01
Light Oxygen Voltage (LOV) domains utilize a conserved blue light-dependent mechanism to control a diverse array of effector domains in biological and engineered proteins. Variations in the kinetics and efficiency of LOV photochemistry fine tune various aspects of the photic response. Characterization of the kinetics of a key aspect of this photochemical mechanism in EL222, a blue-light responsive DNA binding protein from Erythrobacter litoralis HTCC2594, reveals unique non-Arrhenius behavior in the rate of dark state cleavage of the photochemically-generated adduct. Sequence analysis and mutagenesis studies establish that this effect stems from a Gln to Ala mutation unique to EL222 and homologous proteins from marine bacteria. Kinetic and spectroscopic analyses reveal that hydrogen bonding interactions between the FMN N1, O2 and ribityl hydroxyls with the surrounding protein regulate photocycle kinetics and stabilize the LOV active site from temperature-induced alteration in local structure. Substitution of residues interacting with the N1-O2 locus modulates adduct stability, structural flexibility and sequestration of the active site from bulk solvent without perturbation of light-activated DNA binding. Together, these variants link non-Arrhenius behavior to specific alteration of an H-bonding network, while affording tunability of photocycle kinetics. PMID:21923139
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Bonomi, Hernán R.; Posadas, Diana M.; Paris, Gastón; Carrica, Mariela del Carmen; Frederickson, Marcus; Pietrasanta, Lía Isabel; Bogomolni, Roberto A.; Zorreguieta, Angeles; Goldbaum, Fernando A.
2012-01-01
Rhizobium leguminosarum is a soil bacterium that infects root hairs and induces the formation of nitrogen-fixing nodules on leguminous plants. Light, oxygen, and voltage (LOV)-domain proteins are blue-light receptors found in higher plants and many algae, fungi, and bacteria. The genome of R. leguminosarum bv. viciae 3841, a pea-nodulating endosymbiont, encodes a sensor histidine kinase containing a LOV domain at the N-terminal end (R-LOV-HK). R-LOV-HK has a typical LOV domain absorption spectrum with broad bands in the blue and UV-A regions and shows a truncated photocycle. Here we show that the R-LOV-HK protein regulates attachment to an abiotic surface and production of flagellar proteins and exopolysaccharide in response to light. Also, illumination of bacterial cultures before inoculation of pea roots increases the number of nodules per plant and the number of intranodular bacteroids. The effects of light on nodulation are dependent on a functional lov gene. The results presented in this work suggest that light, sensed by R-LOV-HK, is an important environmental factor that controls adaptive responses and the symbiotic efficiency of R. leguminosarum. PMID:22773814
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Lokhandwala, Jameela; Silverman Y de la Vega, Rafael I; Hopkins, Hilary C; Britton, Collin W; Rodriguez-Iglesias, Aroa; Bogomolni, Roberto; Schmoll, Monika; Zoltowski, Brian D
2016-07-08
Light-oxygen-voltage (LOV) domain-containing proteins function as small light-activated modules capable of imparting blue light control of biological processes. Their small modular nature has made them model proteins for allosteric signal transduction and optogenetic devices. Despite intense research, key aspects of their signal transduction mechanisms and photochemistry remain poorly understood. In particular, ordered water has been identified as a possible key mediator of photocycle kinetics, despite the lack of ordered water in the LOV active site. Herein, we use recent crystal structures of a fungal LOV protein ENVOY to interrogate the role of Thr(101) in recruiting water to the flavin active site where it can function as an intrinsic base to accelerate photocycle kinetics. Kinetic and molecular dynamic simulations confirm a role in solvent recruitment to the active site and identify structural changes that correlate with solvent recruitment. In vivo analysis of T101I indicates a direct role of the Thr(101) position in mediating adaptation to osmotic stress, thereby verifying biological relevance of ordered water in LOV signaling. The combined studies identify position 101 as a mediator of both allostery and photocycle catalysis that can impact organism physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Two photon spectroscopy and microscopy of the fluorescent flavoprotein, iLOV.
Homans, Rachael J; Khan, Raja U; Andrews, Michael B; Kjeldsen, Annemette E; Natrajan, Louise S; Marsden, Steven; McKenzie, Edward A; Christie, John M; Jones, Alex R
2018-06-06
LOV-domains are ubiquitous photosensory proteins that are commonly re-engineered to serve as powerful and versatile fluorescent proteins and optogenetic tools. The photoactive, flavin chromophore, however, is excited using short wavelengths of light in the blue and UV regions, which have limited penetration into biological samples and can cause photodamage. Here, we have used non-linear spectroscopy and microscopy of the fluorescent protein, iLOV, to reveal that functional variants of LOV can be activated to great effect by two non-resonant photons of lower energy, near infrared light, not only in solution but also in biological samples. The two photon cross section of iLOV has a significantly blue-shifted S0 → S1 transition compared with the one photon absorption spectrum, suggesting preferential population of excited vibronic states. It is highly likely, therefore, that the two photon absorption wavelength of engineered, LOV-based tools is tuneable. We also demonstrate for the first time two photon imaging using iLOV in human epithelial kidney cells. Consequently, two photon absorption by engineered, flavin-based bio-molecular tools can enable non-invasive activation with high depth resolution and the potential for not only improved image clarity but also enhanced spatiotemporal control for optogenetic applications.
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Rivera-Cancel, Giomar; Motta-Mena, Laura B.; Gardner, Kevin H.
2012-01-01
Light-oxygen-voltage (LOV) domains serve as the photosensory modules for a wide range of plant and bacterial proteins, conferring blue light dependent regulation to effector activities as diverse as enzymes and DNA binding. LOV domains can also be engineered into a variety of exogenous targets, enabling similar regulation for new protein-based reagents. Common to these proteins is the ability for LOV domains to reversibly form a photochemical adduct between an internal flavin chromophore and the surrounding protein, using this to trigger conformational changes that affect output activity. Using the Erythrobacter litoralis protein EL222 model system which links LOV regulation to a helix-turn-helix (HTH) DNA binding domain, we demonstrated that the LOV domain binds and inhibits the HTH domain in the dark, releasing these interactions upon illumination [Nash et al. (2011) Proc. Natl. Acad. Sci. USA 108, 9449–9454]. Here we combine genomic and in vitro selection approaches to identify optimal DNA binding sites for EL222. Within the bacterial host, we observe binding several genomic sites using a 12 bp sequence consensus that is also found by in vitro selection methods. Sequence-specific alterations in the DNA consensus reduce EL222-binding affinity in a manner consistent with the expected binding mode: a protein dimer binding to two repeats. Finally, we demonstrate the light-dependent activation of transcription of two genes adjacent to an EL222 binding site. Taken together, these results shed light on the native function of EL222 and provide useful reagents for further basic and applications research of this versatile protein. PMID:23205774
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TULIPs: tunable, light-controlled interacting protein tags for cell biology.
Strickland, Devin; Lin, Yuan; Wagner, Elizabeth; Hope, C Matthew; Zayner, Josiah; Antoniou, Chloe; Sosnick, Tobin R; Weiss, Eric L; Glotzer, Michael
2012-03-04
Naturally photoswitchable proteins offer a means of directly manipulating the formation of protein complexes that drive a diversity of cellular processes. We developed tunable light-inducible dimerization tags (TULIPs) based on a synthetic interaction between the LOV2 domain of Avena sativa phototropin 1 (AsLOV2) and an engineered PDZ domain (ePDZ). TULIPs can recruit proteins to diverse structures in living yeast and mammalian cells, either globally or with precise spatial control using a steerable laser. The equilibrium binding and kinetic parameters of the interaction are tunable by mutation, making TULIPs readily adaptable to signaling pathways with varying sensitivities and response times. We demonstrate the utility of TULIPs by conferring light sensitivity to functionally distinct components of the yeast mating pathway and by directing the site of cell polarization.
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Sharma, Sulabha; Kharshiing, Eros; Srinivas, Ankanagari; Zikihara, Kazunori; Tokutomi, Satoru; Nagatani, Akira; Fukayama, Hiroshi; Bodanapu, Reddaiah; Behera, Rajendra K.; Sreelakshmi, Yellamaraju; Sharma, Rameshwar
2014-01-01
In higher plants, blue light (BL) phototropism is primarily controlled by the phototropins, which are also involved in stomatal movement and chloroplast relocation. These photoresponses are mediated by two phototropins, phot1 and phot2. Phot1 mediates responses with higher sensitivity than phot2, and phot2 specifically mediates chloroplast avoidance and dark positioning responses. Here, we report the isolation and characterization of a Nonphototropic seedling1 (Nps1) mutant of tomato (Solanum lycopersicum). The mutant is impaired in low-fluence BL responses, including chloroplast accumulation and stomatal opening. Genetic analyses show that the mutant locus is dominant negative in nature. In dark-grown seedlings of the Nps1 mutant, phot1 protein accumulates at a highly reduced level relative to the wild type and lacks BL-induced autophosphorylation. The mutant harbors a single glycine-1484-to-alanine transition in the Hinge1 region of a phot1 homolog, resulting in an arginine-to-histidine substitution (R495H) in a highly conserved A′α helix proximal to the light-oxygen and voltage2 domain of the translated gene product. Significantly, the R495H substitution occurring in the Hinge1 region of PHOT1 abolishes its regulatory activity in Nps1 seedlings, thereby highlighting the functional significance of the A′α helix region in phototropic signaling of tomato. PMID:24515830
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Vanhaelewyn, Lucas; Schumacher, Paolo; Poelman, Dirk; Fankhauser, Christian; Van Der Straeten, Dominique; Vandenbussche, Filip
2016-11-01
Ultraviolet B (UV-B) light is a part of the solar radiation which has significant effects on plant morphology, even at low doses. In Arabidopsis, many of these morphological changes have been attributed to a specific UV-B receptor, UV resistance locus 8 (UVR8). Recent findings showed that next to phototropin regulated phototropism, UVR8 mediated signaling is able of inducing directional bending towards UV-B light in etiolated seedlings of Arabidopsis, in a phototropin independent manner. In this study, kinetic analysis of phototropic bending was used to evaluate the relative contribution of each of these pathways in UV-B mediated phototropism. Diminishing UV-B light intensity favors the importance of phototropins. Molecular and genetic analyses suggest that UV-B is capable of inducing phototropin signaling relying on phototropin kinase activity and regulation of NPH3. Moreover, enhanced UVR8 responses in the UV-B hypersensitive rup1rup2 mutants interferes with the fast phototropin mediated phototropism. Together the data suggest that phototropins are the most important receptors for UV-B induced phototropism in etiolated seedlings, and a RUP mediated negative feedback pathway prevents UVR8 signaling to interfere with the phototropin dependent response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Blue-light-activated phototropin2 trafficking from the cytoplasm to Golgi/post-Golgi vesicles.
Aggarwal, Chhavi; Banaś, Agnieszka Katarzyna; Kasprowicz-Maluśki, Anna; Borghetti, Carolina; Labuz, Justyna; Dobrucki, Jerzy; Gabryś, Halina
2014-07-01
Phototropins are plasma membrane-localized UVA/blue light photoreceptors which mediate phototropism, inhibition of primary hypocotyl elongation, leaf positioning, chloroplast movements, and stomatal opening. Blue light irradiation activates the C-terminal serine/threonine kinase domain of phototropin which autophosphorylates the receptor. Arabidopsis thaliana encodes two phototropins, phot1 and phot2. In response to blue light, phot1 moves from the plasma membrane into the cytosol and phot2 translocates to the Golgi complex. In this study the molecular mechanism and route of blue-light-induced phot2 trafficking are demonstrated. It is shown that Atphot2 behaves in a similar manner when expressed transiently under 35S or its native promoter. The phot2 kinase domain but not blue-light-mediated autophosphorylation is required for the receptor translocation. Using co-localization and western blotting, the receptor was shown to move from the cytoplasm to the Golgi complex, and then to the post-Golgi structures. The results were confirmed by brefeldin A (an inhibitor of the secretory pathway) which disrupted phot2 trafficking. An association was observed between phot2 and the light chain2 of clathrin via bimolecular fluorescence complementation. The fluorescence was observed at the plasma membrane. The results were confirmed using co-immunoprecipitation. However, tyrphostin23 (an inhibitor of clathrin-mediated endocytosis) and wortmannin (a suppressor of receptor endocytosis) were not able to block phot2 trafficking, indicating no involvement of receptor endocytosis in the formation of phot2 punctuate structures. Protein turnover studies indicated that the receptor was continuously degraded in both darkness and blue light. The degradation of phot2 proceeded via a transport route different from translocation to the Golgi complex. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.
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Aggarwal, Chhavi; Labuz, Justyna; Gabryś, Halina
2013-01-01
Phototropins are UVA/blue-light receptors involved in controlling the light-dependent physiological responses which serve to optimize the photosynthetic activity of plants and promote growth. The phototropin-induced phosphoinositide (PI) metabolism has been shown to be essential for stomatal opening and phototropism. However, the role of PIs in phototropin-induced chloroplast movements remains poorly understood. The aim of this work is to determine which PI species are involved in the control of chloroplast movements in Arabidopsis and the nature of their involvement. We present the effects of the inactivation of phospholipase C (PLC), PI3-kinase (PI3K) and PI4-kinase (PI4K) on chloroplast relocations in Arabidopsis. The inhibition of the phosphatidylinositol 4,5-bisphospahte [PI(4,5)P2]-PLC pathway, using neomycin and U73122, suppressed the phot2-mediated chloroplast accumulation and avoidance responses, without affecting movement responses controlled by phot1. On the other hand, PI3K and PI4K activities are more restricted to phot1- and phot2-induced weak-light responses. The inactivation of PI3K and PI4K by wortmannin and LY294002 severely affected the weak blue-light-activated accumulation response but had little effect on the strong blue-light-activated avoidance response. The inhibitory effect observed with PI metabolism inhibitors is, at least partly, due to a disturbance in Ca(2+) ((c)) signaling. Using the transgenic aequorin system, we show that the application of these inhibitors suppresses the blue-light-induced transient Ca(2+) ((c)) rise. These results demonstrate the importance of PIs in chloroplast movements, with the PI(4,5)P2-PLC pathway involved in phot2 signaling while PI3K and PI4K are required for the phot1- and phot2-induced accumulation response. Our results suggest that these PIs modulate cytosolic Ca(2+) signaling during movements.
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Cloning and bioinformatic analysis of lovastatin biosynthesis regulatory gene lovE.
Huang, Xin; Li, Hao-ming
2009-08-05
Lovastatin is an effective drug for treatment of hyperlipidemia. This study aimed to clone lovastatin biosynthesis regulatory gene lovE and analyze the structure and function of its encoding protein. According to the lovastatin synthase gene sequence from genebank, primers were designed to amplify and clone the lovastatin biosynthesis regulatory gene lovE from Aspergillus terrus genomic DNA. Bioinformatic analysis of lovE and its encoding animo acid sequence was performed through internet resources and software like DNAMAN. Target fragment lovE, almost 1500 bp in length, was amplified from Aspergillus terrus genomic DNA and the secondary and three-dimensional structures of LovE protein were predicted. In the lovastatin biosynthesis process lovE is a regulatory gene and LovE protein is a GAL4-like transcriptional factor.
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Whippo, Craig W; Hangarter, Roger P
2003-07-01
Phototropism and hypocotyl growth inhibition are modulated by the coaction of different blue-light photoreceptors and their signaling pathways. How seedlings integrate the activities of the different blue-light photoreceptors to coordinate these hypocotyl growth responses is still unclear. We have used time-lapse imaging and a nontraditional mathematical approach to conduct a detailed examination of phototropism in wild-type Arabidopsis and various blue-light photoreceptor mutants. Our results indicate that high fluence rates of blue light (100 micro mol m(-)(2) s(-)(1)) attenuate phototropism through the coaction of the phototropin and cryptochrome blue-light photoreceptors. In contrast, we also demonstrate that phototropins and cryptochromes function together to enhance phototropism under low fluence rates (<1.0 micro mol m(-)(2) s(-)(1)) of blue light. Based on our results, we hypothesize that phototropins and cryptochromes regulate phototropism by coordinating the balance between stimulation and inhibition of growth of the hypocotyl depending on the fluence rate of blue light.
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Light activation of the LOV protein vivid generates a rapidly exchanging dimer.
Zoltowski, Brian D; Crane, Brian R
2008-07-08
The fungal photoreceptor Vivid (VVD) plays an important role in the adaptation of blue-light responses in Neurospora crassa. VVD, an FAD-binding LOV (light, oxygen, voltage) protein, couples light-induced cysteinyl adduct formation at the flavin ring to conformational changes in the N-terminal cap (Ncap) of the VVD PAS domain. Size-exclusion chromatography (SEC), equilibrium ultracentrifugation, and static and dynamic light scattering show that these conformational changes generate a rapidly exchanging VVD dimer, with an expanded hydrodynamic radius. A three-residue N-terminal beta-turn that assumes two different conformations in a crystal structure of a VVD C71V variant is essential for light-state dimerization. Residue substitutions at a critical hinge between the Ncap and PAS core can inhibit or enhance dimerization, whereas a Tyr to Trp substitution at the Ncap-PAS interface stabilizes the light-state dimer. Cross-linking through engineered disulfides indicates that the light-state dimer differs considerably from the dark-state dimer found in VVD crystal structures. These results verify the role of Ncap conformational changes in gating the photic response of N. crassa and indicate that LOV-LOV homo- or heterodimerization may be a mechanism for regulating light-activated gene expression.
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Whippo, Craig W.; Hangarter, Roger P.
2003-01-01
Phototropism and hypocotyl growth inhibition are modulated by the coaction of different blue-light photoreceptors and their signaling pathways. How seedlings integrate the activities of the different blue-light photoreceptors to coordinate these hypocotyl growth responses is still unclear. We have used time-lapse imaging and a nontraditional mathematical approach to conduct a detailed examination of phototropism in wild-type Arabidopsis and various blue-light photoreceptor mutants. Our results indicate that high fluence rates of blue light (100 μmol m–2 s–1) attenuate phototropism through the coaction of the phototropin and cryptochrome blue-light photoreceptors. In contrast, we also demonstrate that phototropins and cryptochromes function together to enhance phototropism under low fluence rates (<1.0 μmol m–2 s–1) of blue light. Based on our results, we hypothesize that phototropins and cryptochromes regulate phototropism by coordinating the balance between stimulation and inhibition of growth of the hypocotyl depending on the fluence rate of blue light. PMID:12857830
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Light-induced protein degradation in human-derived cells.
Sun, Wansheng; Zhang, Wenyao; Zhang, Chao; Mao, Miaowei; Zhao, Yuzheng; Chen, Xianjun; Yang, Yi
2017-05-27
Controlling protein degradation can be a valuable tool for posttranslational regulation of protein abundance to study complex biological systems. In the present study, we designed a light-switchable degron consisting of a light oxygen voltage (LOV) domain of Avena sativa phototropin 1 (AsLOV2) and a C-terminal degron. Our results showed that the light-switchable degron could be used for rapid and specific induction of protein degradation in HEK293 cells by light in a proteasome-dependent manner. Further studies showed that the light-switchable degron could also be utilized to mediate the degradation of secreted Gaussia princeps luciferase (GLuc), demonstrating the adaptability of the light-switchable degron in different types of protein. We suggest that the light-switchable degron offers a robust tool to control protein levels and may serves as a new and significant method for gene- and cell-based therapies. Copyright © 2017 Elsevier Inc. All rights reserved.
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Light activation of the LOV protein Vivid generates a rapidly exchanging dimer†‡
Zoltowski, Brian D.; Crane, Brian R.
2009-01-01
The fungal photoreceptor Vivid (VVD) plays an important role in the adaptation of blue-light responses in Neurospora crassa. VVD, an FAD-binding LOV (Light, Oxygen, Voltage) protein, couples light-induced cysteinyl-adduct formation at the flavin ring to conformational changes in the N-terminal cap (Ncap) of the VVD PAS domain. Size-exclusion chromatography (SEC), equilibrium ultracentrifugation, and static and dynamic light scattering show that these conformational changes generate a rapidly exchanging VVD dimer, with an expanded hydrodynamic radius. A three-residue N-terminal β-turn that assumes two different conformations in a crystal structure of a VVD C71V variant is essential for light-state dimerization. Residue substitutions at a critical hinge between the Ncap and PAS core can inhibit or enhance dimerization, whereas a Tyr to Trp substitution at the Ncap-to-PAS interface stabilizes the light-state dimer. Cross-linking through engineered disulfides indicates that the light-state dimer differs considerably from the dark-state dimer found in VVD crystal structures. These results verify the role of Ncap conformational changes in gating the photic response of Neurospora crassa, and indicate that LOV:LOV homo or hetero dimerization may be a mechanism for regulating light-activated gene expression. PMID:18553928
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Zhao, Xiang; Wang, Yan-Liang; Qiao, Xin-Rong; Wang, Jin; Wang, Lin-Dan; Xu, Chang-Shui; Zhang, Xiao
2013-07-01
Phototropins (phot1 and phot2), the blue light receptors in plants, regulate hypocotyl phototropism in a fluence-dependent manner. Especially under high fluence rates of blue light (HBL), the redundant function mediated by both phot1 and phot2 drastically restricts the understanding of the roles of phot2. Here, systematic analysis of phototropin-related mutants and overexpression transgenic lines revealed that HBL specifically induced a transient increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in Arabidopsis (Arabidopsis thaliana) hypocotyls and that the increase in [Ca(2+)]cyt was primarily attributed to phot2. Pharmacological and genetic experiments illustrated that HBL-induced Ca(2+) increases were modulated differently by phot1 and phot2. Phot2 mediated the HBL-induced increase in [Ca(2+)]cyt mainly by an inner store-dependent Ca(2+)-release pathway, not by activating plasma membrane Ca(2+) channels. Further analysis showed that the increase in [Ca(2+)]cyt was possibly responsible for HBL-induced hypocotyl phototropism. An inhibitor of auxin efflux carrier exhibited significant inhibitions of both phototropism and increases in [Ca(2+)]cyt, which indicates that polar auxin transport is possibly involved in HBL-induced responses. Moreover, PHYTOCHROME KINASE SUBSTRATE1 (PKS1), the phototropin-related signaling element identified, interacted physically with phototropins, auxin efflux carrier PIN-FORMED1 and calcium-binding protein CALMODULIN4, in vitro and in vivo, respectively, and HBL-induced phototropism was impaired in pks multiple mutants, indicating the role of the PKS family in HBL-induced phototropism. Together, these results provide new insights into the functions of phototropins and highlight a potential integration point through which Ca(2+) signaling-related HBL modulates hypocotyl phototropic responses.
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Ishishita, Kazuhiro; Suetsugu, Noriyuki; Hirose, Yuki; Higa, Takeshi; Doi, Michio; Wada, Masamitsu; Matsushita, Tomonao; Gotoh, Eiji
2016-03-01
The blue light (BL) receptor phototropin (phot) is specifically found in green plants; it regulates various BL-induced responses such as phototropism, chloroplast movement, stomatal opening, and leaf flattening. In Arabidopsis thaliana, two phototropins--phot1 and phot2--respond to blue light in overlapping but distinct ways. These BL-receptor-mediated responses enhance the photosynthetic activity of plants under weak light and minimize photodamage under strong light conditions. Welwitschia mirabilis Hook.f. found in the Namib Desert, and it has adapted to severe environmental stresses such as limiting water and strong sunlight. Although the plant has physiologically and ecologically unique features, it is unknown whether phototropin is functional in this plant. In this study, we assessed the functioning of phot-mediated BL responses in W. mirabilis. BL-dependent phototropism and stomatal opening was observed but light-dependent chloroplast movement was not detected. We performed a functional analysis of the PHOT1 gene of W. mirabilis, WmPHOT1, in Arabidopsis thaliana. We generated transgenic A. thaliana lines expressing WmPHOT1 in a phot1 phot2 double mutant background. Several Wmphot1 transgenic plants showed normal growth, although phot1 phot2 double mutant plants showed stunted growth. Furthermore, Wmphot1 transgenic plants showed normal phot1-mediated responses including phototropism, chloroplast accumulation, stomatal opening, and leaf flattening, but lacked the chloroplast avoidance response that is specifically mediated by phot2. Thus, our findings indicate that W. mirabilis possesses typical phot-mediated BL responses that were at least partially mediated by functional phototropin 1, an ortholog of Atphot1.
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Kraiselburd, Ivana; Daurelio, Lucas D.; Tondo, María Laura; Merelo, Paz; Cortadi, Adriana A.; Talón, Manuel; Tadeo, Francisco R.; Orellano, Elena G.
2013-01-01
Pathogens interaction with a host plant starts a set of immune responses that result in complex changes in gene expression and plant physiology. Light is an important modulator of plant defense response and recent studies have evidenced the novel influence of this environmental stimulus in the virulence of several bacterial pathogens. Xanthomonas citri subsp. citri is the bacterium responsible for citrus canker disease, which affects most citrus cultivars. The ability of this bacterium to colonize host plants is influenced by bacterial blue-light sensing through a LOV-domain protein and disease symptoms are considerably altered upon deletion of this protein. In this work we aimed to unravel the role of this photoreceptor during the bacterial counteraction of plant immune responses leading to citrus canker development. We performed a transcriptomic analysis in Citrus sinensis leaves inoculated with the wild type X. citri subsp. citri and with a mutant strain lacking the LOV protein by a cDNA microarray and evaluated the differentially regulated genes corresponding to specific biological processes. A down-regulation of photosynthesis-related genes (together with a corresponding decrease in photosynthesis rates) was observed upon bacterial infection, this effect being more pronounced in plants infected with the lov-mutant bacterial strain. Infection with this strain was also accompanied with the up-regulation of several secondary metabolism- and defense response-related genes. Moreover, we found that relevant plant physiological alterations triggered by pathogen attack such as cell wall fortification and tissue disruption were amplified during the lov-mutant strain infection. These results suggest the participation of the LOV-domain protein from X. citri subsp. citri in the bacterial counteraction of host plant defense response, contributing in this way to disease development. PMID:24260514
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Tissue-autonomous promotion of palisade cell development by phototropin 2 in Arabidopsis.
Kozuka, Toshiaki; Kong, Sam-Geun; Doi, Michio; Shimazaki, Ken-ichiro; Nagatani, Akira
2011-10-01
Light is an important environmental information source that plants use to modify their growth and development. Palisade parenchyma cells in leaves develop cylindrical shapes in response to blue light; however, the photosensory mechanism for this response has not been elucidated. In this study, we analyzed the palisade cell response in phototropin-deficient mutants. First, we found that two different light-sensing mechanisms contributed to the response in different proportions depending on the light intensity. One response observed under lower intensities of blue light was mediated exclusively by a blue light photoreceptor, phototropin 2 (PHOT2). Another response was elicited under higher intensities of light in a phototropin-independent manner. To determine the tissue in which PHOT2 perceives the light stimulus to regulate the response, green fluorescent protein (GFP)-tagged PHOT2 (P2G) was expressed under the control of tissue-specific promoters in the phot1 phot2 mutant background. The results revealed that the expression of P2G in the mesophyll, but not in the epidermis, promoted palisade cell development. Furthermore, a constitutively active C-terminal kinase fragment of PHOT2 fused to GFP (P2CG) promoted the development of cylindrical palisade cells in the proper direction without the directional cue provided by light. Hence, in response to blue light, PHOT2 promotes the development of cylindrical palisade cells along a predetermined axis in a tissue-autonomous manner.
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Disruption of ROOT PHOTOTROPISM2 gene does not affect phototropin-mediated stomatal opening.
Tsutsumi, Toshifumi; Takemiya, Atsushi; Harada, Akiko; Shimazaki, Ken-ichiro
2013-03-01
Phototropins (phot1 and phot2), blue light-receptor protein kinases in plants, mediate stomatal opening by activating the plasma membrane H(+)-ATPase in guard cells, but the signaling from phototropins to the H(+)-ATPase remains unknown. A recent study concluded that ROOT PHOTOTROPISM2 (RPT2) is involved in the primary step of this process. However, this conclusion is based solely on the determination of stomatal apertures in the epidermis. We investigated the role of RPT2 in blue light-dependent stomatal opening in more detail. We generated double mutants of rpt2 and phototropins (phot1 or phot2) in the Col ecotype background and obtained the typical phenotypes of rpt2 mutants, including the impairment in phototropism. In contrast, neither blue light-dependent H(+) pumping nor blue light-dependent H(+)-ATPase activation in guard cells was affected in the rpt2 mutants of rpt2, phot1 rpt2, and phot2 rpt2. Stomata in these rpt2 mutants opened widely by blue light in both epidermal peels and intact leaves, and no difference in the responses was found between the wild type and the mutants. From these results, we concluded that RPT2 gene disruption does not affect blue light-dependent stomatal opening. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Tissue-Autonomous Promotion of Palisade Cell Development by Phototropin 2 in Arabidopsis[W
Kozuka, Toshiaki; Kong, Sam-Geun; Doi, Michio; Shimazaki, Ken-ichiro; Nagatani, Akira
2011-01-01
Light is an important environmental information source that plants use to modify their growth and development. Palisade parenchyma cells in leaves develop cylindrical shapes in response to blue light; however, the photosensory mechanism for this response has not been elucidated. In this study, we analyzed the palisade cell response in phototropin-deficient mutants. First, we found that two different light-sensing mechanisms contributed to the response in different proportions depending on the light intensity. One response observed under lower intensities of blue light was mediated exclusively by a blue light photoreceptor, phototropin 2 (PHOT2). Another response was elicited under higher intensities of light in a phototropin-independent manner. To determine the tissue in which PHOT2 perceives the light stimulus to regulate the response, green fluorescent protein (GFP)–tagged PHOT2 (P2G) was expressed under the control of tissue-specific promoters in the phot1 phot2 mutant background. The results revealed that the expression of P2G in the mesophyll, but not in the epidermis, promoted palisade cell development. Furthermore, a constitutively active C-terminal kinase fragment of PHOT2 fused to GFP (P2CG) promoted the development of cylindrical palisade cells in the proper direction without the directional cue provided by light. Hence, in response to blue light, PHOT2 promotes the development of cylindrical palisade cells along a predetermined axis in a tissue-autonomous manner. PMID:21972260
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The Role of Distant Mutations and Allosteric Regulation on LovD Active Site Dynamics
Jiménez-Osés, Gonzalo; Osuna, Sílvia; Gao, Xue; Sawaya, Michael R.; Gilson, Lynne; Collier, Steven J.; Huisman, Gjalt W.; Yeates, Todd O.; Tang, Yi; Houk, K. N.
2014-01-01
Natural enzymes have evolved to perform their cellular functions under complex selective pressures, which often require their catalytic activities to be regulated by other proteins. We contrasted a natural enzyme, LovD, which acts on a protein-bound (LovF) acyl substrate, with a laboratory-generated variant that was transformed by directed evolution to accept instead a small free acyl thioester, and no longer requires the acyl carrier protein. The resulting 29-mutant variant is 1000-fold more efficient in the synthesis of the drug simvastatin than the wild-type LovD. This is the first non-patent report of the enzyme currently used for the manufacture of simvastatin, as well as the intermediate evolved variants. Crystal structures and microsecond molecular dynamics simulations revealed the mechanism by which the laboratory-generated mutations free LovD from dependence on protein-protein interactions. Mutations dramatically altered conformational dynamics of the catalytic residues, obviating the need for allosteric modulation by the acyl carrier LovF. PMID:24727900
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Engineering an FMN-based iLOV protein for the detection of arsenic ions.
Ravikumar, Yuvaraj; Nadarajan, Saravanan Prabhu; Lee, Chong-Soon; Yun, Hyungdon
2017-05-15
Over the past few decades, genetically encoded fluorescent proteins have been widely used as efficient probes to explore and investigate the roles of metal ions in biological processes. The discovery of small FMN-based fluorescent proteins, such as iLOV and FbFP, has enabled researchers to exploit these fluorescent reporter proteins for metal-sensing applications. In this study, we report the inherent binding properties of iLOV towards arsenic ions. The fluorescence quenching of iLOV was linearly related to the concentration of arsenic ions, and engineered proteins showed better sensitivity than the wild-type protein. Engineering key residues around the chromophore converted the iLOV protein into a highly sensitive sensor for As 3+ ions. iLOV N468S exhibited an improved binding affinity with a dissociation constant of 1.5 μM. Furthermore, the circular dichroism spectra indicated that the fluorescence quenching mechanism might be related to arsenic-protein complex formation. Thus, the reagentless sensing of arsenic can potentially be exploited to determine intracellular or environmental arsenic using a genetically encoded biosensing approach. Copyright © 2017 Elsevier Inc. All rights reserved.
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Zhao, Xiang; Wang, Yan-Liang; Qiao, Xin-Rong; Wang, Jin; Wang, Lin-Dan; Xu, Chang-Shui; Zhang, Xiao
2013-01-01
Phototropins (phot1 and phot2), the blue light receptors in plants, regulate hypocotyl phototropism in a fluence-dependent manner. Especially under high fluence rates of blue light (HBL), the redundant function mediated by both phot1 and phot2 drastically restricts the understanding of the roles of phot2. Here, systematic analysis of phototropin-related mutants and overexpression transgenic lines revealed that HBL specifically induced a transient increase in cytosolic Ca2+ concentration ([Ca2+]cyt) in Arabidopsis (Arabidopsis thaliana) hypocotyls and that the increase in [Ca2+]cyt was primarily attributed to phot2. Pharmacological and genetic experiments illustrated that HBL-induced Ca2+ increases were modulated differently by phot1 and phot2. Phot2 mediated the HBL-induced increase in [Ca2+]cyt mainly by an inner store-dependent Ca2+-release pathway, not by activating plasma membrane Ca2+ channels. Further analysis showed that the increase in [Ca2+]cyt was possibly responsible for HBL-induced hypocotyl phototropism. An inhibitor of auxin efflux carrier exhibited significant inhibitions of both phototropism and increases in [Ca2+]cyt, which indicates that polar auxin transport is possibly involved in HBL-induced responses. Moreover, PHYTOCHROME KINASE SUBSTRATE1 (PKS1), the phototropin-related signaling element identified, interacted physically with phototropins, auxin efflux carrier PIN-FORMED1 and calcium-binding protein CALMODULIN4, in vitro and in vivo, respectively, and HBL-induced phototropism was impaired in pks multiple mutants, indicating the role of the PKS family in HBL-induced phototropism. Together, these results provide new insights into the functions of phototropins and highlight a potential integration point through which Ca2+ signaling-related HBL modulates hypocotyl phototropic responses. PMID:23674105
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Stowe-Evans, Emily L.; Luesse, Darron R.; Liscum, Emmanuel
2001-01-01
The induction of phototropism in etiolated (dark-grown) seedlings exposed to an unidirectional pulse or extended irradiation with low fluence rate blue light (BL) requires the action of the phototropin (nph1) BL receptor. Although cryptochromes and phytochromes are not required for phototropic induction, these photoreceptors do modulate the magnitude of curvature resulting from phototropin activation. Modulatory increases in the magnitude of phototropic curvature have been termed “enhancement.” Here, we show that phototropic enhancement is primarily a phytochrome A (phyA)-dependent red/far-red-reversible low fluence response. This phyA-dependent response is genetically separable from the basal phototropin-dependent response, as demonstrated by its retention under extended irradiation conditions in the nph4 mutant background, which normally lacks the basal BL-induced response. It is interesting that the nph4 mutants fail to exhibit the basal phototropin-dependent and phyA-dependent enhancement responses under limiting light conditions. Given that NPH4 encodes a transcriptional activator, auxin response factor 7 (ARF7), we hypothesize that the ultimate target(s) of phyA action during the phototropic enhancement response is a rate-limiting ARF-containing transcriptional complex in which the constituent ARFs can vary in identity or activity depending upon the irradiation condition. PMID:11402210
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Sycz, Gabriela; Carrica, Mariela Carmen; Tseng, Tong-Seung; Bogomolni, Roberto A.; Briggs, Winslow R.; Goldbaum, Fernando A.; Paris, Gastón
2015-01-01
Brucella is the causative agent of the zoonotic disease brucellosis, and its success as an intracellular pathogen relies on its ability to adapt to the harsh environmental conditions that it encounters inside the host. The Brucella genome encodes a sensor histidine kinase containing a LOV domain upstream from the kinase, LOVHK, which plays an important role in light-regulated Brucella virulence. In this report we study the intracellular signaling pathway initiated by the light sensor LOVHK using an integrated biochemical and genetic approach. From results of bacterial two-hybrid assays and phosphotransfer experiments we demonstrate that LOVHK functionally interacts with two response regulators: PhyR and LovR, constituting a functional two-component signal-transduction system. LOVHK contributes to the activation of the General Stress Response (GSR) system in Brucella via PhyR, while LovR is proposed to be a phosphate-sink for LOVHK, decreasing its phosphorylation state. We also show that in the absence of LOVHK the expression of the virB operon is down-regulated. In conclusion, our results suggest that LOVHK positively regulates the GSR system in vivo, and has an effect on the expression of the virB operon. The proposed regulatory network suggests a similar role for LOVHK in other microorganisms. PMID:25993430
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Wu, Liang; McGrane, Regina S.; Beattie, Gwyn A.
2013-01-01
ABSTRACT The biological and regulatory roles of photosensory proteins are poorly understood for nonphotosynthetic bacteria. The foliar bacterial pathogen Pseudomonas syringae has three photosensory protein-encoding genes that are predicted to encode the blue-light-sensing LOV (light, oxygen, or voltage) histidine kinase (LOV-HK) and two red/far-red-light-sensing bacteriophytochromes, BphP1 and BphP2. We provide evidence that LOV-HK and BphP1 form an integrated network that regulates swarming motility in response to multiple light wavelengths. The swarming motility of P. syringae B728a deletion mutants indicated that LOV-HK positively regulates swarming motility in response to blue light and BphP1 negatively regulates swarming motility in response to red and far-red light. BphP2 does not detectably regulate swarming motility. The histidine kinase activity of each LOV-HK and BphP1 is required for this regulation based on the loss of complementation upon mutation of residues key to their kinase activity. Surprisingly, mutants lacking both lov and bphP1 were similar in motility to a bphP1 single mutant in blue light, indicating that the loss of bphP1 is epistatic to the loss of lov and also that BphP1 unexpectedly responds to blue light. Moreover, whereas expression of bphP1 did not alter motility under blue light in a bphP1 mutant, it reduced motility in a mutant lacking lov and bphP1, demonstrating that LOV-HK positively regulates motility by suppressing negative regulation by BphP1. These results are the first to show cross talk between the LOV protein and phytochrome signaling pathways in bacteria, and the similarity of this regulatory network to that of photoreceptors in plants suggests a possible common ancestry. PMID:23760465
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Control of flowering time and cold response by a NAC-domain protein in Arabidopsis.
Yoo, So Yeon; Kim, Yunhee; Kim, Soo Young; Lee, Jong Seob; Ahn, Ji Hoon
2007-07-25
Plants must integrate complex signals from environmental and endogenous cues to fine-tune the timing of flowering. Low temperature is one of the most common environmental stresses that affect flowering time; however, molecular mechanisms underlying the cold temperature regulation of flowering time are not fully understood. We report the identification of a novel regulator, LONG VEGETATIVE PHASE 1 (LOV1), that controls flowering time and cold response. An Arabidopsis mutant, longvegetative phase 1-1D (lov1-1D) showing the late-flowering phenotype, was isolated by activation tagging screening. Subsequent analyses demonstrated that the phenotype of the mutant resulted from the overexpression of a NAC-domain protein gene (At2g02450). Both gain- and loss-of-function alleles of LOV1 affected flowering time predominantly under long-day but not short-day conditions, suggesting that LOV1 may act within the photoperiod pathway. The expression of CONSTANS (CO), a floral promoter, was affected by LOV1 level, suggesting that LOV1 controls flowering time by negatively regulating CO expression. The epistatic relationship between CO and LOV1 was consistent with this proposed regulatory pathway. Physiological analyses to elucidate upstream signalling pathways revealed that LOV1 regulates the cold response in plants. Loss of LOV1 function resulted in hypersensitivity to cold temperature, whereas a gain-of-function allele conferred cold tolerance. The freezing tolerance was accompanied by upregulation of cold response genes, COLD-REGULATED 15A (COR15A) and COLD INDUCED 1 (KIN1) without affecting expression of the C-repeat-binding factor/dehydration responsive element-binding factor 1 (CBF/DREB1) family of genes. Our study shows that LOV1 functions as a floral repressor that negatively regulates CO expression under long-day conditions and acts as a common regulator of two intersecting pathways that regulate flowering time and the cold response, respectively. Our results suggest an
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PHYTOCHROME KINASE SUBSTRATE 1 is a phototropin 1 binding protein required for phototropism.
Lariguet, Patricia; Schepens, Isabelle; Hodgson, Daniel; Pedmale, Ullas V; Trevisan, Martine; Kami, Chitose; de Carbonnel, Matthieu; Alonso, José M; Ecker, Joseph R; Liscum, Emmanuel; Fankhauser, Christian
2006-06-27
Phototropism, or plant growth in response to unidirectional light, is an adaptive response of crucial importance. Lateral differences in low fluence rates of blue light are detected by phototropin 1 (phot1) in Arabidopsis. Only NONPHOTOTROPIC HYPOCOTYL 3 (NPH3) and root phototropism 2, both belonging to the same family of proteins, have been previously identified as phototropin-interacting signal transducers involved in phototropism. PHYTOCHROME KINASE SUBSTRATE (PKS) 1 and PKS2 are two phytochrome signaling components belonging to a small gene family in Arabidopsis (PKS1-PKS4). The strong enhancement of PKS1 expression by blue light and its light induction in the elongation zone of the hypocotyl prompted us to study the function of this gene family during phototropism. Photobiological experiments show that the PKS proteins are critical for hypocotyl phototropism. Furthermore, PKS1 interacts with phot1 and NPH3 in vivo at the plasma membrane and in vitro, indicating that the PKS proteins may function directly with phot1 and NPH3 to mediate phototropism. The phytochromes are known to influence phototropism but the mechanism involved is still unclear. We show that PKS1 induction by a pulse of blue light is phytochrome A-dependent, suggesting that the PKS proteins may provide a molecular link between these two photoreceptor families.
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PHYTOCHROME KINASE SUBSTRATE 1 is a phototropin 1 binding protein required for phototropism
Lariguet, Patricia; Schepens, Isabelle; Hodgson, Daniel; Pedmale, Ullas V.; Trevisan, Martine; Kami, Chitose; de Carbonnel, Matthieu; Alonso, José M.; Ecker, Joseph R.; Liscum, Emmanuel; Fankhauser, Christian
2006-01-01
Phototropism, or plant growth in response to unidirectional light, is an adaptive response of crucial importance. Lateral differences in low fluence rates of blue light are detected by phototropin 1 (phot1) in Arabidopsis. Only NONPHOTOTROPIC HYPOCOTYL 3 (NPH3) and root phototropism 2, both belonging to the same family of proteins, have been previously identified as phototropin-interacting signal transducers involved in phototropism. PHYTOCHROME KINASE SUBSTRATE (PKS) 1 and PKS2 are two phytochrome signaling components belonging to a small gene family in Arabidopsis (PKS1–PKS4). The strong enhancement of PKS1 expression by blue light and its light induction in the elongation zone of the hypocotyl prompted us to study the function of this gene family during phototropism. Photobiological experiments show that the PKS proteins are critical for hypocotyl phototropism. Furthermore, PKS1 interacts with phot1 and NPH3 in vivo at the plasma membrane and in vitro, indicating that the PKS proteins may function directly with phot1 and NPH3 to mediate phototropism. The phytochromes are known to influence phototropism but the mechanism involved is still unclear. We show that PKS1 induction by a pulse of blue light is phytochrome A-dependent, suggesting that the PKS proteins may provide a molecular link between these two photoreceptor families. PMID:16777956
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Diversity of bacteria in surface ice of Austre Lovénbreen glacier, Svalbard.
Zeng, Yin-Xin; Yan, Ming; Yu, Yong; Li, Hui-Rong; He, Jian-Feng; Sun, Kun; Zhang, Fang
2013-05-01
Two 16S rRNA gene clone libraries Cores 1U and 2U were constructed using two ice core samples collected from Austre Lovénbreen glacier in Svalbard. The two libraries yielded a total of 262 clones belonging to 59 phylotypes. Sequences fell into 10 major lineages of the domain Bacteria, including Proteobacteria (alpha, beta, gamma and delta subdivisions), Bacteroidetes, Actinobacteria, Firmicutes, Acidobacteria, Deinococcus-Thermus, Chloroflexi, Planctomycetes, Cyanobacteria and candidate division TM7. Among them, Bacteroidetes, Actinobacteria, Alphaproteobacteria and Cyanobacteria were most abundant. UniFrac data showed no significant differences in community composition between the two ice cores. A total of nineteen bacterial strains from the genera Pseudoalteromonas and Psychrobacter were isolated from the ice cores. Phylogenetic and phenotypic analyses revealed a close relationship between the ice core isolates and bacteria in marine environments, indicating a wide distribution of some bacterial phylotypes in both terrestrial and marine ecosystems.
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Development of a Synthetic Switch to Control Protein Stability in Eukaryotic Cells with Light.
Taxis, Christof
2017-01-01
In eukaryotic cells, virtually all regulatory processes are influenced by proteolysis. Thus, synthetic control of protein stability is a powerful approach to influence cellular behavior. To achieve this, selected target proteins are modified with a conditional degradation sequence (degron) that responds to a distinct signal. For development of a synthetic degron, an appropriate sensor domain is fused with a degron such that activity of the degron is under control of the sensor. This chapter describes the development of a light-activated, synthetic degron in the model organism Saccharomyces cerevisiae. This photosensitive degron module is composed of the light-oxygen-voltage (LOV) 2 photoreceptor domain of Arabidopsis thaliana phototropin 1 and a degron derived from murine ornithine decarboxylase (ODC). Excitation of the photoreceptor with blue light induces a conformational change that leads to exposure and activation of the degron. Subsequently, the protein is targeted for degradation by the proteasome. Here, the strategy for degron module development and optimization is described in detail together with experimental aspects, which were pivotal for successful implementation of light-controlled proteolysis. The engineering of the photosensitive degron (psd) module may well serve as a blueprint for future development of sophisticated synthetic switches.
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Lariguet, Patricia; Fankhauser, Christian
2004-12-01
How developing seedlings integrate gravitropic and phototropic stimuli to determine their direction of growth is poorly understood. In this study we tested whether blue light influences hypocotyl gravitropism in Arabidopsis. Phototropin1 (phot1) triggers phototropism under low fluence rates of blue light but, at least in the dark, has no effect on gravitropism. By analyzing the growth orientation of phototropism-deficient seedlings in response to gravitropic and phototropic stimulations we show that blue light not only triggers phototropism but also represses hypocotyl gravitropism. At low fluence rates of blue light phot1 mutants were agravitropic. In contrast, phyAphot1 double mutants grew exclusively according to gravity demonstrating that phytochrome A (phyA) is necessary to inhibit gravitropism. Analyses of phot1cry1cry2 triple mutants indicate that cryptochromes play a minor role in this response. Thus the optimal growth orientation of hypocotyls is determined by the action of phyA-suppressing gravitropism and the phototropin-triggering phototropism. It has long been known that phytochromes promote phototropism but the mechanism involved is still unknown. Our data show that by inhibiting gravitropism phyA acts as a positive regulator of phototropism.
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Xu, Bin; Sathitsuksanoh, Noppadon; Tang, Yuhong; Udvardi, Michael K; Zhang, Ji-Yi; Shen, Zhengxing; Balota, Maria; Harich, Kim; Zhang, Percival Y-H; Zhao, Bingyu
2012-01-01
Switchgrass (Panicum virgatum L.) is a prime candidate crop for biofuel feedstock production in the United States. As it is a self-incompatible polyploid perennial species, breeding elite and stable switchgrass cultivars with traditional breeding methods is very challenging. Translational genomics may contribute significantly to the genetic improvement of switchgrass, especially for the incorporation of elite traits that are absent in natural switchgrass populations. In this study, we constitutively expressed an Arabidopsis NAC transcriptional factor gene, LONG VEGETATIVE PHASE ONE (AtLOV1), in switchgrass. Overexpression of AtLOV1 in switchgrass caused the plants to have a smaller leaf angle by changing the morphology and organization of epidermal cells in the leaf collar region. Also, overexpression of AtLOV1 altered the lignin content and the monolignol composition of cell walls, and caused delayed flowering time. Global gene-expression analysis of the transgenic plants revealed an array of responding genes with predicted functions in plant development, cell wall biosynthesis, and flowering. To our knowledge, this is the first report of a single ectopically expressed transcription factor altering the leaf angle, cell wall composition, and flowering time of switchgrass, therefore demonstrating the potential advantage of translational genomics for the genetic improvement of this crop.
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Zoltowski, Brian D; Nash, Abigail I; Gardner, Kevin H
2011-10-18
Light, oxygen, voltage (LOV) domains utilize a conserved blue light-dependent mechanism to control a diverse array of effector domains in biological and engineered proteins. Variations in the kinetics and efficiency of LOV photochemistry fine-tune various aspects of the photic response. Characterization of the kinetics of a key aspect of this photochemical mechanism in EL222, a blue light responsive DNA binding protein from Erythrobacter litoralis HTCC2594, reveals unique non-Arrhenius behavior in the rate of dark-state cleavage of the photochemically generated adduct. Sequence analysis and mutagenesis studies establish that this effect stems from a Gln to Ala mutation unique to EL222 and homologous proteins from marine bacteria. Kinetic and spectroscopic analyses reveal that hydrogen bonding interactions between the FMN N1, O2, and ribityl hydroxyls and the surrounding protein regulate photocycle kinetics and stabilize the LOV active site from temperature-induced alteration in local structure. Substitution of residues interacting with the N1-O2 locus modulates adduct stability, structural flexibility, and sequestration of the active site from bulk solvent without perturbation of light-activated DNA binding. Together, these variants link non-Arrhenius behavior to specific alteration of an H-bonding network, while affording tunability of photocycle kinetics. © 2011 American Chemical Society
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ERIC Educational Resources Information Center
Kim, Minsung; Ryu, Jae-Myong
2014-01-01
This study introduces the Listening to Others' Voices (LOV) project, an empowering strategy in geography education. This research aims to create a dataset detailing the perspectives of negatively stereotyped countries with respect to how their countries are portrayed in geography textbooks and to investigate the pedagogical effects of the LOV…
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Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto
2016-03-27
In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Folta, Kevin M; Lieg, Erin J; Durham, Tessa; Spalding, Edgar P
2003-12-01
The phototropin photoreceptors transduce blue-light signals into several physiological and developmental responses in plants. A transient rise in cytoplasmic calcium (Ca2+) that begins within seconds of phototropin 1 (phot1) excitation is believed to be an important element in the transduction pathways leading to one or more of the phot1-dependent responses. The goal of the present work was to determine whether the Ca2+ response was necessary for (a). the inhibition of hypocotyl elongation that develops within minutes of the irradiation, and (b). hypocotyl phototropism (curved growth of the stem in response to asymmetric illumination). After determining that pulses of light delivering photon fluences of between 1 and 1000 micromol m-2 induced growth inhibition mediated by phot1 without significant interference from other photosensory pathways, the effect of blocking the Ca2+ rise was assessed. Treatment of seedlings with a Ca2+ chelator prevented the rise in cytoplasmic Ca2+ and prevented phot1-mediated growth inhibition. However, the same chelator treatment did not impair phot1-mediated phototropism. Thus, it appears that the early, transient rise in cytoplasmic Ca2+ is an important intermediary process in at least one but not all phot1-signaling pathways.
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Kagawa, Takatoshi; Kimura, Mitsuhiro; Wada, Masamitsu
2009-10-01
Phototropin family photoreceptors, phot1 and phot2, in Arabidopsis thaliana control the blue light (BL)-mediated phototropic responses of the hypocotyl, chloroplast relocation movement and stomatal opening. Phototropic responses in dark-grown tissues have been well studied but those in de-etiolated green plants are not well understood. Here, we analyzed phototropic responses of inflorescence stems and petioles of wild-type and phototropin mutant plants of A. thaliana. Similar to the results obtained from dark-grown seedlings, inflorescence stems and petioles in wild-type and phot2 mutant plants showed phototropic bending towards low fluence BL, while in phot1 mutant plants, a high fluence rate of BL was required. phot1 phot2 double mutant plants did not show any phototropic responses even under very high fluence rates of BL. We further studied the photoreceptive sites for phototropic responses of stems and petioles by partial tissue irradiation. The whole part of the inflorescence stem is sensitive to BL and shows phototropism, but in the petiole only the irradiated abaxial side is sensitive. Similar to dark-grown etiolated seedlings, phot1 plays a major role in phototropic responses under weak light, but phot2 functions under high fluence rate conditions in green plants.
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Folta, Kevin M.; Lieg, Erin J.; Durham, Tessa; Spalding, Edgar P.
2003-01-01
The phototropin photoreceptors transduce blue-light signals into several physiological and developmental responses in plants. A transient rise in cytoplasmic calcium (Ca2+) that begins within seconds of phototropin 1 (phot1) excitation is believed to be an important element in the transduction pathways leading to one or more of the phot1-dependent responses. The goal of the present work was to determine whether the Ca2+ response was necessary for (a) the inhibition of hypocotyl elongation that develops within minutes of the irradiation, and (b) hypocotyl phototropism (curved growth of the stem in response to asymmetric illumination). After determining that pulses of light delivering photon fluences of between 1 and 1,000 μmol m-2 induced growth inhibition mediated by phot1 without significant interference from other photosensory pathways, the effect of blocking the Ca2+ rise was assessed. Treatment of seedlings with a Ca2+ chelator prevented the rise in cytoplasmic Ca2+ and prevented phot1-mediated growth inhibition. However, the same chelator treatment did not impair phot1-mediated phototropism. Thus, it appears that the early, transient rise in cytoplasmic Ca2+ is an important intermediary process in at least one but not all phot1-signaling pathways. PMID:14645723
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Dimeric Structure of the Blue Light Sensor Protein Photozipper in the Active State.
Ozeki, Kohei; Tsukuno, Hiroyuki; Nagashima, Hiroki; Hisatomi, Osamu; Mino, Hiroyuki
2018-02-06
The light oxygen voltage-sensing (LOV) domain plays a crucial role in blue light (BL) sensing in plants and microorganisms. LOV domains are usually associated with the effector domains and regulate the activities of effector domains in a BL-dependent manner. Photozipper (PZ) is monomeric in the dark state. BL induces reversible dimerization of PZ and subsequently increases its affinity for the target DNA sequence. In this study, we report the analyses of PZ by pulsed electron-electron double resonance (PELDOR). The neutral flavin radical was formed by BL illumination in the presence of dithiothreitol in the LOV-C254S (without the bZIP domain) and PZ-C254S mutants, where the cysteine residue responsible for adduct formation was replaced with serine. The magnetic dipole interactions of 3 MHz between the neutral radicals were detected in both LOV-C254S and PZ-C254S, indicating that these mutants are dimeric in the radical state. The PELDOR simulation showed that the distance between the radical pair is close to that estimated from the dimeric crystal structure in the "light state" [Heintz, U., and Schlichting, I. (2016) eLife 5, e11860], suggesting that in the radical state, LOV domains in PZ-C254S form a dimer similar to that of LOV-C254S, which lacks the bZIP domain.
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Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations
NASA Astrophysics Data System (ADS)
Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng
2017-04-01
VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states.
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Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations
Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng
2017-01-01
VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states. PMID:28425502
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Intramolecular co-action of two independent photosensory modules in the fern phytochrome 3.
Kanegae, Takeshi
2015-01-01
Fern phytochrome3/neochrome1 (phy3/neo1) is a chimeric photoreceptor composed of a phytochrome-chromophore binding domain and an almost full-length phototropin. phy3 thus contains two different light-sensing modules; a red/far-red light receptor phytochrome and a blue light receptor phototropin. phy3 induces both red light- and blue light-dependent phototropism in phototropin-deficient Arabidopsis thaliana (phot1 phot2) seedlings. The red-light response is dependent on the phytochrome module of phy3, and the blue-light response is dependent on the phototropin module. We recently showed that both the phototropin-sensing module and the phytochrome-sensing module mediate the blue light-dependent phototropic response. Particularly under low-light conditions, these two light-sensing modules cooperate to induce the blue light-dependent phototropic response. This intramolecular co-action of two independent light-sensing modules in phy3 enhances light sensitivity, and perhaps allowed ferns to adapt to the low-light canopy conditions present in angiosperm forests.
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Suetsugu, Noriyuki; Takemiya, Atsushi; Kong, Sam-Geun; Higa, Takeshi; Komatsu, Aino; Shimazaki, Ken-Ichiro; Kohchi, Takayuki; Wada, Masamitsu
2016-09-13
In green plants, the blue light receptor kinase phototropin mediates various photomovements and developmental responses, such as phototropism, chloroplast photorelocation movements (accumulation and avoidance), stomatal opening, and leaf flattening, which facilitate photosynthesis. In Arabidopsis, two phototropins (phot1 and phot2) redundantly mediate these responses. Two phototropin-interacting proteins, NONPHOTOTROPIC HYPOCOTYL 3 (NPH3) and ROOT PHOTOTROPISM 2 (RPT2), which belong to the NPH3/RPT2-like (NRL) family of BTB (broad complex, tramtrack, and bric à brac) domain proteins, mediate phototropism and leaf flattening. However, the roles of NRL proteins in chloroplast photorelocation movement remain to be determined. Here, we show that another phototropin-interacting NRL protein, NRL PROTEIN FOR CHLOROPLAST MOVEMENT 1 (NCH1), and RPT2 redundantly mediate the chloroplast accumulation response but not the avoidance response. NPH3, RPT2, and NCH1 are not involved in the chloroplast avoidance response or stomatal opening. In the liverwort Marchantia polymorpha, the NCH1 ortholog, MpNCH1, is essential for the chloroplast accumulation response but not the avoidance response, indicating that the regulation of the phototropin-mediated chloroplast accumulation response by RPT2/NCH1 is conserved in land plants. Thus, the NRL protein combination could determine the specificity of diverse phototropin-mediated responses.
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Automation of ⁹⁹Tc extraction by LOV prior ICP-MS detection: application to environmental samples.
Rodríguez, Rogelio; Leal, Luz; Miranda, Silvia; Ferrer, Laura; Avivar, Jessica; García, Ariel; Cerdà, Víctor
2015-02-01
A new, fast, automated and inexpensive sample pre-treatment method for (99)Tc determination by inductively coupled plasma-mass spectrometry (ICP-MS) detection is presented. The miniaturized approach is based on a lab-on-valve (LOV) system, allowing automatic separation and preconcentration of (99)Tc. Selectivity is provided by the solid phase extraction system used (TEVA resin) which retains selectively pertechnetate ion in diluted nitric acid solution. The proposed system has some advantages such as minimization of sample handling, reduction of reagents volume, improvement of intermediate precision and sample throughput, offering a significant decrease of both time and cost per analysis in comparison to other flow techniques and batch methods. The proposed LOV system has been successfully applied to different samples of environmental interest (water and soil) with satisfactory recoveries, between 94% and 98%. The detection limit (LOD) of the developed method is 0.005 ng. The high durability of the resin and its low amount (32 mg), its good intermediate precision (RSD 3.8%) and repeatability (RSD 2%) and its high extraction frequency (up to 5 h(-1)) makes this method an inexpensive, high precision and fast tool for monitoring (99)Tc in environmental samples. Copyright © 2014 Elsevier B.V. All rights reserved.
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Buchta, V; Spacek, J
2004-01-01
To evaluate the microbiological findings in the patients with the recurrent vulvovaginal candidiasis (RVVC) with a focus on the establishment of fungal etiology and its in vitro antifungal susceptibility. Retrospective clinical and laboratory study. Department of Obstetrics and Gynecology, Medical Faculty Hradec Králové, Charles University, Prague, Department of Clinical Microbiology, Medical Faculty Hradec Králové, Charles University, Prague, Department of Biological and Medical Sciences, Faculty of Pharmacy Hradec Králové, Charles University, Prague. An analysis of clinical and anamnestic data in outpatients of the Dept. of Obstetrics and Gynecology and the laboratory data from the microbiological examinations performed in the Dept. of Clinical Microbiology from 1995 to 2002. Candida albicans accounted for 88.5% of the episodes of RVVC in the setting of 56 patients. Non-albicans Candida species were represented especially by C. glabrata (4.9%) and C. krusei (3.1%). There were no considerable differences between the spectrum of RVVC and acute vulvovaginal candidiasis with the exception of Saccharomyces cerevisiae (0.7% in RVVC vs. 3.7% in acute VVC). Mycological findings in 61 (20.5%) samples were accompanied by bacterial microbiota with the predominance of Streptococcus agalactiae (n = 15) and Gardnerella vaginalis (n = 9). Decreased antifungal susceptibility determined by the disk test was observed in the strains of C. glabrata, C. krusei and S. cerevisiae, the other yeast isolates being susceptible to all ten antifungal drugs tested. The microbiological examination was decisive for the establishment of the diagnosis of RVVC in most cases. The most frequent etiological agents responsible for the attacks of RVVC as well as for acute vulvovaginal candidiasis was C. albicans, which was generally susceptible to antifungal drugs.
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Kadomura-Ishikawa, Yasuko; Miyawaki, Katsuyuki; Noji, Sumihare; Takahashi, Akira
2013-11-01
Anthocyanins are widespread, essential secondary metabolites in higher plants during color development in certain flowers and fruits. In strawberries, anthocyanins are also key contributors to fruit antioxidant capacity and nutritional value. However, the effects of different light qualities on anthocyanin accumulation in strawberry (Fragaria x ananassa, cv. Sachinoka) fruits remain elusive. In the present study, we showed the most efficient increase in anthocyanin content occurred by blue light irradiation. Light sensing at the molecular level was investigated by isolation of two phototropin (FaPHOT1 and FaPHOT2), two cryptochrome (FaCRY1 and FaCRY2), and two phytochrome (FaPHYA and FaPHYB) homologs. Expression analysis revealed only FaPHOT2 transcripts markedly increased depending on fruit developmental stage, and a corresponding increase in anthocyanin content was detected. FaPHOT2 knockdown resulted in decreased anthocyanin content; however, overexpression increased anthocyanin content. These findings suggested blue light induced anthocyanin accumulation, and FaPHOT2 may play a role in sensing blue light, and mediating anthocyanin biosynthesis in strawberry fruits. This is the first report to find a relationship between visible light sensing, and color development in strawberry fruits.
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Functional characterization of Arabidopsis phototropin 1 in the hypocotyl apex.
Sullivan, Stuart; Takemiya, Atsushi; Kharshiing, Eros; Cloix, Catherine; Shimazaki, Ken-Ichiro; Christie, John M
2016-12-01
Phototropin (phot1) is a blue light-activated plasma membrane-associated kinase that acts as the principal photoreceptor for shoot phototropism in Arabidopsis in conjunction with the signalling component Non-Phototropic Hypocotyl 3 (NPH3). PHOT1 is uniformly expressed throughout the Arabidopsis hypocotyl, yet decapitation experiments have localized the site of light perception to the upper hypocotyl. This prompted us to investigate in more detail the functional role of the hypocotyl apex, and the regions surrounding it, in establishing phototropism. We used a non-invasive approach where PHOT1-GFP (P1-GFP) expression was targeted to the hypocotyl apex of the phot-deficient mutant using the promoters of CUP-SHAPED COTYLEDON 3 (CUC3) and AINTEGUMENTA (ANT). Expression of CUC3::P1-GFP was clearly visible at the hypocotyl apex, with weaker expression in the cotyledons, whereas ANT::P1-GFP was specifically targeted to the developing leaves. Both lines showed impaired curvature to 0.005 μmol m -2 sec -1 unilateral blue light, indicating that regions below the apical meristem are necessary for phototropism. Curvature was however apparent at higher fluence rates. Moreover, CUC3::P1-GFP partially or fully complemented petiole positioning, leaf flattening and chloroplast accumulation, but not stomatal opening. Yet, tissue analysis of NPH3 de-phosphorylation showed that CUC3::P1-GFP and ANT::P1-GFP mis-express very low levels of phot1 that likely account for this responsiveness. Our spatial targeting approach therefore excludes the hypocotyl apex as the site for light perception for phototropism and shows that phot1-mediated NPH3 de-phosphorylation is tissue autonomous and occurs more prominently in the basal hypocotyl. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.
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2018-01-01
ABSTRACT The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria. PMID:29789370
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Rodríguez, Rogelio; Borràs, Antoni; Leal, Luz; Cerdà, Víctor; Ferrer, Laura
2016-03-10
An automatic system based on multisyringe flow injection analysis (MSFIA) and lab-on-valve (LOV) flow techniques for separation and pre-concentration of (226)Ra from drinking and natural water samples has been developed. The analytical protocol combines two different procedures: the Ra adsorption on MnO2 and the BaSO4 co-precipitation, achieving more selectivity especially in water samples with low radium levels. Radium is adsorbed on MnO2 deposited on macroporous of bead cellulose. Then, it is eluted with hydroxylamine to transform insoluble MnO2 to soluble Mn(II) thus freeing Ra, which is then coprecipitated with BaSO4. The (226)Ra can be directly detected in off-line mode using a low background proportional counter (LBPC) or through a liquid scintillation counter (LSC), after performing an on-line coprecipitate dissolution. Thus, the versatility of the proposed system allows the selection of the radiometric detection technique depending on the detector availability or the required response efficiency (sample number vs. response time and limit of detection). The MSFIA-LOV system improves the precision (1.7% RSD), and the extraction frequency (up to 3 h(-1)). Besides, it has been satisfactorily applied to different types of water matrices (tap, mineral, well and sea water). The (226)Ra minimum detectable activities (LSC: 0.004 Bq L(-1); LBPC: 0.02 Bq L(-1)) attained by this system allow to reach the guidance values proposed by the relevant international agencies e.g. WHO, EPA and EC. Copyright © 2016 Elsevier B.V. All rights reserved.
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Phototropin 1 and dim-blue light modulate the red light de-etiolation response.
Wang, Yihai; M Folta, Kevin
2014-01-01
Light signals regulate seedling morphological changes during de-etiolation through the coordinated actions of multiple light-sensing pathways. Previously we have shown that red-light-induced hypocotyl growth inhibition can be reversed by addition of dim blue light through the action of phototropin 1 (phot1). Here we further examine the fluence-rate relationships of this blue light effect in short-term (hours) and long-term (days) hypocotyl growth assays. The red stem-growth inhibition and blue promotion is a low-fluence rate response, and blue light delays or attenuates both the red light and far-red light responses. These de-etiolation responses include blue light reversal of red or far-red induced apical hook opening. This response also requires phot1. Cryptochromes (cry1 and cry2) are activated by higher blue light fluence-rates and override phot1's influence on hypocotyl growth promotion. Exogenous application of auxin transport inhibitor naphthylphthalamic acid abolished the blue light stem growth promotion in both hypocotyl growth and hook opening. Results from the genetic tests of this blue light effect in auxin transporter mutants, as well as phytochrome kinase substrate mutants indicated that aux1 may play a role in blue light reversal of red light response. Together, the phot1-mediated adjustment of phytochrome-regulated photomorphogenic events is most robust in dim blue light conditions and is likely modulated by auxin transport through its transporters.
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Phototropin 1 and dim-blue light modulate the red light de-etiolation response
Wang, Yihai; M Folta, Kevin
2014-01-01
Light signals regulate seedling morphological changes during de-etiolation through the coordinated actions of multiple light-sensing pathways. Previously we have shown that red-light-induced hypocotyl growth inhibition can be reversed by addition of dim blue light through the action of phototropin 1 (phot1). Here we further examine the fluence-rate relationships of this blue light effect in short-term (hours) and long-term (days) hypocotyl growth assays. The red stem-growth inhibition and blue promotion is a low-fluence rate response, and blue light delays or attenuates both the red light and far-red light responses. These de-etiolation responses include blue light reversal of red or far-red induced apical hook opening. This response also requires phot1. Cryptochromes (cry1 and cry2) are activated by higher blue light fluence-rates and override phot1's influence on hypocotyl growth promotion. Exogenous application of auxin transport inhibitor naphthylphthalamic acid abolished the blue light stem growth promotion in both hypocotyl growth and hook opening. Results from the genetic tests of this blue light effect in auxin transporter mutants, as well as phytochrome kinase substrate mutants indicated that aux1 may play a role in blue light reversal of red light response. Together, the phot1-mediated adjustment of phytochrome-regulated photomorphogenic events is most robust in dim blue light conditions and is likely modulated by auxin transport through its transporters. PMID:25482790
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Light responses in Photoperiodism in Arabidopsis thaliana
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anthony R. Cashmore
2006-08-01
LOV domains. It is this cysteine residue that forms a covalent adduct with the bound flavin in the photocycle of PHOT1 and FKF1. In the mutant ADO1 this cysteine is replaced by an alanine. We argue that if ADO1 functions as a photoreceptor in a similar fashion to PHOT1, then this mutant ADO1 should not be able to rescue the altered circadian phenotype of ado1 mutant plants. We find under white light, that indeed this is the case. Experiments underway are aimed at determining if the altered circadian phenotype under blue and red light are similarly unable to be rescued by the mutant gene, and we are performing similar experiments under red light with respect to the defect in hypocotyl elongation. The results from these experiments will likely support the hypothesis that ADO1 functions as a blue light photoreceptor, and they will address the question concerning whether or not the altered properties of the ado1 mutant under red light are also a reflection of this photoreceptor function. References. Briggs, W. R., Beck, C. F., Cashmore, A. R., Christie, J. M., Hughes, J., Jarillo, J. A., Kagawa, T., Kanegae, H., Liscum, E., Nagatani, A., et al. (2001). The phototropin family of photoreceptors. Plant Cell 13, 993-997. Christie, J. M., Reymond, P., Powell, G. K., Bernasconi, P., Raibekas, A. A., Liscum, E., and Briggs, W. R. (1998). Arabidopsis NPH1: A flavoprotein with the properties of a photoreceptor for phototropism. Science 282, 1698-1701. Froehlich, A. C., Liu, Y., Loros, J. J., and Dunlap, J. C. (2002). White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter. Science 297, 815-819. Imaizumi, T., Tran, H. G., Swartz, T. E., Briggs, W. R., and Kay, S. A. (2003). FKF1 is essential for photoperiodic-specific light signalling in Arabidopsis. Nature 426, 302-306. Jarillo, J. A., Capel, J., Tang, R.-H., Yang, H.-Q., Alonso, J. M., Ecker, J. R., and Cashmore, A. R. (2001a). An Arabidopsis circadian clock component interacts with both CRY1 and
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Guntas, Gurkan; Hallett, Ryan A.; Zimmerman, Seth P.; ...
2014-12-22
The discovery of light-inducible protein–protein interactions has allowed for the spatial and temporal control of a variety of biological processes. To be effective, a photodimerizer should have several characteristics: it should show a large change in binding affinity upon light stimulation, it should not cross-react with other molecules in the cell, and it should be easily used in a variety of organisms to recruit proteins of interest to each other. In this study, to create a switch that meets these criteria we have embedded the bacterial SsrA peptide in the C-terminal helix of a naturally occurring photoswitch, the light-oxygen-voltage 2more » (LOV2) domain from Avena sativa. In the dark the SsrA peptide is sterically blocked from binding its natural binding partner, SspB. When activated with blue light, the C-terminal helix of the LOV2 domain undocks from the protein, allowing the SsrA peptide to bind SspB. Without optimization, the switch exhibited a twofold change in binding affinity for SspB with light stimulation. Here, we describe the use of computational protein design, phage display, and high-throughput binding assays to create an improved light inducible dimer (iLID) that changes its affinity for SspB by over 50-fold with light stimulation. A crystal structure of iLID shows a critical interaction between the surface of the LOV2 domain and a phenylalanine engineered to more tightly pin the SsrA peptide against the LOV2 domain in the dark. Finally, we demonstrate the functional utility of the switch through light-mediated subcellular localization in mammalian cell culture and reversible control of small GTPase signaling.« less
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Phototropism: translating light into directional growth.
Hohm, Tim; Preuten, Tobias; Fankhauser, Christian
2013-01-01
Phototropism allows plants to align their photosynthetic tissues with incoming light. The direction of incident light is sensed by the phototropin family of blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light-activated protein kinases. The kinase activity of phototropins and phosphorylation of residues in the activation loop of their kinase domains are essential for the phototropic response. These initial steps trigger the formation of the auxin gradient across the hypocotyl that leads to asymmetric growth. The molecular events between photoreceptor activation and the growth response are only starting to be elucidated. In this review, we discuss the major steps leading from light perception to directional growth concentrating on Arabidopsis. In addition, we highlight links that connect these different steps enabling the phototropic response.
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Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.
Smart, Ashley D; Pache, Roland A; Thomsen, Nathan D; Kortemme, Tanja; Davis, Graeme W; Wells, James A
2017-09-26
The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV-induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms.
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Preuten, Tobias; Blackwood, Lisa; Christie, John M; Fankhauser, Christian
2015-05-01
The phototropin 1 (phot1) blue light receptor mediates a number of adaptive responses, including phototropism, that generally serve to optimize photosynthetic capacity. Phot1 is a plasma membrane-associated protein, but upon irradiation, a fraction is internalized into the cytoplasm. Although this phenomenon has been reported for more than a decade, its biological significance remains elusive. Here, we use a genetic approach to revisit the prevalent hypotheses regarding the functional importance of receptor internalization. Transgenic plants expressing lipidated versions of phot1 that are permanently anchored to the plasma membrane were used to analyse the effect of internalization on receptor turnover, phototropism and other phot1-mediated responses. Myristoylation and farnesylation effectively prevented phot1 internalization. Both modified photoreceptors were found to be fully functional in Arabidopsis, rescuing phototropism and all other phot1-mediated responses tested. Light-mediated phot1 turnover occurred as in the native receptor. Furthermore, our work does not provide any evidence of a role of phot1 internalization in the attenuation of receptor signalling during phototropism. Our results demonstrate that phot1 signalling is initiated at the plasma membrane. They furthermore indicate that release of phot1 into the cytosol is not linked to receptor turnover or desensitization. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
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Microclimate Evaluation of the Hradec Králové City using HUMIDEX
NASA Astrophysics Data System (ADS)
Rožnovský, Jaroslav; Litschmann, Tomáš; Středová, Hana; Středa, Tomáš; Salaš, Petr; Horká, Marie
2017-09-01
Urban environment differs from the surrounding landscape in terms of the values of meteorological parameters. This is often referred to as the urban heat island (UHI), which in simple terms means higher air temperatures in cities. The cause of these changes lies in the different active surfaces in cities, which subsequently results in a different radiation balance. The higher temperatures, however, also affect the living conditions in the city and during very high temperature periods can have negative effects on the health of the city inhabitants. The results presented in this paper are based on measurements taken over several years at locations near Hradec Králové, which is surrounded by different surface areas. Environment analysis was performed using the Humidex index. The obtained results show that replacing green areas with built-up areas affects temperatures in the city, when air temperatures are very high they significantly increase the discomfort of the inhabitants. Differences in the frequency of discomfort levels are observed especially during periods of high temperatures, at lower temperatures these differences are not significant. Higher frequencies of discomfort are observed at locations with artificial surfaces (asphalt, cobblestones, concrete) and in closed spaces. In contrast, locations with lots of green areas almost always have the value of this index lower or more balanced. The results should therefore be a valid argument for maintaining and extending green areas in cities.
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Roberts, Diana; Pedmale, Ullas V; Morrow, Johanna; Sachdev, Shrikesh; Lechner, Esther; Tang, Xiaobo; Zheng, Ning; Hannink, Mark; Genschik, Pascal; Liscum, Emmanuel
2011-10-01
Plant phototropism is an adaptive response to changes in light direction, quantity, and quality that results in optimization of photosynthetic light harvesting, as well as water and nutrient acquisition. Though several components of the phototropic signal response pathway have been identified in recent years, including the blue light (BL) receptors phototropin1 (phot1) and phot2, much remains unknown. Here, we show that the phot1-interacting protein NONPHOTOTROPIC HYPOCOTYL3 (NPH3) functions as a substrate adapter in a CULLIN3-based E3 ubiquitin ligase, CRL3(NPH3). Under low-intensity BL, CRL3(NPH3) mediates the mono/multiubiquitination of phot1, likely marking it for clathrin-dependent internalization from the plasma membrane. In high-intensity BL, phot1 is both mono/multi- and polyubiquitinated by CRL3(NPH3), with the latter event targeting phot1 for 26S proteasome-mediated degradation. Polyubiquitination and subsequent degradation of phot1 under high-intensity BL likely represent means of receptor desensitization, while mono/multiubiquitination-stimulated internalization of phot1 may be coupled to BL-induced relocalization of hormone (auxin) transporters.
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Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation
Rivera-Cancel, Giomar; Ko, Wen-huang; Tomchick, Diana R.; ...
2014-12-02
Although histidine kinases (HKs) are critical sensors of external stimuli in prokaryotes, the mechanisms by which their sensor domains control enzymatic activity remain unclear. In this paper, we report the full-length structure of a blue light-activated HK from Erythrobacter litoralis HTCC2594 (EL346) and the results of biochemical and biophysical studies that explain how it is activated by light. Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer. Its structure reveals that the light–oxygen–voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain.more » The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark. Upon light stimulation, interdomain interactions weaken to facilitate activation. Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation. Finally, we suggest parallels between EL346 and dimeric HKs, with sensor-induced movements in the DHp similarly remodeling the DHp/CA interface as part of activation.« less
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Šošovičková, R; Smetana, J; Beranová, E; Kučerová, K; Chlíbek, R
Viral hepatitis A continues to occur in the Czech Republic due to the high susceptibility of the population and existing opportunities for the transmission of the disease. The aim was to describe and analyse the incidence of viral hepatitis A in the Hradec Králové Region in the Czech Republic in 2005-2014, including the study of two outbreaks that required a different approach of field epidemiologists. In 2015, a retrospective analysis was carried out of the data on the incidence of viral hepatitis A in Hradec Králové Region in 2005-2014. The EPIDAT system where cases of infectious diseases and data from epidemiological investigations are reported was used as a data source for the purposes of the present analysis. In addition, two final reports on epidemic outbreaks of viral hepatitis A from 2014 were assessed. The incidence of viral hepatitis A at the regional level follows, to a certain extent, the pattern of the incidence of this disease at the national level. The highest number of cases was reported in 2010 due to a country-wide epidemic. The most affected age groups were children, adolescents, and young adults. The incidence of viral hepatitis A in individual years has a significant effect on the emergence of local outbreaks. The incidence of viral hepatitis A in the Czech Republic has a fluctuating trend, at both the national and regional levels. The highest incidence of viral hepatitis A was observed in the younger and middle-age categories. The high susceptibility of these population groups suggests the importance of vaccination against viral hepatitis A that confers specific personal protection.Key words: viral hepatitis A - incidence - outbreak - Czech Republic.
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Temperature Sensitive Singlet Oxygen Photosensitization by LOV-Derived Fluorescent Flavoproteins.
Westberg, Michael; Bregnhøj, Mikkel; Etzerodt, Michael; Ogilby, Peter R
2017-03-30
Optogenetic sensitizers that selectively produce a given reactive oxygen species (ROS) constitute a promising tool for studying cell signaling processes with high levels of spatiotemporal control. However, to harness the full potential of this tool for live cell studies, the photophysics of currently available systems need to be explored further and optimized. Of particular interest in this regard, are the flavoproteins miniSOG and SOPP, both of which (1) contain the chromophore flavin mononucleotide, FMN, in a LOV-derived protein enclosure, and (2) photosensitize the production of singlet oxygen, O 2 (a 1 Δ g ). Here we present an extensive experimental study of the singlet and triplet state photophysics of FMN in SOPP and miniSOG over a physiologically relevant temperature range. Although changes in temperature only affect the singlet excited state photophysics slightly, the processes that influence the deactivation of the triplet excited state are more sensitive to temperature. Most notably, for both proteins, the rate constant for quenching of 3 FMN by ground state oxygen, O 2 (X 3 Σ g - ), increases ∼10-fold upon increasing the temperature from 10 to 43 °C, while the oxygen-independent channels of triplet state deactivation are less affected. As a consequence, this increase in temperature results in higher yields of O 2 (a 1 Δ g ) formation for both SOPP and miniSOG. We also show that the quantum yields of O 2 (a 1 Δ g ) production by both miniSOG and SOPP are mainly limited by the fraction of FMN triplet states quenched by O 2 (X 3 Σ g - ). The results presented herein provide a much-needed quantitative framework that will facilitate the future development of optogenetic ROS sensitizers.
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Liu, Hongtao; Wang, Qin; Liu, Yawen; Zhao, Xiaoying; Imaizumi, Takato; Somers, David E.; Tobin, Elaine M.; Lin, Chentao
2013-01-01
Plants possess multiple photoreceptors to mediate light regulation of growth and development, but it is not well understood how different photoreceptors coordinate their actions to jointly regulate developmental responses, such as flowering time. In Arabidopsis, the photoexcited cryptochrome 2 interacts with the transcription factor CRYPTOCHROME-INTERACTING basic helix–loop–helix 1 (CIB1) to activate transcription and floral initiation. We show that the CIB1 protein expression is regulated by blue light; CIB1 is highly expressed in plants exposed to blue light, but levels of the CIB1 protein decreases in the absence of blue light. We demonstrate that CIB1 is degraded by the 26S proteasome and that blue light suppresses CIB1 degradation. Surprisingly, although cryptochrome 2 physically interacts with CIB1 in response to blue light, it is not the photoreceptor mediating blue-light suppression of CIB1 degradation. Instead, two of the three light–oxygen–voltage (LOV)-domain photoreceptors, ZEITLUPE and LOV KELCH PROTEIN 2, but not FLAVIN-BINDING KELCH REPEAT 1, are required for the function and blue-light suppression of degradation of CIB1. These results support the hypothesis that the evolutionarily unrelated blue-light receptors, cryptochrome and LOV-domain F-box proteins, mediate blue-light regulation of the same transcription factor by distinct mechanisms. PMID:24101505
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Engineering a light-activated caspase-3 for precise ablation of neurons in vivo
Smart, Ashley D.; Pache, Roland A.; Thomsen, Nathan D.; Kortemme, Tanja; Davis, Graeme W.; Wells, James A.
2017-01-01
The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila. Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV–induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms. PMID:28893998
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Roberts, Diana; Pedmale, Ullas V.; Morrow, Johanna; Sachdev, Shrikesh; Lechner, Esther; Tang, Xiaobo; Zheng, Ning; Hannink, Mark; Genschik, Pascal; Liscum, Emmanuel
2011-01-01
Plant phototropism is an adaptive response to changes in light direction, quantity, and quality that results in optimization of photosynthetic light harvesting, as well as water and nutrient acquisition. Though several components of the phototropic signal response pathway have been identified in recent years, including the blue light (BL) receptors phototropin1 (phot1) and phot2, much remains unknown. Here, we show that the phot1-interacting protein NONPHOTOTROPIC HYPOCOTYL3 (NPH3) functions as a substrate adapter in a CULLIN3-based E3 ubiquitin ligase, CRL3NPH3. Under low-intensity BL, CRL3NPH3 mediates the mono/multiubiquitination of phot1, likely marking it for clathrin-dependent internalization from the plasma membrane. In high-intensity BL, phot1 is both mono/multi- and polyubiquitinated by CRL3NPH3, with the latter event targeting phot1 for 26S proteasome-mediated degradation. Polyubiquitination and subsequent degradation of phot1 under high-intensity BL likely represent means of receptor desensitization, while mono/multiubiquitination-stimulated internalization of phot1 may be coupled to BL-induced relocalization of hormone (auxin) transporters. PMID:21990941
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Wan, Yinglang; Jasik, Jan; Wang, Li; Hao, Huaiqing; Volkmann, Dieter; Menzel, Diedrik; Mancuso, Stefano; Baluška, František; Lin, Jinxing
2012-02-01
Under blue light (BL) illumination, Arabidopsis thaliana roots grow away from the light source, showing a negative phototropic response. However, the mechanism of root phototropism is still unclear. Using a noninvasive microelectrode system, we showed that the BL sensor phototropin1 (phot1), the signal transducer NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and the auxin efflux transporter PIN2 were essential for BL-induced auxin flux in the root apex transition zone. We also found that PIN2-green fluorescent protein (GFP) localized to vacuole-like compartments (VLCs) in dark-grown root epidermal and cortical cells, and phot1/NPH3 mediated a BL-initiated pathway that caused PIN2 redistribution to the plasma membrane. When dark-grown roots were exposed to brefeldin A (BFA), PIN2-GFP remained in VLCs in darkness, and BL caused PIN2-GFP disappearance from VLCs and induced PIN2-GFP-FM4-64 colocalization within enlarged compartments. In the nph3 mutant, both dark and BL BFA treatments caused the disappearance of PIN2-GFP from VLCs. However, in the phot1 mutant, PIN2-GFP remained within VLCs under both dark and BL BFA treatments, suggesting that phot1 and NPH3 play different roles in PIN2 localization. In conclusion, BL-induced root phototropism is based on the phot1/NPH3 signaling pathway, which stimulates the shootward auxin flux by modifying the subcellular targeting of PIN2 in the root apex transition zone.
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Understanding blue-light photoreceptors
NASA Astrophysics Data System (ADS)
Crane, Brian
Blue-light sensing proteins coordinate many biological processes that include phototropism, photomorphism, stress responses, virulence and the entrainment of circadian clocks. Three major types of blue-light sensors all bind flavin nucleotides as chromophores, but the photochemistry employed and conformational responses invoked differ considerably among the classes. Nevertheless, photoinduced electron transfer reactions play a key role in many mechanisms. How such reactivity leads to conformational signaling will be discussed for both cryptochromes (CRYs) and light- oxygen- voltage (LOV) domains. In CRYs, blue-light mediated flavin reduction promotes proton transfer within the active center that then leads to displacement of a key signaling element. For LOV proteins, blue light causes formation of a covalent cysteinyl-flavin adduct, which rearranges hydrogen bonding and restructures the N-terminal region of the protein. Interestingly, a new class of LOV-like sensor does not undergo adduct formation and instead can operate by flavin photoreduction, like CRY. Conserved aspects of reactivity in these proteins provide lessons for the design of new photosensors, which may find use as tools in optogenetics Supported by NIH GM079679.
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Barbesi, Donato; Vicente Vilas, Víctor; Millet, Sylvain; Sandow, Miguel; Colle, Jean-Yves; Aldave de Las Heras, Laura
2017-01-01
A LabVIEW ® -based software for the control of the fully automated multi-sequential flow injection analysis Lab-on-Valve (MSFIA-LOV) platform AutoRAD performing radiochemical analysis is described. The analytical platform interfaces an Arduino ® -based device triggering multiple detectors providing a flexible and fit for purpose choice of detection systems. The different analytical devices are interfaced to the PC running LabVIEW ® VI software using USB and RS232 interfaces, both for sending commands and receiving confirmation or error responses. The AUTORAD platform has been successfully applied for the chemical separation and determination of Sr, an important fission product pertinent to nuclear waste.
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Wan, Yinglang; Jasik, Jan; Wang, Li; Hao, Huaiqing; Volkmann, Dieter; Menzel, Diedrik; Mancuso, Stefano; Baluška, František; Lin, Jinxing
2012-01-01
Under blue light (BL) illumination, Arabidopsis thaliana roots grow away from the light source, showing a negative phototropic response. However, the mechanism of root phototropism is still unclear. Using a noninvasive microelectrode system, we showed that the BL sensor phototropin1 (phot1), the signal transducer NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and the auxin efflux transporter PIN2 were essential for BL-induced auxin flux in the root apex transition zone. We also found that PIN2-green fluorescent protein (GFP) localized to vacuole-like compartments (VLCs) in dark-grown root epidermal and cortical cells, and phot1/NPH3 mediated a BL-initiated pathway that caused PIN2 redistribution to the plasma membrane. When dark-grown roots were exposed to brefeldin A (BFA), PIN2-GFP remained in VLCs in darkness, and BL caused PIN2-GFP disappearance from VLCs and induced PIN2-GFP-FM4-64 colocalization within enlarged compartments. In the nph3 mutant, both dark and BL BFA treatments caused the disappearance of PIN2-GFP from VLCs. However, in the phot1 mutant, PIN2-GFP remained within VLCs under both dark and BL BFA treatments, suggesting that phot1 and NPH3 play different roles in PIN2 localization. In conclusion, BL-induced root phototropism is based on the phot1/NPH3 signaling pathway, which stimulates the shootward auxin flux by modifying the subcellular targeting of PIN2 in the root apex transition zone. PMID:22374399
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Fankhauser, Christian; Christie, John M
2015-05-04
Plants are photoautotrophic sessile organisms that use environmental cues to optimize multiple facets of growth and development. A classic example is phototropism - in shoots this is typically positive, leading to growth towards the light, while roots frequently show negative phototropism triggering growth away from the light. Shoot phototropism optimizes light capture of leaves in low light environments and hence increases photosynthetic productivity. Phototropins are plasma-membrane-associated UV-A/blue-light activated kinases that trigger phototropic growth. Light perception liberates their protein kinase domain from the inhibitory action of the amino-terminal photosensory portion of the photoreceptor. Following a series of still poorly understood events, phototropin activation leads to the formation of a gradient of the growth hormone auxin across the photo-stimulated stem. The greater auxin concentration on the shaded compared with the lit side of the stem enables growth reorientation towards the light. In this Minireview, we briefly summarize the signaling steps starting from photoreceptor activation until the establishment of a lateral auxin gradient, ultimately leading to phototropic growth in shoots. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Boccalandro, Hernán E; Giordano, Carla V; Ploschuk, Edmundo L; Piccoli, Patricia N; Bottini, Rubén; Casal, Jorge J
2012-03-01
Leaf epidermal peels of Arabidopsis (Arabidopsis thaliana) mutants lacking either phototropins 1 and 2 (phot1 and phot2) or cryptochromes 1 and 2 (cry1 and cry2) exposed to a background of red light show severely impaired stomatal opening responses to blue light. Since phot and cry are UV-A/blue light photoreceptors, they may be involved in the perception of the blue light-specific signal that induces the aperture of the stomatal pores. In leaf epidermal peels, the blue light-specific effect saturates at low irradiances; therefore, it is considered to operate mainly under the low irradiance of dawn, dusk, or deep canopies. Conversely, we show that both phot1 phot2 and cry1 cry2 have reduced stomatal conductance, transpiration, and photosynthesis, particularly under the high irradiance of full sunlight at midday. These mutants show compromised responses of stomatal conductance to irradiance. However, the effects of phot and cry on photosynthesis were largely nonstomatic. While the stomatal conductance phenotype of phot1 phot2 was blue light specific, cry1 cry2 showed reduced stomatal conductance not only in response to blue light, but also in response to red light. The levels of abscisic acid were elevated in cry1 cry2. We conclude that considering their effects at high irradiances cry and phot are critical for the control of transpiration and photosynthesis rates in the field. The effects of cry on stomatal conductance are largely indirect and involve the control of abscisic acid levels.
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Seeing the Light: The Roles of Red- and Blue-Light Sensing in Plant Microbes.
Beattie, Gwyn A; Hatfield, Bridget M; Dong, Haili; McGrane, Regina S
2018-05-16
Plants collect, concentrate, and conduct light throughout their tissues, thus enhancing light availability to their resident microbes. This review explores the role of photosensing in the biology of plant-associated bacteria and fungi, including the molecular mechanisms of red-light sensing by phytochromes and blue-light sensing by LOV (light-oxygen-voltage)-domain proteins in these microbes. Bacteriophytochromes function as major drivers of the bacterial transcriptome and mediate light-regulated suppression of virulence, motility, and conjugation in some phytopathogens and light-regulated induction of the photosynthetic apparatus in a stem-nodulating symbiont. Bacterial LOV proteins also influence light-mediated changes in both symbiotic and pathogenic phenotypes. Although red-light sensing by fungal phytopathogens is poorly understood, fungal LOV proteins contribute to blue-light regulation of traits, including asexual development and virulence. Collectively, these studies highlight that plant microbes have evolved to exploit light cues and that light sensing is often coupled with sensing other environmental signals. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Signal transduction in light–oxygen–voltage receptors lacking the adduct-forming cysteine residue
Yee, Estella F.; Diensthuber, Ralph P.; Vaidya, Anand T.; Borbat, Peter P.; Engelhard, Christopher; Freed, Jack H.; Bittl, Robert; Möglich, Andreas; Crane, Brian R.
2015-01-01
Light–oxygen–voltage (LOV) receptors sense blue light through the photochemical generation of a covalent adduct between a flavin-nucleotide chromophore and a strictly conserved cysteine residue. Here we show that, after cysteine removal, the circadian-clock LOV-protein Vivid still undergoes light-induced dimerization and signalling because of flavin photoreduction to the neutral semiquinone (NSQ). Similarly, photoreduction of the engineered LOV histidine kinase YF1 to the NSQ modulates activity and downstream effects on gene expression. Signal transduction in both proteins hence hinges on flavin protonation, which is common to both the cysteinyl adduct and the NSQ. This general mechanism is also conserved by natural cysteine-less, LOV-like regulators that respond to chemical or photoreduction of their flavin cofactors. As LOV proteins can react to light even when devoid of the adduct-forming cysteine, modern LOV photoreceptors may have arisen from ancestral redox-active flavoproteins. The ability to tune LOV reactivity through photoreduction may have important implications for LOV mechanism and optogenetic applications. PMID:26648256
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Long, Xiangbao; Miró, Manuel; Jensen, Rikard; Hansen, Elo Harald
2006-10-01
A highly selective procedure is proposed for the determination of ultra-trace level concentrations of nickel in saline aqueous matrices exploiting a micro-sequential injection Lab-On-Valve (muSI-LOV) sample pretreatment protocol comprising bead injection separation/pre-concentration and detection by electrothermal atomic absorption spectrometry (ETAAS). Based on the dimethylglyoxime (DMG) reaction used for nickel analysis, the sample, as contained in a pH 9.0 buffer, is, after on-line merging with the chelating reagent, transported to a reaction coil attached to one of the external ports of the LOV to assure sufficient reaction time for the formation of Ni(DMG)(2) chelate. The non-ionic coordination compound is then collected in a renewable micro-column packed with a reversed-phase copolymeric sorbent [namely, poly(divinylbenzene-co-N-vinylpyrrolidone)] containing a balanced ratio of hydrophilic and lipophilic monomers. Following elution by a 50-muL methanol plug in an air-segmented modality, the nickel is finally quantified by ETAAS. Under the optimized conditions and for a sample volume of 1.8 mL, a retention efficiency of 70 % and an enrichment factor of 25 were obtained. The proposed methodology showed a high tolerance to the commonly encountered alkaline earth matrix elements in environmental waters, that is, calcium and magnesium, and was successfully applied for the determination of nickel in an NIST standard reference material (NIST 1640-Trace elements in natural water), household tap water of high hardness and local seawater. Satisfying recoveries were achieved for all spiked environmental water samples with maximum deviations of 6 %. The experimental results for the standard reference material were not statistically different to the certified value at a significance level of 0.05.
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Photoreceptor-mediated bending towards UV-B in Arabidopsis.
Vandenbussche, Filip; Tilbrook, Kimberley; Fierro, Ana Carolina; Marchal, Kathleen; Poelman, Dirk; Van Der Straeten, Dominique; Ulm, Roman
2014-06-01
Plants reorient their growth towards light to optimize photosynthetic light capture--a process known as phototropism. Phototropins are the photoreceptors essential for phototropic growth towards blue and ultraviolet-A (UV-A) light. Here we detail a phototropic response towards UV-B in etiolated Arabidopsis seedlings. We report that early differential growth is mediated by phototropins but clear phototropic bending to UV-B is maintained in phot1 phot2 double mutants. We further show that this phototropin-independent phototropic response to UV-B requires the UV-B photoreceptor UVR8. Broad UV-B-mediated repression of auxin-responsive genes suggests that UVR8 regulates directional bending by affecting auxin signaling. Kinetic analysis shows that UVR8-dependent directional bending occurs later than the phototropin response. We conclude that plants may use the full short-wavelength spectrum of sunlight to efficiently reorient photosynthetic tissue with incoming light. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.
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Boancă, M M; Colosi, H A; Crăciun, E C
2014-02-01
Recent studies have shown that vitamin B12 scavenges superoxide anion as effectively as superoxide dismutase (SOD), and has a key role in the defense against oxidative stress. The status of vitamin B12 is suboptimal in a substantial number of vegans and even vegetarians. We therefore evaluated in lacto-ovo vegetarians (LOVs) who did not take vitamin B12 supplements the impact of the duration of this diet on the vitamin B12 status, the erythrocyte SOD activity and the serum malondialdehyde (MDA) concentration. The study group included 38 non-vegetarians and 48 LOVs divided, according to the duration of this diet, into two subgroups: LOV1 (2-10 years) and LOV2 (11-29 years). The erythrocyte SOD activity and the serum concentrations of vitamin B12 and MDA were assayed. In LOVs, the mean serum vitamin B12 concentration, the erythrocyte SOD activity and the mean serum MDA concentration were statistically significantly lower that in non-vegetarians. No significant association between the serum vitamin B12 and MDA concentrations and the duration of the LOV diet were observed. A significant inverse linear correlation between SOD activity and the duration of adherence to LOV diet was observed in LOVs. The duration of LOV diet has impact only on SOD activity. Further researches, both in vitro and in vivo, are necessary to understand the underlying molecular mechanism.
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Polyketide synthases of Diaporthe helianthi and involvement of DhPKS1 in virulence on sunflower.
Ruocco, Michelina; Baroncelli, Riccardo; Cacciola, Santa Olga; Pane, Catello; Monti, Maurilia Maria; Firrao, Giuseppe; Vergara, Mariarosaria; Magnano di San Lio, Gaetano; Vannacci, Giovanni; Scala, Felice
2018-01-06
The early phases of Diaporthe helianthi pathogenesis on sunflower are characterized by the production of phytotoxins that may play a role in host colonisation. In previous studies, phytotoxins of a polyketidic nature were isolated and purified from culture filtrates of virulent strains of D. helianthi isolated from sunflower. A highly aggressive isolate (7/96) from France contained a gene fragment of a putative nonaketide synthase (lovB) which was conserved in a virulent D. helianthi population. In order to investigate the role of polyketide synthases in D. helianthi 7/96, a draft genome of this isolate was examined. We were able to find and phylogenetically analyse 40 genes putatively coding for polyketide synthases (PKSs). Analysis of their domains revealed that most PKS genes of D. helianthi are reducing PKSs, whereas only eight lacked reducing domains. Most of the identified PKSs have orthologs shown to be virulence factors or genetic determinants for toxin production in other pathogenic fungi. One of the genes (DhPKS1) corresponded to the previously cloned D. helianthi lovB gene fragment and clustered with a nonribosomal peptide synthetase (NRPS) -PKS hybrid/lovastatin nonaketide like A. nidulans LovB. We used DhPKS1 as a case study and carried out its disruption through Agrobacterium-mediated transformation in the isolate 7/96. D. helianthi DhPKS1 deleted mutants were less virulent to sunflower compared to the wild type, indicating a role for this gene in the pathogenesis of the fungus. The PKS sequences analysed and reported here constitute a new genomic resource that will be useful for further research on the biology, ecology and evolution of D. helianthi and generally of fungal plant pathogens.
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Horizontal transfer of an adaptive chimeric photoreceptor from bryophytes to ferns
Li, Fay-Wei; Villarreal, Juan Carlos; Kelly, Steven; Rothfels, Carl J.; Melkonian, Michael; Frangedakis, Eftychios; Ruhsam, Markus; Sigel, Erin M.; Der, Joshua P.; Pittermann, Jarmila; Burge, Dylan O.; Pokorny, Lisa; Larsson, Anders; Chen, Tao; Weststrand, Stina; Thomas, Philip; Carpenter, Eric; Zhang, Yong; Tian, Zhijian; Chen, Li; Yan, Zhixiang; Zhu, Ying; Sun, Xiao; Wang, Jun; Stevenson, Dennis W.; Crandall-Stotler, Barbara J.; Shaw, A. Jonathan; Deyholos, Michael K.; Soltis, Douglas E.; Graham, Sean W.; Windham, Michael D.; Langdale, Jane A.; Wong, Gane Ka-Shu; Mathews, Sarah; Pryer, Kathleen M.
2014-01-01
Ferns are well known for their shade-dwelling habits. Their ability to thrive under low-light conditions has been linked to the evolution of a novel chimeric photoreceptor—neochrome—that fuses red-sensing phytochrome and blue-sensing phototropin modules into a single gene, thereby optimizing phototropic responses. Despite being implicated in facilitating the diversification of modern ferns, the origin of neochrome has remained a mystery. We present evidence for neochrome in hornworts (a bryophyte lineage) and demonstrate that ferns acquired neochrome from hornworts via horizontal gene transfer (HGT). Fern neochromes are nested within hornwort neochromes in our large-scale phylogenetic reconstructions of phototropin and phytochrome gene families. Divergence date estimates further support the HGT hypothesis, with fern and hornwort neochromes diverging 179 Mya, long after the split between the two plant lineages (at least 400 Mya). By analyzing the draft genome of the hornwort Anthoceros punctatus, we also discovered a previously unidentified phototropin gene that likely represents the ancestral lineage of the neochrome phototropin module. Thus, a neochrome originating in hornworts was transferred horizontally to ferns, where it may have played a significant role in the diversification of modern ferns. PMID:24733898
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Boccalandro, Hernán E.; Giordano, Carla V.; Ploschuk, Edmundo L.; Piccoli, Patricia N.; Bottini, Rubén; Casal, Jorge J.
2012-01-01
Leaf epidermal peels of Arabidopsis (Arabidopsis thaliana) mutants lacking either phototropins 1 and 2 (phot1 and phot2) or cryptochromes 1 and 2 (cry1 and cry2) exposed to a background of red light show severely impaired stomatal opening responses to blue light. Since phot and cry are UV-A/blue light photoreceptors, they may be involved in the perception of the blue light-specific signal that induces the aperture of the stomatal pores. In leaf epidermal peels, the blue light-specific effect saturates at low irradiances; therefore, it is considered to operate mainly under the low irradiance of dawn, dusk, or deep canopies. Conversely, we show that both phot1 phot2 and cry1 cry2 have reduced stomatal conductance, transpiration, and photosynthesis, particularly under the high irradiance of full sunlight at midday. These mutants show compromised responses of stomatal conductance to irradiance. However, the effects of phot and cry on photosynthesis were largely nonstomatic. While the stomatal conductance phenotype of phot1 phot2 was blue light specific, cry1 cry2 showed reduced stomatal conductance not only in response to blue light, but also in response to red light. The levels of abscisic acid were elevated in cry1 cry2. We conclude that considering their effects at high irradiances cry and phot are critical for the control of transpiration and photosynthesis rates in the field. The effects of cry on stomatal conductance are largely indirect and involve the control of abscisic acid levels. PMID:22147516
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Phototropism: at the crossroads of light-signaling pathways.
Goyal, Anupama; Szarzynska, Bogna; Fankhauser, Christian
2013-07-01
Phototropism enables plants to orient growth towards the direction of light and thereby maximizes photosynthesis in low-light environments. In angiosperms, blue-light photoreceptors called phototropins are primarily involved in sensing the direction of light. Phytochromes and cryptochromes (sensing red/far-red and blue light, respectively) also modulate asymmetric hypocotyl growth, leading to phototropism. Interactions between different light-signaling pathways regulating phototropism occur in cryptogams and angiosperms. In this review, we focus on the molecular mechanisms underlying the co-action between photosensory systems in the regulation of hypocotyl phototropism in Arabidopsis thaliana. Recent studies have shown that phytochromes and cryptochromes enhance phototropism by controlling the expression of important regulators of phototropin signaling. In addition, phytochromes may also regulate growth towards light via direct interaction with the phototropins. Copyright © 2013 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Gourley, Christopher R.
The facultative intracellular pathogen Brucella melitensis utilizes diverse virulence factors. A Brucella light sensing histidine kinase can influence in vitro virulence of the bacteria during intracellular infection. First, we demonstrated that the B. melitensis light sensing kinase (BM-LOV-HK) affects virulence in an IRF-1-/- mouse model of infection. Infection with a Δ BM-LOV-HK strain resulted in less bacterial colonization of IRF-1-/- spleens and extended survivorship compared to mice infected with wild type B. melitensis 16M. Second, using PCR arrays, we observed less expression of innate and adaptive immune system activation markers in ΔBM-LOV-HK infected mouse spleens than wild type B. melitensis 16M infected mouse spleens 6 days after infection. Third, we demonstrated by microarray analysis of B. melitensis that deletion of BM-LOV-HK alters bacterial gene expression. Downregulation of genes involved in control of the general stress response system included the alternative sigma factor RpoE1 and its anti-anti sigma factor PhyR. Conversely, genes involved in flagella production, quorum sensing, and the type IV secretion system (VirB operon) were upregulated in the Δ BM-LOV-HK strain compared to the wild type B. melitensis 16M. Analysis of genes differentially regulated in Δ BM-LOV-HK versus the wild type strain indicated an overlap of 110 genes with data from previous quorum sensing regulator studies of Δ vjbR and/ΔblxR(babR) strains. Also, several predicted RpoE1 binding sites located upstream of genes were differentially regulated in the ΔBM-LOV-HK strain. Our results suggest BM-LOV-HK is important for in vivo Brucella virulence, and reveals that BM-LOV-HK directly or indirect regulates members of the Brucella quorum sensing, type IV secretion, and general stress systems.
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Zhou, Yujie; Yang, Hong; Zhou, Xuedong; Luo, Hongke; Tang, Fan; Yang, Jin; Alterovitz, Gil; Cheng, Lei; Ren, Biao
2018-06-01
The increase of fungal infectious diseases and lack of safe and efficacious antifungal drugs result in the urgent need of new therapeutic strategies. Here, we repurposed the lovastatin (LOV) as a synergistic antifungal potentiator to itraconazole (ITZ) against Candida albicans planktonic cells and biofilms in vitro for the first time. Mutants from ergosterol biosynthesis pathway were employed and key gene expression profiles of ergosterol pathway were also measured. LOV single treatment was unable to inhibit C. albicans strains except the ERG3 and ERG11 double mutant. LOV and ITZ combination was capable of inhibiting the C. albicans planktonic cells and biofilms synergistically including the ITZ resistant mutants. The synergistic antifungal ability was stronger in either ERG11 or ERG3 dysfunctional mutants compared to wild type. The combination lost the synergistic activities in the ERG11 and ERG3 double mutant, while it was sensitive to LOV single treatment. The expression of HMG1, encoding HMG-CoA the target of LOV, was significantly upregulated in ERG11 and ERG3 double mutant strain by the treatment of the combination at 1.5 and 3 h. The combination also significantly increased the HMG1 expression in mutants from ergosterol pathway compared with wild type. The ERG11 and ERG3 gene expressions were upregulated by ITZ and its combination with LOV, but seemingly not by LOV single treatment after 1.5 and 3 h. The combination of LOV and ITZ on C. albicans planktonic cells and biofilms highlights its potential clinical practice especially against the azole drug-resistant mutants.
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Tricking the guard: exploiting plant defense for disease susceptibility.
Lorang, J; Kidarsa, T; Bradford, C S; Gilbert, B; Curtis, M; Tzeng, S-C; Maier, C S; Wolpert, T J
2012-11-02
Typically, pathogens deploy virulence effectors to disable defense. Plants defeat effectors with resistance proteins that guard effector targets. We found that a pathogen exploits a resistance protein by activating it to confer susceptibility in Arabidopsis. The guard mechanism of plant defense is recapitulated by interactions among victorin (an effector produced by the necrotrophic fungus Cochliobolus victoriae), TRX-h5 (a defense-associated thioredoxin), and LOV1 (an Arabidopsis susceptibility protein). In LOV1's absence, victorin inhibits TRX-h5, resulting in compromised defense but not disease by C. victoriae. In LOV1's presence, victorin binding to TRX-h5 activates LOV1 and elicits a resistance-like response that confers disease susceptibility. We propose that victorin is, or mimics, a conventional pathogen virulence effector that was defeated by LOV1 and confers virulence to C. victoriae solely because it incites defense.
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A negative effector of blue light-induced and gravitropic bending in Arabidopsis.
Knauer, Torsten; Dümmer, Michaela; Landgraf, Frank; Forreiter, Christoph
2011-05-01
Although sessile, plants are able to grow toward or away from an environmental stimulus. Important examples are stem or leaf orientation of higher plants in response to the direction of the incident light. The responsible photoreceptors belong to the phototropin photoreceptor family. Although the mode of phototropin action is quite well understood, much less is known of how the light signal is transformed into a bending response. Several lines of evidence indicate that a lateral auxin gradient is responsible for asymmetric cell elongation along the light gradient within the stem. However, some of the molecular key players leading to this asymmetric auxin distribution are, as yet, unidentified. Previously, it was shown that phototropin gets autophosphorylated upon illumination and binds to a scaffold protein termed NPH3 (for nonphototropic hypocotyl 3). Using a yeast three-hybrid approach with phototropin and NPH3 as a bait complex, we isolated a protein, termed EHB1 (for enhanced bending 1), with a so far unknown function, which binds to this binary complex. This novel interacting factor negatively affects hypocotyl bending under blue light conditions in Arabidopsis (Arabidopsis thaliana) and thus seems to be an important component regulating phototropism. Interestingly, it could be shown that the gravitropic response was also affected. Thus, it cannot be ruled out that this protein might also have a more general role in auxin-mediated bending toward an environmental stimulus.
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Singh, Avtar K.; Singh, Inderjit
2013-01-01
We earlier documented that lovastatin (LOV)-mediated inhibition of small Rho GTPases activity protects vulnerable oligodendrocytes (OLs) in mixed glial cell cultures stimulated with Th1 cytokines and in a murine model of multiple sclerosis (MS). However, the precise mechanism of OL protection remains unclear. We here employed genetic and biochemical approaches to elucidate the underlying mechanism that protects LOV treated OLs from Th1 (tumor necrosis factor-α) and Th17 (interleukin-17) cytokines toxicity in in vitro. Cytokines enhanced the reactive oxygen species (ROS) generation and mitochondrial membrane depolarization with corresponding lowering of glutathione (reduced) level in OLs and that were reverted by LOV. In addition, the expression of ROS detoxifying enzymes (catalase and superoxide-dismutase 2) and the transactivation of peroxisome proliferators-activated receptor (PPAR)-α/-β/-γ including PPAR-γ coactivator-1α were enhanced by LOV in similarly treated OLs. Interestingly, LOV-mediated inhibition of small Rho GTPases, i.e., RhoA and cdc42, and Rho-associated kinase (ROCK) activity enhanced the levels of PPAR ligands in OLs via extracellular signal regulated kinase (1/2)/p38 mitogen-activated protein kinase/cytoplasmic phospholipase 2/cyclooxygenase-2 signaling cascade activation. Small hairpin RNA transfection-based studies established that LOV mainly enhances PPAR-α and less so of PPAR-β and PPAR-γ transactivation that enhances ROS detoxifying defense in OLs. In support of this, the observed LOV-mediated protection was lacking in PPAR-α-deficient OLs exposed to cytokines. Collectively, these data provide unprecedented evidence that LOV-mediated inhibition of the Rho–ROCK signaling pathway boosts ROS detoxifying defense in OLs via PPAR-α-dependent mechanism that has implication in neurodegenerative disorders including MS. PMID:23839981
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Peter, Emanuel K; Shea, Joan-Emma; Pivkin, Igor V
2016-05-14
In this paper, we present a coarse replica exchange molecular dynamics (REMD) approach, based on kinetic Monte Carlo (kMC). The new development significantly can reduce the amount of replicas and the computational cost needed to enhance sampling in protein simulations. We introduce 2 different methods which primarily differ in the exchange scheme between the parallel ensembles. We apply this approach on folding of 2 different β-stranded peptides: the C-terminal β-hairpin fragment of GB1 and TrpZip4. Additionally, we use the new simulation technique to study the folding of TrpCage, a small fast folding α-helical peptide. Subsequently, we apply the new methodology on conformation changes in signaling of the light-oxygen voltage (LOV) sensitive domain from Avena sativa (AsLOV2). Our results agree well with data reported in the literature. In simulations of dialanine, we compare the statistical sampling of the 2 techniques with conventional REMD and analyze their performance. The new techniques can reduce the computational cost of REMD significantly and can be used in enhanced sampling simulations of biomolecules.
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Łabuz, Justyna; Samardakiewicz, Sławomir; Hermanowicz, Paweł; Wyroba, Elżbieta; Pilarska, Maria; Gabryś, Halina
2016-01-01
Calcium is involved in the signal transduction pathway from phototropins, the blue light photoreceptor kinases which mediate chloroplast movements. The chloroplast accumulation response in low light is controlled by both phot1 and phot2, while only phot2 is involved in avoidance movement induced by strong light. Phototropins elevate cytosolic Ca2+ after activation by blue light. In higher plants, both types of chloroplast responses depend on Ca2+, and internal calcium stores seem to be crucial for these processes. Yet, the calcium signatures generated after the perception of blue light by phototropins are not well understood. To characterize the localization of calcium in Arabidopsis mesophyll cells, loosely bound (exchangeable) Ca2+ was precipitated with potassium pyroantimonate and analyzed by transmission electron microscopy followed by energy-dispersive X-ray microanalysis. In dark-adapted wild-type Arabidopsis leaves, calcium precipitates were observed at the cell wall, where they formed spherical structures. After strong blue light irradiation, calcium at the apoplast prevailed, and bigger, multilayer precipitates were found. Spherical calcium precipitates were also detected at the tonoplast. After red light treatment as a control, the precipitates at the cell wall were smaller and less numerous. In the phot2 and phot1phot2 mutants, calcium patterns were different from those of wild-type plants. In both mutants, no elevation of calcium after blue light treatment was observed at the cell periphery (including the cell wall and a fragment of cytoplasm). This result confirms the involvement of phototropin2 in the regulation of Ca2+ homeostasis in mesophyll cells. PMID:26957564
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Supra-domains: evolutionary units larger than single protein domains.
Vogel, Christine; Berzuini, Carlo; Bashton, Matthew; Gough, Julian; Teichmann, Sarah A
2004-02-20
Domains are the evolutionary units that comprise proteins, and most proteins are built from more than one domain. Domains can be shuffled by recombination to create proteins with new arrangements of domains. Using structural domain assignments, we examined the combinations of domains in the proteins of 131 completely sequenced organisms. We found two-domain and three-domain combinations that recur in different protein contexts with different partner domains. The domains within these combinations have a particular functional and spatial relationship. These units are larger than individual domains and we term them "supra-domains". Amongst the supra-domains, we identified some 1400 (1203 two-domain and 166 three-domain) combinations that are statistically significantly over-represented relative to the occurrence and versatility of the individual component domains. Over one-third of all structurally assigned multi-domain proteins contain these over-represented supra-domains. This means that investigation of the structural and functional relationships of the domains forming these popular combinations would be particularly useful for an understanding of multi-domain protein function and evolution as well as for genome annotation. These and other supra-domains were analysed for their versatility, duplication, their distribution across the three kingdoms of life and their functional classes. By examining the three-dimensional structures of several examples of supra-domains in different biological processes, we identify two basic types of spatial relationships between the component domains: the combined function of the two domains is such that either the geometry of the two domains is crucial and there is a tight constraint on the interface, or the precise orientation of the domains is less important and they are spatially separate. Frequently, the role of the supra-domain becomes clear only once the three-dimensional structure is known. Since this is the case for only a
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Łabuz, Justyna; Samardakiewicz, Sławomir; Hermanowicz, Paweł; Wyroba, Elżbieta; Pilarska, Maria; Gabryś, Halina
2016-06-01
Calcium is involved in the signal transduction pathway from phototropins, the blue light photoreceptor kinases which mediate chloroplast movements. The chloroplast accumulation response in low light is controlled by both phot1 and phot2, while only phot2 is involved in avoidance movement induced by strong light. Phototropins elevate cytosolic Ca(2+) after activation by blue light. In higher plants, both types of chloroplast responses depend on Ca(2+), and internal calcium stores seem to be crucial for these processes. Yet, the calcium signatures generated after the perception of blue light by phototropins are not well understood. To characterize the localization of calcium in Arabidopsis mesophyll cells, loosely bound (exchangeable) Ca(2+) was precipitated with potassium pyroantimonate and analyzed by transmission electron microscopy followed by energy-dispersive X-ray microanalysis. In dark-adapted wild-type Arabidopsis leaves, calcium precipitates were observed at the cell wall, where they formed spherical structures. After strong blue light irradiation, calcium at the apoplast prevailed, and bigger, multilayer precipitates were found. Spherical calcium precipitates were also detected at the tonoplast. After red light treatment as a control, the precipitates at the cell wall were smaller and less numerous. In the phot2 and phot1phot2 mutants, calcium patterns were different from those of wild-type plants. In both mutants, no elevation of calcium after blue light treatment was observed at the cell periphery (including the cell wall and a fragment of cytoplasm). This result confirms the involvement of phototropin2 in the regulation of Ca(2+) homeostasis in mesophyll cells. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
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Wang, W; Zhang, W; Jiang, R; Luan, Y
2010-05-01
It is of vital importance to find genetic variants that underlie human complex diseases and locate genes that are responsible for these diseases. Since proteins are typically composed of several structural domains, it is reasonable to assume that harmful genetic variants may alter structures of protein domains, affect functions of proteins and eventually cause disorders. With this understanding, the authors explore the possibility of recovering associations between protein domains and complex diseases. The authors define associations between protein domains and disease families on the basis of associations between non-synonymous single nucleotide polymorphisms (nsSNPs) and complex diseases, similarities between diseases, and relations between proteins and domains. Based on a domain-domain interaction network, the authors propose a 'guilt-by-proximity' principle to rank candidate domains according to their average distance to a set of seed domains in the domain-domain interaction network. The authors validate the method through large-scale cross-validation experiments on simulated linkage intervals, random controls and the whole genome. Results show that areas under receiver operating characteristic curves (AUC scores) can be as high as 77.90%, and the mean rank ratios can be as low as 21.82%. The authors further offer a freely accessible web interface for a genome-wide landscape of associations between domains and disease families.
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Leukemia cell-rhabdovirus vaccine: personalized immunotherapy for acute lymphoblastic leukemia.
Conrad, David P; Tsang, Jovian; Maclean, Meaghan; Diallo, Jean-Simon; Le Boeuf, Fabrice; Lemay, Chantal G; Falls, Theresa J; Parato, Kelley A; Bell, John C; Atkins, Harold L
2013-07-15
Acute lymphoblastic leukemia (ALL) remains incurable in most adults. It has been difficult to provide effective immunotherapy to improve outcomes for the majority of patients. Rhabdoviruses induce strong antiviral immune responses. We hypothesized that mice administered ex vivo rhabdovirus-infected ALL cells [immunotherapy by leukemia-oncotropic virus (iLOV)] would develop robust antileukemic immune responses capable of controlling ALL. Viral protein production, replication, and cytopathy were measured in human and murine ALL cells exposed to attenuated rhabdovirus. Survival following injection of graded amounts of ALL cells was compared between cohorts of mice administered γ-irradiated rhabdovirus-infected ALL cells (iLOV) or multiple control vaccines to determine key immunotherapeutic components and characteristics. Host immune requirements were assessed in immunodeficient and bone marrow-transplanted mice or by adoptive splenocyte transfer from immunized donors. Antileukemic immune memory was ascertained by second leukemic challenge in long-term survivors. Human and murine ALL cells were infected and killed by rhabdovirus; this produced a potent antileukemia vaccine. iLOV protected mice from otherwise lethal ALL by developing durable leukemia-specific immune-mediated responses (P < 0.0001), which required an intact CTL compartment. Preexisting antiviral immunity augmented iLOV potency. Splenocytes from iLOV-vaccinated donors protected 60% of naïve recipients from ALL challenge (P = 0.0001). Injecting leukemia cells activated by, or concurrent with, multiple Toll-like receptor agonists could not reproduce the protective effect of iLOV. Similarly, injecting uninfected irradiated viable, apoptotic, or necrotic leukemia cells with/without concurrent rhabdovirus administration was ineffective. Rhabdovirus-infected leukemia cells can be used to produce a vaccine that induces robust specific immunity against aggressive leukemia.
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Domain atrophy creates rare cases of functional partial protein domains.
Prakash, Ananth; Bateman, Alex
2015-04-30
Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements. Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites. Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.
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Yang, Chi; Ma, Lu; Ying, Zhenghe; Jiang, Xiaoling; Lin, Yanquan
2017-04-01
Light is a necessary environmental factor for fruit body formation and development of the cauliflower mushroom Sparassis latifolia, a well-known edible and medicinal fungus. In this study, we firstly characterized the SP-C strain, which belonged to S. latifolia. And then we cloned and sequenced a photoreceptor gene (Slwc-1) from S. latifolia. The product of Slwc-1, SlWC-1 (872 aa residues) contained a coiled-coil region, a LOV domain, and two PAS domains. Phylogenetic tree result showed that SLWC-1 was most close to GfWC-1 from Grifola frondosa in edible and medicinal fungus. The Slwc-1 gene was found to be enhanced by light. This report will help to open the still-unexplored field of fruit body development for this fungus.
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Miró, Manuel; Hansen, Elo Harald
2007-09-26
The analytical capabilities of the microminiaturized lab-on-a-valve (LOV) module integrated into a microsequential injection (muSI) fluidic system in terms of analytical chemical performance, microfluidic handling and on-line sample processing are compared to those of the micro total analysis systems (muTAS), also termed lab-on-a-chip (LOC). This paper illustrates, via selected representative examples, the potentials of the LOV scheme vis-à-vis LOC microdevices for environmental assays. By means of user-friendly programmable flow and the exploitation of the interplay between the thermodynamics and the kinetics of the chemical reactions at will, LOV allows accommodation of reactions which, at least at the present stage, are not feasible by application of microfluidic LOC systems. Thus, in LOV one may take full advantage of kinetic discriminations schemes, where even subtle differences in reactions are utilized for analytical purposes. Furthermore, it is also feasible to handle multi-step sequential reactions of divergent kinetics; to conduct multi-parametric determinations without manifold reconfiguration by utilization of the inherent open-architecture of the micromachined unit for implementation of peripheral modules and automated handling of a variety of reagents; and most importantly, it offers itself as a versatile front end to a plethora of detection schemes. Not the least, LOV is regarded as an emerging downscaled tool to overcome the dilemma of LOC microsystems to admit real-life samples. This is nurtured via its intrinsic flexibility for accommodation of sample pre-treatment schemes aimed at the on-line manipulation of complex samples. Thus, LOV is playing a prominent role in the environmental field, whenever the monitoring of trace level concentration of pollutants is pursued, because both matrix isolation and preconcentration of target analytes is most often imperative, or in fact necessary, prior to sample presentation to the detector.
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Miyazaki, Yuji; Abe, Hiroshi; Takase, Tomoyuki; Kobayashi, Masatomo; Kiyosue, Tomohiro
2015-05-01
The overexpression of LKP2 confers dehydration tolerance in Arabidopsis thaliana ; this is likely due to enhanced expression of dehydration-inducible genes and reduced stomatal opening. LOV KELCH protein 2 (LKP2) modulates the circadian rhythm and flowering time in plants. In this study, we observed that LKP2 overexpression enhanced dehydration tolerance in Arabidopsis. Microarray analysis demonstrated that expression of water deprivation-responsive genes was higher in the absence of dehydration stress in transgenic Arabidopsis plants expressing green fluorescent protein-tagged LKP2 (GFP-LKP2) than in control transgenic plants expressing GFP. After dehydration followed by rehydration, GFP-LKP2 plants developed more leaves and roots and exhibited higher survival rates than control plants. In the absence of dehydration stress, four dehydration-inducible genes, namely DREB1A, DREB1B, DREB1C, and RD29A, were expressed in GFP-LKP2 plants, whereas they were not expressed or were expressed at low levels in control plants. Under dehydration stress, the expression of DREB2B and RD29A peaked faster in the GFP-LKP2 plants than in control plants. The stomatal aperture of GFP-LKP2 plants was smaller than that of control plants. These results suggest that the dehydration tolerance of GFP-LKP2 plants is caused by upregulation of DREB1A-C/CBF1-3 and their downstream targets; restricted stomatal opening in the absence of dehydration stress also appears to contribute to the phenotype. The rapid and high expression of DREB2B and its downstream target genes also likely accounts for some features of the GFP-LKP2 phenotype. Our results suggest that LKP2 can be used for biotechnological applications not only to adjust the flowering time control but also to enhance dehydration tolerance.
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Assembly of a biocompatible triazole-linked gene by one-pot click-DNA ligation
NASA Astrophysics Data System (ADS)
Kukwikila, Mikiembo; Gale, Nittaya; El-Sagheer, Afaf H.; Brown, Tom; Tavassoli, Ali
2017-11-01
The chemical synthesis of oligonucleotides and their enzyme-mediated assembly into genes and genomes has significantly advanced multiple scientific disciplines. However, these approaches are not without their shortcomings; enzymatic amplification and ligation of oligonucleotides into genes and genomes makes automation challenging, and site-specific incorporation of epigenetic information and/or modified bases into large constructs is not feasible. Here we present a fully chemical one-pot method for the assembly of oligonucleotides into a gene by click-DNA ligation. We synthesize the 335 base-pair gene that encodes the green fluorescent protein iLOV from ten functionalized oligonucleotides that contain 5ʹ-azide and 3ʹ-alkyne units. The resulting click-linked iLOV gene contains eight triazoles at the sites of chemical ligation, and yet is fully biocompatible; it is replicated by DNA polymerases in vitro and encodes a functional iLOV protein in Escherichia coli. We demonstrate the power and potential of our one-pot gene-assembly method by preparing an epigenetically modified variant of the iLOV gene.
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Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam
2015-01-01
Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568
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Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis
Khor, Susan
2014-01-01
Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450
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Molecular Genetic Analysis of Phototropism in Arabidopsis
Sakai, Tatsuya; Haga, Ken
2012-01-01
Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes. PMID:22864452
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Molecular genetic analysis of phototropism in Arabidopsis.
Sakai, Tatsuya; Haga, Ken
2012-09-01
Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes.
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Xu, Xinran; Chen, Xiangdong; Yu, Wumengxiao; Liu, Yu; Zhang, Weiwei; Lan, Jin
2017-08-01
Blue light plays an important role during the growth of Ganoderma lucidum, one of the best-known medicinal macrofungi in China. In the present study, we cloned Glwc-1 and Glwc-2, the homologue of the blue light photoreceptors Ncwc-1 and Ncwc-2 of Neurospora crassa, from G. lucidum. The deduced amino acid sequence of Glwc-1 contained the similar function domains as NcWC-1 including LOV, PAS B, PAS C, and PAC domains. The deduced amino acid sequence of Glwc-2 contained PAS domain and GATA-type zinc finger (Znf) domain as well as NcWC-2. Phylogenetic analysis based on fungal WC-1 and WC-2 supported GlWC-1 and GlWC-2 were blue light receptors. The expression of Glwc-1 and Glwc-2 indicated that they might play an important role during the primordium differentiation process of G. lucidum, and the external blue light stimulation increased the expression of Glwc-1 and Glwc-2. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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2010-01-01
Background Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http
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Munekage, Yuri Nakajima; Inoue, Shio; Yoneda, Yuki; Yokota, Akiho
2015-06-01
Plants develop palisade tissue consisting of cylindrical mesophyll cells located at the adaxial side of leaves in response to high light. To understand high light signalling in palisade tissue development, we investigated leaf autonomous and long-distance signal responses of palisade tissue development using Arabidopsis thaliana. Illumination of a developing leaf with high light induced cell height elongation, whereas illumination of mature leaves with high light increased cell density and suppressed cell width expansion in palisade tissue of new leaves. Examination using phototropin1 phototropin2 showed that blue light signalling mediated by phototropins was involved in cell height elongation of the leaf autonomous response rather than the cell density increase induced by long-distance signalling. Hydrogen peroxide treatment induced cylindrical palisade tissue cell formation in both a leaf autonomous and long-distance manner, suggesting involvement of oxidative signals. Although constitutive expression of transcription factors involved in systemic-acquired acclimation to excess light, ZAT10 and ZAT12, induced cylindrical palisade tissue cell formation, knockout of these genes did not affect cylindrical palisade tissue cell formation. We conclude that two distinct signalling pathways - leaf autonomous signalling mostly dependent on blue light signalling and long-distance signalling from mature leaves that sense high light and oxidative stress - control palisade tissue development in A. thaliana. © 2014 John Wiley & Sons Ltd.
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Vishwanath, Sneha
2018-01-01
The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in
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Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy
2018-02-01
The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in
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The PYRIN domain: A member of the death domain-fold superfamily
Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.
2001-01-01
PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682
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Mutation of domain III and domain VI in L gene conserved domain of Nipah virus
NASA Astrophysics Data System (ADS)
Jalani, Siti Aishah; Ibrahim, Nazlina
2016-11-01
Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.
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NASA Astrophysics Data System (ADS)
Catalan, G.; Seidel, J.; Ramesh, R.; Scott, J. F.
2012-01-01
Domains in ferroelectrics were considered to be well understood by the middle of the last century: They were generally rectilinear, and their walls were Ising-like. Their simplicity stood in stark contrast to the more complex Bloch walls or Néel walls in magnets. Only within the past decade and with the introduction of atomic-resolution studies via transmission electron microscopy, electron holography, and atomic force microscopy with polarization sensitivity has their real complexity been revealed. Additional phenomena appear in recent studies, especially of magnetoelectric materials, where functional properties inside domain walls are being directly measured. In this paper these studies are reviewed, focusing attention on ferroelectrics and multiferroics but making comparisons where possible with magnetic domains and domain walls. An important part of this review will concern device applications, with the spotlight on a new paradigm of ferroic devices where the domain walls, rather than the domains, are the active element. Here magnetic wall microelectronics is already in full swing, owing largely to the work of Cowburn and of Parkin and their colleagues. These devices exploit the high domain wall mobilities in magnets and their resulting high velocities, which can be supersonic, as shown by Kreines’ and co-workers 30 years ago. By comparison, nanoelectronic devices employing ferroelectric domain walls often have slower domain wall speeds, but may exploit their smaller size as well as their different functional properties. These include domain wall conductivity (metallic or even superconducting in bulk insulating or semiconducting oxides) and the fact that domain walls can be ferromagnetic while the surrounding domains are not.
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NASA Astrophysics Data System (ADS)
Bjørner, Dines
Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.
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Visualizing domain wall and reverse domain superconductivity.
Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D
2014-08-28
In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.
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Visualizing domain wall and reverse domain superconductivity
Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.
2014-01-01
In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004
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Domain Specific vs Domain General: Implications for Dynamic Assessment
ERIC Educational Resources Information Center
Kaniel, Shlomo
2010-01-01
The article responds to the need for evidence-based dynamic assessment. The article is divided into two sections: In Part 1 we examine the scientific answer to the question of how far human mental activities and capabilities are domain general (DG) / domain specific (DS). A highly complex answer emerges from the literature review of domains such…
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Domain-to-domain coupling in voltage-sensing phosphatase.
Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi
2017-01-01
Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.
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Domain-to-domain coupling in voltage-sensing phosphatase
Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi
2017-01-01
Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain. PMID:28744425
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Skyrmion domain wall collision and domain wall-gated skyrmion logic
NASA Astrophysics Data System (ADS)
Xing, Xiangjun; Pong, Philip W. T.; Zhou, Yan
2016-08-01
Skyrmions and domain walls are significant spin textures of great technological relevance to magnetic memory and logic applications, where they can be used as carriers of information. The unique topology of skyrmions makes them display emergent dynamical properties as compared with domain walls. Some studies have demonstrated that the two topologically inequivalent magnetic objects could be interconverted by using cleverly designed geometric structures. Here, we numerically address the skyrmion domain wall collision in a magnetic racetrack by introducing relative motion between the two objects based on a specially designed junction. An electric current serves as the driving force that moves a skyrmion toward a trapped domain wall pair. We see different types of collision dynamics depending on the driving parameters. Most importantly, the modulation of skyrmion transport using domain walls is realized in this system, allowing a set of domain wall-gated logical NOT, NAND, and NOR gates to be constructed. This work provides a skyrmion-based spin-logic architecture that is fully compatible with racetrack memories.
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MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.
Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu
2013-05-01
The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.
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Eren, Tanju; Atar, Necip; Yola, Mehmet Lütfi; Karimi-Maleh, Hassan
2015-10-15
Lovastatin (LOV) is a statin, used to lower cholesterol which has been found as a hypolipidemic agent in commercial red yeast rice. In present study, a sensitive molecular imprinted quartz crystal microbalance (QCM) sensor was prepared by fabricating a self-assembling monolayer formation of allylmercaptane on QCM chip surface for selective determination of lovastatin (LOV) in red yeast rice. To prepare molecular imprinted quartz crystal microbalance (QCM) nanosensor, LOV imprinted poly(2-hydroxyethyl methacrylate-methacryloylamidoaspartic acid) [p(HEMA-MAAsp)] nanofilm was attached on the modified gold surface of QCM chip. The non-modified and improved surfaces were characterized by using contact angle, atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy. The imprinted QCM sensor was validated according to the ICH guideline (International Conference on Harmonisation). The linearity range was obtained as 0.10-1.25 nM. The detection limit of the prepared material was calculated as 0.030 nM. The developed QCM nanosensor was successfully used to examine red yeast rice. Furthermore, the stability and repeatability of the prepared QCM nanosensor were studied. The spectacular long-term stability and repeatability of the prepared LOV-imprinted QCM nanosensor make them intriguing for use in QCM sensors. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Predicting detection performance with model observers: Fourier domain or spatial domain?
Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia
2016-02-27
The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.
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Predicting detection performance with model observers: Fourier domain or spatial domain?
Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia
2016-01-01
The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086
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Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance
McHugh, R. Kathryn; Otto, Michael W.
2011-01-01
Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed. PMID:21823763
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A new principle technic for the transformation from frequency domain to time domain
NASA Astrophysics Data System (ADS)
Gao, Ben-Qing
2017-03-01
A principle technic for the transformation from frequency domain to time domain is presented. Firstly, a special type of frequency domain transcendental equation is obtained for an expected frequency domain parameter which is a rational or irrational fraction expression. Secondly, the inverse Laplace transformation is performed. When the two time-domain factors corresponding to the two frequency domain factors at two sides of frequency domain transcendental equation are known quantities, a time domain transcendental equation is reached. At last, the expected time domain parameter corresponding to the expected frequency domain parameter can be solved by the inverse convolution process. Proceeding from rational or irrational fraction expression, all solving process is provided. In the meantime, the property of time domain sequence is analyzed and the strategy for choosing the parameter values is described. Numerical examples are presented to verify the proposed theory and technic. Except for rational or irrational fraction expressions, examples of complex relative permittivity of water and plasma are used as verification method. The principle method proposed in the paper can easily solve problems which are difficult to be solved by Laplace transformation.
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A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization
NASA Astrophysics Data System (ADS)
Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool
Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.
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Reconstituting protein interaction networks using parameter-dependent domain-domain interactions
2013-01-01
Background We can describe protein-protein interactions (PPIs) as sets of distinct domain-domain interactions (DDIs) that mediate the physical interactions between proteins. Experimental data confirm that DDIs are more consistent than their corresponding PPIs, lending support to the notion that analyses of DDIs may improve our understanding of PPIs and lead to further insights into cellular function, disease, and evolution. However, currently available experimental DDI data cover only a small fraction of all existing PPIs and, in the absence of structural data, determining which particular DDI mediates any given PPI is a challenge. Results We present two contributions to the field of domain interaction analysis. First, we introduce a novel computational strategy to merge domain annotation data from multiple databases. We show that when we merged yeast domain annotations from six annotation databases we increased the average number of domains per protein from 1.05 to 2.44, bringing it closer to the estimated average value of 3. Second, we introduce a novel computational method, parameter-dependent DDI selection (PADDS), which, given a set of PPIs, extracts a small set of domain pairs that can reconstruct the original set of protein interactions, while attempting to minimize false positives. Based on a set of PPIs from multiple organisms, our method extracted 27% more experimentally detected DDIs than existing computational approaches. Conclusions We have provided a method to merge domain annotation data from multiple sources, ensuring large and consistent domain annotation for any given organism. Moreover, we provided a method to extract a small set of DDIs from the underlying set of PPIs and we showed that, in contrast to existing approaches, our method was not biased towards DDIs with low or high occurrence counts. Finally, we used these two methods to highlight the influence of the underlying annotation density on the characteristics of extracted DDIs. Although
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PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures
NASA Astrophysics Data System (ADS)
Marrows, C. H.; Meier, G.
2012-01-01
Domain structures in magnetic materials are ubiquitous and have been studied for decades. The walls that separate them are topological defects in the magnetic order parameter and have a wide variety of complex forms. In general, their investigation is difficult in bulk materials since only the domain structure on the surface of a specimen is visible. Cutting the sample to reveal the interior causes a rearrangement of the domains into a new form. As with many other areas of magnetism, the study of domain wall physics has been revitalised by the advent of nanotechnology. The ability to fabricate nanoscale structures has permitted the formation of simplified and controlled domain patterns; the development of advanced microscopy methods has permitted them to be imaged and then modelled; subjecting them to ultrashort field and current pulses has permitted their dynamics to be explored. The latest results from all of these advances are described in this special issue. Not only has this led to results of great scientific beauty, but also to concepts of great applicability to future information technologies. In this issue the reader will find the latest results for these domain wall dynamics and the high-speed processes of topological structures such as domain walls and magnetic vortices. These dynamics can be driven by the application of magnetic fields, or by flowing currents through spintronic devices using the novel physics of spin-transfer torque. This complexity has been studied using a wide variety of experimental techniques at the edge of the spatial and temporal resolution currently available, and can be described using sophisticated analytical theory and computational modelling. As a result, the dynamics can be engineered to give rise to finely controlled memory and logic devices with new functionality. Moreover, the field is moving to study not only the conventional transition metal ferromagnets, but also complex heterostructures, novel magnets and even other
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Separated matter and antimatter domains with vanishing domain walls
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.
2015-10-01
We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.
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Mapping networks of light-dark transition in LOV photoreceptors.
Kaur Grewal, Rajdeep; Mitra, Devrani; Roy, Soumen
2015-11-15
In optogenetics, designing modules of long or short signaling state lifetime is necessary for control over precise cellular events. A critical parameter for designing artificial or synthetic photoreceptors is the signaling state lifetime of photosensor modules. Design and engineering of biologically relevant artificial photoreceptors is based on signaling mechanisms characteristic of naturally occurring photoreceptors. Therefore identifying residues important for light-dark transition is a definite first step towards rational design of synthetic photoreceptors. A thorough grasp of detailed mechanisms of photo induced signaling process would be immensely helpful in understanding the behaviour of organisms. Herein, we introduce the technique of differential networks. We identify key biological interactions, using light-oxygen-voltage domains of all organisms whose dark and light state crystal structures are simultaneously available. Even though structural differences between dark and light states are subtle (other than the covalent bond formation between flavin chromophore and active site Cysteine), our results successfully capture functionally relevant residues and are in complete agreement with experimental findings from literature. Additionally, using sequence-structure alignments, we predict functional significance of interactions found to be important from network perspective yet awaiting experimental validation. Our approach would not only help in minimizing extensive photo-cycle kinetics procedure but is also helpful in providing first-hand information on the fundamentals of photo-adaptation and rational design of synthetic photoreceptors in optogenetics. devrani.dbs@presiuniv.ac.in or soumen@jcbose.ac.in Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Internationalized Domain Names.
ERIC Educational Resources Information Center
Wielansky, Marc D.
2002-01-01
Reports on an investigation of what may appear at first to be an arcane topic--the internationalization of domain names on the Internet. Concludes that expanding domain names internationally poses challenges to the inherent open structure of the Internet; to its ease of use for those accustomed to Latin-alphabet-only domain names; and to corporate…
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Comparison of frequency-domain and time-domain rotorcraft vibration control methods
NASA Technical Reports Server (NTRS)
Gupta, N. K.
1984-01-01
Active control of rotor-induced vibration in rotorcraft has received significant attention recently. Two classes of techniques have been proposed. The more developed approach works with harmonic analysis of measured time histories and is called the frequency-domain approach. The more recent approach computes the control input directly using the measured time history data and is called the time-domain approach. The report summarizes the results of a theoretical investigation to compare the two approaches. Five specific areas were addressed: (1) techniques to derive models needed for control design (system identification methods), (2) robustness with respect to errors, (3) transient response, (4) susceptibility to noise, and (5) implementation difficulties. The system identification methods are more difficult for the time-domain models. The time-domain approach is more robust (e.g., has higher gain and phase margins) than the frequency-domain approach. It might thus be possible to avoid doing real-time system identification in the time-domain approach by storing models at a number of flight conditions. The most significant error source is the variation in open-loop vibrations caused by pilot inputs, maneuvers or gusts. The implementation requirements are similar except that the time-domain approach can be much simpler to implement if real-time system identification were not necessary.
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NASA Astrophysics Data System (ADS)
Čížková, Klára; Láska, Kamil; Metelka, Ladislav; Staněk, Martin
2018-02-01
This paper evaluates the variability of erythemal ultraviolet (EUV) radiation from Hradec Králové (Czech Republic) in the period 1964-2013. The EUV radiation time series was reconstructed using a radiative transfer model and additional empirical relationships, with the final root mean square error of 9.9 %. The reconstructed time series documented the increase in EUV radiation doses in the 1980s and the 1990s (up to 15 % per decade), which was linked to the steep decline in total ozone (10 % per decade). The changes in cloud cover were the major factor affecting the EUV radiation doses especially in the 1960s, 1970s, and at the beginning of the new millennium. The mean annual EUV radiation doses in the decade 2004-2013 declined by 5 %. The factors affecting the EUV radiation doses differed also according to the chosen integration period (daily, monthly, and annually): solar zenith angle was the most important for daily doses, cloud cover, and surface UV albedo for their monthly means, and the annual means of EUV radiation doses were most influenced by total ozone column. The number of days with very high EUV radiation doses increased by 22 % per decade, the increase was statistically significant in all seasons except autumn. The occurrence of the days with very high EUV doses was influenced mostly by low total ozone column (82 % of days), clear-sky or partly cloudy conditions (74 % of days) and by increased surface albedo (19 % of days). The principal component analysis documented that the occurrence of days with very high EUV radiation doses was much affected by the positive phase of North Atlantic Oscillation with an Azores High promontory reaching over central Europe. In the stratosphere, a strong Arctic circumpolar vortex and the meridional inflow of ozone-poor air from the southwest were favorable for the occurrence of days with very high EUV radiation doses. This is the first analysis of the relationship between the high EUV radiation doses and macroscale
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Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics
NASA Astrophysics Data System (ADS)
Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.
2018-01-01
The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.
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Domain-Generality versus Domain-Specificity: The Life and Impending Death of a False Dichotomy.
ERIC Educational Resources Information Center
Sternberg, Robert J.
1989-01-01
Argues that the question of whether information representation and processing are domain-general or domain-specific is neither meaningful nor answerable. Researchers should be asking questions about ways in which representation and processing are domain-general and ways in which they are domain-specific. (RH)
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Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.
2014-01-01
With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547
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Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu
2016-01-11
Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease
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Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data
2017-08-20
Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data Bengt J. Borgström1, Elliot Singer1, Douglas...ll.mit.edu.edu, dar@ll.mit.edu, es@ll.mit.edu, omid.sadjadi@nist.gov Abstract This paper addresses speaker verification domain adaptation with...contain speakers with low channel diversity. Existing domain adaptation methods are reviewed, and their shortcomings are discussed. We derive an
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Cohen-Gihon, Inbar; Fong, Jessica H.; Sharan, Roded; Nussinov, Ruth
2012-01-01
Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. PMID:21127809
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Domain architecture conservation in orthologs
2011-01-01
Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the
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Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*
Caplan, Steve; Sorgen, Paul L.
2013-01-01
The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701
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Simplicity and Specificity in Language: Domain-General Biases Have Domain-Specific Effects
Culbertson, Jennifer; Kirby, Simon
2016-01-01
The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be “specific” to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture, and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in domain-specific ways. PMID:26793132
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Albenzio, Marzia; Santillo, Antonella; Caroprese, Mariangela; Marino, Rosaria; Centoducati, Pasquale; Sevi, Agostino
2005-11-01
The influence of three different ventilation regimens on air pollution in sheep houses and on the quality of ewe milk and of Canestrato Pugliese cheese was investigated during the summer season. The experimental treatments were low ventilation regimen (VR=35 m3/h per ewe) split in 30-min ventilation cycles (LOV-30); moderate ventilation regimen (VR=70 m3/h per ewe) split in 30-min ventilation cycles (MOV-30); moderate ventilation regimen (VR=70 m3/h per ewe) split in 60-min ventilation cycles (MOV-60). The LOV-30 milk had higher microbial load and bulk milk somatic cell count (BMSCC) and resulted in a weaker casein matrix in the curd compared with the MOV-30 and MOV-60 treatments. At 45 d of ripening, the LOV-30 cheeses had a lower casein content and higher non-casein nitrogen (NCN) and water-soluble nitrogen (WSN) contents than the MOV-30 and MOV-60 cheeses. Urea-polyacrylamide gel electrophoresis (urea-PAGE) of the pH 4.6-soluble N extract showed that the MOV-60 cheeses had fewer bands derived from casein (CN) hydrolysis than the LOV-30 or MOV-30 cheeses, despite its having exhibited the highest plasmin (PL) activity levels. Our results suggest that the ventilation regimen is critical in dairy sheep housing for optimizing the hygienic quality of ewe milk and the proteolytic processes occurring in Canestrato Pugliese cheese during ripening.
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Protein domain organisation: adding order.
Kummerfeld, Sarah K; Teichmann, Sarah A
2009-01-29
Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and
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Emergence of novel domains in proteins
2013-01-01
Background Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. Results To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. Conclusions We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently. PMID:23425224
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Application of Feature-Oriented Domain Analysis to the Army Movement Control Domain (Appendices A-I)
1992-06-01
Cohen, James A. Hess, William E. Novak, & A. Spen- cer Peterson. Feature-Oriented Domain Analysis ( FODA ) Feasibility Study (CMU/SEI-90- TR-21...Oriented Domain Analysis to the Army Movement Control Domain (Appendices A -1) Sholom G. Cohen Jay L. Stanley, Jr. A. Spencer Peterson Robert W...Appendices) June 1992 Application of Feature-Oriented Domain Analysis to the Army Movement Control Domain (Appendices A -1) Sholom G. Cohen Jay L
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Mazloom, Amin R.; Dannenfelser, Ruth; Clark, Neil R.; Grigoryan, Arsen V.; Linder, Kathryn M.; Cardozo, Timothy J.; Bond, Julia C.; Boran, Aislyn D. W.; Iyengar, Ravi; Malovannaya, Anna; Lanz, Rainer B.; Ma'ayan, Avi
2011-01-01
Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/. PMID:22219718
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Full waveform inversion in the frequency domain using classified time-domain residual wavefields
NASA Astrophysics Data System (ADS)
Son, Woohyun; Koo, Nam-Hyung; Kim, Byoung-Yeop; Lee, Ho-Young; Joo, Yonghwan
2017-04-01
We perform the acoustic full waveform inversion in the frequency domain using residual wavefields that have been separated in the time domain. We sort the residual wavefields in the time domain according to the order of absolute amplitudes. Then, the residual wavefields are separated into several groups in the time domain. To analyze the characteristics of the residual wavefields, we compare the residual wavefields of conventional method with those of our residual separation method. From the residual analysis, the amplitude spectrum obtained from the trace before separation appears to have little energy at the lower frequency bands. However, the amplitude spectrum obtained from our strategy is regularized by the separation process, which means that the low-frequency components are emphasized. Therefore, our method helps to emphasize low-frequency components of residual wavefields. Then, we generate the frequency-domain residual wavefields by taking the Fourier transform of the separated time-domain residual wavefields. With these wavefields, we perform the gradient-based full waveform inversion in the frequency domain using back-propagation technique. Through a comparison of gradient directions, we confirm that our separation method can better describe the sub-salt image than the conventional approach. The proposed method is tested on the SEG/EAGE salt-dome model. The inversion results show that our algorithm is better than the conventional gradient based waveform inversion in the frequency domain, especially for deeper parts of the velocity model.
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Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings
NASA Technical Reports Server (NTRS)
Epel, B. L.; Bandurski, R. S.
1990-01-01
Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.
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Domains in Ferroelectric Nanostructures
NASA Astrophysics Data System (ADS)
Gregg, Marty
2010-03-01
Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device
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Institutionalizing the Human Domain: Achieving Cross Domain Synergy for Every Day Missions
2017-04-06
AIR WAR COLLEGE AIR UNIVERSITY INSTITUTIONALIZING THE HUMAN DOMAIN: ACHIEVING CROSS DOMAIN SYNERGY FOR “EVERY DAY ” MISSIONS by...war. Next, this paper will focus on the importance of the Human Domain as it relates to success within every day missions of the U.S. Military and...socially complex environment. History demonstrates that the U.S. Military has and will continue to conduct these every day missions amongst the
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DIMA 3.0: Domain Interaction Map.
Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij
2011-01-01
Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.
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Domain fusion analysis by applying relational algebra to protein sequence and domain databases.
Truong, Kevin; Ikura, Mitsuhiko
2003-05-06
Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.
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Domain fusion analysis by applying relational algebra to protein sequence and domain databases
Truong, Kevin; Ikura, Mitsuhiko
2003-01-01
Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020
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2018-01-01
Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control. SIGNIFICANCE STATEMENT We used human neuroimaging to investigate processes supporting memory and perceptual metacognition. It remains controversial whether metacognition relies on a global resource that is applied to different tasks or if self-evaluative processes are specific to particular tasks. Using multivariate decoding methods, we provide evidence that perceptual- and memory-specific metacognitive representations coexist with generic confidence signals. Our findings reconcile previously conflicting results on the domain specificity/generality of metacognition and lay the groundwork for a mechanistic understanding of metacognitive judgments. PMID:29519851
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Topological domain walls in helimagnets
NASA Astrophysics Data System (ADS)
Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.
2018-05-01
Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.
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A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.
Li-Smerin, Y; Hackos, D H; Swartz, K J
2000-02-01
Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.
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Mao, Guanzhong; Srivastava, Abhishek S.; Wu, Shiying; Kosek, David; Lindell, Magnus
2018-01-01
The natural trans-acting ribozyme RNase P RNA (RPR) is composed of two domains in which the catalytic (C-) domain mediates cleavage of various substrates. The C-domain alone, after removal of the second specificity (S-) domain, catalyzes this reaction as well, albeit with reduced efficiency. Here we provide experimental evidence indicating that efficient cleavage mediated by the Escherichia coli C-domain (Eco CP RPR) with and without the C5 protein likely depends on an interaction referred to as the "P6-mimic". Moreover, the P18 helix connects the C- and S-domains between its loop and the P8 helix in the S-domain (the P8/ P18-interaction). In contrast to the "P6-mimic", the presence of P18 does not contribute to the catalytic performance by the C-domain lacking the S-domain in cleavage of an all ribo model hairpin loop substrate while deletion or disruption of the P8/ P18-interaction in full-size RPR lowers the catalytic efficiency in cleavage of the same model hairpin loop substrate in keeping with previously reported data using precursor tRNAs. Consistent with that P18 is not required for cleavage mediated by the C-domain we show that the archaeal Pyrococcus furiosus RPR C-domain, which lacks the P18 helix, is catalytically active in trans without the S-domain and any protein. Our data also suggest that the S-domain has a larger impact on catalysis for E. coli RPR compared to P. furiosus RPR. Finally, we provide data indicating that the absence of the S-domain and P18, or the P8/ P18-interaction in full-length RPR influences the charge distribution near the cleavage site in the RPR-substrate complex to a small but reproducible extent. PMID:29509761
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Domain adaptation via transfer component analysis.
Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang
2011-02-01
Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.
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Stabilization and Amorphization of Lovastatin Using Different Types of Silica.
Khanfar, Mai; Al-Nimry, Suhair
2017-08-01
Lovastatin (LOV), an antihyperlipidimic agent, is characterized by low solubility/poor dissolution and, thus, low bioavailability (<5%). A beneficial effect on its bioavailability could result from improving its dissolution. One of the most common methods used to enhance dissolution is the preparation of solid dispersions. Solid dispersions of LOV and silica with different surface areas were prepared. The effects of the type of silica, ratio of drug/silica, incubation period with silica, and the effect of surface area were all studied. Characterization of the prepared formulae for possible interaction between drug and polymer was carried out using differential scanning calorimetery, Fourier transform infrared spectroscopy, powder X-ray diffraction, surface area determination, and scanning electron microscopy. The dissolution profiles of all prepared formulae were constructed and evaluated. It was found that the formula made of LOV and Sylysia 350 FCP in a ratio of 1:5 after an incubation period of 48 h resulted in the best release, and it was stable after 3 months storage at 75% RH and 40°C.
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Multifunctionalities driven by ferroic domains
NASA Astrophysics Data System (ADS)
Yang, J. C.; Huang, Y. L.; He, Q.; Chu, Y. H.
2014-08-01
Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.
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Text Processing of Domain-Related Information for Individuals with High and Low Domain Knowledge.
ERIC Educational Resources Information Center
Spilich, George J.; And Others
1979-01-01
The way in which previously acquired knowledge affects the processing on new domain-related information was investigated. Text processing was studied in two groups differing in knowledge of the domain of baseball. A knowledge structure for the domain was constructed, and text propositions were classified. (SW)
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Koehler Leman, Julia; Bonneau, Richard
2018-04-03
Membrane proteins composed of soluble and membrane domains are often studied one domain at a time. However, to understand the biological function of entire protein systems and their interactions with each other and drugs, knowledge of full-length structures or models is required. Although few computational methods exist that could potentially be used to model full-length constructs of membrane proteins, none of these methods are perfectly suited for the problem at hand. Existing methods require an interface or knowledge of the relative orientations of the domains or are not designed for domain assembly, and none of them are developed for membrane proteins. Here we describe the first domain assembly protocol specifically designed for membrane proteins that assembles intra- and extracellular soluble domains and the transmembrane domain into models of the full-length membrane protein. Our protocol does not require an interface between the domains and samples possible domain orientations based on backbone dihedrals in the flexible linker regions, created via fragment insertion, while keeping the transmembrane domain fixed in the membrane. For five examples tested, our method mp_domain_assembly, implemented in RosettaMP, samples domain orientations close to the known structure and is best used in conjunction with experimental data to reduce the conformational search space.
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The C-Terminal Domain of the Virulence Factor MgtC Is a Divergent ACT Domain
Yang, Yinshan; Labesse, Gilles; Carrère-Kremer, Séverine; Esteves, Kevin; Kremer, Laurent
2012-01-01
MgtC is a virulence factor of unknown function important for survival inside macrophages in several intracellular bacterial pathogens, including Mycobacterium tuberculosis. It is also involved in adaptation to Mg2+ deprivation, but previous work suggested that MgtC is not a Mg2+ transporter. In this study, we demonstrated that the amount of the M. tuberculosis MgtC protein is not significantly increased by Mg2+ deprivation. Members of the MgtC protein family share a conserved membrane N-terminal domain and a more divergent cytoplasmic C-terminal domain. To get insights into MgtC functional and structural organization, we have determined the nuclear magnetic resonance (NMR) structure of the C-terminal domain of M. tuberculosis MgtC. This structure is not affected by the Mg2+ concentration, indicating that it does not bind Mg2+. The structure of the C-terminal domain forms a βαββαβ fold found in small molecule binding domains called ACT domains. However, the M. tuberculosis MgtC ACT domain differs from canonical ACT domains because it appears to lack the ability to dimerize and to bind small molecules. We have shown, using a bacterial two-hybrid system, that the M. tuberculosis MgtC protein can dimerize and that the C-terminal domain somehow facilitates this dimerization. Taken together, these results indicate that M. tuberculosis MgtC does not have an intrinsic function related to Mg2+ uptake or binding but could act as a regulatory factor based on protein-protein interaction that could be facilitated by its ACT domain. PMID:22984256
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Discussion summary: Fictitious domain methods
NASA Technical Reports Server (NTRS)
Glowinski, Rowland; Rodrigue, Garry
1991-01-01
Fictitious Domain methods are constructed in the following manner: Suppose a partial differential equation is to be solved on an open bounded set, Omega, in 2-D or 3-D. Let R be a rectangle domain containing the closure of Omega. The partial differential equation is first solved on R. Using the solution on R, the solution of the equation on Omega is then recovered by some procedure. The advantage of the fictitious domain method is that in many cases the solution of a partial differential equation on a rectangular region is easier to compute than on a nonrectangular region. Fictitious domain methods for solving elliptic PDEs on general regions are also very efficient when used on a parallel computer. The reason is that one can use the many domain decomposition methods that are available for solving the PDE on the fictitious rectangular region. The discussion on fictitious domain methods began with a talk by R. Glowinski in which he gave some examples of a variational approach to ficititious domain methods for solving the Helmholtz and Navier-Stokes equations.
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Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments.
Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter
2017-01-01
Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments - one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.
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Costa, H M; Nicholson, B; Donlan, C; Van Herwegen, J
2018-04-01
Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether this also holds for preschool low achievers (LAs) and how domain-specific and domain-general abilities contribute to mathematical difficulties at a young age. The aim of this study was to explore the cognitive characteristics of a sample of preschool LAs and identify sub-types of LAs. 81 children were identified as LAs from 283 preschoolers aged 3 to 5 years old and were assessed on a number of domain-general and domain-specific tasks. Cluster analysis revealed four subgroups of LAs in mathematics: (1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of the groups showed specific domain-general difficulties, none showed only domain-specific difficulties. Current findings suggest that preschool LAs constitute a heterogeneous group and stress the importance of domain-general factors for the development of mathematical abilities during the preschool years. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.
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Polar Domain Discovery with Sparkler
NASA Astrophysics Data System (ADS)
Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.
2017-12-01
The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.
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Modeling software systems by domains
NASA Technical Reports Server (NTRS)
Dippolito, Richard; Lee, Kenneth
1992-01-01
The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.
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Ferroelectric negative capacitance domain dynamics
NASA Astrophysics Data System (ADS)
Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas
2018-05-01
Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transient negative capacitance is shown to originate from reverse domain nucleation and unrestricted domain growth. However, with the onset of domain coalescence, the capacitance becomes positive again. The persistence of the negative capacitance state is therefore limited by the speed of domain wall motion. By changing the applied electric field, capacitor area or external resistance, this domain wall velocity can be varied predictably over several orders of magnitude. Additionally, detailed insights into the intrinsic material properties of the ferroelectric are obtainable through these measurements. A new method for reliable extraction of the average negative capacitance of the ferroelectric is presented. Furthermore, a simple analytical model is developed, which accurately describes the negative capacitance transient time as a function of the material properties and the experimental boundary conditions.
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NASA Technical Reports Server (NTRS)
Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.
1997-01-01
A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.
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NASA Astrophysics Data System (ADS)
Oh, Kyoung Joon; Senzel, Lisa; Collier, R. John; Finkelstein, Alan
1999-07-01
The T domain of diphtheria toxin is known to participate in the pH-dependent translocation of the catalytic C domain of the toxin across the endosomal membrane, but how it does so, and whether cellular proteins are also required for this process, remain unknown. Here, we report results showing that the T domain alone is capable of translocating the entire C domain across model, planar phospholipid bilayers in the absence of other proteins. The T domain therefore contains the entire molecular machinery for mediating transfer of the catalytic domain of diphtheria toxin across membranes.
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Scientific Reasoning across Different Domains.
ERIC Educational Resources Information Center
Glaser, Robert; And Others
This study seeks to establish which scientific reasoning skills are primarily domain-general and which appear to be domain-specific. The subjects, 12 university undergraduates, each participated in self-directed experimentation with three different content domains. The experimentation contexts were computer-based laboratories in d.c. circuits…
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Dhir, Somdutta; Pacurar, Mircea; Franklin, Dino; Gáspári, Zoltán; Kertész-Farkas, Attila; Kocsor, András; Eisenhaber, Frank; Pongor, Sándor
2010-11-01
SBASE is a project initiated to detect known domain types and predicting domain architectures using sequence similarity searching (Simon et al., Protein Seq Data Anal, 5: 39-42, 1992, Pongor et al, Nucl. Acids. Res. 21:3111-3115, 1992). The current approach uses a curated collection of domain sequences - the SBASE domain library - and standard similarity search algorithms, followed by postprocessing which is based on a simple statistics of the domain similarity network (http://hydra.icgeb.trieste.it/sbase/). It is especially useful in detecting rare, atypical examples of known domain types which are sometimes missed even by more sophisticated methodologies. This approach does not require multiple alignment or machine learning techniques, and can be a useful complement to other domain detection methodologies. This article gives an overview of the project history as well as of the concepts and principles developed within this the project.
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Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II.
Chang, A; Cheang, S; Espanel, X; Sudol, M
2000-07-07
RSP5 is an essential gene in Saccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific "imperfect" CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.
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Suzuki, Hiromi; Okamoto, Ai; Kojima, Akane; Nishimura, Takeshi; Takano, Makoto; Kagawa, Takatoshi; Kadota, Akeo; Kanegae, Takeshi; Koshiba, Tomokazu
2014-08-01
ZmPHOT1 and ZmPHOT2 are expressed differentially in maize coleoptiles and leaves, with Zmphot1 possibly involved in first-positive phototropic curvature of red-light-adapted maize coleoptiles exposed to pulsed low-fluence blue light. Unilateral blue-light perception by phototropin(s) is the first event of phototropism, with the subsequent signal causing lateral transport of auxin at the coleoptile tip region of monocots. In this study, we analyzed the behavior of two maize phototropin genes: ZmPHOT1 and ZmPHOT2, the latter identified from the maize genome database and newly characterized. Quantitative real-time PCR analysis demonstrated that ZmPHOT1 was abundantly expressed in etiolated coleoptiles, while lower expressions of both ZmPHOT1 and ZmPHOT2 were observed in young leaves. Interestingly, these genes were not specifically expressed in the coleoptile tip region, a key position for photoperception in phototropism. Exposure to pulsed low-fluence blue light (LBL) (0.33 µmol m(-2) s(-1) × 8 s) and continuous high-fluence blue light (HBL) (10 µmol m(-2) s(-1)) rapidly decreased ZmPHOT1 gene expression in coleoptiles, with levels of ZmPHOT2 not significantly altered in that tissue. In young leaves, no drastic expression changes were induced in either ZmPHOT1 or ZmPHOT2 by LBL or HBL irradiation. The Zmphot1 protein was investigated by Western blot analysis with anti-Osphot1 antibodies. Zmphot1 was detected in microsomal fractions, with higher levels in coleoptiles than in leaves. HBL caused rapid phosphorylation of the protein, whereas no phot1 phosphorylation was induced by LBL. The involvement of Zmphot1 in LBL-induced phototropic curvature of maize coleoptiles is discussed.
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Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments
Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter
2018-01-01
Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments — one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.† PMID:29457801
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NASA Technical Reports Server (NTRS)
Tolliver, C. L.
1989-01-01
The quest for the highest resolution microwave imaging and principle of time-domain imaging has been the primary motivation for recent developments in time-domain techniques. With the present technology, fast time varying signals can now be measured and recorded both in magnitude and in-phase. It has also enhanced our ability to extract relevant details concerning the scattering object. In the past, the interface of object geometry or shape for scattered signals has received substantial attention in radar technology. Various scattering theories were proposed to develop analytical solutions to this problem. Furthermore, the random inversion, frequency swept holography, and the synthetic radar imaging, have two things in common: (1) the physical optic far-field approximation, and (2) the utilization of channels as an extra physical dimension, were also advanced. Despite the inherent vectorial nature of electromagnetic waves, these scalar treatments have brought forth some promising results in practice with notable examples in subsurface and structure sounding. The development of time-domain techniques are studied through the theoretical aspects as well as experimental verification. The use of time-domain imaging for space robotic vision applications has been suggested.
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Koczyk, Grzegorz; Berezovsky, Igor N.
2008-01-01
Domain hierarchy and closed loops (DHcL) (http://sitron.bccs.uib.no/dhcl/) is a web server that delineates energy hierarchy of protein domain structure and detects domains at different levels of this hierarchy. The server also identifies closed loops and van der Waals locks, which constitute a structural basis for the protein domain hierarchy. The DHcL can be a useful tool for an express analysis of protein structures and their alternative domain decompositions. The user submits a PDB identifier(s) or uploads a 3D protein structure in a PDB format. The results of the analysis are the location of domains at different levels of hierarchy, closed loops, van der Waals locks and their interactive visualization. The server maintains a regularly updated database of domains, closed loop and van der Waals locks for all X-ray structures in PDB. DHcL server is available at: http://sitron.bccs.uib.no/dhcl. PMID:18502776
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Two conformations of the integrin A-domain (I-domain): a pathway for activation?
Lee, J O; Bankston, L A; Arnaout, M A; Liddington, R C
1995-12-15
Integrins are plasma membrane proteins that mediate adhesion to other cells and to components of the extracellular matrix. Most integrins are constitutively inactive in resting cells, but are rapidly and reversibly activated in response to agonists, leading to highly regulated cell adhesion. This activation is associated with conformational changes in their extracellular portions, but the nature of the structural changes that lead to a change in adhesiveness is not understood. The interactions of several integrins with their extracellular ligands are mediated by an A-type domain (generally called the I-domain in integrins). Binding of the I-domain to protein ligands is dependent on divalent cations. We have described previously the structure of the I-domain from complement receptor 3 with bound Mg2+, in which the glutamate side chain from a second I-domain completes the octahedral coordination sphere of the metal, acting as a ligand mimetic. We now describe a new crystal form of the I-domain with bound Mn2+, in which water completes the metal coordination sphere and there is no equivalent of the glutamate ligand. Comparison of the two crystal forms reveals a change in metal coordination which is linked to a large (10 A) shift of the C-terminal helix and the burial of two phenylalanine residues into the hydrophobic core of the Mn2+ form. These structural changes, analogous to those seen in the signal-transducing G-proteins, alter the electrophilicity of the metal, reducing its ability to bind ligand-associated acidic residues, and dramatically alter the surface of the protein implicated in binding ligand. Our observations provide the first atomic resolution view of conformational changes in an integrin domain, and suggest how these changes are linked to a change in integrin adhesiveness. We propose that the Mg2+ form represents the conformation of the domain in the active state and the Mn2+ form the conformation in the inactive state of the integrin.
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Domain Adaptation with Conditional Transferable Components
Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard
2017-01-01
Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433
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Monte Carlo simulation of ferroelectric domain growth
NASA Astrophysics Data System (ADS)
Li, B. L.; Liu, X. P.; Fang, F.; Zhu, J. L.; Liu, J.-M.
2006-01-01
The kinetics of two-dimensional isothermal domain growth in a quenched ferroelectric system is investigated using Monte Carlo simulation based on a realistic Ginzburg-Landau ferroelectric model with cubic-tetragonal (square-rectangle) phase transitions. The evolution of the domain pattern and domain size with annealing time is simulated, and the stability of trijunctions and tetrajunctions of domain walls is analyzed. It is found that in this much realistic model with strong dipole alignment anisotropy and long-range Coulomb interaction, the powerlaw for normal domain growth still stands applicable. Towards the late stage of domain growth, both the average domain area and reciprocal density of domain wall junctions increase linearly with time, and the one-parameter dynamic scaling of the domain growth is demonstrated.
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Domain-Specific Control of Selective Attention
Lin, Szu-Hung; Yeh, Yei-Yu
2014-01-01
Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977
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Wang, Zhiming; Qiao, Zhu; Ye, Sheng; Zhang, Rongguang
2015-04-01
Tandem duplications and fusions of single genes have led to magnificent expansions in the divergence of protein structures and functions over evolutionary timescales. One of the possible results is polydomain enzymes with interdomain cooperativities, few examples of which have been structurally characterized at the full-length level to explore their innate synergistic mechanisms. This work reports the crystal structures of a double-domain phosphagen kinase in both apo and ligand-bound states, revealing a novel asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain connections are not based on a flexible hinge linker but on a rigid secondary-structure element: a long α-helix that tethers the tandem domains in relatively fixed positions. Besides the connective helix, the two domains also contact each other directly and form an interdomain interface in which hydrogen bonds and hydrophobic interactions further stabilize the L-shaped domain arrangement. Molecular-dynamics simulations show that the interface is generally stable, suggesting that the asymmetric domain arrangement crystallographically observed in the present study is not a conformational state simply restrained by crystal-packing forces. It is possible that the asymmetrically arranged tandem domains could provide a structural basis for further studies of the interdomain synergy.
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Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou
2017-05-03
Electroencephalography (EEG)-based emotion recognition is an important element in psychiatric health diagnosis for patients. However, the underlying EEG sensor signals are always non-stationary if they are sampled from different experimental sessions or subjects. This results in the deterioration of the classification performance. Domain adaptation methods offer an effective way to reduce the discrepancy of marginal distribution. However, for EEG sensor signals, both marginal and conditional distributions may be mismatched. In addition, the existing domain adaptation strategies always require a high level of additional computation. To address this problem, a novel strategy named adaptive subspace feature matching (ASFM) is proposed in this paper in order to integrate both the marginal and conditional distributions within a unified framework (without any labeled samples from target subjects). Specifically, we develop a linear transformation function which matches the marginal distributions of the source and target subspaces without a regularization term. This significantly decreases the time complexity of our domain adaptation procedure. As a result, both marginal and conditional distribution discrepancies between the source domain and unlabeled target domain can be reduced, and logistic regression (LR) can be applied to the new source domain in order to train a classifier for use in the target domain, since the aligned source domain follows a distribution which is similar to that of the target domain. We compare our ASFM method with six typical approaches using a public EEG dataset with three affective states: positive, neutral, and negative. Both offline and online evaluations were performed. The subject-to-subject offline experimental results demonstrate that our component achieves a mean accuracy and standard deviation of 80.46% and 6.84%, respectively, as compared with a state-of-the-art method, the subspace alignment auto-encoder (SAAE), which achieves values
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Phylogeny of the TRAF/MATH domain.
Zapata, Juan M; Martínez-García, Vanesa; Lefebvre, Sophie
2007-01-01
The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel p-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes. The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.
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Fuller, Brian M; Ferguson, Ian; Mohr, Nicholas M; Stephens, Robert J; Briscoe, Cristopher C; Kolomiets, Angelina A; Hotchkiss, Richard S; Kollef, Marin H
2016-04-11
In critically ill patients, acute respiratory distress syndrome (ARDS) and ventilator-associated conditions (VACs) are associated with increased mortality, survivor morbidity and healthcare resource utilisation. Studies conclusively demonstrate that initial ventilator settings in patients with ARDS, and at risk for it, impact outcome. No studies have been conducted in the emergency department (ED) to determine if lung-protective ventilation in patients at risk for ARDS can reduce its incidence. Since the ED is the entry point to the intensive care unit for hundreds of thousands of mechanically ventilated patients annually in the USA, this represents a knowledge gap in this arena. A lung-protective ventilation strategy was instituted in our ED in 2014. It aims to address the parameters in need of quality improvement, as demonstrated by our previous research: (1) prevention of volutrauma; (2) appropriate positive end-expiratory pressure setting; (3) prevention of hyperoxia; and (4) aspiration precautions. The lung-protective ventilation initiated in the emergency department (LOV-ED) trial is a single-centre, quasi-experimental before-after study testing the hypothesis that lung-protective ventilation, initiated in the ED, is associated with reduced pulmonary complications. An intervention cohort of 513 mechanically ventilated adult ED patients will be compared with over 1000 preintervention control patients. The primary outcome is a composite outcome of pulmonary complications after admission (ARDS and VACs). Multivariable logistic regression with propensity score adjustment will test the hypothesis that ED lung-protective ventilation decreases the incidence of pulmonary complications. Approval of the study was obtained prior to data collection on the first patient. As the study is a before-after observational study, examining the effect of treatment changes over time, it is being conducted with waiver of informed consent. This work will be disseminated by
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García-Valverde, María Teresa; Rosende, María; Lucena, Rafael; Cárdenas, Soledad; Miró, Manuel
2018-04-03
Mesofluidic lab-on-a-valve (LOV) platforms have been proven suitable to accommodate automatic micro-solid-phase extraction (μSPE) approaches with on-chip handling of micrometer-bead materials in a fully disposable mode to prevent sample cross-contamination and pressure-drop effects. The efficiency of the extraction process notably depends upon the sorptive capacity of the material because the sorbent mass is usually down to 10 mg in LOV devices. Nanomaterials, capitalizing upon their enhanced surface-to-volume ratio and diversity of potential chemical moieties, are appealing alternatives to microbead sorbents. However, the handling and confinement of nanomaterials in fluidic chip structures have been challenging to date. This is most likely a consequence of the aggregation tendency of a number of nanomaterials, including carbon-based sorbents, that leads to excessive back-pressure in flowing systems along with irreproducible bead loading. This paper addresses these challenges by ad hoc synthesis of hybrid nanomaterials, such as porous carbon-coated titanium dioxide nanotubes (TiO 2 -NT@pC). Tailoring of the surface polarity of the carbon coating is proven to foster the dispersion of TiO 2 -NT@pC in LOV settings while affording superior extraction capability of moderately nonpolar species from aqueous matrices. The determination of trace-level concentrations of butylparaben (BPB) and triclosan (TCS) in seawater samples is herein selected as a proof-of-concept of the exploitation of disposable nanomaterials in LOV. The mesofluidic platform accommodating μSPE features online hyphenation to liquid chromatography/tandem mass spectrometry (LC/MS/MS) for reliable determination of the target analytes with excellent limits of detection (0.5 and 0.6 ng/L for BPB and TCS, respectively) and intermediate precision (relative standard deviation <5.8%). For 5.0 mL of sample and 200 μL of eluent, enrichment factors of 23 and 14 with absolute extraction efficiencies of 90% ± 14
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Domain and Specification Models for Software Engineering
NASA Technical Reports Server (NTRS)
Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui
1992-01-01
This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.
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Kim, Heejae; Chen, Wilfred
2016-09-20
Protein purification using inverse phase transition of elastin-like polypeptide (ELP) domains is a useful alternative to chromatography. Genetic fusions of ELP domains to various proteins have the ability to reversibly transition between soluble monomers and micron-sized aggregates and this has been used to selectively purify many ELP fusions. Affinity domains can enhance this technology by using specific protein binding domains to enable ELP mediated affinity capture (EMAC) of proteins of interest (POI) that have been fused to corresponding affinity ligands. In this paper, we highlight the use of Src homology 3 (SH3) domains and corresponding peptide ligands in EMAC that have differential binding affinities towards SH3 for efficient capture and elution of proteins. Furthermore, differences between capture and elution of a monomeric and a multimeric protein were also studied. Copyright © 2016 Elsevier B.V. All rights reserved.
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Multiple graph regularized protein domain ranking.
Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin
2012-11-19
Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.
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Time-Domain Stability Margin Assessment
NASA Technical Reports Server (NTRS)
Clements, Keith
2016-01-01
The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.
2012-10-23
The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studiesmore » of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.« less
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Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou
2017-01-01
Electroencephalography (EEG)-based emotion recognition is an important element in psychiatric health diagnosis for patients. However, the underlying EEG sensor signals are always non-stationary if they are sampled from different experimental sessions or subjects. This results in the deterioration of the classification performance. Domain adaptation methods offer an effective way to reduce the discrepancy of marginal distribution. However, for EEG sensor signals, both marginal and conditional distributions may be mismatched. In addition, the existing domain adaptation strategies always require a high level of additional computation. To address this problem, a novel strategy named adaptive subspace feature matching (ASFM) is proposed in this paper in order to integrate both the marginal and conditional distributions within a unified framework (without any labeled samples from target subjects). Specifically, we develop a linear transformation function which matches the marginal distributions of the source and target subspaces without a regularization term. This significantly decreases the time complexity of our domain adaptation procedure. As a result, both marginal and conditional distribution discrepancies between the source domain and unlabeled target domain can be reduced, and logistic regression (LR) can be applied to the new source domain in order to train a classifier for use in the target domain, since the aligned source domain follows a distribution which is similar to that of the target domain. We compare our ASFM method with six typical approaches using a public EEG dataset with three affective states: positive, neutral, and negative. Both offline and online evaluations were performed. The subject-to-subject offline experimental results demonstrate that our component achieves a mean accuracy and standard deviation of 80.46% and 6.84%, respectively, as compared with a state-of-the-art method, the subspace alignment auto-encoder (SAAE), which achieves values
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Dual-domain point diffraction interferometer
Naulleau, Patrick P.; Goldberg, Kenneth Alan
2000-01-01
A hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI is provided. The dual-domain PS/PDI combines the separate noise-suppression capabilities of the widely-used phase-shifting and Fourier-transform fringe pattern analysis methods. The dual-domain PS/PDI relies on both a more restrictive implementation of the image plane PS/PDI mask and a new analysis method to be applied to the interferograms generated and recorded by the modified PS/PDI. The more restrictive PS/PDI mask guarantees the elimination of spatial-frequency crosstalk between the signal and the scattered-light noise arising from scattered-reference-light interfering with the test beam. The new dual-domain analysis method is then used to eliminate scattered-light noise arising from both the scattered-reference-light interfering with the test beam and the scattered-reference-light interfering with the "true" pinhole-diffracted reference light. The dual-domain analysis method has also been demonstrated to provide performance enhancement when using the non-optimized standard PS/PDI design. The dual-domain PS/PDI is essentially a three-tiered filtering system composed of lowpass spatial-filtering the test-beam electric field using the more restrictive PS/PDI mask, bandpass spatial-filtering the individual interferogram irradiance frames making up the phase-shifting series, and bandpass temporal-filtering the phase-shifting series as a whole.
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Domain decomposition and matching for time-domain analysis of motions of ships advancing in head sea
NASA Astrophysics Data System (ADS)
Tang, Kai; Zhu, Ren-chuan; Miao, Guo-ping; Fan, Ju
2014-08-01
A domain decomposition and matching method in the time-domain is outlined for simulating the motions of ships advancing in waves. The flow field is decomposed into inner and outer domains by an imaginary control surface, and the Rankine source method is applied to the inner domain while the transient Green function method is used in the outer domain. Two initial boundary value problems are matched on the control surface. The corresponding numerical codes are developed, and the added masses, wave exciting forces and ship motions advancing in head sea for Series 60 ship and S175 containership, are presented and verified. A good agreement has been obtained when the numerical results are compared with the experimental data and other references. It shows that the present method is more efficient because of the panel discretization only in the inner domain during the numerical calculation, and good numerical stability is proved to avoid divergence problem regarding ships with flare.
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Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S
2017-07-15
Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.
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ERIC Educational Resources Information Center
Costa, H. M.; Nicholson, B.; Donlan, C.; Van Herwegen, J.
2018-01-01
Background: Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether…
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Spectral identification of topological domains
Chen, Jie; Hero, Alfred O.; Rajapakse, Indika
2016-01-01
Motivation: Topological domains have been proposed as the backbone of interphase chromosome structure. They are regions of high local contact frequency separated by sharp boundaries. Genes within a domain often have correlated transcription. In this paper, we present a computational efficient spectral algorithm to identify topological domains from chromosome conformation data (Hi-C data). We consider the genome as a weighted graph with vertices defined by loci on a chromosome and the edge weights given by interaction frequency between two loci. Laplacian-based graph segmentation is then applied iteratively to obtain the domains at the given compactness level. Comparison with algorithms in the literature shows the advantage of the proposed strategy. Results: An efficient algorithm is presented to identify topological domains from the Hi-C matrix. Availability and Implementation: The Matlab source code and illustrative examples are available at http://bionetworks.ccmb.med.umich.edu/ Contact: indikar@med.umich.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153657
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Multiple graph regularized protein domain ranking
2012-01-01
Background Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. Results To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. Conclusion The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. PMID:23157331
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McGugin, Rankin W.; Richler, Jennifer J.; Herzmann, Grit; Speegle, Magen; Gauthier, Isabel
2012-01-01
Individual differences in face recognition are often contrasted with differences in object recognition using a single object category. Likewise, individual differences in perceptual expertise for a given object domain have typically been measured relative to only a single category baseline. In Experiment 1, we present a new test of object recognition, the Vanderbilt Expertise Test (VET), which is comparable in methods to the Cambridge Face Memory Task (CFMT) but uses eight different object categories. Principal component analysis reveals that the underlying structure of the VET can be largely explained by two independent factors, which demonstrate good reliability and capture interesting sex differences inherent in the VET structure. In Experiment 2, we show how the VET can be used to separate domain-specific from domain-general contributions to a standard measure of perceptual expertise. While domain-specific contributions are found for car matching for both men and women and for plane matching in men, women in this sample appear to use more domain-general strategies to match planes. In Experiment 3, we use the VET to demonstrate that holistic processing of faces predicts face recognition independently of general object recognition ability, which has a sex-specific contribution to face recognition. Overall, the results suggest that the VET is a reliable and valid measure of object recognition abilities and can measure both domain-general skills and domain-specific expertise, which were both found to depend on the sex of observers. PMID:22877929
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Human-computer interface incorporating personal and application domains
Anderson, Thomas G [Albuquerque, NM
2011-03-29
The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.
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Human-computer interface incorporating personal and application domains
Anderson, Thomas G.
2004-04-20
The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.
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1992-12-01
and add new attributes as needed (11:129). 2.2.3.2 Feature Oriented Domain Analysis In their Feature-Oriented Domain Analysis ( FODA ) study, the...dissertation, The University of Texas at Austin, Austin Texas, 1990. 12. Kang, Kyo C. and others. Feature-Oriented Domain Analysis ( FODA ) Feasibil- ity Study...2-1 2.2.2 Requirements Languages ..................... 2-2 2.2.3 Domain Analysis ............................ 2-3 2.2.4
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Modeling Protein Domain Function
ERIC Educational Resources Information Center
Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth
2007-01-01
This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…
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Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven
2010-05-01
Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.
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Generic domain models in software engineering
NASA Technical Reports Server (NTRS)
Maiden, Neil
1992-01-01
This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.
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Lietzan, Adam D.; Menefee, Ann L.; Zeczycki, Tonya N.; Kumar, Sudhanshu; Attwood, Paul V.; Wallace, John C.; Cleland, W. Wallace; Maurice, Martin St.
2011-01-01
Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in mammalian tissues. To effect catalysis, the tethered biotin of PC must gain access to active sites in both the biotin carboxylase domain and the carboxyl transferase domain. Previous studies have demonstrated that a mutation of threonine 882 to alanine in PC from Rhizobium etli renders the carboxyl transferase domain inactive and favors the positioning of biotin in the biotin carboxylase domain. We report the 2.4 Å resolution X-ray crystal structure of the Rhizobium etli PC T882A mutant which reveals the first high-resolution description of the domain interaction between the biotin carboxyl carrier protein domain and the biotin carboxylase domain. The overall quaternary arrangement of Rhizobium etli PC remains highly asymmetrical and is independent of the presence of allosteric activator. While biotin is observed in the biotin carboxylase domain, its access to the active site is precluded by the interaction between Arg353 and Glu248, revealing a mechanism for regulating carboxybiotin access to the BC domain active site. The binding location for the biotin carboxyl carrier protein domain demonstrates that tethered biotin cannot bind in the biotin carboxylase domain active site in the same orientation as free biotin, helping to explain the difference in catalysis observed between tethered biotin and free biotin substrates in biotin carboxylase enzymes. Electron density located in the biotin carboxylase domain active site is assigned to phosphonoacetate, offering a probable location for the putative carboxyphosphate intermediate formed during biotin carboxylation. The insights gained from the T882A Rhizobium etli PC crystal structure provide a new series of catalytic snapshots in PC and offer a revised perspective on catalysis in the biotin-dependent enzyme family. PMID:21958016
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Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; ...
2014-12-31
In this study, inverted bulk heterojunction solar cells were fabricated using poly(3-hexylthiophene) (P3HT) blended with two different fullerene derivatives namely phenyl-C61-butyric acid methyl ester (PC 60BM) and indene-C 60 bis-adduct (IC 60BA). The effects of annealing temperatures on the morphology, optical and structural properties were studied and correlated to differences in photovoltaic device performance. It was observed that annealing temperature significantly improved the performance of P3HT:IC 60BA solar cells while P3HT:PC 60BM cells showed relatively less improvement. The performance improvement is attributed to the extent of fullerene mixing with polymer domains. Energy filtered transmission electron microscopy (EFTEM) and x-ray diffractionmore » (XRD) results showed that ICBA mixes with disordered P3HT much more readily than PC 60BM which leads to lower short circuit current density and fill factor for P3HT:IC 60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC 60BA whereas in P3HT:PC 60BM films, annealing above 80°C leads to negligible change in crystallinity. Crystallization of P3HT also leads to higher domain purity as seen EFTEM. Further it is seen that cells processed with additive nitrobenzene (NB) showed enhanced short circuit current density and power conversion efficiency regardless of the fullerene derivative used. Addition of NB led to nanoscale phase separation between purer polymer and fullerene domains. Kelvin probe force microscopy (KPFM) images showed that enhanced domain purity in additive casted films led to a sharper interface between polymer and fullerene. Lastly, enhanced domain purity and interfacial sharpness led to lower bimolecular recombination and higher mobility and charge carrier lifetime in NB modified devices.« less
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A thermodynamic definition of protein domains.
Porter, Lauren L; Rose, George D
2012-06-12
Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous, thermodynamically-based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and completely unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, we redefine structural domains in thermodynamic terms as cooperative folding units, based on m-values, which measure the cooperativity of a protein or its substructures. In our analysis, a domain is equated to a contiguous segment of the folded protein whose m-value is largely unaffected when that segment is excised from its parent structure. Defined in this way, a domain is a self-contained cooperative unit; i.e., its cooperativity depends primarily upon intrasegment interactions, not intersegment interactions. Implementing this concept computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Specifically, our domain divisions correspond to the experimentally determined equilibrium folding intermediates in a set of nine proteins. The approach was also proofed against a representative set of 71 additional proteins, again with confirmatory results. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property grounded in solution thermodynamics.
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Wang, L; Wu, L; Ji, G; Zhang, X; Chen, T; Wang, L
1998-12-01
Effects of upright tilt on mechanism of autonomic nervous regulation of cardiovascular system and characteristics of heart rate variability (HRV) were observed in sixty healthy male pilots. Relation between time domain and frequency domain indexes of short-time HRV (5 min) were analysed before and after upright tilt. The results showed that there are significant difference in short time HRV parameters before and after upright tilt. Significant relationship was formed between time domain and frequency domain indexes of HRV. It suggests that time domain and frequency domain HRV analysis is capable of revealing certain informations embedded in a short series of R-R intervals and can help to evaluate the status of autonomic regulation of cardiovascular function in pilots.
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Tell, G; Perrone, L; Fabbro, D; Pellizzari, L; Pucillo, C; De Felice, M; Acquaviva, R; Formisano, S; Damante, G
1998-01-01
The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development. PMID:9425125
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Mechanical switching of ferroelectric domains beyond flexoelectricity
NASA Astrophysics Data System (ADS)
Chen, Weijin; Liu, Jianyi; Ma, Lele; Liu, Linjie; Jiang, G. L.; Zheng, Yue
2018-02-01
The resurgence of interest in flexoelectricity has prompted discussions on the feasibility of switching ferroelectric domains 'non-electrically'. In this work, we perform three-dimensional thermodynamic simulations in combination with ab initio calculations and effective Hamiltonian simulations to demonstrate the great effects of surface screening and surface bonding on ferroelectric domain switching triggered by local tip loading. A three-dimensional simulation scheme has been developed to capture the tip-induced domain switching behavior in ferroelectric thin films by adequately taking into account the surface screening effect and surface bonding effect of the ferroelectric film, as well as the finite elastic stiffness of the substrate and the electrode layers. The major findings are as follows. (i) Compared with flexoelectricity, surface effects can be overwhelming and lead to much more efficient mechanical switching caused by tip loading. (ii) The surface-assisted mechanical switching can be bi-directional without the necessity of reversing strain gradients. (iii) A mode transition from local to propagating domain switching occurs when the screening below a critical value. A ripple effect of domain switching appears with the formation of concentric loop domains. (iv) The ripple effect can lead to 'domain interference' and a deterministic writing of confined loop domain patterns by local excitations. Our study reveals the hidden switching mechanisms of ferroelectric domains and the possible roles of surface in mechanical switching. The ripple effect of domain switching, which is believed to be general in dipole systems, broadens our current knowledge of domain engineering.
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Requirements analysis, domain knowledge, and design
NASA Technical Reports Server (NTRS)
Potts, Colin
1988-01-01
Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.
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When a domain isn’t a domain, and why it’s important to properly filter proteins in databases
Towse, Clare-Louise; Daggett, Valerie
2013-01-01
Summary Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our Consensus Domain Dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1695 folds in the CDD as being non-autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predicted estimates suggest 40% of proteins to have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. PMID:23108912
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Geary, David C.; Nicholas, Alan; Li, Yaoran; Sun, Jianguo
2016-01-01
The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects and domain-specific effects were indexed by prior grade mathematics achievement and mathematical cognition measures of prior grade number knowledge, addition skills, and fraction knowledge. Use of functional data analysis enabled grade-by-grade estimation of overall domain-general and domain-specific effects on subsequent mathematics achievement, the relative importance of individual domain-general and domain-specific variables on this achievement, and linear and non-linear across-grade estimates of these effects. The overall importance of domain-general abilities for subsequent achievement was stable across grades, with working memory emerging as the most important domain-general ability in later grades. The importance of prior mathematical competencies on subsequent mathematics achievement increased across grades, with number knowledge and arithmetic skills critical in all grades and fraction knowledge in later grades. Overall, domain-general abilities were more important than domain-specific knowledge for mathematics learning in early grades but general abilities and domain-specific knowledge were equally important in later grades. PMID:28781382
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Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; ...
2016-04-06
Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun
Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less
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Evolutionary dynamics of protein domain architecture in plants
2012-01-01
Background Protein domains are the structural, functional and evolutionary units of the protein. Protein domain architectures are the linear arrangements of domain(s) in individual proteins. Although the evolutionary history of protein domain architecture has been extensively studied in microorganisms, the evolutionary dynamics of domain architecture in the plant kingdom remains largely undefined. To address this question, we analyzed the lineage-based protein domain architecture content in 14 completed green plant genomes. Results Our analyses show that all 14 plant genomes maintain similar distributions of species-specific, single-domain, and multi-domain architectures. Approximately 65% of plant domain architectures are universally present in all plant lineages, while the remaining architectures are lineage-specific. Clear examples are seen of both the loss and gain of specific protein architectures in higher plants. There has been a dynamic, lineage-wise expansion of domain architectures during plant evolution. The data suggest that this expansion can be largely explained by changes in nuclear ploidy resulting from rounds of whole genome duplications. Indeed, there has been a decrease in the number of unique domain architectures when the genomes were normalized into a presumed ancestral genome that has not undergone whole genome duplications. Conclusions Our data show the conservation of universal domain architectures in all available plant genomes, indicating the presence of an evolutionarily conserved, core set of protein components. However, the occurrence of lineage-specific domain architectures indicates that domain architecture diversity has been maintained beyond these core components in plant genomes. Although several features of genome-wide domain architecture content are conserved in plants, the data clearly demonstrate lineage-wise, progressive changes and expansions of individual protein domain architectures, reinforcing the notion that plant
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Albenzio, Marzia; Marino, Rosaria; Caroprese, Mariangela; Santillo, Antonella; Annicchiarico, Giovanni; Sevi, Agostino
2004-11-01
Effects of ventilation regimen on the quality of ewes' milk and on proteolysis in Canestrato Pugliese cheese during ripening were studied. Cheeses were manufactured from the bulk milk of Comisana ewes subjected to three different ventilation regimens, which were designated low (LOV, 23 m3/h per ewe), moderate (MOV, 47 m3/h per ewe) and programmed ventilation regimen (PROV, 73 m3/h per ewe; fan set to maintain 70% relative humidity). Bulk milk was analysed for chemical and microbial composition, renneting parameters and plasmin-plasminogen activities. At 1, 15, 30 and 45 d of ripening, the cheeses were analysed for gross chemical composition, nitrogen fractions, and plasmin and plasminogen activities. The pH 4.6-insoluble nitrogen fractions were analysed by urea-PAGE. Free amino acid content was determined at the end of ripening. Lower concentrations of bulk milk somatic cell count (BMSCC) and of mesophilic bacteria were found in the MOV group than in the LOV and the PROV groups. A lower plasminogen (PG) to plasmin (PL) ratio (PG/PL) was observed in the MOV and PROV than in the LOV cheeses. Irrespective of treatment, PL activity in cheeses was higher at 15d of ripening, while a sudden decrease of PL and PG activities was observed at 30 d, which was associated with a marked increase in non-protein nitrogen. The peptide profile characterized in the urea-PAGE showed a greater intensity of alpha- and beta-CN hydrolysis in the MOV than in the PROV and LOV cheeses. The results provide evidence that a proper ventilation regimen is critical for optimizing the hygienic quality of milk and the proteolysis of Canestrato Pugliese cheese during ripening.
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Ibrahim, Nurul 'Izzah; Khamis, Mohd Fadhli; Mod Yunoh, Mohd Faridz; Abdullah, Shahrum; Mohamed, Norazlina; Shuid, Ahmad Nazrun
2014-01-01
Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.
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A Method to Examine Content Domain Structures
ERIC Educational Resources Information Center
D'Agostino, Jerome; Karpinski, Aryn; Welsh, Megan
2011-01-01
After a test is developed, most content validation analyses shift from ascertaining domain definition to studying domain representation and relevance because the domain is assumed to be set once a test exists. We present an approach that allows for the examination of alternative domain structures based on extant test items. In our example based on…
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Predicting PDZ domain mediated protein interactions from structure
2013-01-01
Background PDZ domains are structural protein domains that recognize simple linear amino acid motifs, often at protein C-termini, and mediate protein-protein interactions (PPIs) in important biological processes, such as ion channel regulation, cell polarity and neural development. PDZ domain-peptide interaction predictors have been developed based on domain and peptide sequence information. Since domain structure is known to influence binding specificity, we hypothesized that structural information could be used to predict new interactions compared to sequence-based predictors. Results We developed a novel computational predictor of PDZ domain and C-terminal peptide interactions using a support vector machine trained with PDZ domain structure and peptide sequence information. Performance was estimated using extensive cross validation testing. We used the structure-based predictor to scan the human proteome for ligands of 218 PDZ domains and show that the predictions correspond to known PDZ domain-peptide interactions and PPIs in curated databases. The structure-based predictor is complementary to the sequence-based predictor, finding unique known and novel PPIs, and is less dependent on training–testing domain sequence similarity. We used a functional enrichment analysis of our hits to create a predicted map of PDZ domain biology. This map highlights PDZ domain involvement in diverse biological processes, some only found by the structure-based predictor. Based on this analysis, we predict novel PDZ domain involvement in xenobiotic metabolism and suggest new interactions for other processes including wound healing and Wnt signalling. Conclusions We built a structure-based predictor of PDZ domain-peptide interactions, which can be used to scan C-terminal proteomes for PDZ interactions. We also show that the structure-based predictor finds many known PDZ mediated PPIs in human that were not found by our previous sequence-based predictor and is less dependent on
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Structural classification of small, disulfide-rich protein domains.
Cheek, Sara; Krishna, S Sri; Grishin, Nick V
2006-05-26
Disulfide-rich domains are small protein domains whose global folds are stabilized primarily by the formation of disulfide bonds and, to a much lesser extent, by secondary structure and hydrophobic interactions. Disulfide-rich domains perform a wide variety of roles functioning as growth factors, toxins, enzyme inhibitors, hormones, pheromones, allergens, etc. These domains are commonly found both as independent (single-domain) proteins and as domains within larger polypeptides. Here, we present a comprehensive structural classification of approximately 3000 small, disulfide-rich protein domains. We find that these domains can be arranged into 41 fold groups on the basis of structural similarity. Our fold groups, which describe broader structural relationships than existing groupings of these domains, bring together representatives with previously unacknowledged similarities; 18 of the 41 fold groups include domains from several SCOP folds. Within the fold groups, the domains are assembled into families of homologs. We define 98 families of disulfide-rich domains, some of which include newly detected homologs, particularly among knottin-like domains. On the basis of this classification, we have examined cases of convergent and divergent evolution of functions performed by disulfide-rich proteins. Disulfide bonding patterns in these domains are also evaluated. Reducible disulfide bonding patterns are much less frequent, while symmetric disulfide bonding patterns are more common than expected from random considerations. Examples of variations in disulfide bonding patterns found within families and fold groups are discussed.
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ERIC Educational Resources Information Center
Hong, Eunsook; Peng, Yun; O'Neil, Harold F., Jr.; Wu, Junbin
2013-01-01
The study examined the effects of gender and item content of domain-general and domain-specific creative-thinking tests on four subscale scores of creative-thinking (fluency, flexibility, originality, and elaboration). Chinese tenth-grade students (234 males and 244 females) participated in the study. Domain-general creative thinking was measured…
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Separating Cognitive and Content Domains in Mathematical Competence
ERIC Educational Resources Information Center
Harks, Birgit; Klieme, Eckhard; Hartig, Johannes; Leiss, Dominik
2014-01-01
The present study investigates the empirical separability of mathematical (a) content domains, (b) cognitive domains, and (c) content-specific cognitive domains. There were 122 items representing two content domains (linear equations vs. theorem of Pythagoras) combined with two cognitive domains (modeling competence vs. technical competence)…
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Gelman, Susan A; Noles, Nicholaus S
2011-09-01
Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This article examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children's classification of biological and nonbiological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning. WIREs Cogni Sci 2011 2 490-502 DOI: 10.1002/wcs.124 This article is categorized under: Psychology > Reasoning and Decision Making. Copyright © 2010 John Wiley & Sons, Ltd.
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Functional domains of the poliovirus receptor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koike, Satoshi; Ise, Iku; Nomoto, Akio
1991-05-15
A number of mutant cDNAs of the human poliovirus receptor were constructed to identify essential regions of the molecule as the receptor. All mutant cDNAs carrying the sequence coding for the entire N-terminal immunoglobulin-like domain (domain I) confer permissiveness for poliovirus to mouse L cells, but a mutant cDNA lacking the sequence for domain I does not. The transformants permissive for poliovirus were able to bind the virus and were also recognized by monoclonal antibody D171, which competes with poliovirus for the cellular receptor. These results strongly suggest that the poliovirus binding site resides in domain I of the receptor.more » Mutant cDNAs for the sequence encoding the intracellular peptide were also constructed and expressed in mouse L cells. Susceptibility of these cells to poliovirus revealed that the entire putative cytoplasmic domain is not essential for virus infection. Thus, the cytoplasmic domain of the molecule appears not to play a role in the penetration of poliovirus.« less
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Domain analysis of Ras-association domain family member 6 upon interaction with MDM2.
Sarkar, Aradhan; Iwasa, Hiroaki; Hossain, Shakhawoat; Xu, Xiaoyin; Sawada, Takeru; Shimizu, Takanobu; Maruyama, Junichi; Arimoto-Matsuzaki, Kyoko; Hata, Yutaka
2017-01-01
The tumor suppressor Ras-association domain family member 6 (RASSF6) has Ras-association domain (RA) and Salvador/RASSF/Hippo domain (SARAH). RASSF6 antagonizes MDM2, stabilizes p53, and induces apoptosis and cell cycle arrest. We previously demonstrated the interaction between RASSF6 and MDM2, but did not determine how both proteins interact with each other. We have shown here that N-terminal, RA, and SARAH domains of RASSF6 interact with MDM2 at distinct regions. RA binds to the RING-finger region of MDM2 and stabilizes p53. SARAH binds RA and blocks the interaction between RA and MDM2. RA overexpression induces p53-dependent apoptosis and senescence. In the presence of active KRas, the interaction between RA and MDM2 is recovered. In this way, RA and SARAH play an important role in Ras-mediated regulation of p53. © 2017 Federation of European Biochemical Societies.
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Domain Decomposition By the Advancing-Partition Method
NASA Technical Reports Server (NTRS)
Pirzadeh, Shahyar Z.
2008-01-01
A new method of domain decomposition has been developed for generating unstructured grids in subdomains either sequentially or using multiple computers in parallel. Domain decomposition is a crucial and challenging step for parallel grid generation. Prior methods are generally based on auxiliary, complex, and computationally intensive operations for defining partition interfaces and usually produce grids of lower quality than those generated in single domains. The new technique, referred to as "Advancing Partition," is based on the Advancing-Front method, which partitions a domain as part of the volume mesh generation in a consistent and "natural" way. The benefits of this approach are: 1) the process of domain decomposition is highly automated, 2) partitioning of domain does not compromise the quality of the generated grids, and 3) the computational overhead for domain decomposition is minimal. The new method has been implemented in NASA's unstructured grid generation code VGRID.
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Mikkola, Esa T; Gahmberg, Carl G
2010-06-18
The protein tyrosine kinase C-terminal Src kinase (Csk) is activated by the engagement of its Src homology (SH) 2 domain. However, the molecular mechanism required for this is not completely understood. The crystal structure of the active Csk indicates that Csk could be activated by contact between the SH2 domain and the beta3-alphaC loop in the N-terminal lobe of the kinase domain. To study the importance of this interaction for the SH2-domain-mediated activation of Csk, we mutated the amino acid residues forming the contacts between the SH2 domain and the beta3-alphaC loop. The mutation of the beta3-alphaC loop Ala228 to glycine and of the SH2 domain Tyr116, Tyr133, Leu138, and Leu149 to alanine resulted in the inability of the SH2 domain ligand to activate Csk. Furthermore, the overexpressed Csk mutants A228G, Y133A/Y116A, L138A, and L149A were unable to efficiently inactivate endogenous Src in human embryonic kidney 293 cells. The results suggest that the SH2-domain-mediated activation of Csk is dependent on the binding of the beta3-alphaC loop Ala228 to the hydrophobic pocket formed by the side chains of Tyr116, Tyr133, Leu138, and Leu149 on the surface of the SH2 domain. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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The Classification of Protein Domains.
Dawson, Natalie; Sillitoe, Ian; Marsden, Russell L; Orengo, Christine A
2017-01-01
The significant expansion in protein sequence and structure data that we are now witnessing brings with it a pressing need to bring order to the protein world. Such order enables us to gain insights into the evolution of proteins, their function and the extent to which the functional repertoire can vary across the three kingdoms of life. This has lead to the creation of a wide range of protein family classifications that aim to group proteins based upon their evolutionary relationships.In this chapter we discuss the approaches and methods that are frequently used in the classification of proteins, with a specific emphasis on the classification of protein domains. The construction of both domain sequence and domain structure databases is considered and we show how the use of domain family annotations to assign structural and functional information is enhancing our understanding of genomes.
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Time-domain wavefield reconstruction inversion
NASA Astrophysics Data System (ADS)
Li, Zhen-Chun; Lin, Yu-Zhao; Zhang, Kai; Li, Yuan-Yuan; Yu, Zhen-Nan
2017-12-01
Wavefield reconstruction inversion (WRI) is an improved full waveform inversion theory that has been proposed in recent years. WRI method expands the searching space by introducing the wave equation into the objective function and reconstructing the wavefield to update model parameters, thereby improving the computing efficiency and mitigating the influence of the local minimum. However, frequency-domain WRI is difficult to apply to real seismic data because of the high computational memory demand and requirement of time-frequency transformation with additional computational costs. In this paper, wavefield reconstruction inversion theory is extended into the time domain, the augmented wave equation of WRI is derived in the time domain, and the model gradient is modified according to the numerical test with anomalies. The examples of synthetic data illustrate the accuracy of time-domain WRI and the low dependency of WRI on low-frequency information.
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Mechanistic insights into phosphoprotein-binding FHA domains.
Liang, Xiangyang; Van Doren, Steven R
2008-08-01
[Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family
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Cross-domain active learning for video concept detection
NASA Astrophysics Data System (ADS)
Li, Huan; Li, Chao; Shi, Yuan; Xiong, Zhang; Hauptmann, Alexander G.
2011-08-01
As video data from a variety of different domains (e.g., news, documentaries, entertainment) have distinctive data distributions, cross-domain video concept detection becomes an important task, in which one can reuse the labeled data of one domain to benefit the learning task in another domain with insufficient labeled data. In this paper, we approach this problem by proposing a cross-domain active learning method which iteratively queries labels of the most informative samples in the target domain. Traditional active learning assumes that the training (source domain) and test data (target domain) are from the same distribution. However, it may fail when the two domains have different distributions because querying informative samples according to a base learner that initially learned from source domain may no longer be helpful for the target domain. In our paper, we use the Gaussian random field model as the base learner which has the advantage of exploring the distributions in both domains, and adopt uncertainty sampling as the query strategy. Additionally, we present an instance weighting trick to accelerate the adaptability of the base learner, and develop an efficient model updating method which can significantly speed up the active learning process. Experimental results on TRECVID collections highlight the effectiveness.
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Curvature-induced domain wall pinning
NASA Astrophysics Data System (ADS)
Yershov, Kostiantyn V.; Kravchuk, Volodymyr P.; Sheka, Denis D.; Gaididei, Yuri
2015-09-01
It is shown that a local bend of a nanowire is a source of pinning potential for a transversal head-to-head (tail-to-tail) domain wall. Eigenfrequency of the domain wall free oscillations at the pinning potential and the effective friction are determined as functions of the curvature and domain wall width. The pinning potential originates from the effective curvature-induced Dzyaloshinsky-like term in the exchange energy. The theoretical results are verified by means of micromagnetic simulations for the case of parabolic shape of the wire bend.
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Hou, Tingjun; Zhang, Wei; Case, David A; Wang, Wei
2008-02-29
Many important protein-protein interactions are mediated by peptide recognition modular domains, such as the Src homology 3 (SH3), SH2, PDZ, and WW domains. Characterizing the interaction interface of domain-peptide complexes and predicting binding specificity for modular domains are critical for deciphering protein-protein interaction networks. Here, we propose the use of an energetic decomposition analysis to characterize domain-peptide interactions and the molecular interaction energy components (MIECs), including van der Waals, electrostatic, and desolvation energy between residue pairs on the binding interface. We show a proof-of-concept study on the amphiphysin-1 SH3 domain interacting with its peptide ligands. The structures of the human amphiphysin-1 SH3 domain complexed with 884 peptides were first modeled using virtual mutagenesis and optimized by molecular mechanics (MM) minimization. Next, the MIECs between domain and peptide residues were computed using the MM/generalized Born decomposition analysis. We conducted two types of statistical analyses on the MIECs to demonstrate their usefulness for predicting binding affinities of peptides and for classifying peptides into binder and non-binder categories. First, combining partial least squares analysis and genetic algorithm, we fitted linear regression models between the MIECs and the peptide binding affinities on the training data set. These models were then used to predict binding affinities for peptides in the test data set; the predicted values have a correlation coefficient of 0.81 and an unsigned mean error of 0.39 compared with the experimentally measured ones. The partial least squares-genetic algorithm analysis on the MIECs revealed the critical interactions for the binding specificity of the amphiphysin-1 SH3 domain. Next, a support vector machine (SVM) was employed to build classification models based on the MIECs of peptides in the training set. A rigorous training-validation procedure was
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ERIC Educational Resources Information Center
Demetriadis, Stavros; Egerter, Tina; Hanisch, Frank; Fischer, Frank
2011-01-01
This study investigates the effectiveness of using peer review in the context of scripted collaboration to foster both domain-specific and domain-general knowledge acquisition in the computer science domain. Using a one-factor design with a script and a control condition, students worked in small groups on a series of computer science problems…
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Effective description of domain wall strings
NASA Astrophysics Data System (ADS)
Rodrigues, Davi R.; Abanov, Ar.; Sinova, J.; Everschor-Sitte, K.
2018-04-01
The analysis of domain wall dynamics is often simplified to one-dimensional physics. For domain walls in thin films, more realistic approaches require the description as two-dimensional objects. This includes the study of vortices and curvatures along the domain walls as well as the influence of boundary effects. Here we provide a theory in terms of soft modes that allows us to analytically study the physics of extended domain walls and their stability. By considering irregularly shaped skyrmions as closed domain walls, we analyze their plasticity and compare their dynamics with those of circular skyrmions. Our theory directly provides an analytical description of the excitation modes of magnetic skyrmions, previously accessible only through sophisticated micromagnetic numerical calculations and spectral analysis. These analytical expressions provide the scaling behavior of the different physics on parameters that experiments can test.
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Grb7 protein RA domain oligomerization.
Godamudunage, Malika P; Foster, Albert; Warren, Darius; Lyons, Barbara A
2017-08-01
The growth factor receptor bound protein 7 (Grb7) is an adaptor protein that is often coamplified with the erythroblastosis oncogene B 2 receptor in 20% to 30% of breast cancer patients. Grb7 overexpression has been linked to increased cell migration and cancer metastasis. The ras associating and pleckstrin homology domain region of Grb7 has been reported to interact with various other downstream signaling proteins such as four and half Lin11, Isl-1, Mec-3 (LIM) domains isoform 2 and filamin α. These interactions are believed to play a role in regulating Grb7-mediated cell migration function. The full-length Grb7 protein has been shown to dimerize, and the oligomeric state of the Grb7SH2 domain has been extensively studied; however, the oligomerization state of the ras associating and pleckstrin homology domains, and the importance of this oligomerization in Grb7 function, is yet to be fully known. In this study, we characterize the oligomeric state of the Grb7RA domain using size exclusion chromatography, nuclear magnetic resonance, nuclear relaxation studies, glutaraldehyde cross linking, and dynamic light scattering. We report the Grb7RA domain can exist in transient multimeric forms and, based upon modeling results, postulate the potential role of Grb7RA domain oligomerization in Grb7 function. Copyright © 2017 John Wiley & Sons, Ltd.
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Differences between time domain and Fourier domain optical coherence tomography in imaging tissues.
Gao, W; Wu, X
2017-11-01
It has been numerously demonstrated that both time domain and Fourier domain optical coherence tomography (OCT) can generate high-resolution depth-resolved images of living tissues and cells. In this work, we compare the common points and differences between two methods when the continuous and random properties of live tissue are taken into account. It is found that when relationships that exist between the scattered light and tissue structures are taken into account, spectral interference measurements in Fourier domain OCT (FDOCT) is more advantageous than interference fringe envelope measurements in time domain OCT (TDOCT) in the cases where continuous property of tissue is taken into account. It is also demonstrated that when random property of tissue is taken into account FDOCT measures the Fourier transform of the spatial correlation function of the refractive index and speckle phenomena will limit the effective limiting imaging resolution in both TDOCT and FDOCT. Finally, the effective limiting resolution of both TDOCT and FDOCT are given which can be used to estimate the effective limiting resolution in various practical applications. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.
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Domain topology and domain switching kinetics in a hybrid improper ferroelectric
Huang, F. -T.; Xue, F.; Gao, B.; Wang, L. H.; Luo, X.; Cai, W.; Lu, X. -Z.; Rondinelli, J. M.; Chen, L. Q.; Cheong, S. -W.
2016-01-01
Charged polar interfaces such as charged ferroelectric walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO3/SrTiO3, across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric walls, which are energetically unfavourable in general, were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr)3Ti2O7 crystals. From the exploration of antiphase boundaries in bilayer-perovskites, here we discover that each of four polarization-direction states is degenerate with two antiphase domains, and these eight structural variants form a Z4 × Z2 domain structure with Z3 vortices and five distinct types of domain walls, whose topology is directly relevant to the presence of abundant charged walls. We also discover a zipper-like nature of antiphase boundaries, which are the reversible creation/annihilation centres of pairs of two types of ferroelectric walls (and also Z3-vortex pairs) in 90° and 180° polarization switching. Our results demonstrate the unexpectedly rich nature of hybrid improper ferroelectricity. PMID:27215944
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Schulz, Craig M; Scampavia, Louis; Ruzicka, Jaromir
2002-12-01
Microsequential injection (microST) provides microfluidic operations that are ideally suited for cellular function studies and as a means of validating targets for drug discovery. MicroSI carried out within the lab-on-valve (LOV) manifold, is an ideal platform for spectroscopic studies on living cells that are grown on microcarrier beads and kept thermostated while their metabolism is probed in real-time. In this paper a microbioreactor is integrated into the LOV manifold allowing measurement of cellular lactate extrusion and glucose consumption rates of a cell culture that is automatically renewed prior to each measurement. Glucose consumption and lactate extrusion are monitored using NAD-linked enzymatic assays. The microSI-LOV setup has demonstrated a linear analysis range of 0.05-1.00 mM for lactate and 0.1-5.6 mM for glucose. These assays were conducted in a serial fashion requiring 3 microL of cellular perfusate and 10 s for glucose determination and 30 s for the lactate assay. Overall waste generated per lactate/glucose assay is < 200 microL. This work was performed using two different transfected hepatocyte cell lines, which adhere to Cytopore microcarrier beads. This novel approach to metabolic screening allows for the rapid evaluation of the effects of dosing cells with chemical agents.
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Van Damme, Els J. M.; Nakamura-Tsuruta, Sachiko; Smith, David F.; Ongenaert, Maté; Winter, Harry C.; Rougé, Pierre; Goldstein, Irwin J.; Mo, Hanqing; Kominami, Junko; Culerrier, Raphaël; Barre, Annick; Hirabayashi, Jun; Peumans, Willy J.
2007-01-01
A re-investigation of the occurrence and taxonomic distribution of proteins built up of protomers consisting of two tandem arrayed domains equivalent to the GNA [Galanthus nivalis (snowdrop) agglutinin] revealed that these are widespread among monotyledonous plants. Phylogenetic analysis of the available sequences indicated that these proteins do not represent a monophylogenetic group but most probably result from multiple independent domain duplication/in tandem insertion events. To corroborate the relationship between inter-domain sequence divergence and the widening of specificity range, a detailed comparative analysis was made of the sequences and specificity of a set of two-domain GNA-related lectins. Glycan microarray analyses, frontal affinity chromatography and surface plasmon resonance measurements demonstrated that the two-domain GNA-related lectins acquired a marked diversity in carbohydrate-binding specificity that strikingly contrasts the canonical exclusive specificity of their single domain counterparts towards mannose. Moreover, it appears that most two-domain GNA-related lectins interact with both high mannose and complex N-glycans and that this dual specificity relies on the simultaneous presence of at least two different independently acting binding sites. The combined phylogenetic, specificity and structural data strongly suggest that plants used domain duplication followed by divergent evolution as a mechanism to generate multispecific lectins from a single mannose-binding domain. Taking into account that the shift in specificity of some binding sites from high mannose to complex type N-glycans implies that the two-domain GNA-related lectins are primarily directed against typical animal glycans, it is tempting to speculate that plants developed two-domain GNA-related lectins for defence purposes. PMID:17288538
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Cooperative interactions between paired domain and homeodomain.
Jun, S; Desplan, C
1996-09-01
The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.
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Underwater Advanced Time-Domain Electromagnetic System
2017-03-03
SUPPLEMENTARY NOTES 14. ABSTRACT The overall objective of the project is to design , build and demonstrate an underwater advanced time -domain...Description The overall objective of the project is to design , build and demonstrate an underwater advanced time - domain electromagnetic (TEM) system...Electromagnetic System Design (July, 2015), and in the Underwater Advanced Time -Domain Electromagnetic System Evaluation Plan (October, 2016). A
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Jothi, Raja; Cherukuri, Praveen F.; Tasneem, Asba; Przytycka, Teresa M.
2006-01-01
Recent advances in functional genomics have helped generate large-scale high-throughput protein interaction data. Such networks, though extremely valuable towards molecular level understanding of cells, do not provide any direct information about the regions (domains) in the proteins that mediate the interaction. Here, we performed co-evolutionary analysis of domains in interacting proteins in order to understand the degree of co-evolution of interacting and non-interacting domains. Using a combination of sequence and structural analysis, we analyzed protein–protein interactions in F1-ATPase, Sec23p/Sec24p, DNA-directed RNA polymerase and nuclear pore complexes, and found that interacting domain pair(s) for a given interaction exhibits higher level of co-evolution than the noninteracting domain pairs. Motivated by this finding, we developed a computational method to test the generality of the observed trend, and to predict large-scale domain–domain interactions. Given a protein–protein interaction, the proposed method predicts the domain pair(s) that is most likely to mediate the protein interaction. We applied this method on the yeast interactome to predict domain–domain interactions, and used known domain–domain interactions found in PDB crystal structures to validate our predictions. Our results show that the prediction accuracy of the proposed method is statistically significant. Comparison of our prediction results with those from two other methods reveals that only a fraction of predictions are shared by all the three methods, indicating that the proposed method can detect known interactions missed by other methods. We believe that the proposed method can be used with other methods to help identify previously unrecognized domain–domain interactions on a genome scale, and could potentially help reduce the search space for identifying interaction sites. PMID:16949097
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Hutcherson, Cendri A
2018-01-01
Are some people generally more successful using cognitive regulation or does it depend on the choice domain? Why? We combined behavioral computational modeling and multivariate decoding of fMRI responses to identify neural loci of regulation-related shifts in value representations across goals and domains (dietary or altruistic choice). Surprisingly, regulatory goals did not alter integrative value representations in the ventromedial prefrontal cortex, which represented all choice-relevant attributes across goals and domains. Instead, the dorsolateral prefrontal cortex (DLPFC) flexibly encoded goal-consistent values and predicted regulatory success for the majority of choice-relevant attributes, using attribute-specific neural codes. We also identified domain-specific exceptions: goal-dependent encoding of prosocial attributes localized to precuneus and temporo-parietal junction (not DLPFC). Our results suggest that cognitive regulation operated by changing specific attribute representations (not integrated values). Evidence of domain-general and domain-specific neural loci reveals important divisions of labor, explaining when and why regulatory success generalizes (or doesn’t) across contexts and domains. PMID:29813018
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Domain-Invariant Partial-Least-Squares Regression.
Nikzad-Langerodi, Ramin; Zellinger, Werner; Lughofer, Edwin; Saminger-Platz, Susanne
2018-05-11
Multivariate calibration models often fail to extrapolate beyond the calibration samples because of changes associated with the instrumental response, environmental condition, or sample matrix. Most of the current methods used to adapt a source calibration model to a target domain exclusively apply to calibration transfer between similar analytical devices, while generic methods for calibration-model adaptation are largely missing. To fill this gap, we here introduce domain-invariant partial-least-squares (di-PLS) regression, which extends ordinary PLS by a domain regularizer in order to align the source and target distributions in the latent-variable space. We show that a domain-invariant weight vector can be derived in closed form, which allows the integration of (partially) labeled data from the source and target domains as well as entirely unlabeled data from the latter. We test our approach on a simulated data set where the aim is to desensitize a source calibration model to an unknown interfering agent in the target domain (i.e., unsupervised model adaptation). In addition, we demonstrate unsupervised, semisupervised, and supervised model adaptation by di-PLS on two real-world near-infrared (NIR) spectroscopic data sets.
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Time Domain Stability Margin Assessment Method
NASA Technical Reports Server (NTRS)
Clements, Keith
2017-01-01
The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.
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Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H; Du, Fang K
2014-01-01
Predicting protein domains is essential for understanding a protein's function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion.
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Rating knowledge sharing in cross-domain collaborative filtering.
Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi
2015-05-01
Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.
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Supporting multiple domains in a single reuse repository
NASA Technical Reports Server (NTRS)
Eichmann, David A.
1992-01-01
Domain analysis typically results in the construction of a domain-specific repository. Such a repository imposes artificial boundaries on the sharing of similar assets between related domains. A lattice-based approach to repository modeling can preserve a reuser's domain specific view of the repository, while avoiding replication of commonly used assets and supporting a more general perspective on domain interrelationships.
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NASA Technical Reports Server (NTRS)
Mcgreevy, Michael W.
1995-01-01
An objective and quantitative method has been developed for deriving models of complex and specialized spheres of activity (domains) from domain-generated verbal data. The method was developed for analysis of interview transcripts, incident reports, and other text documents whose original source is people who are knowledgeable about, and participate in, the domain in question. To test the method, it is applied here to a report describing a remote sensing project within the scope of the Earth Observing System (EOS). The method has the potential to improve the designs of domain-related computer systems and software by quickly providing developers with explicit and objective models of the domain in a form which is useful for design. Results of the analysis include a network model of the domain, and an object-oriented relational analysis report which describes the nodes and relationships in the network model. Other products include a database of relationships in the domain, and an interactive concordance. The analysis method utilizes a newly developed relational metric, a proximity-weighted frequency of co-occurrence. The metric is applied to relations between the most frequently occurring terms (words or multiword entities) in the domain text, and the terms found within the contexts of these terms. Contextual scope is selectable. Because of the discriminating power of the metric, data reduction from the association matrix to the network is simple. In addition to their value for design. the models produced by the method are also useful for understanding the domains themselves. They can, for example, be interpreted as models of presence in the domain.
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Transitioning Domain Analysis: An Industry Experience.
1996-06-01
References 6 Implementation 6.1 Analysis of Operator Services’ Requirements Process 21 6.2 Preliminary Planning for FODA Training by SEI 21...an academic and industry partnership took feature oriented domain analysis ( FODA ) from a methodology that is still being defined to a well-documented...to pilot the use of the Software Engineering Institute (SEI) domain analysis methodology known as feature-oriented domain analysis ( FODA ). Supported
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Domain switching in single-phase multiferroics
NASA Astrophysics Data System (ADS)
Jia, Tingting; Cheng, Zhenxiang; Zhao, Hongyang; Kimura, Hideo
2018-06-01
Multiferroics are a time-honoured research subject by reason for their tremendous application potential in the information industry, such as in multi-state information storage devices and new types of sensors. An outburst of studies on multiferroicity has been witnessed in the 21st century, although this field has a long research history since the 19th century. Multiferroicity has now become one of the hottest research topics in condensed matter physics and materials science. Numerous efforts have been made to investigate the cross-coupling phenomena among ferroic orders such as ferroelectricity, (anti-)ferromagnetism, and ferroelasticity, especially the coupling between electric and magnetic orderings that would account for the magnetoelectric (ME) effect in multiferroic materials. The magnetoelectric properties and coupling behavior of single phase multiferroics are dominated by their domain structures. It was also noted that, however, the multiferroic materials exhibit very complicated domain structures. Studies on domain structure characterization and domain switching are a crucial step in the exploration of approaches to the control and manipulation of magnetic (electric) properties using an electric (magnetic) field or other means. In this review, following a concise outline of our current basic knowledge on the magnetoelectric (ME) effect, we summarize some important research activities on domain switching in single-phase multiferroic materials in the form of single crystals and thin films, especially domain switching behavior involving strain and the related physics in the last decade. We also introduce recent developments in characterization techniques for domain structures of ferroelectric or multiferroic materials, which have significantly advanced our understanding of domain switching dynamics and interactions. The effects of a series of issues such as electric field, magnetic field, and stress effects on domain switching are been discussed as well. It
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Ribosomal small subunit domains radiate from a central core
NASA Astrophysics Data System (ADS)
Gulen, Burak; Petrov, Anton S.; Okafor, C. Denise; Vander Wood, Drew; O'Neill, Eric B.; Hud, Nicholas V.; Williams, Loren Dean
2016-02-01
The domain architecture of a large RNA can help explain and/or predict folding, function, biogenesis and evolution. We offer a formal and general definition of an RNA domain and use that definition to experimentally characterize the rRNA of the ribosomal small subunit. Here the rRNA comprising a domain is compact, with a self-contained system of molecular interactions. A given rRNA helix or stem-loop must be allocated uniquely to a single domain. Local changes such as mutations can give domain-wide effects. Helices within a domain have interdependent orientations, stabilities and interactions. With these criteria we identify a core domain (domain A) of small subunit rRNA. Domain A acts as a hub, linking the four peripheral domains and imposing orientational and positional restraints on the other domains. Experimental characterization of isolated domain A, and mutations and truncations of it, by methods including selective 2‧OH acylation analyzed by primer extension and circular dichroism spectroscopy are consistent with our architectural model. The results support the utility of the concept of an RNA domain. Domain A, which exhibits structural similarity to tRNA, appears to be an essential core of the small ribosomal subunit.
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Current polarity-dependent manipulation of antiferromagnetic domains
NASA Astrophysics Data System (ADS)
Wadley, Peter; Reimers, Sonka; Grzybowski, Michal J.; Andrews, Carl; Wang, Mu; Chauhan, Jasbinder S.; Gallagher, Bryan L.; Campion, Richard P.; Edmonds, Kevin W.; Dhesi, Sarnjeet S.; Maccherozzi, Francesco; Novak, Vit; Wunderlich, Joerg; Jungwirth, Tomas
2018-05-01
Antiferromagnets have several favourable properties as active elements in spintronic devices, including ultra-fast dynamics, zero stray fields and insensitivity to external magnetic fields1. Tetragonal CuMnAs is a testbed system in which the antiferromagnetic order parameter can be switched reversibly at ambient conditions using electrical currents2. In previous experiments, orthogonal in-plane current pulses were used to induce 90° rotations of antiferromagnetic domains and demonstrate the operation of all-electrical memory bits in a multi-terminal geometry3. Here, we demonstrate that antiferromagnetic domain walls can be manipulated to realize stable and reproducible domain changes using only two electrical contacts. This is achieved by using the polarity of the current to switch the sign of the current-induced effective field acting on the antiferromagnetic sublattices. The resulting reversible domain and domain wall reconfigurations are imaged using X-ray magnetic linear dichroism microscopy, and can also be detected electrically. Switching by domain-wall motion can occur at much lower current densities than those needed for coherent domain switching.
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J domain independent functions of J proteins.
Ajit Tamadaddi, Chetana; Sahi, Chandan
2016-07-01
Heat shock proteins of 40 kDa (Hsp40s), also called J proteins, are obligate partners of Hsp70s. Via their highly conserved and functionally critical J domain, J proteins interact and modulate the activity of their Hsp70 partners. Mutations in the critical residues in the J domain often result in the null phenotype for the J protein in question. However, as more J proteins have been characterized, it is becoming increasingly clear that a significant number of J proteins do not "completely" rely on their J domains to carry out their cellular functions, as previously thought. In some cases, regions outside the highly conserved J domain have become more important making the J domain dispensable for some, if not for all functions of a J protein. This has profound effects on the evolution of such J proteins. Here we present selected examples of J proteins that perform J domain independent functions and discuss this in the context of evolution of J proteins with dispensable J domains and J-like proteins in eukaryotes.
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Fractional diffusion on bounded domains
Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...
2015-03-13
We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.
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Domain engineering of the metastable domains in the 4f-uniaxial-ferromagnet CeRu2Ga2B
NASA Astrophysics Data System (ADS)
Wulferding, D.; Kim, H.; Yang, I.; Jeong, J.; Barros, K.; Kato, Y.; Martin, I.; Ayala-Valenzuela, O. E.; Lee, M.; Choi, H. C.; Ronning, F.; Civale, L.; Baumbach, R. E.; Bauer, E. D.; Thompson, J. D.; Movshovich, R.; Kim, Jeehoon
2017-04-01
In search of novel, improved materials for magnetic data storage and spintronic devices, compounds that allow a tailoring of magnetic domain shapes and sizes are essential. Good candidates are materials with intrinsic anisotropies or competing interactions, as they are prone to host various domain phases that can be easily and precisely selected by external tuning parameters such as temperature and magnetic field. Here, we utilize vector magnetic fields to visualize directly the magnetic anisotropy in the uniaxial ferromagnet CeRu2Ga2B. We demonstrate a feasible control both globally and locally of domain shapes and sizes by the external field as well as a smooth transition from single stripe to bubble domains, which opens the door to future applications based on magnetic domain tailoring.
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NASA Astrophysics Data System (ADS)
Xuan, Albert L.; Shinghal, Rajjan
1989-03-01
As the need for knowledge-based systems increases, an increasing number of domain experts are becoming interested in taking more active part in the building of knowledge-based systems. However, such a domain expert often must deal with a large number of unfamiliar terms concepts, facts, procedures and principles based on different approaches and schools of thought. He (for brevity, we shall use masculine pronouns for both genders) may need the help of a knowledge engineer (KE) in building the knowledge-based system but may encounter a number of problems. For instance, much of the early interaction between him and the knowl edge engineer may be spent in educating each other about their seperate kinds of expertise. Since the knowledge engineer will usually be ignorant of the knowledge domain while the domain expert (DE) will have little knowledge about knowledge-based systems, a great deal of time will be wasted on these issues ad the DE and the KE train each other to the point where a fruitful interaction can occur. In some situations, it may not even be possible for the DE to find a suitable KE to work with because he has no time to train the latter in his domain. This will engender the need for the DE to be more knowledgeable about knowledge-based systems and for the KE to find methods and techniques which will allow them to learn new domains as fast as they can. In any event, it is likely that the process of building knowledge-based systems will be smooth, er and more efficient if the domain expert is knowledgeable about the methods and techniques of knowledge-based systems building.
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Pectin Homogalacturonans: Nanostructural Characterization of Methylesterified Domains
USDA-ARS?s Scientific Manuscript database
Functionality of pectic hydrocolloids is largely dependent on the two major domains commonly found in their homogalacturonan (HG) regions, i.e., methylester protected domains (MPDs)and non methylesterified domains (NMDs). MPDs can participate in hydrogen bonding and hydrophobic interactions but unli...
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Formal Language Design in the Context of Domain Engineering
2000-03-28
73 Related Work 75 5.1 Feature oriented domain analysis ( FODA ) 75 5.2 Organizational domain modeling (ODM) 76 5.3 Domain-Specific Software...However there are only a few that are well defined and used repeatedly in practice. These include: Feature oriented domain analysis ( FODA ), Organizational...Feature oriented domain analysis ( FODA ) Feature oriented domain analysis ( FODA ) is a domain analysis method being researched and applied by the SEI
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Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi
2006-03-31
Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of "domain-specific" second-generation ACE inhibitors.
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Raman, Rajeev; Rajanikanth, V; Palaniappan, Raghavan U M; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P; Sharma, Yogendra; Chang, Yung-Fu
2010-12-29
Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th) (Lig A9) and 10(th) repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.
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Mechanical Properties of Nanoscopic Lipid Domains
Nickels, Jonathan D.; Cheng, Xiaolin; Mostofian, Barmak; ...
2015-09-28
We found that the lipid raft hypothesis presents insight into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. Thus, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approachesmore » with inelastic neutron scattering, we isolate the bending modulus of ~13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. Moreover, from additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.« less
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Domain engineering of the metastable domains in the 4f-uniaxial-ferromagnet CeRu 2Ga 2B
Wulferding, Dirk; Kim, Hoon; Yang, Ilkyu; ...
2017-04-10
In search of novel, improved materials for magnetic data storage and spintronic devices, compounds that allow a tailoring of magnetic domain shapes and sizes are essential. Good candidates are materials with intrinsic anisotropies or competing interactions, as they are prone to host various domain phases that can be easily and precisely selected by external tuning parameters such as temperature and magnetic field. Here, we utilize vector magnetic fields to visualize directly the magnetic anisotropy in the uniaxial ferromagnet CeRu 2Ga 2B. We demonstrate a feasible control both globally and locally of domain shapes and sizes by the external field asmore » well as a smooth transition from single stripe to bubble domains, which opens the door to future applications based on magnetic domain tailoring.« less
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A Unified Approach to Intra-Domain Security
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shue, Craig A; Kalafut, Andrew J.; Gupta, Prof. Minaxi
2009-01-01
While a variety of mechanisms have been developed for securing individual intra-domain protocols, none address the issue in a holistic manner. We develop a unified framework to secure prominent networking protocols within a single domain. We begin with a secure version of the DHCP protocol, which has the additional feature of providing each host with a certificate. We then leverage these certificates to secure ARP, prevent spoofing within the domain, and secure SSH and VPN connections between the domain and hosts which have previously interacted with it locally. In doing so, we also develop an incrementally deployable public key infrastructuremore » which can later be leveraged to support inter-domain authentication.« less
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2017 Emerging Technology Domains Risk Survey
2017-10-01
REV-03.18.2016.0 2017 Emerging Technology Domains Risk Survey Daniel Klinedinst Joel Land Kyle O’Meara October 2017 TECHNICAL REPORT CMU/SEI...to the CERT/CC 2016 Emerging Technol- ogy Domains Risk Survey [King 2016]. This list does not supersede previous reports. Many of the previously... Survey [King 2016]. Table 1: New and Emerging Technologies Gartner’s 2015 List of New Technology CERT’s List of Emerging Domains Trust Boundary
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Further insight into BRUTUS domain composition and functionality
Matthiadis, Anna; Long, Terri A.
2016-01-01
ABSTRACT BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis. PMID:27359166
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Further insight into BRUTUS domain composition and functionality.
Matthiadis, Anna; Long, Terri A
2016-08-02
BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis.
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ERIC Educational Resources Information Center
Tiruneh, Dawit Tibebu; Weldeslassie, Ataklti G.; Kassa, Abrham; Tefera, Zinaye; De Cock, Mieke; Elen, Jan
2016-01-01
Identifying effective instructional approaches that stimulate students' critical thinking (CT) has been the focus of a large body of empirical research. However, there is little agreement on the instructional principles and procedures that are theoretically sound and empirically valid to developing both domain-specific and domain-general CT…
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Yarkoni, Orr; Donlon, Lynn; Frankel, Daniel
2012-12-01
Manipulation of signal transduction pathways presents a viable mechanism to interface cells with electronics. In this work, we present a two-step signal transduction pathway involving cellular and electronic transduction elements. In order to circumvent many of the conventional difficulties encountered when harnessing chemical signalling for the purpose of electronics communication, gaseous nitric oxide (NO) was selected as the signalling molecule. By genetic engineering of the nitric oxide synthase protein eNOS and insertion of light-oxygen-voltage (LOV) domains, we have created a photoactive version of the protein. The novel chimeric eNOS was found to be capable of producing NO in response to excitation by visible light. By coupling these mutant cells to a surface modified platinum electrode, it was possible to convert an optical signal into a chemical one, followed by subsequent conversion of the chemical signal into an electrical output.
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Light-Inducible Gene Regulation with Engineered Zinc Finger Proteins
Polstein, Lauren R.; Gersbach, Charles A.
2014-01-01
The coupling of light-inducible protein-protein interactions with gene regulation systems has enabled the control of gene expression with light. In particular, heterodimer protein pairs from plants can be used to engineer a gene regulation system in mammalian cells that is reversible, repeatable, tunable, controllable in a spatiotemporal manner, and targetable to any DNA sequence. This system, Light-Inducible Transcription using Engineered Zinc finger proteins (LITEZ), is based on the blue light-induced interaction of GIGANTEA and the LOV domain of FKF1 that drives the localization of a transcriptional activator to the DNA-binding site of a highly customizable engineered zinc finger protein. This chapter provides methods for modifying LITEZ to target new DNA sequences, engineering a programmable LED array to illuminate cell cultures, and using the modified LITEZ system to achieve spatiotemporal control of transgene expression in mammalian cells. PMID:24718797
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Robust ferromagnetism carried by antiferromagnetic domain walls
NASA Astrophysics Data System (ADS)
Hirose, Hishiro T.; Yamaura, Jun-Ichi; Hiroi, Zenji
2017-02-01
Ferroic materials, such as ferromagnetic or ferroelectric materials, have been utilized as recording media for memory devices. A recent trend for downsizing, however, requires an alternative, because ferroic orders tend to become unstable for miniaturization. The domain wall nanoelectronics is a new developing direction for next-generation devices, in which atomic domain walls, rather than conventional, large domains themselves, are the active elements. Here we show that atomically thin magnetic domain walls generated in the antiferromagnetic insulator Cd2Os2O7 carry unusual ferromagnetic moments perpendicular to the wall as well as electron conductivity: the ferromagnetic moments are easily polarized even by a tiny field of 1 mT at high temperature, while, once cooled down, they are surprisingly robust even in an inverse magnetic field of 7 T. Thus, the magnetic domain walls could serve as a new-type of microscopic, switchable and electrically readable magnetic medium which is potentially important for future applications in the domain wall nanoelectronics.
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Robust ferromagnetism carried by antiferromagnetic domain walls
Hirose, Hishiro T.; Yamaura, Jun-ichi; Hiroi, Zenji
2017-01-01
Ferroic materials, such as ferromagnetic or ferroelectric materials, have been utilized as recording media for memory devices. A recent trend for downsizing, however, requires an alternative, because ferroic orders tend to become unstable for miniaturization. The domain wall nanoelectronics is a new developing direction for next-generation devices, in which atomic domain walls, rather than conventional, large domains themselves, are the active elements. Here we show that atomically thin magnetic domain walls generated in the antiferromagnetic insulator Cd2Os2O7 carry unusual ferromagnetic moments perpendicular to the wall as well as electron conductivity: the ferromagnetic moments are easily polarized even by a tiny field of 1 mT at high temperature, while, once cooled down, they are surprisingly robust even in an inverse magnetic field of 7 T. Thus, the magnetic domain walls could serve as a new-type of microscopic, switchable and electrically readable magnetic medium which is potentially important for future applications in the domain wall nanoelectronics. PMID:28195565
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Stable spin domains in a nondegenerate ultracold gas
NASA Astrophysics Data System (ADS)
Graham, S. D.; Niroomand, D.; Ragan, R. J.; McGuirk, J. M.
2018-05-01
We study the stability of two-domain spin structures in an ultracold gas of magnetically trapped 87Rb atoms above quantum degeneracy. Adding a small effective magnetic field gradient stabilizes the domains via coherent collective spin rotation effects, despite negligibly perturbing the potential energy relative to the thermal energy. We demonstrate that domain stabilization is accomplished through decoupling the dynamics of longitudinal magnetization, which remains in time-independent domains, from transverse magnetization, which undergoes a purely transverse spin wave trapped within the domain wall. We explore the effect of temperature and density on the steady-state domains, and compare our results to a hydrodynamic solution to a quantum Boltzmann equation.
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Domain wall conductivity in KTiOPO4 crystals
NASA Astrophysics Data System (ADS)
Lindgren, G.; Canalias, C.
2017-07-01
We study the local ionic conductivity of ferroelectric domain walls and domains in KTiOPO4 single-crystals. We show a fourfold increase in conductivity at the domain walls, compared to that of the domains, attributed to an increased concentration of defects. Our current-voltage measurements reveal memristive-like behavior associated with topographic changes and permanent charge displacement. This behavior is observed for all the voltage sweep-rates at the domain walls, while it only occurs for low frequencies at the domains. We attribute these findings to the redistribution of ions due to the applied bias and their effect on the tip-sample barrier.
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Chaikam, Vijay; Karlson, Dale T
2010-01-01
The cold shock domain (CSD) is among the most ancient and well conserved nucleic acid binding domains from bacteria to higher animals and plants. The CSD facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold shock domain proteins are mediated by this nucleic acid binding activity. In prokaryotes, cold shock domain proteins only contain a single CSD and are termed cold shock proteins (Csps). In animal model systems, various auxiliary domains are present in addition to the CSD and are commonly named Y-box proteins. Similar to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to their N-terminal CSD. Cold shock domain proteins have been shown to play important roles in development and stress adaptation in wide variety of organisms. In this review, the structure, function and regulation of plant CSPs are compared and contrasted to the characteristics of bacterial and animal CSPs. [BMB reports 2010; 43(1): 1-8].
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ERIC Educational Resources Information Center
Geary, David C.; Nicholas, Alan; Li, Yaoran; Sun, Jianguo
2017-01-01
The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects, and domain-specific effects were indexed by prior grade…
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Optimal domain decomposition strategies
NASA Technical Reports Server (NTRS)
Yoon, Yonghyun; Soni, Bharat K.
1995-01-01
The primary interest of the authors is in the area of grid generation, in particular, optimal domain decomposition about realistic configurations. A grid generation procedure with optimal blocking strategies has been developed to generate multi-block grids for a circular-to-rectangular transition duct. The focus of this study is the domain decomposition which optimizes solution algorithm/block compatibility based on geometrical complexities as well as the physical characteristics of flow field. The progress realized in this study is summarized in this paper.
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Graph-theoretic approach to quantum correlations.
Cabello, Adán; Severini, Simone; Winter, Andreas
2014-01-31
Correlations in Bell and noncontextuality inequalities can be expressed as a positive linear combination of probabilities of events. Exclusive events can be represented as adjacent vertices of a graph, so correlations can be associated to a subgraph. We show that the maximum value of the correlations for classical, quantum, and more general theories is the independence number, the Lovász number, and the fractional packing number of this subgraph, respectively. We also show that, for any graph, there is always a correlation experiment such that the set of quantum probabilities is exactly the Grötschel-Lovász-Schrijver theta body. This identifies these combinatorial notions as fundamental physical objects and provides a method for singling out experiments with quantum correlations on demand.
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Drin, Guillaume; Douguet, Dominique; Scarlata, Suzanne
2008-01-01
Phospholipase C-beta (PLCβ) enzymes are activated by Gαq and Gβγ subunits and catalyze the hydrolysis of the minor membrane lipid phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2). Activation of PLCβ2 by Gβγ subunits has been shown to be conferred through its N-terminal pleckstrin homology (PH) domain although the underlying mechanism is unclear. Also unclear are observations that the extent of Gβγ activation differs on different membrane surfaces. In this study, we have identified a unique region of the PH domain of PLCβ2 domain (residues 71-88) which, when added to the enzyme as a peptide, causes enzyme activation similar to Gβγ subunits. This PH domain segment interacts strongly with membranes composed of lipid mixtures but not those containing lipids with electrically neutral zwitterionic head groups. Moreso, addition of this segment perturbs interaction of the catalytic domain, but not the PH domain, with membrane surfaces. We monitored the orientation of the PH and catalytic domains of PLC by intermolecular fluorescence resonance energy transfer (FRET) using the Gβγ activatable mutant, PLCβ2/δ1(C193S). We find an increase in FRET with binding to membranes with mixed lipids but not to those containing only lipids with electrically neutral head groups. These results suggest that enzymatic activation can be conferred through optimal association of the PHβ71-88 region to specific membrane surfaces. These studies allow us to understand the basis of variations of Gβγ activation on different membrane surfaces. PMID:16669615
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Domain similarity based orthology detection.
Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich
2015-05-13
Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .
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The SH2 domain interaction landscape.
Tinti, Michele; Kiemer, Lars; Costa, Stefano; Miller, Martin L; Sacco, Francesca; Olsen, Jesper V; Carducci, Martina; Paoluzi, Serena; Langone, Francesca; Workman, Christopher T; Blom, Nikolaj; Machida, Kazuya; Thompson, Christopher M; Schutkowski, Mike; Brunak, Søren; Mann, Matthias; Mayer, Bruce J; Castagnoli, Luisa; Cesareni, Gianni
2013-04-25
Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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OST-HTH: a novel predicted RNA-binding domain
2010-01-01
Background The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. Results Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Conclusions Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. Reviewers This article was reviewed by Sandor Pongor and Arcady Mushegian. PMID:20302647
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tian, Lei; School of Materials Science and Engineering, Dalian Jiaotong University, Dalian, Liaoning 116028; Wang, Yumei, E-mail: wangym@iphy.ac.cn
2015-03-16
Using the advanced spherical aberration-corrected high angle annular dark field scanning transmission electron microscope imaging techniques, we investigated atomic-scale structural features of domain walls and domain patterns in YMnO{sub 3} single crystal. Three different types of interlocked ferroelectric-antiphase domain walls and two abnormal topological four-state vortex-like domain patterns are identified. Each ferroelectric domain wall is accompanied by a translation vector, i.e., 1/6[210] or −1/6[210], demonstrating its interlocked nature. Different from the four-state vortex domain patterns caused by a partial edge dislocation, two four-state vortex-like domain configurations have been obtained at atomic level. These observed phenomena can further extend our understandingmore » of the fascinating vortex domain patterns in multiferroic hexagonal rare-earth manganites.« less
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ERIC Educational Resources Information Center
Kolata, Stefan; Light, Kenneth; Matzel, Louis D.
2008-01-01
It has been established that both domain-specific (e.g. spatial) as well as domain-general (general intelligence) factors influence human cognition. However, the separation of these processes has rarely been attempted in studies using laboratory animals. Previously, we have found that the performances of outbred mice across a wide range of…
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Multiple hypothesis tracking for the cyber domain
NASA Astrophysics Data System (ADS)
Schwoegler, Stefan; Blackman, Sam; Holsopple, Jared; Hirsch, Michael J.
2011-09-01
This paper discusses how methods used for conventional multiple hypothesis tracking (MHT) can be extended to domain-agnostic tracking of entities from non-kinematic constraints such as those imposed by cyber attacks in a potentially dense false alarm background. MHT is widely recognized as the premier method to avoid corrupting tracks with spurious data in the kinematic domain but it has not been extensively applied to other problem domains. The traditional approach is to tightly couple track maintenance (prediction, gating, filtering, probabilistic pruning, and target confirmation) with hypothesis management (clustering, incompatibility maintenance, hypothesis formation, and Nassociation pruning). However, by separating the domain specific track maintenance portion from the domain agnostic hypothesis management piece, we can begin to apply the wealth of knowledge gained from ground and air tracking solutions to the cyber (and other) domains. These realizations led to the creation of Raytheon's Multiple Hypothesis Extensible Tracking Architecture (MHETA). In this paper, we showcase MHETA for the cyber domain, plugging in a well established method, CUBRC's INFormation Engine for Real-time Decision making, (INFERD), for the association portion of the MHT. The result is a CyberMHT. We demonstrate the power of MHETA-INFERD using simulated data. Using metrics from both the tracking and cyber domains, we show that while no tracker is perfect, by applying MHETA-INFERD, advanced nonkinematic tracks can be captured in an automated way, perform better than non-MHT approaches, and decrease analyst response time to cyber threats.
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Membrane-Sculpting BAR Domains Generate Stable Lipid Microdomains
Zhao, Hongxia; Michelot, Alphée; Koskela, Essi V.; Tkach, Vadym; Stamou, Dimitrios; Drubin, David G.; Lappalainen, Pekka
2014-01-01
SUMMARY Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of many cellular processes involving membrane dynamics. BAR domains sculpt phosphoinositide-rich membranes to generate membrane protrusions or invaginations. Here, we report that, in addition to regulating membrane geometry, BAR domains can generate extremely stable lipid microdomains by “freezing” phosphoinositide dynamics. This is a general feature of BAR domains, because the yeast endocytic BAR and Fes/CIP4 homology BAR (F-BAR) domains, the inverse BAR domain of Pinkbar, and the eisosomal BAR protein Lsp1 induced phosphoinositide clustering and halted lipid diffusion, despite differences in mechanisms of membrane interactions. Lsp1 displays comparable low diffusion rates in vitro and in vivo, suggesting that BAR domain proteins also generate stable phosphoinositide microdomains in cells. These results uncover a conserved role for BAR superfamily proteins in regulating lipid dynamics within membranes. Stable microdomains induced by BAR domain scaffolds and specific lipids can generate phase boundaries and diffusion barriers, which may have profound impacts on diverse cellular processes. PMID:24055060
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Membrane-sculpting BAR domains generate stable lipid microdomains.
Zhao, Hongxia; Michelot, Alphée; Koskela, Essi V; Tkach, Vadym; Stamou, Dimitrios; Drubin, David G; Lappalainen, Pekka
2013-09-26
Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of many cellular processes involving membrane dynamics. BAR domains sculpt phosphoinositide-rich membranes to generate membrane protrusions or invaginations. Here, we report that, in addition to regulating membrane geometry, BAR domains can generate extremely stable lipid microdomains by "freezing" phosphoinositide dynamics. This is a general feature of BAR domains, because the yeast endocytic BAR and Fes/CIP4 homology BAR (F-BAR) domains, the inverse BAR domain of Pinkbar, and the eisosomal BAR protein Lsp1 induced phosphoinositide clustering and halted lipid diffusion, despite differences in mechanisms of membrane interactions. Lsp1 displays comparable low diffusion rates in vitro and in vivo, suggesting that BAR domain proteins also generate stable phosphoinositide microdomains in cells. These results uncover a conserved role for BAR superfamily proteins in regulating lipid dynamics within membranes. Stable microdomains induced by BAR domain scaffolds and specific lipids can generate phase boundaries and diffusion barriers, which may have profound impacts on diverse cellular processes. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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Magnetic thin-film split-domain current sensor-recorder
Hsieh, Edmund J.
1979-01-01
A sensor-recorder for recording a representation of the direction and peak amplitude of a transient current. A magnetic thin film is coated on a glass substrate under the influence of a magnetic field so that the finished film is magnetically uniaxial and anisotropic. The film is split into two oppositely magnetized contiguous domains with a central boundary by subjecting adjacent portions of the film simultaneously to magnetic fields that are opposed 180.degree.. With the split-domain sensor-recorder placed with the film plane and domain boundary either perpendicular or parallel to the expected conductive path of a transient current, the occurrence of the transient causes switching of a portion of one domain to the direction of the other domain. The amount of the switched domain portion is indicative of the amplitude of the peak current of the transient, while the particular domain that is switched is indicative of the direction of the current. The resulting domain patterns may be read with a passive magnetic tape viewer.
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Stress-induced reversible and irreversible ferroelectric domain switching
NASA Astrophysics Data System (ADS)
Chen, Zibin; Huang, Qianwei; Wang, Feifei; Ringer, Simon P.; Luo, Haosu; Liao, Xiaozhou
2018-04-01
Ferroelectric materials have been extensively explored for applications in electronic devices because of their ferroelectric/ferroelastic domain switching behaviour under electric bias or mechanical stress. Recent findings on applying mechanical loading to manipulate reversible logical signals in non-volatile ferroelectric memory devices make ferroelectric materials more attractive to scientists and engineers. However, the dynamical microscopic structural behaviour of ferroelectric domains under stress is not well understood, which limits the applications of ferroelectric/ferroelastic switching in memory devices. Here, the kinetics of reversible and irreversible ferroelectric domain switching induced by mechanical stress in relaxor-based ferroelectrics was explored. In-situ transmission electron microscopy investigation revealed that 90° ferroelastic and 180° ferroelectric domain switching can be induced by low and high mechanical stresses. The nucleation and growth of nanoscale domains overwhelm the defect-induced pinning effect on the stable micro-domain walls. This study provides deep insights for exploring the mechanical kinetics for ferroelectric/ferroelastic domains and a clear pathway to overcome the domain pinning effect of defects in ferroelectrics.
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On the domain of the Nelson Hamiltonian
NASA Astrophysics Data System (ADS)
Griesemer, M.; Wünsch, A.
2018-04-01
The Nelson Hamiltonian is unitarily equivalent to a Hamiltonian defined through a closed, semibounded quadratic form, the unitary transformation being explicitly known and due to Gross. In this paper, we study the mapping properties of the Gross-transform in order to characterize the regularity properties of vectors in the form domain of the Nelson Hamiltonian. Since the operator domain is a subset of the form domain, our results apply to vectors in the domain of the Hamiltonian as well. This work is a continuation of our previous work on the Fröhlich Hamiltonian.
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Palaniappan, Raghavan U. M.; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P.; Sharma, Yogendra; Chang, Yung-Fu
2010-01-01
Background Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca2+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca2+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. Principal Findings We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9th (Lig A9) and 10th repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca2+ with dissociation constants of 2–4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. Conclusions We demonstrate that the Lig are Ca2+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca2+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca2+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca2+ binding. PMID:21206924
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SH2 domains: modulators of nonreceptor tyrosine kinase activity.
Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan
2009-12-01
The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members. However, biochemical characterization showed that the presence of the SH2 domain is frequently required for catalytic activity, suggesting a crucial function stabilizing the active state of many nonreceptor tyrosine kinases. Recently, the structure of the SH2-kinase domain of Fes revealed that the SH2 domain stabilizes the active kinase conformation by direct interactions with the regulatory helix alphaC. Stabilizing interactions between the SH2 and the kinase domains have also been observed in the structures of active Csk and Abl. Interestingly, mutations in the SH2 domain found in human disease can be explained by SH2 domain destabilization or incorrect positioning of the SH2. Here we summarize our understanding of mechanisms that lead to tyrosine kinase activation by direct interactions mediated by the SH2 domain and discuss how mutations in the SH2 domain trigger kinase inactivation.
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Substructure coupling in the frequency domain
NASA Technical Reports Server (NTRS)
1985-01-01
Frequency domain analysis was found to be a suitable method for determining the transient response of systems subjected to a wide variety of loads. However, since a large number of calculations are performed within the discrete frequency loop, the method loses it computational efficiency if the loads must be represented by a large number of discrete frequencies. It was also discovered that substructure coupling in the frequency domain work particularly well for analyzing structural system with a small number of interface and loaded degrees of freedom. It was discovered that substructure coupling in the frequency domain can lead to an efficient method of obtaining natural frequencies of undamped structures. It was also found that the damped natural frequencies of a system may be determined using frequency domain techniques.
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Thermal stability of bubble domains in ferromagnetic discs
NASA Astrophysics Data System (ADS)
Hrkac, G.; Bance, S.; Goncharov, A.; Schrefl, T.; Suess, D.
2007-05-01
The transition and thermal stability of disc-shaped ferromagnetic particles at the temperature of T = 300 K with a uniaxial anisotropy along the symmetry axis from a bi-domain to a single domain state has been studied. The nudge elastic band method was used to map the energy landscape and to calculate the energy barrier between the transition states. For single FePt disc-shaped particles with perpendicular anisotropy three transition configurations have been found: single domain, stripe- and stable bubble domains at zero applied field. The single domain configuration along the positive anisotropy axis is reached by an annihilation process of the domain wall and the all-down state by a complex domain expansion process. Magnetization configurations in two interacting discs show an increase in thermal stability compared with single disc systems, which is attributed to the interacting magnetostatic energy between the two particles.
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Recombinant spider silk genetically functionalized with affinity domains.
Jansson, Ronnie; Thatikonda, Naresh; Lindberg, Diana; Rising, Anna; Johansson, Jan; Nygren, Per-Åke; Hedhammar, My
2014-05-12
Functionalization of biocompatible materials for presentation of active protein domains is an area of growing interest. Herein, we describe a strategy for functionalization of recombinant spider silk via gene fusion to affinity domains of broad biotechnological use. Four affinity domains of different origin and structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and the biotin-binding domain M4, were all successfully produced as soluble silk fusion proteins under nondenaturing purification conditions. Silk films and fibers produced from the fusion proteins were demonstrated to be chemically and thermally stable. Still, the bioactive domains are concluded to be folded and accessible, since their respective targets could be selectively captured from complex samples, including rabbit serum and human plasma. Interestingly, materials produced from mixtures of two different silk fusion proteins displayed combined binding properties, suggesting that tailor-made materials with desired stoichiometry and surface distributions of several binding domains can be produced. Further, use of the IgG binding ability as a general mean for presentation of desired biomolecules could be demonstrated for a human vascular endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken together, this study demonstrates the potential of recombinant silk, genetically functionalized with affinity domains, for construction of biomaterials capable of presentation of almost any desired biomolecule.
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Barrera, Alejandro; Alastruey-Izquierdo, Ana; Martín, María J.; Cuesta, Isabel; Vizcaíno, Juan Antonio
2014-01-01
Over the past several years fungal infections have shown an increasing incidence in the susceptible population, and caused high mortality rates. In parallel, multi-resistant fungi are emerging in human infections. Therefore, the identification of new potential antifungal targets is a priority. The first task of this study was to analyse the protein domain and domain architecture content of the 137 fungal proteomes (corresponding to 111 species) available in UniProtKB (UniProt KnowledgeBase) by January 2013. The resulting list of core and exclusive domain and domain architectures is provided in this paper. It delineates the different levels of fungal taxonomic classification: phylum, subphylum, order, genus and species. The analysis highlighted Aspergillus as the most diverse genus in terms of exclusive domain content. In addition, we also investigated which domains could be considered promiscuous in the different organisms. As an application of this analysis, we explored three different ways to detect potential targets for antifungal drugs. First, we compared the domain and domain architecture content of the human and fungal proteomes, and identified those domains and domain architectures only present in fungi. Secondly, we looked for information regarding fungal pathways in public repositories, where proteins containing promiscuous domains could be involved. Three pathways were identified as a result: lovastatin biosynthesis, xylan degradation and biosynthesis of siroheme. Finally, we classified a subset of the studied fungi in five groups depending on their occurrence in clinical samples. We then looked for exclusive domains in the groups that were more relevant clinically and determined which of them had the potential to bind small molecules. Overall, this study provides a comprehensive analysis of the available fungal proteomes and shows three approaches that can be used as a first step in the detection of new antifungal targets. PMID:25033262
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Barrera, Alejandro; Alastruey-Izquierdo, Ana; Martín, María J; Cuesta, Isabel; Vizcaíno, Juan Antonio
2014-07-01
Over the past several years fungal infections have shown an increasing incidence in the susceptible population, and caused high mortality rates. In parallel, multi-resistant fungi are emerging in human infections. Therefore, the identification of new potential antifungal targets is a priority. The first task of this study was to analyse the protein domain and domain architecture content of the 137 fungal proteomes (corresponding to 111 species) available in UniProtKB (UniProt KnowledgeBase) by January 2013. The resulting list of core and exclusive domain and domain architectures is provided in this paper. It delineates the different levels of fungal taxonomic classification: phylum, subphylum, order, genus and species. The analysis highlighted Aspergillus as the most diverse genus in terms of exclusive domain content. In addition, we also investigated which domains could be considered promiscuous in the different organisms. As an application of this analysis, we explored three different ways to detect potential targets for antifungal drugs. First, we compared the domain and domain architecture content of the human and fungal proteomes, and identified those domains and domain architectures only present in fungi. Secondly, we looked for information regarding fungal pathways in public repositories, where proteins containing promiscuous domains could be involved. Three pathways were identified as a result: lovastatin biosynthesis, xylan degradation and biosynthesis of siroheme. Finally, we classified a subset of the studied fungi in five groups depending on their occurrence in clinical samples. We then looked for exclusive domains in the groups that were more relevant clinically and determined which of them had the potential to bind small molecules. Overall, this study provides a comprehensive analysis of the available fungal proteomes and shows three approaches that can be used as a first step in the detection of new antifungal targets.
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Testing domain general learning in an Australian lizard.
Qi, Yin; Noble, Daniel W A; Fu, Jinzhong; Whiting, Martin J
2018-06-02
A key question in cognition is whether animals that are proficient in a specific cognitive domain (domain specific hypothesis), such as spatial learning, are also proficient in other domains (domain general hypothesis) or whether there is a trade-off. Studies testing among these hypotheses are biased towards mammals and birds. To understand constraints on the evolution of cognition more generally, we need broader taxonomic and phylogenetic coverage. We used Australian eastern water skinks (Eulamprus quoyii) with known spatial learning ability in three additional tasks: an instrumental and two discrimination tasks. Under domain specific learning we predicted that lizards that were good at spatial learning would perform less well in the discrimination tasks. Conversely, we predicted that lizards that did not meet our criterion for spatial learning would likewise perform better in discrimination tasks. Lizards with domain general learning should perform approximately equally well (or poorly) in these tasks. Lizards classified as spatial learners performed no differently to non-spatial learners in both the instrumental and discrimination learning tasks. Nevertheless, lizards were proficient in all tasks. Our results reveal two patterns: domain general learning in spatial learners and domain specific learning in non-spatial learners. We suggest that delineating learning into domain general and domain specific may be overly simplistic and we need to instead focus on individual variation in learning ability, which ultimately, is likely to play a key role in fitness. These results, in combination with previously published work on this species, suggests that this species has behavioral flexibility because they are competent across multiple cognitive domains and are capable of reversal learning.
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Sempombe, Joseph; Elmore, Bradley O; Sun, Xi; Dupont, Andrea; Ghosh, Dipak K; Guillemette, J Guy; Kirk, Martin L; Feng, Changjian
2009-05-27
The nitric oxide synthase (NOS) output state for NO production is a complex of the flavin mononucleotide (FMN)-binding domain and the heme domain, and thereby it facilitates the interdomain electron transfer from the FMN to the catalytic heme site. Emerging evidence suggests that interdomain FMN-heme interactions are important in the formation of the output state because they guide the docking of the FMN domain to the heme domain. In this study, notable effects of mutations in the adjacent FMN domain on the heme structure in a human iNOS bidomain oxygenase/FMN construct have been observed by using low-temperature magnetic circular dichroism (MCD) spectroscopy. The comparative MCD study of wild-type and mutant proteins clearly indicates that a properly docked FMN domain contributes to the observed L-Arg perturbation of the heme MCD spectrum in the wild-type protein and that the conserved surface residues in the FMN domain (E546 and E603) play key roles in facilitating a productive alignment of the FMN and heme domains in iNOS.
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Functional innovation from changes in protein domains and their combinations.
Lees, Jonathan G; Dawson, Natalie L; Sillitoe, Ian; Orengo, Christine A
2016-06-01
Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions. Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins. We discuss the mechanisms by which domain and domain combinations support functional innovations. We highlight interesting examples where changes in domain combination promote changes at the domain level. Copyright © 2016 Elsevier Ltd. All rights reserved.
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XML Based Markup Languages for Specific Domains
NASA Astrophysics Data System (ADS)
Varde, Aparna; Rundensteiner, Elke; Fahrenholz, Sally
A challenging area in web based support systems is the study of human activities in connection with the web, especially with reference to certain domains. This includes capturing human reasoning in information retrieval, facilitating the exchange of domain-specific knowledge through a common platform and developing tools for the analysis of data on the web from a domain expert's angle. Among the techniques and standards related to such work, we have XML, the eXtensible Markup Language. This serves as a medium of communication for storing and publishing textual, numeric and other forms of data seamlessly. XML tag sets are such that they preserve semantics and simplify the understanding of stored information by users. Often domain-specific markup languages are designed using XML, with a user-centric perspective. Standardization bodies and research communities may extend these to include additional semantics of areas within and related to the domain. This chapter outlines the issues to be considered in developing domain-specific markup languages: the motivation for development, the semantic considerations, the syntactic constraints and other relevant aspects, especially taking into account human factors. Illustrating examples are provided from domains such as Medicine, Finance and Materials Science. Particular emphasis in these examples is on the Materials Markup Language MatML and the semantics of one of its areas, namely, the Heat Treating of Materials. The focus of this chapter, however, is not the design of one particular language but rather the generic issues concerning the development of domain-specific markup languages.
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NASA Astrophysics Data System (ADS)
Eriksen, Vibeke R.; Hahn, Gitte H.; Greisen, Gorm
2015-03-01
The aim was to compare two conventional methods used to describe cerebral autoregulation (CA): frequency-domain analysis and time-domain analysis. We measured cerebral oxygenation (as a surrogate for cerebral blood flow) and mean arterial blood pressure (MAP) in 60 preterm infants. In the frequency domain, outcome variables were coherence and gain, whereas the cerebral oximetry index (COx) and the regression coefficient were the outcome variables in the time domain. Correlation between coherence and COx was poor. The disagreement between the two methods was due to the MAP and cerebral oxygenation signals being in counterphase in three cases. High gain and high coherence may arise spuriously when cerebral oxygenation decreases as MAP increases; hence, time-domain analysis appears to be a more robust-and simpler-method to describe CA.
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Frequency domain FIR and IIR adaptive filters
NASA Technical Reports Server (NTRS)
Lynn, D. W.
1990-01-01
A discussion of the LMS adaptive filter relating to its convergence characteristics and the problems associated with disparate eigenvalues is presented. This is used to introduce the concept of proportional convergence. An approach is used to analyze the convergence characteristics of block frequency-domain adaptive filters. This leads to a development showing how the frequency-domain FIR adaptive filter is easily modified to provide proportional convergence. These ideas are extended to a block frequency-domain IIR adaptive filter and the idea of proportional convergence is applied. Experimental results illustrating proportional convergence in both FIR and IIR frequency-domain block adaptive filters is presented.
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Investigation of multilayer magnetic domain lattice file
NASA Technical Reports Server (NTRS)
Torok, E. J.; Kamin, M.; Tolman, C. H.
1980-01-01
The feasibility of the self structured multilayered bubble domain memory as a mass memory medium for satellite applications is examined. Theoretical considerations of multilayer bubble supporting materials are presented, in addition to the experimental evaluation of current accessed circuitry for various memory functions. The design, fabrication, and test of four device designs is described, and a recommended memory storage area configuration is presented. Memory functions which were demonstrated include the current accessed propagation of bubble domains and stripe domains, pinning of stripe domain ends, generation of single and double bubbles, generation of arrays of coexisting strip and bubble domains in a single garnet layer, and demonstration of different values of the strip out field for single and double bubbles indicating adequate margins for data detection. All functions necessary to develop a multilayer self structured bubble memory device were demonstrated in individual experiments.
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Stochastic lattice model of synaptic membrane protein domains.
Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A
2017-05-01
Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.
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McIntosh, Anne; Meikle, Lynsey M.; Ormsby, Michael J.; McCormick, Beth A.; Christie, John M.; Brewer, James M.; Roberts, Mark
2017-01-01
ABSTRACT Salmonella invasion protein A (SipA) is a dual-function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection. This activation required a threshold level of SipA linked to multiplicity of infection and may be a limiting factor controlling bacterial numbers in infected macrophages. In polymorphonuclear leukocytes, SipA or other Salmonella pathogenicity island 1 effectors had no effect on induction of caspase-3 activation either alone or in the presence of whole bacteria. Tagging of SipA with the small fluorescent phiLOV tag, which can pass through the type three secretion system, allowed visualization and quantification of caspase-3 activation by SipA-phiLOV in macrophages. Additionally, SipA-phiLOV activation of caspase-3 could be tracked in the intestine through multiphoton laser scanning microscopy in an ex vivo intestinal model. This allowed visualization of areas where the intestinal epithelium had been compromised and demonstrated the potential use of this fluorescent tag for in vivo tracking of individual effectors. PMID:28630067
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Skyrmions from Instantons inside Domain Walls
NASA Astrophysics Data System (ADS)
Eto, Minoru; Nitta, Muneto; Ohashi, Keisuke; Tong, David
2005-12-01
Some years ago, Atiyah and Manton described a method to construct approximate Skyrmion solutions from Yang-Mills instantons. Here we present a dynamical realization of this construction using domain walls in a five-dimensional gauge theory. The non-Abelian gauge symmetry is broken in each vacuum but restored in the core of the domain wall, allowing instantons to nestle inside the wall. We show that the world volume dynamics of the wall is given by the Skyrme model, including the four-derivative term, and the instantons appear as domain wall Skyrmions.
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Magnetization reversal in ferromagnetic spirals via domain wall motion
NASA Astrophysics Data System (ADS)
Schumm, Ryan D.; Kunz, Andrew
2016-11-01
Domain wall dynamics have been investigated in a variety of ferromagnetic nanostructures for potential applications in logic, sensing, and recording. We present a combination of analytic and simulated results describing the reliable field driven motion of a domain wall through the arms of a ferromagnetic spiral nanowire. The spiral geometry is capable of taking advantage of the benefits of both straight and circular wires. Measurements of the in-plane components of the spirals' magnetization can be used to determine the angular location of the domain wall, impacting the magnetoresistive applications dependent on the domain wall location. The spirals' magnetization components are found to depend on the spiral parameters: the initial radius and spacing between spiral arms, along with the domain wall location. The magnetization is independent of the parameters of the rotating field used to move the domain wall, and therefore the model is valid for current induced domain wall motion as well. The speed of the domain wall is found to depend on the frequency of the rotating driving field, and the domain wall speeds can be reliably varied over several orders of magnitude. We further demonstrate a technique capable of injecting multiple domain walls and show the reliable and unidirectional motion of domain walls through the arms of the spiral.
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The evolution of filamin-a protein domain repeat perspective.
Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne
2012-09-01
Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.
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Optimising predictor domains for spatially coherent precipitation downscaling
NASA Astrophysics Data System (ADS)
Radanovics, S.; Vidal, J.-P.; Sauquet, E.; Ben Daoud, A.; Bontron, G.
2013-10-01
Statistical downscaling is widely used to overcome the scale gap between predictors from numerical weather prediction models or global circulation models and predictands like local precipitation, required for example for medium-term operational forecasts or climate change impact studies. The predictors are considered over a given spatial domain which is rarely optimised with respect to the target predictand location. In this study, an extended version of the growing rectangular domain algorithm is proposed to provide an ensemble of near-optimum predictor domains for a statistical downscaling method. This algorithm is applied to find five-member ensembles of near-optimum geopotential predictor domains for an analogue downscaling method for 608 individual target zones covering France. Results first show that very similar downscaling performances based on the continuous ranked probability score (CRPS) can be achieved by different predictor domains for any specific target zone, demonstrating the need for considering alternative domains in this context of high equifinality. A second result is the large diversity of optimised predictor domains over the country that questions the commonly made hypothesis of a common predictor domain for large areas. The domain centres are mainly distributed following the geographical location of the target location, but there are apparent differences between the windward and the lee side of mountain ridges. Moreover, domains for target zones located in southeastern France are centred more east and south than the ones for target locations on the same longitude. The size of the optimised domains tends to be larger in the southeastern part of the country, while domains with a very small meridional extent can be found in an east-west band around 47° N. Sensitivity experiments finally show that results are rather insensitive to the starting point of the optimisation algorithm except for zones located in the transition area north of this east
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Villarino, Gonzalo H.; Hu, Qiwen; Flores-Vergara, Miguel; Sehra, Bhupinder; Brumos, Javier; Stepanova, Anna N.; Sundberg, Eva; Heber, Steffen
2016-01-01
Plant meristems, like animal stem cell niches, maintain a pool of multipotent, undifferentiated cells that divide and differentiate to give rise to organs. In Arabidopsis (Arabidopsis thaliana), the carpel margin meristem is a vital meristematic structure that generates ovules from the medial domain of the gynoecium, the female floral reproductive structure. The molecular mechanisms that specify this meristematic region and regulate its organogenic potential are poorly understood. Here, we present a novel approach to analyze the transcriptional signature of the medial domain of the Arabidopsis gynoecium, highlighting the developmental stages that immediately proceed ovule initiation, the earliest stages of seed development. Using a floral synchronization system and a SHATTERPROOF2 (SHP2) domain-specific reporter, paired with FACS and RNA sequencing, we assayed the transcriptome of the gynoecial medial domain with temporal and spatial precision. This analysis reveals a set of genes that are differentially expressed within the SHP2 expression domain, including genes that have been shown previously to function during the development of medial domain-derived structures, including the ovules, thus validating our approach. Global analyses of the transcriptomic data set indicate a similarity of the pSHP2-expressing cell population to previously characterized meristematic domains, further supporting the meristematic nature of this gynoecial tissue. Our method identifies additional genes including novel isoforms, cis-natural antisense transcripts, and a previously unrecognized member of the REPRODUCTIVE MERISTEM family of transcriptional regulators that are potential novel regulators of medial domain development. This data set provides genome-wide transcriptional insight into the development of the carpel margin meristem in Arabidopsis. PMID:26983993
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Idnurm, Alexander; Rodríguez-Romero, Julio; Corrochano, Luis M; Sanz, Catalina; Iturriaga, Enrique A; Eslava, Arturo P; Heitman, Joseph
2006-03-21
Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served as a model for the detection of environmental signals as diverse as light, chemicals, touch, wind, gravity, and adjacent objects. In particular, sporangiophore growth is regulated by light, and it exhibits phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses. The Phycomyces madA mutants were first isolated more than 40 years ago, and they exhibit reduced sensitivity to light. Here, we identify two (duplicated) homologs in the White Collar 1 family of blue-light photoreceptors in Phycomyces. We describe that the madA mutant strains contain point mutations in one of these genes and that these mutations cosegregate with a defect in phototropism after genetic crosses. Thus, the phototropic responses of fungi through madA and plants through phototropin rely on diverse proteins; however, these proteins share a conserved flavin-binding domain for photon detection.
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Idnurm, Alexander; Rodríguez-Romero, Julio; Corrochano, Luis M.; Sanz, Catalina; Iturriaga, Enrique A.; Eslava, Arturo P.; Heitman, Joseph
2006-01-01
Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served as a model for the detection of environmental signals as diverse as light, chemicals, touch, wind, gravity, and adjacent objects. In particular, sporangiophore growth is regulated by light, and it exhibits phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses. The Phycomyces madA mutants were first isolated more than 40 years ago, and they exhibit reduced sensitivity to light. Here, we identify two (duplicated) homologs in the White Collar 1 family of blue-light photoreceptors in Phycomyces. We describe that the madA mutant strains contain point mutations in one of these genes and that these mutations cosegregate with a defect in phototropism after genetic crosses. Thus, the phototropic responses of fungi through madA and plants through phototropin rely on diverse proteins; however, these proteins share a conserved flavin-binding domain for photon detection. PMID:16537433
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Murciano-Calles, Javier; Güell-Bosch, Jofre; Villegas, Sandra; Martinez, Jose C
2016-01-12
PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.
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ERIC Educational Resources Information Center
Swanson, H. Lee
2011-01-01
This study examined whether children's growth on measures of fluid (Raven Colored Progressive Matrices) and crystallized (reading and math achievement) intelligence was attributable to domain-specific or domain-general functions of working memory (WM). A sample of 290 elementary school children was tested on measures of intelligence across three…
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Swiderski, Michal R; Birker, Doris; Jones, Jonathan D G
2009-02-01
In plants, the TIR (toll interleukin 1 receptor) domain is found almost exclusively in nucleotide-binding (NB) leucine-rich repeat resistance proteins and their truncated homologs, and has been proposed to play a signaling role during resistance responses mediated by TIR containing R proteins. Transient expression in Nicotiana benthamiana leaves of "TIR + 80", the RPS4 truncation without the NB-ARC domain, leads to EDS1-, SGT1-, and HSP90-dependent cell death. Transgenic Arabidopsis plants expressing the RPS4 TIR+80 from either dexamethasone or estradiol-inducible promoters display inducer-dependent cell death. Cell death is also elicited by transient expression of similarly truncated constructs from two other R proteins, RPP1A and At4g19530, but is not elicited by similar constructs representing RPP2A and RPP2B proteins. Site-directed mutagenesis of the RPS4 TIR domain identified many loss-of-function mutations but also revealed several gain-of function substitutions. Lack of cell death induction by the E160A substitution suggests that amino acids outside of the TIR domain contribute to cell death signaling in addition to the TIR domain itself. This is consistent with previous observations that the TIR domain itself is insufficient to induce cell death upon transient expression.
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Pinheiro, Anderson S; Proell, Martina; Eibl, Clarissa; Page, Rebecca; Schwarzenbacher, Robert; Peti, Wolfgang
2010-08-27
The innate immune system provides an initial line of defense against infection. Nucleotide-binding domain- and leucine-rich repeat-containing protein (NLR or (NOD-like)) receptors play a critical role in the innate immune response by surveying the cytoplasm for traces of intracellular invaders and endogenous stress signals. NLRs themselves are multi-domain proteins. Their N-terminal effector domains (typically a pyrin or caspase activation and recruitment domain) are responsible for driving downstream signaling and initiating the formation of inflammasomes, multi-component complexes necessary for cytokine activation. However, the currently available structures of NLR effector domains have not yet revealed the mechanism of their differential modes of interaction. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP7 (NLRP7 PYD) obtained by NMR spectroscopy. The NLRP7 PYD adopts a six-alpha-helix bundle death domain fold. A comparison of conformational and dynamics features of the NLRP7 PYD with other PYDs showed distinct differences for helix alpha3 and loop alpha2-alpha3, which, in NLRP7, is stabilized by a strong hydrophobic cluster. Moreover, the NLRP7 and NLRP1 PYDs have different electrostatic surfaces. This is significant, because death domain signaling is driven by electrostatic contacts and stabilized by hydrophobic interactions. Thus, these results provide new insights into NLRP signaling and provide a first molecular understanding of inflammasome formation.
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Domains of awareness in schizophrenia.
Gilleen, J; Greenwood, K; David, A S
2011-01-01
Patients with schizophrenia are often characterized as lacking insight or awareness into their illness and symptoms, yet despite considerable research, we still lack a full understanding of the factors involved in causing poor awareness. Within schizophrenia, there has been shown to be a fractionation across dimensions of awareness into mental illness: of being ill, of symptoms, and of treatment compliance. Recently, attention has turned to evidence of a fractionation between awareness of illness and of cognitive impairments and functioning. The current study investigated the degree of fractionation across a broad range of domains of function in schizophrenia and how each domain may be associated with neuropsychological functioning, clinical, mood, and demographic variables. Thirty-one mostly chronic stable patients with schizophrenia completed a battery of neuropsychological tests and measures of psychopathology, including mood. Cognitive insight and awareness of illness, symptoms, memory, and behavioral functioning were also measured. Insight and awareness were assessed using a combination of semistructured interview, observer-rated, self-rated, and objective measures, and included measures of the discrepancy between carer and self-ratings of impairment. Results revealed that awareness of functioning in each domain was largely independent and that awareness in each domain was predicted by different factors. Insight into symptoms was relatively poor while insight into cognitive deficits was preserved. Relative to neuropsychological variables, cognitive insight, comprising self-certainty and self-reflexivity, was a greater predictor of awareness. In conclusion, awareness is multiply fractionated and multiply determined. Therapeutic interventions could, therefore, produce beneficial changes within specific domains of awareness.
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Domains of Awareness in Schizophrenia
Gilleen, J.; Greenwood, K.; David, A. S.
2011-01-01
Patients with schizophrenia are often characterized as lacking insight or awareness into their illness and symptoms, yet despite considerable research, we still lack a full understanding of the factors involved in causing poor awareness. Within schizophrenia, there has been shown to be a fractionation across dimensions of awareness into mental illness: of being ill, of symptoms, and of treatment compliance. Recently, attention has turned to evidence of a fractionation between awareness of illness and of cognitive impairments and functioning. The current study investigated the degree of fractionation across a broad range of domains of function in schizophrenia and how each domain may be associated with neuropsychological functioning, clinical, mood, and demographic variables. Thirty-one mostly chronic stable patients with schizophrenia completed a battery of neuropsychological tests and measures of psychopathology, including mood. Cognitive insight and awareness of illness, symptoms, memory, and behavioral functioning were also measured. Insight and awareness were assessed using a combination of semistructured interview, observer-rated, self-rated, and objective measures, and included measures of the discrepancy between carer and self-ratings of impairment. Results revealed that awareness of functioning in each domain was largely independent and that awareness in each domain was predicted by different factors. Insight into symptoms was relatively poor while insight into cognitive deficits was preserved. Relative to neuropsychological variables, cognitive insight, comprising self-certainty and self-reflexivity, was a greater predictor of awareness. In conclusion, awareness is multiply fractionated and multiply determined. Therapeutic interventions could, therefore, produce beneficial changes within specific domains of awareness. PMID:20851850
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Prashek, Jennifer; Bouyain, Samuel; Fu, Mingui
De novo synthesis of the sphingolipid sphingomyelin requires non-vesicular transport of ceramide from the endoplasmic reticulum to the Golgi by the multidomain protein ceramide transfer protein (CERT). CERT's N-terminal pleckstrin homology (PH) domain targets it to the Golgi by binding to phosphatidylinositol 4-phosphate (PtdIns(4)P) in the Golgi membrane, whereas its C-terminal StAR-related lipid transfer domain (START) carries out ceramide transfer. Hyperphosphorylation of a serine-rich motif immediately after the PH domain decreases both PtdIns(4)P binding and ceramide transfer by CERT. This down-regulation requires both the PH and START domains, suggesting a possible inhibitory interaction between the two domains. In this studymore » we show that isolated PH and START domains interact with each other. The crystal structure of a PH–START complex revealed that the START domain binds to the PH domain at the same site for PtdIns(4)P-binding, suggesting that the START domain competes with PtdIns(4)P for association with the PH domain. We further report that mutations disrupting the PH–START interaction increase both PtdIns(4)P-binding affinity and ceramide transfer activity of a CERT-serine–rich phosphorylation mimic. We also found that these mutations increase the Golgi localization of CERT inside the cell, consistent with enhanced PtdIns(4)P binding of the mutant. Collectively, our structural, biochemical, and cellular investigations provide important structural insight into the regulation of CERT function and localization.« less
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Buhs, Sophia; Nollau, Peter
2017-01-01
Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.
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Partial protein domains: evolutionary insights and bioinformatics challenges.
Kelley, Lawrence A; Sternberg, Michael J E
2015-05-19
Protein domains are generally thought to correspond to units of evolution. New research raises questions about how such domains are defined with bioinformatics tools and sheds light on how evolution has enabled partial domains to be viable.
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Formation and stability of synaptic receptor domains.
Haselwandter, Christoph A; Calamai, Martino; Kardar, Mehran; Triller, Antoine; da Silveira, Rava Azeredo
2011-06-10
Neurotransmitter receptor molecules, concentrated in postsynaptic domains along with scaffold and a number of other molecules, are key regulators of signal transmission across synapses. Combining experiment and theory, we develop a quantitative description of synaptic receptor domains in terms of a reaction-diffusion model. We show that interactions between only receptors and scaffolds, together with the rapid diffusion of receptors on the cell membrane, are sufficient for the formation and stable characteristic size of synaptic receptor domains. Our work reconciles long-term stability of synaptic receptor domains with rapid turnover and diffusion of individual receptors, and suggests novel mechanisms for a form of short-term, postsynaptic plasticity.
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Expression and Production of SH2 Domain Proteins.
Liu, Bernard A; Ogiue-Ikeda, Mari; Machida, Kazuya
2017-01-01
The Src Homology 2 (SH2) domain lies at the heart of phosphotyrosine signaling, coordinating signaling events downstream of receptor tyrosine kinases (RTKs), adaptors, and scaffolds. Over a hundred SH2 domains are present in mammals, each having a unique specificity which determines its interactions with multiple binding partners. One of the essential tools necessary for studying and determining the role of SH2 domains in phosphotyrosine signaling is a set of soluble recombinant SH2 proteins. Here we describe methods, based on a broad experience with purification of all SH2 domains, for the production of SH2 domain proteins needed for proteomic and biochemical-based studies such as peptide arrays, mass-spectrometry, protein microarrays, reverse-phase microarrays, and high-throughput fluorescence polarization (HTP-FP). We describe stepwise protocols for expression and purification of SH2 domains using GST or poly His-tags, two widely adopted affinity tags. In addition, we address alternative approaches, challenges, and validation studies for assessing protein quality and provide general characteristics of purified human SH2 domains.
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Roth, Dan
2013-01-01
Objective This paper presents a coreference resolution system for clinical narratives. Coreference resolution aims at clustering all mentions in a single document to coherent entities. Materials and methods A knowledge-intensive approach for coreference resolution is employed. The domain knowledge used includes several domain-specific lists, a knowledge intensive mention parsing, and task informed discourse model. Mention parsing allows us to abstract over the surface form of the mention and represent each mention using a higher-level representation, which we call the mention's semantic representation (SR). SR reduces the mention to a standard form and hence provides better support for comparing and matching. Existing coreference resolution systems tend to ignore discourse aspects and rely heavily on lexical and structural cues in the text. The authors break from this tradition and present a discourse model for “person” type mentions in clinical narratives, which greatly simplifies the coreference resolution. Results This system was evaluated on four different datasets which were made available in the 2011 i2b2/VA coreference challenge. The unweighted average of F1 scores (over B-cubed, MUC and CEAF) varied from 84.2% to 88.1%. These experiments show that domain knowledge is effective for different mention types for all the datasets. Discussion Error analysis shows that most of the recall errors made by the system can be handled by further addition of domain knowledge. The precision errors, on the other hand, are more subtle and indicate the need to understand the relations in which mentions participate for building a robust coreference system. Conclusion This paper presents an approach that makes an extensive use of domain knowledge to significantly improve coreference resolution. The authors state that their system and the knowledge sources developed will be made publicly available. PMID:22781192
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Single-domain epitaxial silicene on diboride thin films
Fleurence, A.; Gill, T. G.; Friedlein, R.; ...
2016-04-12
Epitaxial silicene, which forms spontaneously on ZrB 2(0001) thin films grown on Si(111) wafers, has a periodic stripe domain structure. By adsorbing additional Si atoms on this surface, we find that the domain boundaries vanish, and a single-domain silicene sheet can be prepared without altering its buckled honeycomb structure. The amount of Si required to induce this change suggests that the domain boundaries are made of a local distortion of the silicene honeycomb lattice. LastlThe realization of a single domain sheet with structural and electronic properties close to those of the original striped state demonstrates the high structural flexibility ofmore » silicene.« less
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Single-domain epitaxial silicene on diboride thin films
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fleurence, A., E-mail: antoine@jaist.ac.jp; Friedlein, R.; Aoyagi, K.
2016-04-11
Epitaxial silicene, which forms spontaneously on ZrB{sub 2}(0001) thin films grown on Si(111) wafers, has a periodic stripe domain structure. By adsorbing additional Si atoms on this surface, we find that the domain boundaries vanish, and a single-domain silicene sheet can be prepared without altering its buckled honeycomb structure. The amount of Si required to induce this change suggests that the domain boundaries are made of a local distortion of the silicene honeycomb lattice. The realization of a single domain sheet with structural and electronic properties close to those of the original striped state demonstrates the high structural flexibility ofmore » silicene.« less
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Jungert, Tomas; Hesser, Hugo; Träff, Ulf
2014-10-01
In social cognitive theory, self-efficacy is domain-specific. An alternative model, the cross-domain influence model, would predict that self-efficacy beliefs in one domain might influence performance in other domains. Research has also found that children who receive special instruction are not good at estimating their performance. The aim was to test two models of how self-efficacy beliefs influence achievement, and to contrast children receiving special instruction in mathematics with normally-achieving children. The participants were 73 fifth-grade children who receive special instruction and 70 children who do not receive any special instruction. In year four and five, the children's skills in mathematics and reading were assessed by national curriculum tests, and in their fifth year, self-efficacy in mathematics and reading were measured. Structural equation modeling showed that in domains where children do not receive special instruction in mathematics, self-efficacy is a mediating variable between earlier and later achievement in the same domain. Achievement in mathematics was not mediated by self-efficacy in mathematics for children who receive special instruction. For normal achieving children, earlier achievement in the language domain had an influence on later self-efficacy in the mathematics domain, and self-efficacy beliefs in different domains were correlated. Self-efficacy is mostly domain specific, but may play a different role in academic performance depending on whether children receive special instruction. The results of the present study provided some support of the Cross-Domain Influence Model for normal achieving children. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.
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Correlation between spin structure oscillations and domain wall velocities
Bisig, André; Stärk, Martin; Mawass, Mohamad-Assaad; Moutafis, Christoforos; Rhensius, Jan; Heidler, Jakoba; Büttner, Felix; Noske, Matthias; Weigand, Markus; Eisebitt, Stefan; Tyliszczak, Tolek; Van Waeyenberge, Bartel; Stoll, Hermann; Schütz, Gisela; Kläui, Mathias
2013-01-01
Magnetic sensing and logic devices based on the motion of magnetic domain walls rely on the precise and deterministic control of the position and the velocity of individual magnetic domain walls in curved nanowires. Varying domain wall velocities have been predicted to result from intrinsic effects such as oscillating domain wall spin structure transformations and extrinsic pinning due to imperfections. Here we use direct dynamic imaging of the nanoscale spin structure that allows us for the first time to directly check these predictions. We find a new regime of oscillating domain wall motion even below the Walker breakdown correlated with periodic spin structure changes. We show that the extrinsic pinning from imperfections in the nanowire only affects slow domain walls and we identify the magnetostatic energy, which scales with the domain wall velocity, as the energy reservoir for the domain wall to overcome the local pinning potential landscape. PMID:23978905
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Structural and Histone Binding Ability Characterizations of Human PWWP Domains
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Hong; Zeng, Hong; Lam, Robert
2013-09-25
The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members,more » implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.« less
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NASA Technical Reports Server (NTRS)
Sreenivas, Kidambi; Whitfield, David L.
1995-01-01
Two linearized solvers (time and frequency domain) based on a high resolution numerical scheme are presented. The basic approach is to linearize the flux vector by expressing it as a sum of a mean and a perturbation. This allows the governing equations to be maintained in conservation law form. A key difference between the time and frequency domain computations is that the frequency domain computations require only one grid block irrespective of the interblade phase angle for which the flow is being computed. As a result of this and due to the fact that the governing equations for this case are steady, frequency domain computations are substantially faster than the corresponding time domain computations. The linearized equations are used to compute flows in turbomachinery blade rows (cascades) arising due to blade vibrations. Numerical solutions are compared to linear theory (where available) and to numerical solutions of the nonlinear Euler equations.
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Defining the site of light perception and initiation of phototropism in Arabidopsis.
Preuten, Tobias; Hohm, Tim; Bergmann, Sven; Fankhauser, Christian
2013-10-07
Phototropism is an adaptive response allowing plants to optimize photosynthetic light capture. This is achieved by asymmetric growth between the shaded and lit sides of the stimulated organ. In grass seedlings, the site of phototropin-mediated light perception is distinct from the site of bending; however, in dicotyledonous plants (e.g., Arabidopsis), spatial aspects of perception remain debatable. We use morphological studies and genetics to show that phototropism can occur in the absence of the root, lower hypocotyl, hypocotyl apex, and cotyledons. Tissue-specific expression of the phototropin1 (phot1) photoreceptor demonstrates that light sensing occurs in the upper hypocotyl and that expression of phot1 in the hypocotyl elongation zone is sufficient to enable a normal phototropic response. Moreover, we show that efficient phototropism occurs when phot1 is expressed from endodermal, cortical, or epidermal cells and that its local activation rapidly leads to a global response throughout the seedling. We propose that spatial aspects in the steps leading from light perception to growth reorientation during phototropism differ between grasses and dicots. These results are important to properly interpret genetic experiments and establish a model connecting light perception to the growth response, including cellular and morphological aspects. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Development of transgenic crops based on photo-biotechnology.
Ganesan, Markkandan; Lee, Hyo-Yeon; Kim, Jeong-Il; Song, Pill-Soon
2017-11-01
The phenotypes associated with plant photomorphogenesis such as the suppressed shade avoidance response and de-etiolation offer the potential for significant enhancement of crop yields. Of many light signal transducers and transcription factors involved in the photomorphogenic responses of plants, this review focuses on the transgenic overexpression of the photoreceptor genes at the uppermost stream of the signalling events, particularly phytochromes, crytochromes and phototropins as the transgenes for the genetic engineering of crops with improved harvest yields. In promoting the harvest yields of crops, the photoreceptors mediate the light regulation of photosynthetically important genes, and the improved yields often come with the tolerance to abiotic stresses such as drought, salinity and heavy metal ions. As a genetic engineering approach, the term photo-biotechnology has been coined to convey the idea that the greater the photosynthetic efficiency that crop plants can be engineered to possess, the stronger the resistance to biotic and abiotic stresses. Development of GM crops based on photoreceptor transgenes (mainly phytochromes, crytochromes and phototropins) is reviewed with the proposal of photo-biotechnology that the photoreceptors mediate the light regulation of photosynthetically important genes, and the improved yields often come with the added benefits of crops' tolerance to environmental stresses. © 2016 John Wiley & Sons Ltd.
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Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck
2009-08-07
DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.
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The Evolutionary History of Protein Domains Viewed by Species Phylogeny
Yang, Song; Bourne, Philip E.
2009-01-01
Background Protein structural domains are evolutionary units whose relationships can be detected over long evolutionary distances. The evolutionary history of protein domains, including the origin of protein domains, the identification of domain loss, transfer, duplication and combination with other domains to form new proteins, and the formation of the entire protein domain repertoire, are of great interest. Methodology/Principal Findings A methodology is presented for providing a parsimonious domain history based on gain, loss, vertical and horizontal transfer derived from the complete genomic domain assignments of 1015 organisms across the tree of life. When mapped to species trees the evolutionary history of domains and domain combinations is revealed, and the general evolutionary trend of domain and combination is analyzed. Conclusions/Significance We show that this approach provides a powerful tool to study how new proteins and functions emerged and to study such processes as horizontal gene transfer among more distant species. PMID:20041107
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Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J Preben; Andreasen, Peter A; Jensen, Jan K
2016-07-01
Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Moreno-Martínez, F Javier; Goñi-Imízcoz, Miguel; Spitznagel, Mary Beth
2011-10-01
Category specific semantic impairment (e.g. living versus nonliving things) has been reported in association with various pathologies, including herpes simplex encephalitis and semantic dementia. However, evidence is inconsistent regarding whether this effect exists in diseases progressively impacting diverse cortical regions, such as Alzheimer's disease (AD). Ceiling effects producing non-Gaussian distributions and poor control for confounds such as nuisance variables (e.g. familiarity) may contribute to this discrepancy. Fourteen AD patients were longitudinally studied examining category effects on three semantic tasks (picture naming, naming to description and word to picture matching) matched across domain on all known nuisance variables (NV). To address non-Gaussian distributions, we run bootstrap analyses to determine whether NV, semantic domain or control performance best predicted AD patient performance. Multiple hierarchical regression analyses revealed that, whilst NV accounted for most of the explained variance in patients in the three tasks, the influence of semantic domain was substantially lower. Individual logistic regression demonstrated a significant category effect in only a few patients and healthy controls. No significant qualitative changes were observed in patients over time. Our results confirm the importance of NVs as predictors of AD patient performance, suggesting that the role of semantic domain is not a useful predictor of the progressive deterioration in AD. Copyright © 2011 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Borie, B.; Kehlberger, A.; Wahrhusen, J.; Grimm, H.; Kläui, M.
2017-08-01
We study the key domain-wall properties in segmented nanowire loop-based structures used in domain-wall-based sensors. The two reasons for device failure, namely, distribution of the domain-wall propagation field (depinning) and the nucleation field are determined with magneto-optical Kerr effect and giant-magnetoresistance (GMR) measurements for thousands of elements to obtain significant statistics. Single layers of Ni81 Fe19 , a complete GMR stack with Co90 Fe10 /Ni81Fe19 as a free layer, and a single layer of Co90 Fe10 are deposited and industrially patterned to determine the influence of the shape anisotropy, the magnetocrystalline anisotropy, and the fabrication processes. We show that the propagation field is influenced only slightly by the geometry but significantly by material parameters. Simulations for a realistic wire shape yield a curling-mode type of magnetization configuration close to the nucleation field. Nonetheless, we find that the domain-wall nucleation fields can be described by a typical Stoner-Wohlfarth model related to the measured geometrical parameters of the wires and fitted by considering the process parameters. The GMR effect is subsequently measured in a substantial number of devices (3000) in order to accurately gauge the variation between devices. This measurement scheme reveals a corrected upper limit to the nucleation fields of the sensors that can be exploited for fast characterization of the working elements.
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Solution structure of leptospiral LigA4 Big domain
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mei, Song; Zhang, Jiahai; Zhang, Xuecheng
Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Bigmore » domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.« less
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Health numeracy: the importance of domain in assessing numeracy.
Levy, Helen; Ubel, Peter A; Dillard, Amanda J; Weir, David R; Fagerlin, Angela
2014-01-01
Existing research concludes that measures of general numeracy can be used to predict individuals' ability to assess health risks. We posit that the domain in which questions are posed affects the ability to perform mathematical tasks, raising the possibility of a separate construct of "health numeracy" that is distinct from general numeracy. The objective was to determine whether older adults' ability to perform simple math depends on domain. Community-based participants completed 4 math questions posed in 3 different domains: a health domain, a financial domain, and a pure math domain. Participants were 962 individuals aged 55 and older, representative of the community-dwelling US population over age 54. We found that respondents performed significantly worse when questions were posed in the health domain (54% correct) than in either the pure math domain (66% correct) or the financial domain (63% correct). Our experimental measure of numeracy consisted of only 4 questions, and it is possible that the apparent effect of domain is specific to the mathematical tasks that these questions require. These results suggest that health numeracy is strongly related to general numeracy but that the 2 constructs may not be the same. Further research is needed into how different aspects of general numeracy and health numeracy translate into actual medical decisions.
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Vortex Ring Dynamics in Radially Confined Domains
NASA Astrophysics Data System (ADS)
Stewart, Kelley; Niebel, Casandra; Jung, Sunghwan; Vlachos, Pavlos
2010-11-01
Vortex ring dynamics have been studied extensively in semi-infinite quiescent volumes. However, very little is known about vortex-ring formation in wall-bounded domains where vortex wall interaction will affect both the vortex ring pinch-off and propagation velocity. This study addresses this limitation and studies vortex formation in radially confined domains to analyze the affect of vortex-ring wall interaction on the formation and propagation of the vortex ring. Vortex rings were produced using a pneumatically driven piston cylinder arrangement and were ejected into a long cylindrical tube which defined the confined downstream domain. A range of confinement domains were studied with varying confinement diameters Velocity field measurements were performed using planar Time Resolved Digital Particle Image Velocimetry (TRDPIV) and were processed using an in-house developed cross-correlation PIV algorithm. The experimental analysis was used to facilitate the development of a theoretical model to predict the variations in vortex ring circulation over time within confined domains.
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Remote-sensing image encryption in hybrid domains
NASA Astrophysics Data System (ADS)
Zhang, Xiaoqiang; Zhu, Guiliang; Ma, Shilong
2012-04-01
Remote-sensing technology plays an important role in military and industrial fields. Remote-sensing image is the main means of acquiring information from satellites, which always contain some confidential information. To securely transmit and store remote-sensing images, we propose a new image encryption algorithm in hybrid domains. This algorithm makes full use of the advantages of image encryption in both spatial domain and transform domain. First, the low-pass subband coefficients of image DWT (discrete wavelet transform) decomposition are sorted by a PWLCM system in transform domain. Second, the image after IDWT (inverse discrete wavelet transform) reconstruction is diffused with 2D (two-dimensional) Logistic map and XOR operation in spatial domain. The experiment results and algorithm analyses show that the new algorithm possesses a large key space and can resist brute-force, statistical and differential attacks. Meanwhile, the proposed algorithm has the desirable encryption efficiency to satisfy requirements in practice.
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Possible impact solutions of asteroid (99942) Apophis
NASA Astrophysics Data System (ADS)
Wlodarczyk, Ireneusz
2017-07-01
We computed impact solutions of the potentially dangerous asteroid (99942) Apophis based on 4469 optical observations from March 15.10789 UTC, 2004 through January 03.26308 UTC, 2015, and 20 radar observations from January 27.97986 UTC, 2005 through March 15.99931 UTC, 2013. However, we computed possible impact solutions by using the Line Of Variation method out to σ LOV = 5 computing 3000 virtual asteroids (VAs) on both sides of the LOV which gives 6001 VAs and propagated their orbits to JD 2495000.5 TDT=December 24, 2118. We computed the non-gravitational parameter A2=-5.586×10^{-14} au/d^{2} with 1-σ uncertainty 2.965×10^{-14} au/d^{2} and possible impacts until 2096. The possible impact corridor for 2068 is presented.
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NASA Astrophysics Data System (ADS)
Cafiero, M.; Lloberas-Valls, O.; Cante, J.; Oliver, J.
2016-04-01
A domain decomposition technique is proposed which is capable of properly connecting arbitrary non-conforming interfaces. The strategy essentially consists in considering a fictitious zero-width interface between the non-matching meshes which is discretized using a Delaunay triangulation. Continuity is satisfied across domains through normal and tangential stresses provided by the discretized interface and inserted in the formulation in the form of Lagrange multipliers. The final structure of the global system of equations resembles the dual assembly of substructures where the Lagrange multipliers are employed to nullify the gap between domains. A new approach to handle floating subdomains is outlined which can be implemented without significantly altering the structure of standard industrial finite element codes. The effectiveness of the developed algorithm is demonstrated through a patch test example and a number of tests that highlight the accuracy of the methodology and independence of the results with respect to the framework parameters. Considering its high degree of flexibility and non-intrusive character, the proposed domain decomposition framework is regarded as an attractive alternative to other established techniques such as the mortar approach.
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Seeing faces is necessary for face-domain formation.
Arcaro, Michael J; Schade, Peter F; Vincent, Justin L; Ponce, Carlos R; Livingstone, Margaret S
2017-10-01
Here we report that monkeys raised without exposure to faces did not develop face domains, but did develop domains for other categories and did show normal retinotopic organization, indicating that early face deprivation leads to a highly selective cortical processing deficit. Therefore, experience must be necessary for the formation (or maintenance) of face domains. Gaze tracking revealed that control monkeys looked preferentially at faces, even at ages prior to the emergence of face domains, but face-deprived monkeys did not, indicating that face looking is not innate. A retinotopic organization is present throughout the visual system at birth, so selective early viewing behavior could bias category-specific visual responses toward particular retinotopic representations, thereby leading to domain formation in stereotyped locations in inferotemporal cortex, without requiring category-specific templates or biases. Thus, we propose that environmental importance influences viewing behavior, viewing behavior drives neuronal activity, and neuronal activity sculpts domain formation.
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Zaki, Jamil; Hennigan, Kelly; Weber, Jochen; Ochsner, Kevin N.
2010-01-01
Cognitive control mechanisms allow individuals to behave adaptively in the face of complex and sometimes conflicting information. While the neural bases of these control mechanisms have been examined in many contexts, almost no attention has been paid to their role in resolving conflicts between competing social cues, which is surprising, given that cognitive conflicts are part of many social interactions. Evidence about the neural processing of social information suggests that two systems—the mirror neuron system (MNS) and mental state attribution system (MSAS)—are specialized for processing nonverbal and contextual social cues, respectively. This could support a model of social cognitive conflict resolution in which competition between social cues would recruit domain-general cognitive control mechanisms, which in turn would bias processing towards the MNS or MSAS. Such biasing could also alter social behaviors, such as inferences made about the internal states of others. We tested this model by scanning participants using fMRI while they drew inferences about social targets' emotional states based on congruent or incongruent nonverbal and contextual social cues. Conflicts between social cues recruited the anterior cingulate and lateral prefrontal cortex, brain areas associated with domain-general control processes. This activation was accompanied by biasing of neural activity towards areas in the MNS or MSAS, which tracked, respectively, with perceivers' behavioral reliance on nonverbal or contextual cues when drawing inferences about targets' emotions. Together, these data provide evidence about both domain general and domain specific mechanisms involved in resolving social cognitive conflicts. PMID:20573895
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Learning and Reasoning in Unknown Domains
NASA Astrophysics Data System (ADS)
Strannegård, Claes; Nizamani, Abdul Rahim; Juel, Jonas; Persson, Ulf
2016-12-01
In the story Alice in Wonderland, Alice fell down a rabbit hole and suddenly found herself in a strange world called Wonderland. Alice gradually developed knowledge about Wonderland by observing, learning, and reasoning. In this paper we present the system Alice In Wonderland that operates analogously. As a theoretical basis of the system, we define several basic concepts of logic in a generalized setting, including the notions of domain, proof, consistency, soundness, completeness, decidability, and compositionality. We also prove some basic theorems about those generalized notions. Then we model Wonderland as an arbitrary symbolic domain and Alice as a cognitive architecture that learns autonomously by observing random streams of facts from Wonderland. Alice is able to reason by means of computations that use bounded cognitive resources. Moreover, Alice develops her belief set by continuously forming, testing, and revising hypotheses. The system can learn a wide class of symbolic domains and challenge average human problem solvers in such domains as propositional logic and elementary arithmetic.
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Multi-Domain SDN Survivability for Agricultural Wireless Sensor Networks
Huang, Tao; Yan, Siyu; Yang, Fan; Liu, Jiang
2016-01-01
Wireless sensor networks (WSNs) have been widely applied in agriculture field; meanwhile, the advent of multi-domain software-defined networks (SDNs) have improved the wireless resource utilization rate and strengthened network management. In recent times, multi-domain SDNs have been applied to agricultural sensor networks, namely multi-domain software-defined wireless sensor networks (SDWSNs). However, when the SDNs controlling agriculture networks suddenly become unavailable, whether intra-domain or inter-domain, sensor network communication is abnormal because of the loss of control. Moreover, there are controller and switch info-updating problems even if the controller becomes available again. To resolve these problems, this paper proposes a new approach based on an Open vSwitch extension for multi-domain SDWSNs, which can enhance agriculture network survivability and stability. We achieved this by designing a connection-state mechanism, a communication mechanism on both L2 and L3, and an info-updating mechanism based on Open vSwitch. The experimental results show that, whether it is agricultural inter-domain or intra-domain during the controller failure period, the sensor switches can enter failure recovery mode as soon as possible so that the sensor network keeps a stable throughput, a short failure recovery time below 300 ms, and low packet loss. Further, the domain can smoothly control the domain network again once the controller becomes available. This approach based on an Open vSwitch extension can enhance the survivability and stability of multi-domain SDWSNs in precision agriculture. PMID:27827971
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Multi-Domain SDN Survivability for Agricultural Wireless Sensor Networks.
Huang, Tao; Yan, Siyu; Yang, Fan; Liu, Jiang
2016-11-06
Wireless sensor networks (WSNs) have been widely applied in agriculture field; meanwhile, the advent of multi-domain software-defined networks (SDNs) have improved the wireless resource utilization rate and strengthened network management. In recent times, multi-domain SDNs have been applied to agricultural sensor networks, namely multi-domain software-defined wireless sensor networks (SDWSNs). However, when the SDNs controlling agriculture networks suddenly become unavailable, whether intra-domain or inter-domain, sensor network communication is abnormal because of the loss of control. Moreover, there are controller and switch info-updating problems even if the controller becomes available again. To resolve these problems, this paper proposes a new approach based on an Open vSwitch extension for multi-domain SDWSNs, which can enhance agriculture network survivability and stability. We achieved this by designing a connection-state mechanism, a communication mechanism on both L2 and L3, and an info-updating mechanism based on Open vSwitch. The experimental results show that, whether it is agricultural inter-domain or intra-domain during the controller failure period, the sensor switches can enter failure recovery mode as soon as possible so that the sensor network keeps a stable throughput, a short failure recovery time below 300 ms, and low packet loss. Further, the domain can smoothly control the domain network again once the controller becomes available. This approach based on an Open vSwitch extension can enhance the survivability and stability of multi-domain SDWSNs in precision agriculture.
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Basson, M D; Zeng, B; Wang, S
2015-10-01
Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means
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Application of Wavelet Transform for PDZ Domain Classification
Daqrouq, Khaled; Alhmouz, Rami; Balamesh, Ahmed; Memic, Adnan
2015-01-01
PDZ domains have been identified as part of an array of signaling proteins that are often unrelated, except for the well-conserved structural PDZ domain they contain. These domains have been linked to many disease processes including common Avian influenza, as well as very rare conditions such as Fraser and Usher syndromes. Historically, based on the interactions and the nature of bonds they form, PDZ domains have most often been classified into one of three classes (class I, class II and others - class III), that is directly dependent on their binding partner. In this study, we report on three unique feature extraction approaches based on the bigram and trigram occurrence and existence rearrangements within the domain's primary amino acid sequences in assisting PDZ domain classification. Wavelet packet transform (WPT) and Shannon entropy denoted by wavelet entropy (WE) feature extraction methods were proposed. Using 115 unique human and mouse PDZ domains, the existence rearrangement approach yielded a high recognition rate (78.34%), which outperformed our occurrence rearrangements based method. The recognition rate was (81.41%) with validation technique. The method reported for PDZ domain classification from primary sequences proved to be an encouraging approach for obtaining consistent classification results. We anticipate that by increasing the database size, we can further improve feature extraction and correct classification. PMID:25860375
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Effective Moment Feature Vectors for Protein Domain Structures
Shi, Jian-Yu; Yiu, Siu-Ming; Zhang, Yan-Ning; Chin, Francis Yuk-Lun
2013-01-01
Imaging processing techniques have been shown to be useful in studying protein domain structures. The idea is to represent the pairwise distances of any two residues of the structure in a 2D distance matrix (DM). Features and/or submatrices are extracted from this DM to represent a domain. Existing approaches, however, may involve a large number of features (100–400) or complicated mathematical operations. Finding fewer but more effective features is always desirable. In this paper, based on some key observations on DMs, we are able to decompose a DM image into four basic binary images, each representing the structural characteristics of a fundamental secondary structure element (SSE) or a motif in the domain. Using the concept of moments in image processing, we further derive 45 structural features based on the four binary images. Together with 4 features extracted from the basic images, we represent the structure of a domain using 49 features. We show that our feature vectors can represent domain structures effectively in terms of the following. (1) We show a higher accuracy for domain classification. (2) We show a clear and consistent distribution of domains using our proposed structural vector space. (3) We are able to cluster the domains according to our moment features and demonstrate a relationship between structural variation and functional diversity. PMID:24391828
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Domain structure of the ribozyme from eubacterial ribonuclease P.
Loria, A; Pan, T
1996-01-01
Large RNAs can be composed of discrete domains that fold independently. One such "folding domain" has been identified previously in the ribozyme from Bacillus subtilis ribonuclease P (denoted P RNA). This domain contains roughly one-third of all residues. Folding of an RNA construct consisting of the remaining two-thirds of B. subtilis P RNA was examined by Fe(II)-EDTA hydroxyl radical protection. This molecule folds into the proper higher-order structure under identical conditions as the full-length P RNA, suggesting the presence of a second folding domain in B. subtilis P RNA. Folding analysis of the Escherichia coli P RNA by hydroxyl radical protection shows that this P RNA is completely folded at 5-6 mM Mg2+. In order to analyze the structural organization of folding domains in E. coli P RNA, constructs were designed based on the domain structure of B. subtilis P RNA. Fe(II)-EDTA protection indicates that E. coli P RNA also contains two folding domains. Despite the significant differences at the secondary structure level, both P RNAs appear to converge structurally at the folding domain level. The pre-tRNA substrate, localized in previous studies, may bind across the folding domains with the acceptor stem/3'CCA contacting the domain including the active site and the T stem-loop contacting the other. Because all eubacterial P RNAs share considerable homology in secondary structure to either B. subtilis or E. coli P RNA, these results suggest that this domain structure may be applicable for most, if not all, eubacterial P RNAs. Identification of folding domains should be valuable in dissecting structure-function relationship of large RNAs. PMID:8718684
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Siddiqui, Meena; Vakoc, Benjamin J.
2012-01-01
Recent advances in optical coherence tomography (OCT) have led to higher-speed sources that support imaging over longer depth ranges. Limitations in the bandwidth of state-of-the-art acquisition electronics, however, prevent adoption of these advances into the clinical applications. Here, we introduce optical-domain subsampling as a method for imaging at high-speeds and over extended depth ranges but with a lower acquisition bandwidth than that required using conventional approaches. Optically subsampled laser sources utilize a discrete set of wavelengths to alias fringe signals along an extended depth range into a bandwidth limited frequency window. By detecting the complex fringe signals and under the assumption of a depth-constrained signal, optical-domain subsampling enables recovery of the depth-resolved scattering signal without overlapping artifacts from this bandwidth-limited window. We highlight key principles behind optical-domain subsampled imaging, and demonstrate this principle experimentally using a polygon-filter based swept-source laser that includes an intra-cavity Fabry-Perot (FP) etalon. PMID:23038343
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NASA Astrophysics Data System (ADS)
Shur, V. Ya.; Akhmatkhanov, A. R.; Chuvakova, M. A.; Dolbilov, M. A.; Zelenovskiy, P. S.; Lobov, A. I.
2017-03-01
We have studied the self-organized dendrite domain structures appeared as a result of polarization reversal in the uniform field in lithium niobate single crystals with the artificial surface layer created by proton exchange. We have revealed the self-organized sub-micron scale dendrite domain patterns consisting of domain stripes oriented along the X crystallographic directions separated by arrays of dashed residual domains at the surface by scanning probe microscopy. Raman confocal microscopy allowed visualizing the quasi-regular dendrite domain structures with similar geometry in the vicinity of both polar surfaces. The depth of the structure was about 20 μm for Z+ polar surface and 70 μm for Z- one. According to the proposed mechanism, the dendrite structure formation at the surface was related to the ineffective screening of the residual depolarization field. The computer simulation of the structure formation based on the cellular automata model with probabilistic switching rule proved the eligibility of the proposed scheme, the simulated dendrite domain patterns at various depths being similar to the experimental ones.
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Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer's Disease.
Cheng, Bo; Liu, Mingxia; Shen, Dinggang; Li, Zuoyong; Zhang, Daoqiang
2017-04-01
Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer's Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multi-domain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods.
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Impact of Domain Analysis on Reuse Methods
1989-11-06
return on the investment. The potential negative effects a "bad" domain analysis has on developing systems in the domain also increases the risks of a...importance of domain analysis as part of a software reuse program. A particular goal is to assist in avoiding the potential negative effects of ad hoc or...are specification objects discovered by performing object-oriented analysis. Object-based analysis approaches thus serve to capture a model of reality
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Internet Domain Names: Background and Policy Issues
2010-04-05
was enacted to create a “ kids -friendly top level domain name” that would contain only age- appropriate content. The Dot Kids Implementation and...were introduced to require the Department of Commerce to compel ICANN to establish a mandatory top level domain name (such as . ) for material that...ICANN announced that it had entered into commercial and technical negotiations with a registry company (ICM Registry) to operate a new “. ” domain
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Domain Specificity between Peer Support and Self-Concept
ERIC Educational Resources Information Center
Leung, Kim Chau; Marsh, Herbert W.; Craven, Rhonda G.; Yeung, Alexander S.; Abduljabbar, Adel S.
2013-01-01
Peer support interventions have mostly neglected the domain specificity of intervention effects. In two studies, the present investigation examined the domain specificity of peer support interventions targeting specific domains of self-concept. In Study 1, participants ("n" = 50) who had received an academically oriented peer support…
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Classification and Lineage Tracing of SH2 Domains Throughout Eukaryotes.
Liu, Bernard A
2017-01-01
Today there exists a rapidly expanding number of sequenced genomes. Cataloging protein interaction domains such as the Src Homology 2 (SH2) domain across these various genomes can be accomplished with ease due to existing algorithms and predictions models. An evolutionary analysis of SH2 domains provides a step towards understanding how SH2 proteins integrated with existing signaling networks to position phosphotyrosine signaling as a crucial driver of robust cellular communication networks in metazoans. However organizing and tracing SH2 domain across organisms and understanding their evolutionary trajectory remains a challenge. This chapter describes several methodologies towards analyzing the evolutionary trajectory of SH2 domains including a global SH2 domain classification system, which facilitates annotation of new SH2 sequences essential for tracing the lineage of SH2 domains throughout eukaryote evolution. This classification utilizes a combination of sequence homology, protein domain architecture and the boundary positions between introns and exons within the SH2 domain or genes encoding these domains. Discrete SH2 families can then be traced across various genomes to provide insight into its origins. Furthermore, additional methods for examining potential mechanisms for divergence of SH2 domains from structural changes to alterations in the protein domain content and genome duplication will be discussed. Therefore a better understanding of SH2 domain evolution may enhance our insight into the emergence of phosphotyrosine signaling and the expansion of protein interaction domains.
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Health Numeracy: The Importance of Domain in Assessing Numeracy
Levy, Helen; Ubel, Peter A.; Dillard, Amanda J.; Weir, David R.; Fagerlin, Angela
2014-01-01
Background Existing research concludes that measures of general numeracy can be used to predict individuals’ ability to assess health risks. We posit that the domain in which questions are posed affects the ability to perform mathematical tasks, raising the possibility of a separate construct of “health numeracy” that is distinct from general numeracy. Objective To determine whether older adults’ ability to perform simple math depends on domain. Design Community-based participants completed four math questions posed in three different domains: a health domain, a financial domain, and a pure math domain. Participants 962 individuals aged 55 and older, representative of the community-dwelling U.S. population over age 54. Results We found that respondents performed significantly worse when questions were posed in the health domain (54 percent correct) than in either the pure math domain (66 percent correct) or the financial domain (63 percent correct). Limitations Our experimental measure of numeracy consisted of only four questions, and it is possible that the apparent effect of domain is specific to the mathematical tasks that these questions require. Conclusions These results suggest that health numeracy is strongly related to general numeracy but that the two constructs may not be the same. Further research is needed into how different aspects of general numeracy and health numeracy translate into actual medical decisions. PMID:23824401
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Velocity Enhancement by Synchronization of Magnetic Domain Walls
NASA Astrophysics Data System (ADS)
Hrabec, Aleš; Křižáková, Viola; Pizzini, Stefania; Sampaio, João; Thiaville, André; Rohart, Stanislas; Vogel, Jan
2018-06-01
Magnetic domain walls are objects whose dynamics is inseparably connected to their structure. In this Letter, we investigate magnetic bilayers, which are engineered such that a coupled pair of domain walls, one in each layer, is stabilized by a cooperation of Dzyaloshinskii-Moriya interaction and flux-closing mechanism. The dipolar field mediating the interaction between the two domain walls links not only their position but also their structure. We show that this link has a direct impact on their magnetic-field-induced dynamics. We demonstrate that in such a system the coupling leads to an increased domain wall velocity with respect to single domain walls. Since the domain wall dynamics is observed in a precessional regime, the dynamics involves the synchronization between the two walls to preserve the flux closure during motion. Properties of these coupled oscillating walls can be tuned by an additional in-plane magnetic field enabling a rich variety of states, from perfect synchronization to complete detuning.
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[Family of ribosomal proteins S1 contains unique conservative domain].
Deriusheva, E I; Machulin, A V; Selivanova, O M; Serdiuk, I N
2010-01-01
Different representatives of bacteria have different number of amino acid residues in the ribosomal proteins S1. This number varies from 111 (Spiroplasma kunkelii) to 863 a.a. (Treponema pallidum). Traditionally and for lack of this protein three-dimensional structure, its architecture is represented as repeating S1 domains. Number of these domains depends on the protein's length. Domain's quantity and its boundaries data are contained in the specialized databases, such as SMART, Pfam and PROSITE. However, for the same object these data may be very different. For search of domain's quantity and its boundaries, new approach, based on the analysis of dicted secondary structure (PsiPred), was used. This approach allowed us to reveal structural domains in amino acid sequences of S1 proteins and at that number varied from one to six. Alignment of S1 proteins, containing different domain's number, with the S1 RNAbinding domain of Escherichia coli PNPase elicited a fact that in family of ribosomal proteins SI one domain has maximal homology with S1 domain from PNPase. This conservative domain migrates along polypeptide chain and locates in proteins, containing different domain's number, according to specified pattern. In this domain as well in the S1 domain from PNPase, residues Phe-19, Phe-22, His-34, Asp-64 and Arg-68 are clustered on the surface and formed RNA binding site.
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A novel essential domain perspective for exploring gene essentiality.
Lu, Yao; Lu, Yulan; Deng, Jingyuan; Peng, Hai; Lu, Hui; Lu, Long Jason
2015-09-15
Genes with indispensable functions are identified as essential; however, the traditional gene-level studies of essentiality have several limitations. In this study, we characterized gene essentiality from a new perspective of protein domains, the independent structural or functional units of a polypeptide chain. To identify such essential domains, we have developed an Expectation-Maximization (EM) algorithm-based Essential Domain Prediction (EDP) Model. With simulated datasets, the model provided convergent results given different initial values and offered accurate predictions even with noise. We then applied the EDP model to six microbial species and predicted 1879 domains to be essential in at least one species, ranging 10-23% in each species. The predicted essential domains were more conserved than either non-essential domains or essential genes. Comparing essential domains in prokaryotes and eukaryotes revealed an evolutionary distance consistent with that inferred from ribosomal RNA. When utilizing these essential domains to reproduce the annotation of essential genes, we received accurate results that suggest protein domains are more basic units for the essentiality of genes. Furthermore, we presented several examples to illustrate how the combination of essential and non-essential domains can lead to genes with divergent essentiality. In summary, we have described the first systematic analysis on gene essentiality on the level of domains. huilu.bioinfo@gmail.com or Long.Lu@cchmc.org Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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An information theory framework for dynamic functional domain connectivity.
Vergara, Victor M; Miller, Robyn; Calhoun, Vince
2017-06-01
Dynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains. Our method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI). Strong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found. Other methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains. Identified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity. Copyright © 2017 Elsevier B.V. All rights reserved.
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Maltby, John; Day, Liz; Hall, Sophie S; Chivers, Sally
2017-10-01
Research suggests that trait resilience may be best understood within an ecological resilient systems theory, comprising engineering, ecological, and adaptive capacity resilience. However, there is no evidence as to how this theory translates to specific life domains. Data from two samples (the United States, n = 1,278; the United Kingdom, n = 211) facilitated five studies that introduce the Domain-Specific Resilient Systems Scales for assessing ecological resilient systems theory within work, health, marriage, friendships, and education. The Domain-Specific Resilient Systems Scales are found to predict unique variance in job satisfaction, lower job burnout, quality-of-life following illness, marriage commitment, and educational engagement, while controlling for factors including sex, age, personality, cognitive ability, and trait resilience. The findings also suggest a distinction between the three resilience dimensions in terms of the types of systems to which they contribute. Engineering resilience may contribute most to life domains where an established system needs to be maintained, for example, one's health. Ecological resilience may contribute most to life domains where the system needs sustainability in terms of present and future goal orientation, for example, one's work. Adaptive Capacity may contribute most to life domains where the system needs to be retained, preventing it from reaching a crisis state, for example, work burnout.
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The application of modular protein domains in proteomics
Jadwin, Joshua A.; Ogiue-Ikeda, Mari; Machida, Kazuya
2012-01-01
The ability of modular protein domains to independently fold and bind short peptide ligands both in vivo and in vitro has allowed a significant number of protein-protein interaction studies to take advantage of them as affinity and detection reagents. Here, we refer to modular domain based proteomics as “domainomics” to draw attention to the potential of using domains and their motifs as tools in proteomics. In this review we describe core concepts of domainomics, established and emerging technologies, and recent studies by functional category. Accumulation of domain-motif binding data should ultimately provide the foundation for domain-specific interactomes, which will likely reveal the underlying substructure of protein networks as well as the selectivity and plasticity of signal transduction. PMID:22710164
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How can EPR spectroscopy help to unravel molecular mechanisms of flavin-dependent photoreceptors?
Nohr, Daniel; Rodriguez, Ryan; Weber, Stefan; Schleicher, Erik
2015-01-01
Electron paramagnetic resonance (EPR) spectroscopy is a well-established spectroscopic method for the examination of paramagnetic molecules. Proteins can contain paramagnetic moieties in form of stable cofactors, transiently formed intermediates, or spin labels artificially introduced to cysteine sites. The focus of this review is to evaluate potential scopes of application of EPR to the emerging field of optogenetics. The main objective for EPR spectroscopy in this context is to unravel the complex mechanisms of light-active proteins, from their primary photoreaction to downstream signal transduction. An overview of recent results from the family of flavin-containing, blue-light dependent photoreceptors is given. In detail, mechanistic similarities and differences are condensed from the three classes of flavoproteins, the cryptochromes, LOV (Light-oxygen-voltage), and BLUF (blue-light using FAD) domains. Additionally, a concept that includes spin-labeled proteins and examination using modern pulsed EPR is introduced, which allows for a precise mapping of light-induced conformational changes.
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How can EPR spectroscopy help to unravel molecular mechanisms of flavin-dependent photoreceptors?
Nohr, Daniel; Rodriguez, Ryan; Weber, Stefan; Schleicher, Erik
2015-01-01
Electron paramagnetic resonance (EPR) spectroscopy is a well-established spectroscopic method for the examination of paramagnetic molecules. Proteins can contain paramagnetic moieties in form of stable cofactors, transiently formed intermediates, or spin labels artificially introduced to cysteine sites. The focus of this review is to evaluate potential scopes of application of EPR to the emerging field of optogenetics. The main objective for EPR spectroscopy in this context is to unravel the complex mechanisms of light-active proteins, from their primary photoreaction to downstream signal transduction. An overview of recent results from the family of flavin-containing, blue-light dependent photoreceptors is given. In detail, mechanistic similarities and differences are condensed from the three classes of flavoproteins, the cryptochromes, LOV (Light-oxygen-voltage), and BLUF (blue-light using FAD) domains. Additionally, a concept that includes spin-labeled proteins and examination using modern pulsed EPR is introduced, which allows for a precise mapping of light-induced conformational changes. PMID:26389123
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Generalized vector calculus on convex domain
NASA Astrophysics Data System (ADS)
Agrawal, Om P.; Xu, Yufeng
2015-06-01
In this paper, we apply recently proposed generalized integral and differential operators to develop generalized vector calculus and generalized variational calculus for problems defined over a convex domain. In particular, we present some generalization of Green's and Gauss divergence theorems involving some new operators, and apply these theorems to generalized variational calculus. For fractional power kernels, the formulation leads to fractional vector calculus and fractional variational calculus for problems defined over a convex domain. In special cases, when certain parameters take integer values, we obtain formulations for integer order problems. Two examples are presented to demonstrate applications of the generalized variational calculus which utilize the generalized vector calculus developed in the paper. The first example leads to a generalized partial differential equation and the second example leads to a generalized eigenvalue problem, both in two dimensional convex domains. We solve the generalized partial differential equation by using polynomial approximation. A special case of the second example is a generalized isoperimetric problem. We find an approximate solution to this problem. Many physical problems containing integer order integrals and derivatives are defined over arbitrary domains. We speculate that future problems containing fractional and generalized integrals and derivatives in fractional mechanics will be defined over arbitrary domains, and therefore, a general variational calculus incorporating a general vector calculus will be needed for these problems. This research is our first attempt in that direction.
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Visualizing ferromagnetic domains in magnetic topological insulators
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Wenbo; Gu, G. D.; Yang, Fang
2015-05-13
We report a systematic study of ferromagnetic domains in both single-crystal and thin-film specimens of magnetic topological insulators Cr doped (Bi 0.1Sb 0.9) 2Te 3 using magnetic force microscopy (MFM). The temperature and field dependences of MFM and in situ resistance data are consistent with previous bulk transport and magnetic characterization. Bubble-like ferromagnetic domains were observed in both single crystals and thin films. Significantly, smaller domain size (~500 nm) with narrower domain wall (~150 – 300 nm) was observed in thin films of magnetic topological insulators, likely due to vertical confinement effect. As a result, these results suggest that thinmore » films are more promising for visualization of chiral edge states.« less
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A multi-objective optimization approach accurately resolves protein domain architectures
Bernardes, J.S.; Vieira, F.R.J.; Zaverucha, G.; Carbone, A.
2016-01-01
Motivation: Given a protein sequence and a number of potential domains matching it, what are the domain content and the most likely domain architecture for the sequence? This problem is of fundamental importance in protein annotation, constituting one of the main steps of all predictive annotation strategies. On the other hand, when potential domains are several and in conflict because of overlapping domain boundaries, finding a solution for the problem might become difficult. An accurate prediction of the domain architecture of a multi-domain protein provides important information for function prediction, comparative genomics and molecular evolution. Results: We developed DAMA (Domain Annotation by a Multi-objective Approach), a novel approach that identifies architectures through a multi-objective optimization algorithm combining scores of domain matches, previously observed multi-domain co-occurrence and domain overlapping. DAMA has been validated on a known benchmark dataset based on CATH structural domain assignments and on the set of Plasmodium falciparum proteins. When compared with existing tools on both datasets, it outperforms all of them. Availability and implementation: DAMA software is implemented in C++ and the source code can be found at http://www.lcqb.upmc.fr/DAMA. Contact: juliana.silva_bernardes@upmc.fr or alessandra.carbone@lip6.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26458889
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Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M. F.; Downes, C. Peter; Batty, Ian H.
2012-01-01
Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105–107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules. PMID:22493426
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IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dixon, Miles J.; Gray, Alexander; Schenning, Martijn
2012-10-16
Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those ofmore » the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.« less
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Matter antimatter domains: A possible solution to the CP domain wall problem in the early universe
NASA Technical Reports Server (NTRS)
Mohanty, A. K.; Stecker, F. W.
1984-01-01
An SU(5) grand unified theory model is used to show how the degeneracy between vacua with different spontaneously broken charge parity can be dynamically lifted by a condensate of heavy fermion pairs. This drives a phase transition to a unique vacuum state with definite charge parity. The transition eliminates the domain walls in a matter antimatter symmetric domain cosmology.
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A structural portrait of the PDZ domain family.
Ernst, Andreas; Appleton, Brent A; Ivarsson, Ylva; Zhang, Yingnan; Gfeller, David; Wiesmann, Christian; Sidhu, Sachdev S
2014-10-23
PDZ (PSD-95/Discs-large/ZO1) domains are interaction modules that typically bind to specific C-terminal sequences of partner proteins and assemble signaling complexes in multicellular organisms. We have analyzed the existing database of PDZ domain structures in the context of a specificity tree based on binding specificities defined by peptide-phage binding selections. We have identified 16 structures of PDZ domains in complex with high-affinity ligands and have elucidated four additional structures to assemble a structural database that covers most of the branches of the PDZ specificity tree. A detailed comparison of the structures reveals features that are responsible for the diverse specificities across the PDZ domain family. Specificity differences can be explained by differences in PDZ residues that are in contact with the peptide ligands, but these contacts involve both side-chain and main-chain interactions. Most PDZ domains bind peptides in a canonical conformation in which the ligand main chain adopts an extended β-strand conformation by interacting in an antiparallel fashion with a PDZ β-strand. However, a subset of PDZ domains bind peptides with a bent main-chain conformation and the specificities of these non-canonical domains could not be explained based on canonical structures. Our analysis provides a structural portrait of the PDZ domain family, which serves as a guide in understanding the structural basis for the diverse specificities across the family. Copyright © 2014 Elsevier Ltd. All rights reserved.
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The Loyal Opposition Comments on Plan Domain Description Languages
NASA Technical Reports Server (NTRS)
Frank, Jeremy; Golden, Keith; Jonsson, Ari
2003-01-01
In this paper we take a critical look at PDDL 2.1 as designers and users of plan domain description languages. We describe planning domains that have features which are hard to model using PDDL 2.1. We then offer some suggestions on domain description language design, and describe how these suggestions make modeling our chosen domains easier.
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Quantifying the mechanisms of domain gain in animal proteins.
Buljan, Marija; Frankish, Adam; Bateman, Alex
2010-01-01
Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms. Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events. The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.
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Tunable inertia of chiral magnetic domain walls
Torrejon, Jacob; Martinez, Eduardo; Hayashi, Masamitsu
2016-01-01
The time it takes to accelerate an object from zero to a given velocity depends on the applied force and the environment. If the force ceases, it takes exactly the same time to completely decelerate. A magnetic domain wall is a topological object that has been observed to follow this behaviour. Here we show that acceleration and deceleration times of chiral Neel walls driven by current are different in a system with low damping and moderate Dzyaloshinskii–Moriya exchange constant. The time needed to accelerate a domain wall with current via the spin Hall torque is much faster than the time it needs to decelerate once the current is turned off. The deceleration time is defined by the Dzyaloshinskii–Moriya exchange constant whereas the acceleration time depends on the spin Hall torque, enabling tunable inertia of chiral domain walls. Such unique feature of chiral domain walls can be utilized to move and position domain walls with lower current, key to the development of storage class memory devices. PMID:27882932
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Investigation of Ferroelectric Domain Walls by Raman Spectroscopy
NASA Astrophysics Data System (ADS)
Stone, Gregory A.
Ferroelectric materials are characterized by an intrinsic spontaneous electric dipole moment that can be manipulated by the application of an electric field. Regions inside the crystal, known as domains, can have the spontaneous dipole moments oriented in a different direction than the surrounding crystal. Due to favorable piezoelectric, pyroelectric, electro-optic, and nonlinear optical properties, ferroelectric materials are attractive for commercial applications. Many devices, such as nonlinear frequency converters, require precisely engineered domain patterns. The properties of domains and their boundaries, known as domain walls, are vital to the performance and limitations of these devices. As a result, ferroelectric domains and the domain walls have been the focus of many scientific studies. Despite all this work, questions remain regarding their properties. This work is aimed at developing a better understanding of the properties of the domain wall using confocal Raman spectroscopy. Raman spectra taken from domain walls in Lithium Niobate and Lithium Tantalate reveal two distinct changes in the Raman spectra: (1) Shifts in frequency of the bulk Raman modes, which persists over a range of 0.2-0.5 mu m from the domain wall. The absence of this effect in defect free stoichiometric Lithium Tantalate indicates that the shifts are related to defects inside the crystal. (2) The presence of Raman modes corresponding to phonons propagating orthogonal to the laser beam axis, which are not collected in the bulk crystal. The phonons also preferential propagate normal to the domain wall. These modes are detected up to 0.35 mum from the domain wall. The observation and separation of these effects was made possible by the optimized spatial resolution (0.23 mum) of a home-built scanning confocal microscope and the fact that degeneracy of the transverse and longitudinal phonon polarization is lifted by polar phonons in Lithium Niobate and Lithium Tantalate. Raman
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Generation of a consensus protein domain dictionary
Schaeffer, R. Dustin; Jonsson, Amanda L.; Simms, Andrew M.; Daggett, Valerie
2011-01-01
Motivation: The discovery of new protein folds is a relatively rare occurrence even as the rate of protein structure determination increases. This rarity reinforces the concept of folds as reusable units of structure and function shared by diverse proteins. If the folding mechanism of proteins is largely determined by their topology, then the folding pathways of members of existing folds could encompass the full set used by globular protein domains. Results: We have used recent versions of three common protein domain dictionaries (SCOP, CATH and Dali) to generate a consensus domain dictionary (CDD). Surprisingly, 40% of the metafolds in the CDD are not composed of autonomous structural domains, i.e. they are not plausible independent folding units. This finding has serious ramifications for bioinformatics studies mining these domain dictionaries for globular protein properties. However, our main purpose in deriving this CDD was to generate an updated CDD to choose targets for MD simulation as part of our dynameomics effort, which aims to simulate the native and unfolding pathways of representatives of all globular protein consensus folds (metafolds). Consequently, we also compiled a list of representative protein targets of each metafold in the CDD. Availability and implementation: This domain dictionary is available at www.dynameomics.org. Contact: daggett@u.washington.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21068000
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Libbrecht, Maxwell W.; Ay, Ferhat; Hoffman, Michael M.; Gilbert, David M.; Bilmes, Jeffrey A.; Noble, William Stafford
2015-01-01
The genomic neighborhood of a gene influences its activity, a behavior that is attributable in part to domain-scale regulation. Previous genomic studies have identified many types of regulatory domains. However, due to the difficulty of integrating genomics data sets, the relationships among these domain types are poorly understood. Semi-automated genome annotation (SAGA) algorithms facilitate human interpretation of heterogeneous collections of genomics data by simultaneously partitioning the human genome and assigning labels to the resulting genomic segments. However, existing SAGA methods cannot integrate inherently pairwise chromatin conformation data. We developed a new computational method, called graph-based regularization (GBR), for expressing a pairwise prior that encourages certain pairs of genomic loci to receive the same label in a genome annotation. We used GBR to exploit chromatin conformation information during genome annotation by encouraging positions that are close in 3D to occupy the same type of domain. Using this approach, we produced a model of chromatin domains in eight human cell types, thereby revealing the relationships among known domain types. Through this model, we identified clusters of tightly regulated genes expressed in only a small number of cell types, which we term “specific expression domains.” We found that domain boundaries marked by promoters and CTCF motifs are consistent between cell types even when domain activity changes. Finally, we showed that GBR can be used to transfer information from well-studied cell types to less well-characterized cell types during genome annotation, making it possible to produce high-quality annotations of the hundreds of cell types with limited available data. PMID:25677182
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Libbrecht, Maxwell W; Ay, Ferhat; Hoffman, Michael M; Gilbert, David M; Bilmes, Jeffrey A; Noble, William Stafford
2015-04-01
The genomic neighborhood of a gene influences its activity, a behavior that is attributable in part to domain-scale regulation. Previous genomic studies have identified many types of regulatory domains. However, due to the difficulty of integrating genomics data sets, the relationships among these domain types are poorly understood. Semi-automated genome annotation (SAGA) algorithms facilitate human interpretation of heterogeneous collections of genomics data by simultaneously partitioning the human genome and assigning labels to the resulting genomic segments. However, existing SAGA methods cannot integrate inherently pairwise chromatin conformation data. We developed a new computational method, called graph-based regularization (GBR), for expressing a pairwise prior that encourages certain pairs of genomic loci to receive the same label in a genome annotation. We used GBR to exploit chromatin conformation information during genome annotation by encouraging positions that are close in 3D to occupy the same type of domain. Using this approach, we produced a model of chromatin domains in eight human cell types, thereby revealing the relationships among known domain types. Through this model, we identified clusters of tightly regulated genes expressed in only a small number of cell types, which we term "specific expression domains." We found that domain boundaries marked by promoters and CTCF motifs are consistent between cell types even when domain activity changes. Finally, we showed that GBR can be used to transfer information from well-studied cell types to less well-characterized cell types during genome annotation, making it possible to produce high-quality annotations of the hundreds of cell types with limited available data. © 2015 Libbrecht et al.; Published by Cold Spring Harbor Laboratory Press.
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A Probabilistic Graphical Model to Detect Chromosomal Domains
NASA Astrophysics Data System (ADS)
Heermann, Dieter; Hofmann, Andreas; Weber, Eva
To understand the nature of a cell, one needs to understand the structure of its genome. For this purpose, experimental techniques such as Hi-C detecting chromosomal contacts are used to probe the three-dimensional genomic structure. These experiments yield topological information, consistently showing a hierarchical subdivision of the genome into self-interacting domains across many organisms. Current methods for detecting these domains using the Hi-C contact matrix, i.e. a doubly-stochastic matrix, are mostly based on the assumption that the domains are distinct, thus non-overlapping. For overcoming this simplification and for being able to unravel a possible nested domain structure, we developed a probabilistic graphical model that makes no a priori assumptions on the domain structure. Within this approach, the Hi-C contact matrix is analyzed using an Ising like probabilistic graphical model whose coupling constant is proportional to each lattice point (entry in the contact matrix). The results show clear boundaries between identified domains and the background. These domain boundaries are dependent on the coupling constant, so that one matrix yields several clusters of different sizes, which show the self-interaction of the genome on different scales. This work was supported by a Grant from the International Human Frontier Science Program Organization (RGP0014/2014).
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Characterizing protein domain associations by Small-molecule ligand binding
Li, Qingliang; Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.
2012-01-01
Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing. PMID:23745168
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Domain walls in single-chain magnets
NASA Astrophysics Data System (ADS)
Pianet, Vivien; Urdampilleta, Matias; Colin, Thierry; Clérac, Rodolphe; Coulon, Claude
2017-12-01
The topology and creation energy of domain walls in different magnetic chains (called Single-Chain Magnets or SCMs) are discussed. As these domain walls, that can be seen as "defects", are known to control both static and dynamic properties of these one-dimensional systems, their study and understanding are necessary first steps before a deeper discussion of the SCM properties at finite temperature. The starting point of the paper is the simple regular ferromagnetic chain for which the characteristics of the domain walls are well known. Then two cases will be discussed (i) the "mixed chains" in which isotropic and anisotropic classical spins alternate, and (ii) the so-called "canted chains" where two different easy axis directions are present. In particular, we show that "strictly narrow" domain walls no longer exist in these more complex cases, while a cascade of phase transitions is found for canted chains as the canting angle approaches 45∘. The consequence for thermodynamic properties is briefly discussed in the last part of the paper.
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Protein domain assignment from the recurrence of locally similar structures
Tai, Chin-Hsien; Sam, Vichetra; Gibrat, Jean-Francois; Garnier, Jean; Munson, Peter J.
2010-01-01
Domains are basic units of protein structure and essential for exploring protein fold space and structure evolution. With the structural genomics initiative, the number of protein structures in the Protein Databank (PDB) is increasing dramatically and domain assignments need to be done automatically. Most existing structural domain assignment programs define domains using the compactness of the domains and/or the number and strength of intra-domain versus inter-domain contacts. Here we present a different approach based on the recurrence of locally similar structural pieces (LSSPs) found by one-against-all structure comparisons with a dataset of 6,373 protein chains from the PDB. Residues of the query protein are clustered using LSSPs via three different procedures to define domains. This approach gives results that are comparable to several existing programs that use geometrical and other structural information explicitly. Remarkably, most of the proteins that contribute the LSSPs defining a domain do not themselves contain the domain of interest. This study shows that domains can be defined by a collection of relatively small locally similar structural pieces containing, on average, four secondary structure elements. In addition, it indicates that domains are indeed made of recurrent small structural pieces that are used to build protein structures of many different folds as suggested by recent studies. PMID:21287617
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Domain Specific Language Support for Exascale
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sadayappan, Ponnuswamy
Domain-Specific Languages (DSLs) offer an attractive path to Exascale software since they provide expressive power through appropriate abstractions and enable domain-specific optimizations. But the advantages of a DSL compete with the difficulties of implementing a DSL, even for a narrowly defined domain. The DTEC project addresses how a variety of DSLs can be easily implemented to leverage existing compiler analysis and transformation capabilities within the ROSE open source compiler as part of a research program focusing on Exascale challenges. The OSU contributions to the DTEC project are in the area of code generation from high-level DSL descriptions, as well asmore » verification of the automatically-generated code.« less
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NASA Astrophysics Data System (ADS)
Jiang, Jun; Bai, Zi Long; Chen, Zhi Hui; He, Long; Zhang, David Wei; Zhang, Qing Hua; Shi, Jin An; Park, Min Hyuk; Scott, James F.; Hwang, Cheol Seong; Jiang, An Quan
2018-01-01
Erasable conductive domain walls in insulating ferroelectric thin films can be used for non-destructive electrical read-out of the polarization states in ferroelectric memories. Still, the domain-wall currents extracted by these devices have not yet reached the intensity and stability required to drive read-out circuits operating at high speeds. This study demonstrated non-destructive read-out of digital data stored using specific domain-wall configurations in epitaxial BiFeO3 thin films formed in mesa-geometry structures. Partially switched domains, which enable the formation of conductive walls during the read operation, spontaneously retract when the read voltage is removed, reducing the accumulation of mobile defects at the domain walls and potentially improving the device stability. Three-terminal memory devices produced 14 nA read currents at an operating voltage of 5 V, and operated up to T = 85 °C. The gap length can also be smaller than the film thickness, allowing the realization of ferroelectric memories with device dimensions far below 100 nm.
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A Methodology to Develop Ontologies for Emerging Domains
ERIC Educational Resources Information Center
Meenorngwar, Chai
2013-01-01
The characteristic of complex, dynamic domains, such as an emerging domain, is that the information necessary to describe them is not fully established. Standards are not yet established for these domains, and hence they are difficult to describe and present, and methods are needed that will reflect the changes that will occur as the domains…
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Domain wall remote pinning in magnetic nano wires
NASA Astrophysics Data System (ADS)
Read, Dan; Miguel, Jorge; Maccherozzi, Francesco; Cavill, Stuart; Dhesi, Sarnjeet; Cardiff University Collaboration; Diamond Light Source Collaboration
2013-03-01
In the current race for information storage media with ever increasing density the position of magnetic domain walls, the region in a magnetic system where the local magnetization continually rotates its direction between adjacent magnetic domains, is one of the most promising routes for future storage media devices. Information storage requires ultrafast read-out and writing operations, but domain walls need to be pinned so that the information is safely stored in the long term. Here we investigate the use of remote magnetostatic charges to trap domain walls. By using X-ray photoelectron emission microscopy we have followed the position of domain walls of opposite charge being pinned or repelled by pinning potentials of increasing strength. Micromagnetic simulations show an excellent agreement with the experimental results. We demonstrate the attractive or repulsive character of the interaction between domain wall and trap depending upon the sign of their magnetic charges. These quasi-static experiments are the antecedent to ultrafast time-resolved XMCD-PEEM experiments where the spin-transfer torque effect will be studied dynamically by applying picosecond-long current pulses across the magnetic nanowire.
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The KASE approach to domain-specific software systems
NASA Technical Reports Server (NTRS)
Bhansali, Sanjay; Nii, H. Penny
1992-01-01
Designing software systems, like all design activities, is a knowledge-intensive task. Several studies have found that the predominant cause of failures among system designers is lack of knowledge: knowledge about the application domain, knowledge about design schemes, knowledge about design processes, etc. The goal of domain-specific software design systems is to explicitly represent knowledge relevant to a class of applications and use it to partially or completely automate various aspects of the designing systems within that domain. The hope is that this would reduce the intellectual burden on the human designers and lead to more efficient software development. In this paper, we present a domain-specific system built on top of KASE, a knowledge-assisted software engineering environment being developed at the Stanford Knowledge Systems Laboratory. We introduce the main ideas underlying the construction of domain specific systems within KASE, illustrate the application of the idea in the synthesis of a system for tracking aircraft from radar signals, and discuss some of the issues in constructing domain-specific systems.
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Tailoring magnetic domains in Gd-Fe thin films
NASA Astrophysics Data System (ADS)
Talapatra, A.; Chelvane, J. Arout; Mohanty, J.
2018-05-01
This paper presents the global modification of magnetic domains and magnetic properties in amorphous Gd19Fe81 thin films with rapid thermal processing at two distinct temperatures (250oC and 450oC), and with different time intervals viz., 2, 5, 10 and 20 minutes. 100 nm thick as-prepared films display nano-scale meandering stripe domains with high magnetic phase contrast which is the signature of perpendicular magnetic anisotropy. The films processed at 250oC for various time intervals show successive reduction in magnetic phase contrast and domain size. The domain pattern completely disappeared, and topography dominated mixed magnetic phase has been obtained for the films processed at 450oC for time intervals greater than 2 minutes. The magnetization measurements indicate the reduction in perpendicular magnetic anisotropy with increase in saturation magnetization for all the rapid thermal processed films. The experimental outputs have been used to simulate the domain pattern. Reduction in uniaxial anisotropy along with the increase in saturation magnetization successfully explain the experimental trend of decrease in domain size and magnetic contrast.
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Introduction: History of SH2 Domains and Their Applications.
Liu, Bernard A; Machida, Kazuya
2017-01-01
The Src Homology 2 (SH2) domain is the prototypical protein interaction module that lies at the heart of phosphotyrosine signaling. Since its serendipitous discovery, there has been a tremendous advancement in technologies and an array of techniques available for studying SH2 domains and phosphotyrosine signaling. In this chapter, we provide a glimpse of the history of SH2 domains and describe many of the tools and techniques that have been developed along the way and discuss future directions for SH2 domain studies. We highlight the gist of each chapter in this volume in the context of: the structural biology and phosphotyrosine binding; characterizing SH2 specificity and generating prediction models; systems biology and proteomics; SH2 domains in signal transduction; and SH2 domains in disease, diagnostics, and therapeutics. Many of the individual chapters provide an in-depth approach that will allow scientists to interrogate the function and role of SH2 domains.
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Progress towards the development of SH2 domain inhibitors.
Kraskouskaya, Dziyana; Duodu, Eugenia; Arpin, Carolynn C; Gunning, Patrick T
2013-04-21
Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions. This review summarizes the progress towards the development of synthetic agents that disrupt the function of the SH2 domains in different proteins as well as the clinical relevance of targeting a specific SH2 domain. Since 1986, SH2 domains have been identified in over 110 human proteins, including kinases, transcription factors, and adaptor proteins. A number of these proteins are over-activated in many diseases, including cancer, and their function is highly dependent on their SH2 domain. Thus, inhibition of a protein's function through disrupting that of its SH2 domain has emerged as a promising approach towards the development of novel therapeutic modalities. Although targeting the SH2 domain is a challenging task in molecular recognition, the progress reported here demonstrates the feasibility of such an approach.
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Feature-level sentiment analysis by using comparative domain corpora
NASA Astrophysics Data System (ADS)
Quan, Changqin; Ren, Fuji
2016-06-01
Feature-level sentiment analysis (SA) is able to provide more fine-grained SA on certain opinion targets and has a wider range of applications on E-business. This study proposes an approach based on comparative domain corpora for feature-level SA. The proposed approach makes use of word associations for domain-specific feature extraction. First, we assign a similarity score for each candidate feature to denote its similarity extent to a domain. Then we identify domain features based on their similarity scores on different comparative domain corpora. After that, dependency grammar and a general sentiment lexicon are applied to extract and expand feature-oriented opinion words. Lastly, the semantic orientation of a domain-specific feature is determined based on the feature-oriented opinion lexicons. In evaluation, we compare the proposed method with several state-of-the-art methods (including unsupervised and semi-supervised) using a standard product review test collection. The experimental results demonstrate the effectiveness of using comparative domain corpora.
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A Domain Decomposition Parallelization of the Fast Marching Method
NASA Technical Reports Server (NTRS)
Herrmann, M.
2003-01-01
In this paper, the first domain decomposition parallelization of the Fast Marching Method for level sets has been presented. Parallel speedup has been demonstrated in both the optimal and non-optimal domain decomposition case. The parallel performance of the proposed method is strongly dependent on load balancing separately the number of nodes on each side of the interface. A load imbalance of nodes on either side of the domain leads to an increase in communication and rollback operations. Furthermore, the amount of inter-domain communication can be reduced by aligning the inter-domain boundaries with the interface normal vectors. In the case of optimal load balancing and aligned inter-domain boundaries, the proposed parallel FMM algorithm is highly efficient, reaching efficiency factors of up to 0.98. Future work will focus on the extension of the proposed parallel algorithm to higher order accuracy. Also, to further enhance parallel performance, the coupling of the domain decomposition parallelization to the G(sub 0)-based parallelization will be investigated.
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Bernardes, Juliana; Zaverucha, Gerson; Vaquero, Catherine; Carbone, Alessandra
2016-01-01
Traditional protein annotation methods describe known domains with probabilistic models representing consensus among homologous domain sequences. However, when relevant signals become too weak to be identified by a global consensus, attempts for annotation fail. Here we address the fundamental question of domain identification for highly divergent proteins. By using high performance computing, we demonstrate that the limits of state-of-the-art annotation methods can be bypassed. We design a new strategy based on the observation that many structural and functional protein constraints are not globally conserved through all species but might be locally conserved in separate clades. We propose a novel exploitation of the large amount of data available: 1. for each known protein domain, several probabilistic clade-centered models are constructed from a large and differentiated panel of homologous sequences, 2. a decision-making protocol combines outcomes obtained from multiple models, 3. a multi-criteria optimization algorithm finds the most likely protein architecture. The method is evaluated for domain and architecture prediction over several datasets and statistical testing hypotheses. Its performance is compared against HMMScan and HHblits, two widely used search methods based on sequence-profile and profile-profile comparison. Due to their closeness to actual protein sequences, clade-centered models are shown to be more specific and functionally predictive than the broadly used consensus models. Based on them, we improved annotation of Plasmodium falciparum protein sequences on a scale not previously possible. We successfully predict at least one domain for 72% of P. falciparum proteins against 63% achieved previously, corresponding to 30% of improvement over the total number of Pfam domain predictions on the whole genome. The method is applicable to any genome and opens new avenues to tackle evolutionary questions such as the reconstruction of ancient domain
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Hilbert, Brendan J.; Hayes, Janelle A.; Stone, Nicholas P.; Xu, Rui-Gang
2017-01-01
Abstract Many viruses use a powerful terminase motor to pump their genome inside an empty procapsid shell during virus maturation. The large terminase (TerL) protein contains both enzymatic activities necessary for packaging in such viruses: the adenosine triphosphatase (ATPase) that powers DNA translocation and an endonuclease that cleaves the concatemeric genome at both initiation and completion of genome packaging. However, how TerL binds DNA during translocation and cleavage remains mysterious. Here we investigate DNA binding and cleavage using TerL from the thermophilic phage P74-26. We report the structure of the P74-26 TerL nuclease domain, which allows us to model DNA binding in the nuclease active site. We screened a large panel of TerL variants for defects in binding and DNA cleavage, revealing that the ATPase domain is the primary site for DNA binding, and is required for nuclease activity. The nuclease domain is dispensable for DNA binding but residues lining the active site guide DNA for cleavage. Kinetic analysis of DNA cleavage suggests flexible tethering of the nuclease domains during DNA cleavage. We propose that interactions with the procapsid during DNA translocation conformationally restrict the nuclease domain, inhibiting cleavage; TerL release from the capsid upon completion of packaging unlocks the nuclease domains to cleave DNA. PMID:28082398
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Mesencephalic basolateral domain specification is dependent on Sonic Hedgehog
Martinez-Lopez, Jesus E.; Moreno-Bravo, Juan A.; Madrigal, M. Pilar; Martinez, Salvador; Puelles, Eduardo
2015-01-01
In the study of central nervous system morphogenesis, the identification of new molecular markers allows us to identify domains along the antero-posterior and dorso-ventral (DV) axes. In the past years, the alar and basal plates of the midbrain have been divided into different domains. The precise location of the alar-basal boundary is still under discussion. We have identified Barhl1, Nhlh1 and Six3 as appropriate molecular markers to the adjacent domains of this transition. The description of their expression patterns and the contribution to the different mesencephalic populations corroborated their role in the specification of these domains. We studied the influence of Sonic Hedgehog on these markers and therefore on the specification of these territories. The lack of this morphogen produced severe alterations in the expression pattern of Barhl1 and Nhlh1 with consequent misspecification of the basolateral (BL) domain. Six3 expression was apparently unaffected, however its distribution changed leading to altered basal domains. In this study we confirmed the localization of the alar-basal boundary dorsal to the BL domain and demonstrated that the development of the BL domain highly depends on Shh. PMID:25741244
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Significant expansion of exon-bordering protein domains during animal proteome evolution
Liu, Mingyi; Walch, Heiko; Wu, Shaoping; Grigoriev, Andrei
2005-01-01
We present evidence of remarkable genome-wide mobility and evolutionary expansion for a class of protein domains whose borders locate close to the borders of their encoding exons. These exon-bordering domains are more numerous and widely distributed in the human genome than other domains. They also co-occur with more diverse domains to form a larger variety of domain architectures in human proteins. A systematic comparison of nine animal genomes from nematodes to mammals revealed that exon-bordering domains expanded faster than other protein domains in both abundance and distribution, as well as the diversity of co-occurring domains and the domain architectures of harboring proteins. Furthermore, exon-bordering domains exhibited a particularly strong preference for class 1-1 intron phase. Our findings suggest that exon-bordering domains were amplified and interchanged within a genome more often and/or more successfully than other domains during evolution, probably the result of extensive exon shuffling and gene duplication events. The diverse biological functions of these domains underscore the important role they play in the expansion and diversification of animal proteomes. PMID:15640447
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The evolution of filamin – A protein domain repeat perspective
Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne
2013-01-01
Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427
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An ambiguity principle for assigning protein structural domains.
Postic, Guillaume; Ghouzam, Yassine; Chebrek, Romain; Gelly, Jean-Christophe
2017-01-01
Ambiguity is the quality of being open to several interpretations. For an image, it arises when the contained elements can be delimited in two or more distinct ways, which may cause confusion. We postulate that it also applies to the analysis of protein three-dimensional structure, which consists in dividing the molecule into subunits called domains. Because different definitions of what constitutes a domain can be used to partition a given structure, the same protein may have different but equally valid domain annotations. However, knowledge and experience generally displace our ability to accept more than one way to decompose the structure of an object-in this case, a protein. This human bias in structure analysis is particularly harmful because it leads to ignoring potential avenues of research. We present an automated method capable of producing multiple alternative decompositions of protein structure (web server and source code available at www.dsimb.inserm.fr/sword/). Our innovative algorithm assigns structural domains through the hierarchical merging of protein units, which are evolutionarily preserved substructures that describe protein architecture at an intermediate level, between domain and secondary structure. To validate the use of these protein units for decomposing protein structures into domains, we set up an extensive benchmark made of expert annotations of structural domains and including state-of-the-art domain parsing algorithms. The relevance of our "multipartitioning" approach is shown through numerous examples of applications covering protein function, evolution, folding, and structure prediction. Finally, we introduce a measure for the structural ambiguity of protein molecules.
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An ambiguity principle for assigning protein structural domains
Postic, Guillaume; Ghouzam, Yassine; Chebrek, Romain; Gelly, Jean-Christophe
2017-01-01
Ambiguity is the quality of being open to several interpretations. For an image, it arises when the contained elements can be delimited in two or more distinct ways, which may cause confusion. We postulate that it also applies to the analysis of protein three-dimensional structure, which consists in dividing the molecule into subunits called domains. Because different definitions of what constitutes a domain can be used to partition a given structure, the same protein may have different but equally valid domain annotations. However, knowledge and experience generally displace our ability to accept more than one way to decompose the structure of an object—in this case, a protein. This human bias in structure analysis is particularly harmful because it leads to ignoring potential avenues of research. We present an automated method capable of producing multiple alternative decompositions of protein structure (web server and source code available at www.dsimb.inserm.fr/sword/). Our innovative algorithm assigns structural domains through the hierarchical merging of protein units, which are evolutionarily preserved substructures that describe protein architecture at an intermediate level, between domain and secondary structure. To validate the use of these protein units for decomposing protein structures into domains, we set up an extensive benchmark made of expert annotations of structural domains and including state-of-the-art domain parsing algorithms. The relevance of our “multipartitioning” approach is shown through numerous examples of applications covering protein function, evolution, folding, and structure prediction. Finally, we introduce a measure for the structural ambiguity of protein molecules. PMID:28097215
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Harper, Stephen; Besong, Tabot M D; Emsley, Jonas; Scott, David J; Dreveny, Ingrid
2011-09-20
Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 Å resolution crystal structure of the human USP15 N-terminal domains revealing a 80 Å elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily. © 2011 American Chemical Society
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Examining, Documenting, and Modeling the Problem Space of a Variable Domain
2002-06-14
Feature-Oriented Domain Analysis ( FODA ) .............................................................................................. 9...development of this proposed process include: Feature-Oriented Domain Analysis ( FODA ) [3,4], Organization Domain Modeling (ODM) [2,5,6], Family-Oriented...configuration knowledge using generators [2]. 8 Existing Methods of Domain Engineering Feature-Oriented Domain Analysis ( FODA ) FODA is a domain
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IMPLICATIONS OF CROSS DOMAIN FIRES IN MULTI-DOMAIN BATTLE
2017-04-06
States Air Force 6 April 2017 DISTRIBUTION A. Approved for public release: distribution unlimited. 1 DISCLAIMER The views expressed in this...their cyber capability that will ultimately reinforce their influence and power across the Middle East. In viewing North Korea threat capabilities...land-based assets operating in cross domain denial type operations. In viewing the historical warfare capabilities captured in 13 the case study
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Cross-β Polymerization of Low Complexity Sequence Domains.
Kato, Masato; McKnight, Steven L
2017-03-01
Most transcription factors and RNA regulatory proteins encoded by eukaryotic genomes ranging from yeast to humans contain polypeptide domains variously described as intrinsically disordered, prion-like, or of low complexity (LC). These LC domains exist in an unfolded state when DNA and RNA regulatory proteins are studied in biochemical isolation from cells. Upon incubation in the purified state, many of these LC domains polymerize into homogeneous, labile amyloid-like fibers. Here, we consider several lines of evidence that may favor biologic utility for LC domain polymers. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.
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The DIMA web resource--exploring the protein domain network.
Pagel, Philipp; Oesterheld, Matthias; Stümpflen, Volker; Frishman, Dmitrij
2006-04-15
Conserved domains represent essential building blocks of most known proteins. Owing to their role as modular components carrying out specific functions they form a network based both on functional relations and direct physical interactions. We have previously shown that domain interaction networks provide substantially novel information with respect to networks built on full-length protein chains. In this work we present a comprehensive web resource for exploring the Domain Interaction MAp (DIMA), interactively. The tool aims at integration of multiple data sources and prediction techniques, two of which have been implemented so far: domain phylogenetic profiling and experimentally demonstrated domain contacts from known three-dimensional structures. A powerful yet simple user interface enables the user to compute, visualize, navigate and download domain networks based on specific search criteria. http://mips.gsf.de/genre/proj/dima
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Cross-domain latent space projection for person re-identification
NASA Astrophysics Data System (ADS)
Pu, Nan; Wu, Song; Qian, Li; Xiao, Guoqiang
2018-04-01
In this paper, we research the problem of person re-identification and propose a cross-domain latent space projection (CDLSP) method to address the problems of the absence or insufficient labeled data in the target domain. Under the assumption that the visual features in the source domain and target domain share the similar geometric structure, we transform the visual features from source domain and target domain to a common latent space by optimizing the object function defined in the manifold alignment method. Moreover, the proposed object function takes into account the specific knowledge in the re-id with the aim to improve the performance of re-id under complex situations. Extensive experiments conducted on four benchmark datasets show the proposed CDLSP outperforms or is competitive with stateof- the-art methods for person re-identification.
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DOT National Transportation Integrated Search
1995-07-01
An objective and quantitative method has been developed for deriving models of complex and specialized spheres of activity (domains) from domain-generated verbal data. The method was developed for analysis of interview transcripts, incident reports, ...
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Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs.
Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen E; Prestidge, Clive A
2016-07-01
Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.
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Domain Processes in Ferroelectric Ceramics
1994-04-14
elastic strain tensor and eikl is the Levi - Civita density. Eqs (11) and (12) has three nontrivial solutions: Xr3 = 0 (13) Xr"= -1 { [ 2sj2Q 12 -Sl I...ABSTRACT (aA~iMUM 200 wardt) This report Outlines the progres achieved during a two year effort sponsored by the AFOSR on the theoretical study of domain...INTRODUCTION This is the final progress report for this two year program sponsored by the Air Force Office of Scientific Research on "Domain Processes in
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Screening retinal transplants with Fourier-domain OCT
NASA Astrophysics Data System (ADS)
Rao, Bin
2009-02-01
Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.
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Work domain constraints for modelling surgical performance.
Morineau, Thierry; Riffaud, Laurent; Morandi, Xavier; Villain, Jonathan; Jannin, Pierre
2015-10-01
Three main approaches can be identified for modelling surgical performance: a competency-based approach, a task-based approach, both largely explored in the literature, and a less known work domain-based approach. The work domain-based approach first describes the work domain properties that constrain the agent's actions and shape the performance. This paper presents a work domain-based approach for modelling performance during cervical spine surgery, based on the idea that anatomical structures delineate the surgical performance. This model was evaluated through an analysis of junior and senior surgeons' actions. Twenty-four cervical spine surgeries performed by two junior and two senior surgeons were recorded in real time by an expert surgeon. According to a work domain-based model describing an optimal progression through anatomical structures, the degree of adjustment of each surgical procedure to a statistical polynomial function was assessed. Each surgical procedure showed a significant suitability with the model and regression coefficient values around 0.9. However, the surgeries performed by senior surgeons fitted this model significantly better than those performed by junior surgeons. Analysis of the relative frequencies of actions on anatomical structures showed that some specific anatomical structures discriminate senior from junior performances. The work domain-based modelling approach can provide an overall statistical indicator of surgical performance, but in particular, it can highlight specific points of interest among anatomical structures that the surgeons dwelled on according to their level of expertise.
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Mapping the Shh long-range regulatory domain
Anderson, Eve; Devenney, Paul S.; Hill, Robert E.; Lettice, Laura A.
2014-01-01
Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains. PMID:25252942
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Functional domains of the Drosophila Engrailed protein.
Han, K; Manley, J L
1993-01-01
We have studied the transcriptional activity of the Drosophila homeodomain protein Engrailed (En) by using a transient expression assay employing Schneider L2 cells. En was found to very strongly repress promoters activated by a variety of different activator proteins. However, unlike another Drosophila homeodomain-containing repressor, Even-skipped (Eve), En was unable to repress the activity of several basal promoters in the absence of activator expression. These findings indicate that En is a specific repressor of activated transcription, and suggest that En may repress transcription by a different mechanism than Eve, perhaps by interfering with interactions between transcriptional activators and the general transcription machinery. By analyzing the properties of a variety of En mutants, we identified a minimal repression domain composed of 55 residues, which can function when fused to a heterologous DNA binding domain. Like repression domains identified in the Drosophila repressors Eve and Krüppel, the En repression domain is rich in alanine residues (26%), but unlike these other domains, is moderately charged (six arginine and three glutamic acid residues). Separate regions of En that may in some circumstances function in transcriptional activation were also identified. Images PMID:8334991
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Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks
2011-01-01
Background Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. Results A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Conclusions Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking
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Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks.
Xie, Xueying; Jin, Jing; Mao, Yongyi
2011-08-18
Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary
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National Concept of Operations for Maritime Domain Awareness
2007-12-01
Maritime Domain Awareness (MDA) is the effective understanding of anything associated with the global maritime domain that could impact the security... Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding... Awareness (MDA) is the effective understanding of anything associated with the global maritime domain that could impact the security, safety
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Underwater Advanced Time-Domain Electromagnetic System
2017-03-01
distribution statement initially submitted with AD1042986, entitled Underwater Advanced Time Domain Electromagnetic System (MR-201313), has been appealed...Advanced Time -Domain Electromagnetic System ESTCP Project MR-201313 MARCH 2017 Mr. Steve Saville CH2M Distribution Statement D: Distribution...is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and
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Jarrold, Christopher; Tam, Helen; Baddeley, Alan D; Harvey, Caroline E
2011-05-01
Two studies that examine whether the forgetting caused by the processing demands of working memory tasks is domain-general or domain-specific are presented. In each, separate groups of adult participants were asked to carry out either verbal or nonverbal operations on exactly the same processing materials while maintaining verbal storage items. The imposition of verbal processing tended to produce greater forgetting even though verbal processing operations took no longer to complete than did nonverbal processing operations. However, nonverbal processing did cause forgetting relative to baseline control conditions, and evidence from the timing of individuals' processing responses suggests that individuals in both processing groups slowed their responses in order to "refresh" the memoranda. Taken together the data suggest that processing has a domain-general effect on working memory performance by impeding refreshment of memoranda but can also cause effects that appear domain-specific and that result from either blocking of rehearsal or interference.
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The cysteine-rich domain regulates ADAM protease function in vivo.
Smith, Katherine M; Gaultier, Alban; Cousin, Helene; Alfandari, Dominique; White, Judith M; DeSimone, Douglas W
2002-12-09
ADAMs are membrane-anchored proteases that regulate cell behavior by proteolytically modifying the cell surface and ECM. Like other membrane-anchored proteases, ADAMs contain candidate "adhesive" domains downstream of their metalloprotease domains. The mechanism by which membrane-anchored cell surface proteases utilize these putative adhesive domains to regulate protease function in vivo is not well understood. We address this important question by analyzing the relative contributions of downstream extracellular domains (disintegrin, cysteine rich, and EGF-like repeat) of the ADAM13 metalloprotease during Xenopus laevis development. When expressed in embryos, ADAM13 induces hyperplasia of the cement gland, whereas ADAM10 does not. Using chimeric constructs, we find that the metalloprotease domain of ADAM10 can substitute for that of ADAM13, but that specificity for cement gland expansion requires a downstream extracellular domain of ADAM13. Analysis of finer resolution chimeras indicates an essential role for the cysteine-rich domain and a supporting role for the disintegrin domain. These and other results reveal that the cysteine-rich domain of ADAM13 cooperates intramolecularly with the ADAM13 metalloprotease domain to regulate its function in vivo. Our findings thus provide the first evidence that a downstream extracellular adhesive domain plays an active role in regulating ADAM protease function in vivo. These findings are likely relevant to other membrane-anchored cell surface proteases.
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d-Omix: a mixer of generic protein domain analysis tools.
Wichadakul, Duangdao; Numnark, Somrak; Ingsriswang, Supawadee
2009-07-01
Domain combination provides important clues to the roles of protein domains in protein function, interaction and evolution. We have developed a web server d-Omix (a Mixer of Protein Domain Analysis Tools) aiming as a unified platform to analyze, compare and visualize protein data sets in various aspects of protein domain combinations. With InterProScan files for protein sets of interest provided by users, the server incorporates four services for domain analyses. First, it constructs protein phylogenetic tree based on a distance matrix calculated from protein domain architectures (DAs), allowing the comparison with a sequence-based tree. Second, it calculates and visualizes the versatility, abundance and co-presence of protein domains via a domain graph. Third, it compares the similarity of proteins based on DA alignment. Fourth, it builds a putative protein network derived from domain-domain interactions from DOMINE. Users may select a variety of input data files and flexibly choose domain search tools (e.g. hmmpfam, superfamily) for a specific analysis. Results from the d-Omix could be interactively explored and exported into various formats such as SVG, JPG, BMP and CSV. Users with only protein sequences could prepare an InterProScan file using a service provided by the server as well. The d-Omix web server is freely available at http://www.biotec.or.th/isl/Domix.
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Seo, Min-Duk; Park, Sung Jean; Kim, Hyun-Jung; Lee, Bong Jin
2007-01-09
Epstein-Barr virus latency is maintained by the latent membrane protein (LMP) 2A, which mimics the B-cell receptor (BCR) and perturbs BCR signaling. The cytoplasmic N-terminal domain of LMP2A is composed of 119 amino acids. The N-terminal domain of LMP2A (LMP2A NTD) contains two PY motifs (PPPPY) that interact with the WW domains of Nedd4 family ubiquitin-protein ligases. Based on our analysis of NMR data, we found that the LMP2A NTD adopts an overall random-coil structure in its native state. However, the region between residues 60 and 90 was relatively ordered, and seemed to form the hydrophobic core of the LMP2A NTD. This region resides between two PY motifs and is important for WW domain binding. Mapping of the residues involved in the interaction between the LMP2A NTD and WW domains was achieved by chemical shift perturbation, by the addition of WW2 and WW3 peptides. Interestingly, the binding of the WW domains mainly occurred in the hydrophobic core of the LMP2A NTD. In addition, we detected a difference in the binding modes of the two PY motifs against the two WW peptides. The binding of the WW3 peptide caused the resonances of five residues (Tyr(60), Glu(61), Asp(62), Trp(65), and Gly(66)) just behind the N-terminal PY motif of the LMP2A NTD to disappear. A similar result was obtained with WW2 binding. However, near the C-terminal PY motif, the chemical shift perturbation caused by WW2 binding was different from that due to WW3 binding, indicating that the residues near the PY motifs are involved in selective binding of WW domains. The present work represents the first structural study of the LMP2A NTD and provides fundamental structural information about its interaction with ubiquitin-protein ligase.
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Enabling Interoperability in Heliophysical Domains
NASA Astrophysics Data System (ADS)
Bentley, Robert
2013-04-01
There are many aspects of science in the Solar System that are overlapping - phenomena observed in one domain can have effects in other domains. However, there are many problems related to exploiting the data in cross-disciplinary studies because of lack of interoperability of the data and services. The CASSIS project is a Coordination Action funded under FP7 that has the objective of improving the interoperability of data and services related Solar System science. CASSIS has been investigating how the data could be made more accessible with some relatively minor changes to the observational metadata. The project has been looking at the services that are used within the domain and determining whether they are interoperable with each other and if not what would be required make them so. It has also been examining all types of metadata that are used when identifying and using observations and trying to make them more compliant with techniques and standards developed by bodies such as the International Virtual Observatory Alliance (IVOA). Many of the lessons that are being learnt in the study are applicable to domains that go beyond those directly involved in heliophysics. Adopting some simple standards related to the design of the services interfaces and metadata that are used would make it much easier to investigate interdisciplinary science topics. We will report on our finding and describe a roadmap for the future. For more information about CASSIS, please visit the project Web site on cassis-vo.eu
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Protein domains of unknown function are essential in bacteria.
Goodacre, Norman F; Gerloff, Dietlind L; Uetz, Peter
2013-12-31
More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens. The functional units of proteins are domains. Typically, each domain has a distinct structure and function. Genomes encode thousands of domains, and many of the domains have no known function (domains of unknown function [DUFs]). They are often ignored as of little relevance, given that many of them are found in only a few genomes. Here we show that many DUFs are essential DUFs (eDUFs) based on their presence in essential proteins. We also show that eDUFs are often essential even if they are found in relatively few genomes. However, in general, more common DUFs are more often essential than rare DUFs.
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Going from microscopic to macroscopic on nonuniform growing domains.
Yates, Christian A; Baker, Ruth E; Erban, Radek; Maini, Philip K
2012-08-01
Throughout development, chemical cues are employed to guide the functional specification of underlying tissues while the spatiotemporal distributions of such chemicals can be influenced by the growth of the tissue itself. These chemicals, termed morphogens, are often modeled using partial differential equations (PDEs). The connection between discrete stochastic and deterministic continuum models of particle migration on growing domains was elucidated by Baker, Yates, and Erban [Bull. Math. Biol. 72, 719 (2010)] in which the migration of individual particles was modeled as an on-lattice position-jump process. We build on this work by incorporating a more physically reasonable description of domain growth. Instead of allowing underlying lattice elements to instantaneously double in size and divide, we allow incremental element growth and splitting upon reaching a predefined threshold size. Such a description of domain growth necessitates a nonuniform partition of the domain. We first demonstrate that an individual-based stochastic model for particle diffusion on such a nonuniform domain partition is equivalent to a PDE model of the same phenomenon on a nongrowing domain, providing the transition rates (which we derive) are chosen correctly and we partition the domain in the correct manner. We extend this analysis to the case where the domain is allowed to change in size, altering the transition rates as necessary. Through application of the master equation formalism we derive a PDE for particle density on this growing domain and corroborate our findings with numerical simulations.
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Domain Adaptation for Pedestrian Detection Based on Prediction Consistency
Huan-ling, Tang; Zhi-yong, An
2014-01-01
Pedestrian detection is an active area of research in computer vision. It remains a quite challenging problem in many applications where many factors cause a mismatch between source dataset used to train the pedestrian detector and samples in the target scene. In this paper, we propose a novel domain adaptation model for merging plentiful source domain samples with scared target domain samples to create a scene-specific pedestrian detector that performs as well as rich target domain simples are present. Our approach combines the boosting-based learning algorithm with an entropy-based transferability, which is derived from the prediction consistency with the source classifications, to selectively choose the samples showing positive transferability in source domains to the target domain. Experimental results show that our approach can improve the detection rate, especially with the insufficient labeled data in target scene. PMID:25013850
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Displacement Current in Domain Walls of Bismuth Ferrite
NASA Astrophysics Data System (ADS)
Prosandeev, Sergey; Yang, Yurong; Paillard, Charles; Bellaiche, L.
2018-03-01
In 1861, Maxwell conceived the idea of the displacement current, which then made laws of electrodynamics more complete and also resulted in the realization of devices exploiting such displacement current. Interestingly, it is presently unknown if such displacement current can result in large intrinsic ac current in ferroic systems possessing domains, despite the flurry of recent activities that have been devoted to domains and their corresponding conductivity in these compounds. Here, we report first-principles-based atomistic simulations that predict that the transverse (polarization-related) displacement currents of 71° and 109° domains in the prototypical BiFeO3 multiferroic material are significant at the walls of such domains and in the GHz regime, and, in fact, result in currents that are at least of the same order of magnitude than previously reported dc currents (that are likely extrinsic in nature and due to electrons). Such large, localized and intrinsic ac currents are found to originate from low-frequency vibrations at the domain walls, and may open the door to the design of novel devices functioning in the GHz or THz range and in which currents would be confined within the domain wall.
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Functional and topological characteristics of mammalian regulatory domains
Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François
2014-01-01
Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455
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Ferroelectric domain wall motion induced by polarized light
Rubio-Marcos, Fernando; Del Campo, Adolfo; Marchet, Pascal; Fernández, Jose F.
2015-01-01
Ferroelectric materials exhibit spontaneous and stable polarization, which can usually be reoriented by an applied external electric field. The electrically switchable nature of this polarization is at the core of various ferroelectric devices. The motion of the associated domain walls provides the basis for ferroelectric memory, in which the storage of data bits is achieved by driving domain walls that separate regions with different polarization directions. Here we show the surprising ability to move ferroelectric domain walls of a BaTiO3 single crystal by varying the polarization angle of a coherent light source. This unexpected coupling between polarized light and ferroelectric polarization modifies the stress induced in the BaTiO3 at the domain wall, which is observed using in situ confocal Raman spectroscopy. This effect potentially leads to the non-contact remote control of ferroelectric domain walls by light. PMID:25779918
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Generalization of the Schwarz-Christoffel mapping to multiply connected polygonal domains.
Vasconcelos, Giovani L
2014-06-08
A generalization of the Schwarz-Christoffel mapping to multiply connected polygonal domains is obtained by making a combined use of two preimage domains, namely, a rectilinear slit domain and a bounded circular domain. The conformal mapping from the circular domain to the polygonal region is written as an indefinite integral whose integrand consists of a product of powers of the Schottky-Klein prime functions, which is the same irrespective of the preimage slit domain, and a prefactor function that depends on the choice of the rectilinear slit domain. A detailed derivation of the mapping formula is given for the case where the preimage slit domain is the upper half-plane with radial slits. Representation formulae for other canonical slit domains are also obtained but they are more cumbersome in that the prefactor function contains arbitrary parameters in the interior of the circular domain.
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Time-Domain Impedance Boundary Conditions for Computational Aeroacoustics
NASA Technical Reports Server (NTRS)
Tam, Christopher K. W.; Auriault, Laurent
1996-01-01
It is an accepted practice in aeroacoustics to characterize the properties of an acoustically treated surface by a quantity known as impedance. Impedance is a complex quantity. As such, it is designed primarily for frequency-domain analysis. Time-domain boundary conditions that are the equivalent of the frequency-domain impedance boundary condition are proposed. Both single frequency and model broadband time-domain impedance boundary conditions are provided. It is shown that the proposed boundary conditions, together with the linearized Euler equations, form well-posed initial boundary value problems. Unlike ill-posed problems, they are free from spurious instabilities that would render time-marching computational solutions impossible.
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Domain-wall trapping in a ferromagnetic nanowire network
NASA Astrophysics Data System (ADS)
Saitoh, E.; Tanaka, M.; Miyajima, H.; Yamaoka, T.
2003-05-01
The magnetic domain configuration in a submicron Ni81Fe19 wire network has been investigated by magnetic force microscopy. To improve the responsivity of the magnetic force microscope, an active quality factor autocontrol method was adopted. In the remanent state, domain walls were observed trapped firmly at the vertexes of the network. The magnetic domain configurations appear to minimize the exchange energy at the vertexes. These results indicate that the magnetic property of the ferromagnetic network can be described in terms of the uniform magnetic moments of the wires and interwire magnetic interactions at the vertexes. The observed structure of the domain walls is well reproduced by micromagnetic simulations.
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Deposition and growth of domains in one dimension
NASA Astrophysics Data System (ADS)
Rodgers, G. J.; Tavassoli, Z.
1998-09-01
A model of deposition and growth in one dimension is studied in which finite sized domains are deposited by the random sequential adsorption process. The domains then grow with a time dependent growth rate. When the initial deposited domains are monomers and dimers the coverage is found exactly for a number of different growth rates. A continuum version of this model is also considered.
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Histone Code Modulation by Oncogenic PWWP-Domain Protein in Breast Cancers
2010-06-01
athanogene 4 * DDHD2 DDHD domain containing 2 * PPAPDC1B phosphatidic acid phosphatase type 2 domain containing 1B * WHSC1L1 Wolf-Hirschhorn syndrome...from alternative splicing of exon 10. The WHSC1L1 long isoform encodes a 1437 amino acid protein containing 2 PWWP domains, 2 PHD-type zinc finger...motifs, a TANG2 domain, an AWS domain and a SET domain. The short isoform encodes a 645 amino acid protein containing a PWWP domain only. Our western
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A domain-centric solution to functional genomics via dcGO Predictor
2013-01-01
Background Computational/manual annotations of protein functions are one of the first routes to making sense of a newly sequenced genome. Protein domain predictions form an essential part of this annotation process. This is due to the natural modularity of proteins with domains as structural, evolutionary and functional units. Sometimes two, three, or more adjacent domains (called supra-domains) are the operational unit responsible for a function, e.g. via a binding site at the interface. These supra-domains have contributed to functional diversification in higher organisms. Traditionally functional ontologies have been applied to individual proteins, rather than families of related domains and supra-domains. We expect, however, to some extent functional signals can be carried by protein domains and supra-domains, and consequently used in function prediction and functional genomics. Results Here we present a domain-centric Gene Ontology (dcGO) perspective. We generalize a framework for automatically inferring ontological terms associated with domains and supra-domains from full-length sequence annotations. This general framework has been applied specifically to primary protein-level annotations from UniProtKB-GOA, generating GO term associations with SCOP domains and supra-domains. The resulting 'dcGO Predictor', can be used to provide functional annotation to protein sequences. The functional annotation of sequences in the Critical Assessment of Function Annotation (CAFA) has been used as a valuable opportunity to validate our method and to be assessed by the community. The functional annotation of all completely sequenced genomes has demonstrated the potential for domain-centric GO enrichment analysis to yield functional insights into newly sequenced or yet-to-be-annotated genomes. This generalized framework we have presented has also been applied to other domain classifications such as InterPro and Pfam, and other ontologies such as mammalian phenotype and
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Gourlay, Louise J; Peano, Clelia; Deantonio, Cecilia; Perletti, Lucia; Pietrelli, Alessandro; Villa, Riccardo; Matterazzo, Elena; Lassaux, Patricia; Santoro, Claudio; Puccio, Simone; Sblattero, Daniele; Bolognesi, Martino
2015-11-01
The 1.8 Å resolution crystal structure of a conserved domain of the potential Burkholderia pseudomallei antigen and trimeric autotransporter BPSL2063 is presented as a structural vaccinology target for melioidosis vaccine development. Since BPSL2063 (1090 amino acids) hosts only one conserved domain, and the expression/purification of the full-length protein proved to be problematic, a domain-filtering library was generated using β-lactamase as a reporter gene to select further BPSL2063 domains. As a result, two domains (D1 and D2) were identified and produced in soluble form in Escherichia coli. Furthermore, as a general tool, a genomic open reading frame-filtering library from the B. pseudomallei genome was also constructed to facilitate the selection of domain boundaries from the entire ORFeome. Such an approach allowed the selection of three potential protein antigens that were also produced in soluble form. The results imply the further development of ORF-filtering methods as a tool in protein-based research to improve the selection and production of soluble proteins or domains for downstream applications such as X-ray crystallography.
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Generating target system specifications from a domain model using CLIPS
NASA Technical Reports Server (NTRS)
Sugumaran, Vijayan; Gomaa, Hassan; Kerschberg, Larry
1991-01-01
The quest for reuse in software engineering is still being pursued and researchers are actively investigating the domain modeling approach to software construction. There are several domain modeling efforts reported in the literature and they all agree that the components that are generated from domain modeling are more conducive to reuse. Once a domain model is created, several target systems can be generated by tailoring the domain model or by evolving the domain model and then tailoring it according to the specified requirements. This paper presents the Evolutionary Domain Life Cycle (EDLC) paradigm in which a domain model is created using multiple views, namely, aggregation hierarchy, generalization/specialization hierarchies, object communication diagrams and state transition diagrams. The architecture of the Knowledge Based Requirements Elicitation Tool (KBRET) which is used to generate target system specifications is also presented. The preliminary version of KBRET is implemented in the C Language Integrated Production System (CLIPS).
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Domain knowledge patterns in pedagogical diagnostics
NASA Astrophysics Data System (ADS)
Miarka, Rostislav
2017-07-01
This paper shows a proposal of representation of knowledge patterns in RDF(S) language. Knowledge patterns are used for reuse of knowledge. They can be divided into two groups - Top-level knowledge patterns and Domain knowledge patterns. Pedagogical diagnostics is aimed at testing of knowledge of students at primary and secondary school. An example of domain knowledge pattern from pedagogical diagnostics is part of this paper.
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Protein domain definition should allow for conditional disorder
Yegambaram, Kavestri; Bulloch, Esther MM; Kingston, Richard L
2013-01-01
Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding. PMID:23963781
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Generalization of the Schwarz–Christoffel mapping to multiply connected polygonal domains
Vasconcelos, Giovani L.
2014-01-01
A generalization of the Schwarz–Christoffel mapping to multiply connected polygonal domains is obtained by making a combined use of two preimage domains, namely, a rectilinear slit domain and a bounded circular domain. The conformal mapping from the circular domain to the polygonal region is written as an indefinite integral whose integrand consists of a product of powers of the Schottky-Klein prime functions, which is the same irrespective of the preimage slit domain, and a prefactor function that depends on the choice of the rectilinear slit domain. A detailed derivation of the mapping formula is given for the case where the preimage slit domain is the upper half-plane with radial slits. Representation formulae for other canonical slit domains are also obtained but they are more cumbersome in that the prefactor function contains arbitrary parameters in the interior of the circular domain. PMID:24910523
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Proteins with an Euonymus lectin-like domain are ubiquitous in Embryophyta
2009-01-01
Background Cloning of the Euonymus lectin led to the discovery of a novel domain that also occurs in some stress-induced plant proteins. The distribution and the diversity of proteins with an Euonymus lectin (EUL) domain were investigated using detailed analysis of sequences in publicly accessible genome and transcriptome databases. Results Comprehensive in silico analyses indicate that the recently identified Euonymus europaeus lectin domain represents a conserved structural unit of a novel family of putative carbohydrate-binding proteins, which will further be referred to as the Euonymus lectin (EUL) family. The EUL domain is widespread among plants. Analysis of retrieved sequences revealed that some sequences consist of a single EUL domain linked to an unrelated N-terminal domain whereas others comprise two in tandem arrayed EUL domains. A new classification system for these lectins is proposed based on the overall domain architecture. Evolutionary relationships among the sequences with EUL domains are discussed. Conclusion The identification of the EUL family provides the first evidence for the occurrence in terrestrial plants of a highly conserved plant specific domain. The widespread distribution of the EUL domain strikingly contrasts the more limited or even narrow distribution of most other lectin domains found in plants. The apparent omnipresence of the EUL domain is indicative for a universal role of this lectin domain in plants. Although there is unambiguous evidence that several EUL domains possess carbohydrate-binding activity further research is required to corroborate the carbohydrate-binding properties of different members of the EUL family. PMID:19930663
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Kernel Manifold Alignment for Domain Adaptation.
Tuia, Devis; Camps-Valls, Gustau
2016-01-01
The wealth of sensory data coming from different modalities has opened numerous opportunities for data analysis. The data are of increasing volume, complexity and dimensionality, thus calling for new methodological innovations towards multimodal data processing. However, multimodal architectures must rely on models able to adapt to changes in the data distribution. Differences in the density functions can be due to changes in acquisition conditions (pose, illumination), sensors characteristics (number of channels, resolution) or different views (e.g. street level vs. aerial views of a same building). We call these different acquisition modes domains, and refer to the adaptation problem as domain adaptation. In this paper, instead of adapting the trained models themselves, we alternatively focus on finding mappings of the data sources into a common, semantically meaningful, representation domain. This field of manifold alignment extends traditional techniques in statistics such as canonical correlation analysis (CCA) to deal with nonlinear adaptation and possibly non-corresponding data pairs between the domains. We introduce a kernel method for manifold alignment (KEMA) that can match an arbitrary number of data sources without needing corresponding pairs, just few labeled examples in all domains. KEMA has interesting properties: 1) it generalizes other manifold alignment methods, 2) it can align manifolds of very different complexities, performing a discriminative alignment preserving each manifold inner structure, 3) it can define a domain-specific metric to cope with multimodal specificities, 4) it can align data spaces of different dimensionality, 5) it is robust to strong nonlinear feature deformations, and 6) it is closed-form invertible, which allows transfer across-domains and data synthesis. To authors' knowledge this is the first method addressing all these important issues at once. We also present a reduced-rank version of KEMA for computational
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Extensions of PDZ domains as important structural and functional elements.
Wang, Conan K; Pan, Lifeng; Chen, Jia; Zhang, Mingjie
2010-08-01
'Divide and conquer' has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions 'extensions'. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Using bioinformatics, we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results ( http://bcz102.ust.hk/pdzex/ ). We propose, using well-studied PDZ domains as illustrative examples, that the roles of PDZ extensions can be classified into at least four categories: 1) protein dynamics-based modulation of target binding affinity, 2) provision of binding sites for macro-molecular assembly, 3) structural integration of multi-domain modules, and 4) expansion of the target ligand-binding pocket. Our review highlights the potential structural and functional importance of domain extensions, highlighting the significance of looking beyond the canonical boundaries of protein domains in general.
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Satisfaction with life domains in people with epilepsy☆
Kobau, Rosemarie; Luncheon, Cecily; Zack, Matthew M.; Shegog, Ross; Price, Patricia H.
2017-01-01
While commonly used quality-of-life instruments assess perceived epilepsy-associated limitations in life domains and formally document patient concerns, less is known of community-dwelling adults with epilepsy about their satisfaction with broader life domains, such as satisfaction with housing, education, neighborhood, ability to help others, and achievement of goals. The purpose of this study was to examine satisfaction with life domains in a representative sample of community-dwelling adults with self-reported epilepsy from the 2008 HealthStyles survey. Following adjustment for sex, age group, race/ethnicity, education, and income, people with epilepsy were more likely to report frustration in the domains of achievement (e.g., dissatisfaction with education and life goals), compromised social interactions (dissatisfaction with family life, friends, and social life), and compromised physical capability (dissatisfaction with health and energy level). Life satisfaction and other well-being domains can supplement health indicators to guide treatment and program services for people with epilepsy to maximize their well-being. PMID:23153720
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Functional electronic inversion layers at ferroelectric domain walls
NASA Astrophysics Data System (ADS)
Mundy, J. A.; Schaab, J.; Kumagai, Y.; Cano, A.; Stengel, M.; Krug, I. P.; Gottlob, D. M.; Doğanay, H.; Holtz, M. E.; Held, R.; Yan, Z.; Bourret, E.; Schneider, C. M.; Schlom, D. G.; Muller, D. A.; Ramesh, R.; Spaldin, N. A.; Meier, D.
2017-06-01
Ferroelectric domain walls hold great promise as functional two-dimensional materials because of their unusual electronic properties. Particularly intriguing are the so-called charged walls where a polarity mismatch causes local, diverging electrostatic potentials requiring charge compensation and hence a change in the electronic structure. These walls can exhibit significantly enhanced conductivity and serve as a circuit path. The development of all-domain-wall devices, however, also requires walls with controllable output to emulate electronic nano-components such as diodes and transistors. Here we demonstrate electric-field control of the electronic transport at ferroelectric domain walls. We reversibly switch from resistive to conductive behaviour at charged walls in semiconducting ErMnO3. We relate the transition to the formation--and eventual activation--of an inversion layer that acts as the channel for the charge transport. The findings provide new insight into the domain-wall physics in ferroelectrics and foreshadow the possibility to design elementary digital devices for all-domain-wall circuitry.
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Satisfaction with life domains in people with epilepsy.
Kobau, Rosemarie; Luncheon, Cecily; Zack, Matthew M; Shegog, Ross; Price, Patricia H
2012-12-01
While commonly used quality-of-life instruments assess perceived epilepsy-associated limitations in life domains and formally document patient concerns, less is known of community-dwelling adults with epilepsy about their satisfaction with broader life domains, such as satisfaction with housing, education, neighborhood, ability to help others, and achievement of goals. The purpose of this study was to examine satisfaction with life domains in a representative sample of community-dwelling adults with self-reported epilepsy from the 2008 HealthStyles survey. Following adjustment for sex, age group, race/ethnicity, education, and income, people with epilepsy were more likely to report frustration in the domains of achievement (e.g., dissatisfaction with education and life goals), compromised social interactions (dissatisfaction with family life, friends, and social life), and compromised physical capability (dissatisfaction with health and energy level). Life satisfaction and other well-being domains can supplement health indicators to guide treatment and program services for people with epilepsy to maximize their well-being. Published by Elsevier Inc.
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Frequency-domain multiscale quantum mechanics/electromagnetics simulation method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meng, Lingyi; Yin, Zhenyu; Yam, ChiYung, E-mail: yamcy@yangtze.hku.hk, E-mail: ghc@everest.hku.hk
A frequency-domain quantum mechanics and electromagnetics (QM/EM) method is developed. Compared with the time-domain QM/EM method [Meng et al., J. Chem. Theory Comput. 8, 1190–1199 (2012)], the newly developed frequency-domain QM/EM method could effectively capture the dynamic properties of electronic devices over a broader range of operating frequencies. The system is divided into QM and EM regions and solved in a self-consistent manner via updating the boundary conditions at the QM and EM interface. The calculated potential distributions and current densities at the interface are taken as the boundary conditions for the QM and EM calculations, respectively, which facilitate themore » information exchange between the QM and EM calculations and ensure that the potential, charge, and current distributions are continuous across the QM/EM interface. Via Fourier transformation, the dynamic admittance calculated from the time-domain and frequency-domain QM/EM methods is compared for a carbon nanotube based molecular device.« less
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Domain walls and ferroelectric reversal in corundum derivatives
NASA Astrophysics Data System (ADS)
Ye, Meng; Vanderbilt, David
2017-01-01
Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180∘ domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall-mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond-valence sums. Our results thus provide both theoretical and empirical guidance for future searches for ferroelectric candidates in materials of the corundum derivative family.
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Shape design sensitivity analysis using domain information
NASA Technical Reports Server (NTRS)
Seong, Hwal-Gyeong; Choi, Kyung K.
1985-01-01
A numerical method for obtaining accurate shape design sensitivity information for built-up structures is developed and demonstrated through analysis of examples. The basic character of the finite element method, which gives more accurate domain information than boundary information, is utilized for shape design sensitivity improvement. A domain approach for shape design sensitivity analysis of built-up structures is derived using the material derivative idea of structural mechanics and the adjoint variable method of design sensitivity analysis. Velocity elements and B-spline curves are introduced to alleviate difficulties in generating domain velocity fields. The regularity requirements of the design velocity field are studied.
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Cross domains Arabic named entity recognition system
NASA Astrophysics Data System (ADS)
Al-Ahmari, S. Saad; Abdullatif Al-Johar, B.
2016-07-01
Named Entity Recognition (NER) plays an important role in many Natural Language Processing (NLP) applications such as; Information Extraction (IE), Question Answering (QA), Text Clustering, Text Summarization and Word Sense Disambiguation. This paper presents the development and implementation of domain independent system to recognize three types of Arabic named entities. The system works based on a set of domain independent grammar-rules along with Arabic part of speech tagger in addition to gazetteers and lists of trigger words. The experimental results shown, that the system performed as good as other systems with better results in some cases of cross-domains corpora.
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Fibromyalgia syndrome module at OMERACT 9: domain construct.
Mease, Philip; Arnold, Lesley M; Choy, Ernest H; Clauw, Daniel J; Crofford, Leslie J; Glass, Jennifer M; Martin, Susan A; Morea, Jessica; Simon, Lee; Strand, C Vibeke; Williams, David A
2009-10-01
The objective of the module was to (1) establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measure performance characteristics, (3) discuss development of a responder index for assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, and (6) establish a research agenda for outcomes research. Presentations at the module included: (1) Results of univariate and multivariate analysis of 10 FM clinical trials of 4 drugs, mapping key domains identified in previous patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, and breakout discussions to vote on possible essential domains and reliable measures; (2) Updates regarding outcome measure status; (3) Update on objective markers to measure FM disease state; and (4) Review of the issue of cognitive dysfunction (dyscognition) in FM. Consensus was reached as follows: (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials; dyscognition and depression should be measured in some trials; and stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers were identified as domains of research interest. (2) FM domain outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing numbers of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. In conclusion, a multidimensional symptom core set is proposed for evaluation of FM in clinical trials. Research on improved measures of single domains and composite measures is ongoing.
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Domainal cleavage as an Anisotropic Reaction-diffusion Process
NASA Astrophysics Data System (ADS)
Mulchrone, Kieran; Meere, Patrick
2017-04-01
Domainal cleavage comprises zones dominated by quartz and feldspar (QF-domains) and zones dominated by Mica (M-domains) which form at low metamorphic grades. The protolith is typically fairly homogeneous mudstone, siltstone, sandstone or limestone. Wet diffusion or pressure solution along grain boundaries is a key mechanism in the development of domanial cleavage. However, this does not explain why M-domains become sub-regularly spaced, visually evident in coarser-grained rocks, and take on an anastomising morphology. The ratio of M to QF-domains by volume can range from 1 to 0.1 and lower i.e. in extreme cases M-domains are intermittent but regularly spaced. It is suggested here that an anisotropic reaction-diffusion process model can explain these features. The imposed stress field instantaneously leads to anisotropy of diffusion by narrowing intergranular channels perpendicular to the principal stress. This leads to a preferred diffusion of chemicals parallel to the principal stress direction and lower diffusion rates in the normal direction. Combining this with the chemical reaction of pressure solution produces an anisotropic reaction-diffusion system. Both isotropic and anistropic reaction diffusion systems lead to pattern formation as discovered by Alan Turing on the 1950's as an explanation for patterns found in animal skins such as spots and stripes. Thus domanial cleavage is a striped pattern induced by diffusion anisotropy combined with a chemical reaction. Furthermore, rates of chemical reaction in intergranular fluids is likely to be many orders of magnitude greater that rates of deformation. Therefore we expect domanial cleavage to form relatively rapidly. As deformation progresses the M-domains behave less competently and may be the site of enhanced shearing. An example from Co. Cork, Ireland demonstrates shear folding in low-grade metasedimentary rocks with reverse shear along M-domains at a high angle to the maximum compressive stress.
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ERIC Educational Resources Information Center
Jarrold, Christopher; Tam, Helen; Baddeley, Alan D.; Harvey, Caroline E.
2011-01-01
Two studies that examine whether the forgetting caused by the processing demands of working memory tasks is domain-general or domain-specific are presented. In each, separate groups of adult participants were asked to carry out either verbal or nonverbal operations on exactly the same processing materials while maintaining verbal storage items.…
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Region and Domain Dependent Action of Nomifensine
Shu, Zhan; Taylor, I. Mitch; Walters, Seth H.; Michael, Adrian C.
2014-01-01
The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast-scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain-dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked dopamine overflow in the slow compared to the fast domains. To seek a kinetic explanation for nomifensine’s selective actions, we quantified the apparent KM of DA clearance by numerically evaluating the derivative of the descending phase of the DA signal after the end of the stimulus. For comparison, we likewise quantified apparent KM in the domains of the DS. As expected because it is a competitive inhibitor, nomifensine significantly increased the apparent KM in both the fast and slow domains of both the NAcc and DS. However, our analysis also leads to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared to the DS: apparent KM increased by ~500% in the NAcc and ~200% in the DS. PMID:24766210
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Fungal mediator tail subunits contain classical transcriptional activation domains.
Liu, Zhongle; Myers, Lawrence C
2015-04-01
Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their incorporation into Mediator but do not possess the ability to activate transcription when fused to a DNA binding domain. This suggests that Mediator fusion proteins actually are functioning in a manner similar to that of a classical DNA-bound activator rather than just recruiting Mediator. Our finding that deletion of the activation domains of S. cerevisiae Med2 and Med3, as well as C. dubliniensis Tlo1 (a Med2 ortholog), impairs the induction of certain genes shows these domains function at native promoters. Activation domains within coactivators are likely an important feature of these complexes and one that may have been uniquely leveraged by a common fungal pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Classification of Domain Movements in Proteins Using Dynamic Contact Graphs
Taylor, Daniel; Cawley, Gavin; Hayward, Steven
2013-01-01
A new method for the classification of domain movements in proteins is described and applied to 1822 pairs of structures from the Protein Data Bank that represent a domain movement in two-domain proteins. The method is based on changes in contacts between residues from the two domains in moving from one conformation to the other. We argue that there are five types of elemental contact changes and that these relate to five model domain movements called: “free”, “open-closed”, “anchored”, “sliding-twist”, and “see-saw.” A directed graph is introduced called the “Dynamic Contact Graph” which represents the contact changes in a domain movement. In many cases a graph, or part of a graph, provides a clear visual metaphor for the movement it represents and is a motif that can be easily recognised. The Dynamic Contact Graphs are often comprised of disconnected subgraphs indicating independent regions which may play different roles in the domain movement. The Dynamic Contact Graph for each domain movement is decomposed into elemental Dynamic Contact Graphs, those that represent elemental contact changes, allowing us to count the number of instances of each type of elemental contact change in the domain movement. This naturally leads to sixteen classes into which the 1822 domain movements are classified. PMID:24260562
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Domain wall formation in late-time phase transitions
NASA Technical Reports Server (NTRS)
Kolb, Edward W.; Wang, Yun
1992-01-01
We examine domain wall formulation in late time phase transitions. We find that in the invisible axion domain wall phenomenon, thermal effects alone are insufficient to drive different parts of the disconnected vacuum manifold. This suggests that domain walls do not form unless either there is some supplemental (but perhaps not unreasonable) dynamics to localize the scalar field responsible for the phase transition to the low temperature maximum (to an extraordinary precision) before the onset of the phase transition, or there is some non-thermal mechanism to produce large fluctuations in the scalar field. The fact that domain wall production is not a robust prediction of late time transitions may suggest future directions in model building.
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Docking analysis of verteporfin with YAP WW domain.
Kandoussi, Ilham; Lakhlili, Wiame; Taoufik, Jamal; Ibrahimi, Azeddine
2017-01-01
The YAP oncogene is a known cancer target. Therefore, it is of interest to understand the molecular docking interaction of verteporfin (a derivative of benzo-porphyrin) with the WW domain of YAP (clinically used for photo-dynamic therapy in macular degeneration) as a potential WW domain-ligand modulator by inhibition. A homology protein SWISS MODEL of the human YAP protein was constructed to dock (using AutoDock vina) with the PubChem verteporfin structure for interaction analysis. The docking result shows the possibilities of verteporfin interaction with the oncogenic transcription cofactor YAP having WW1 and WW2 domains. Thus, the ability of verteporfin to bind with the YAP WW domain having modulator activity is implied in this analysis.
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Gráczer, Eva; Varga, Andrea; Melnik, Bogdan; Semisotnov, Gennady; Závodszky, Péter; Vas, Mária
2009-02-10
The refolding mechanism of the homodimeric two-domain 3-isopropylmalate dehydrogenase (IPMDH) from the organisms adapted to different temperatures, Thermus thermophilus (Tt), Escherichia coli (Ec), and Vibrio sp. I5 (Vib), is described. In all three cases, instead of a self-template mechanism, the high extent of symmetry and cooperativity in folding of subunits and domains have been concluded from the following experimental findings: The complex time course of refolding, monitored by Trp fluorescence, consists of a fast (the rate constant varies as 16.5, 25.0, and 11.7 min-1 in the order of Tt, Ec, and Vib IPMDHs) and a slow (the rate constants are 0.11, 0.80, and 0.23 min-1 for the three different species) first-order process. However, a burst increase of Trp fluorescence anisotropy to the value of the native states indicates that in all three cases the association of the two polypeptide chains occurs at the beginning of refolding. This dimeric species binds the substrate IPM, but the native-like interactions of the tertiary and quaternary structures are only formed during the slow phase of refolding, accompanied by further increase of protein fluorescence and appearance of FRET between Trp side chain(s) and the bound NADH. Joining the contacting arms of each subunit also takes place exclusively during this slow phase. To monitor refolding of each domain within the intact molecule of T. thermophilus IPMDH, Trp's (located in separate domains) were systematically replaced with Phe's. The refolding processes of the mutants were followed by measuring changes in Trp fluorescence and in FRET between the particular Trp and NADH. The high similarity of time courses (both in biphasicity and in their rates) strongly suggests cooperative folding of the domains during formation of the native three-dimensional structure of IPMDH.
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Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G
2015-06-01
The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.
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East, Michael P.; Bowzard, J. Bradford; Dacks, Joel B.; Kahn, Richard A.
2012-01-01
The human family of ELMO domain-containing proteins (ELMODs) consists of six members and is defined by the presence of the ELMO domain. Within this family are two subclassifications of proteins, based on primary sequence conservation, protein size, and domain architecture, deemed ELMOD and ELMO. In this study, we used homology searching and phylogenetics to identify ELMOD family homologs in genomes from across eukaryotic diversity. This demonstrated not only that the protein family is ancient but also that ELMOs are potentially restricted to the supergroup Opisthokonta (Metazoa and Fungi), whereas proteins with the ELMOD organization are found in diverse eukaryotes and thus were likely the form present in the last eukaryotic common ancestor. The segregation of the ELMO clade from the larger ELMOD group is consistent with their contrasting functions as unconventional Rac1 guanine nucleotide exchange factors and the Arf family GTPase-activating proteins, respectively. We used unbiased, phylogenetic sorting and sequence alignments to identify the most highly conserved residues within the ELMO domain to identify a putative GAP domain within the ELMODs. Three independent but complementary assays were used to provide an initial characterization of this domain. We identified a highly conserved arginine residue critical for both the biochemical and cellular GAP activity of ELMODs. We also provide initial evidence of the function of human ELMOD1 as an Arf family GAP at the Golgi. These findings provide the basis for the future study of the ELMOD family of proteins and a new avenue for the study of Arf family GTPases. PMID:23014990
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Abl N-terminal Cap stabilization of SH3 domain dynamics†
Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E.; Engen, John R.
2008-01-01
Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears important for locking the SH3/SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydrogen exchange (HX) and mass spectrometry (MS) were used to determine if the NCap contributes to intramolecular interactions involving the Abl SH3 domain. Under physiological conditions, the Abl SH3 domain underwent partial unfolding and its unfolding half-life was slowed during binding to the SH2-kinase linker, providing a unique assay to test NCap-induced stabilization of the SH3 domain in various constructs. The results showed that NCap stabilizes the dynamics of the SH3 domain in certain constructs but does not increase the relative affinity of the SH3 domain for the native SH2-kinase linker. The stabilization effect was absent in constructs of just NCap + SH3 but was obvious when the SH2 domain and the SH2-kinase linker were present. These results suggest that interactions between NCap and the SH3 domain can contribute to c-Abl stabilization in constructs that contain at least the SH2 domain, an effect that may partially compensate for the absence of the negative regulatory C-terminal tail found in the related Src family of kinases. PMID:18452309
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Superbinder SH2 domains act as antagonists of cell signaling.
Kaneko, Tomonori; Huang, Haiming; Cao, Xuan; Li, Xing; Li, Chengjun; Voss, Courtney; Sidhu, Sachdev S; Li, Shawn S C
2012-09-25
Protein-ligand interactions mediated by modular domains, which often play important roles in regulating cellular functions, are generally of moderate affinities. We examined the Src homology 2 (SH2) domain, a modular domain that recognizes phosphorylated tyrosine (pTyr) residues, to investigate how the binding affinity of a modular domain for its ligand influences the structure and cellular function of the protein. We used the phage display method to perform directed evolution of the pTyr-binding residues in the SH2 domain of the tyrosine kinase Fyn and identified three amino acid substitutions that critically affected binding. We generated three SH2 domain triple-point mutants that were "superbinders" with much higher affinities for pTyr-containing peptides than the natural domain. Crystallographic analysis of one of these superbinders revealed that the superbinder SH2 domain recognized the pTyr moiety in a bipartite binding mode: A hydrophobic surface encompassed the phenyl ring, and a positively charged site engaged the phosphate. When expressed in mammalian cells, the superbinder SH2 domains blocked epidermal growth factor receptor signaling and inhibited anchorage-independent cell proliferation, suggesting that pTyr superbinders might be explored for therapeutic applications and useful as biological research tools. Although the SH2 domain fold can support much higher affinity for its ligand than is observed in nature, our results suggest that natural SH2 domains are not optimized for ligand binding but for specificity and flexibility, which are likely properties important for their function in signaling and regulatory processes.
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Ferroelastic domain switching dynamics under electrical and mechanical excitations.
Gao, Peng; Britson, Jason; Nelson, Christopher T; Jokisaari, Jacob R; Duan, Chen; Trassin, Morgan; Baek, Seung-Hyub; Guo, Hua; Li, Linze; Wang, Yiran; Chu, Ying-Hao; Minor, Andrew M; Eom, Chang-Beom; Ramesh, Ramamoorthy; Chen, Long-Qing; Pan, Xiaoqing
2014-05-02
In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.
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Ferroelastic domain switching dynamics under electrical and mechanical excitations
NASA Astrophysics Data System (ADS)
Gao, Peng; Britson, Jason; Nelson, Christopher T.; Jokisaari, Jacob R.; Duan, Chen; Trassin, Morgan; Baek, Seung-Hyub; Guo, Hua; Li, Linze; Wang, Yiran; Chu, Ying-Hao; Minor, Andrew M.; Eom, Chang-Beom; Ramesh, Ramamoorthy; Chen, Long-Qing; Pan, Xiaoqing
2014-05-01
In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.
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Field enhancement of electronic conductance at ferroelectric domain walls
Vasudevan, Rama K.; Cao, Ye; Laanait, Nouamane; ...
2017-11-06
Ferroelectric domain walls have continued to attract widespread attention due to both the novelty of the phenomena observed and the ability to reliably pattern them in nanoscale dimensions. But, the conductivity mechanisms remain in debate, particularly around nominally uncharged walls. Here, we posit a conduction mechanism relying on field-modification effect from polarization re-orientation and the structure of the reverse-domain nucleus. Through conductive atomic force microscopy measurements on an ultra-thin (001) BiFeO 3 thin film, in combination with phase-field simulations, we show that the field-induced twisted domain nucleus formed at domain walls results in local-field enhancement around the region of themore » atomic force microscope tip. In conjunction with slight barrier lowering, these two effects are sufficient to explain the observed emission current distribution. Our results suggest that different electronic properties at domain walls are not necessary to observe localized enhancement in domain wall currents.« less
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Sub-domain methods for collaborative electromagnetic computations
NASA Astrophysics Data System (ADS)
Soudais, Paul; Barka, André
2006-06-01
In this article, we describe a sub-domain method for electromagnetic computations based on boundary element method. The benefits of the sub-domain method are that the computation can be split between several companies for collaborative studies; also the computation time can be reduced by one or more orders of magnitude especially in the context of parametric studies. The accuracy and efficiency of this technique is assessed by RCS computations on an aircraft air intake with duct and rotating engine mock-up called CHANNEL. Collaborative results, obtained by combining two sets of sub-domains computed by two companies, are compared with measurements on the CHANNEL mock-up. The comparisons are made for several angular positions of the engine to show the benefits of the method for parametric studies. We also discuss the accuracy of two formulations of the sub-domain connecting scheme using edge based or modal field expansion. To cite this article: P. Soudais, A. Barka, C. R. Physique 7 (2006).
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Domain growth kinetics in stratifying foam films
NASA Astrophysics Data System (ADS)
Zhang, Yiran; Sharma, Vivek
2015-11-01
Baking bread, brewing cappuccino, pouring beer, washing dishes, shaving, shampooing, whipping eggs and blowing bubbles all involve creation of aqueous foam films. Typical foam films consist of two surfactant-laden surfaces that are ~ 5 nm - 10 micron apart. Sandwiched between these interfacial layers is a fluid that drains primarily under the influence of viscous and interfacial forces, including disjoining pressure. Interestingly, a layered ordering of micelles inside the foam films (thickness <100 nm) leads to a stepwise thinning phenomena called stratification, which results in a thickness-dependent variation in reflected light intensity, visualized as progressively darker shades of gray. Thinner, darker domains spontaneously grow within foam films. We show that the domain expansion dynamics exhibit two distinct growth regimes with characteristic scaling laws. Though several studies have focused on the expansion dynamics of isolated domains that exhibit a diffusion-like scaling, the change in expansion kinetics observed after domains contact with the Plateau border has not been reported and analyzed before.
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Life sciences domain analysis model
Freimuth, Robert R; Freund, Elaine T; Schick, Lisa; Sharma, Mukesh K; Stafford, Grace A; Suzek, Baris E; Hernandez, Joyce; Hipp, Jason; Kelley, Jenny M; Rokicki, Konrad; Pan, Sue; Buckler, Andrew; Stokes, Todd H; Fernandez, Anna; Fore, Ian; Buetow, Kenneth H
2012-01-01
Objective Meaningful exchange of information is a fundamental challenge in collaborative biomedical research. To help address this, the authors developed the Life Sciences Domain Analysis Model (LS DAM), an information model that provides a framework for communication among domain experts and technical teams developing information systems to support biomedical research. The LS DAM is harmonized with the Biomedical Research Integrated Domain Group (BRIDG) model of protocol-driven clinical research. Together, these models can facilitate data exchange for translational research. Materials and methods The content of the LS DAM was driven by analysis of life sciences and translational research scenarios and the concepts in the model are derived from existing information models, reference models and data exchange formats. The model is represented in the Unified Modeling Language and uses ISO 21090 data types. Results The LS DAM v2.2.1 is comprised of 130 classes and covers several core areas including Experiment, Molecular Biology, Molecular Databases and Specimen. Nearly half of these classes originate from the BRIDG model, emphasizing the semantic harmonization between these models. Validation of the LS DAM against independently derived information models, research scenarios and reference databases supports its general applicability to represent life sciences research. Discussion The LS DAM provides unambiguous definitions for concepts required to describe life sciences research. The processes established to achieve consensus among domain experts will be applied in future iterations and may be broadly applicable to other standardization efforts. Conclusions The LS DAM provides common semantics for life sciences research. Through harmonization with BRIDG, it promotes interoperability in translational science. PMID:22744959
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Aperiodic topological order in the domain configurations of functional materials
NASA Astrophysics Data System (ADS)
Huang, Fei-Ting; Cheong, Sang-Wook
2017-03-01
In numerous functional materials, such as steels, ferroelectrics and magnets, new functionalities can be achieved through the engineering of the domain structures, which are associated with the ordering of certain parameters within the material. The recent progress in technologies that enable imaging at atomic-scale spatial resolution has transformed our understanding of domain topology, revealing that, along with simple stripe-like or irregularly shaped domains, intriguing vortex-type topological domain configurations also exist. In this Review, we present a new classification scheme of 'Zm Zn domains with Zl vortices' for 2D macroscopic domain structures with m directional variants and n translational antiphases. This classification, together with the concepts of topological protection and topological charge conservation, can be applied to a wide range of materials, such as multiferroics, improper ferroelectrics, layered transition metal dichalcogenides and magnetic superconductors, as we discuss using selected examples. The resulting topological considerations provide a new basis for the understanding of the formation, kinetics, manipulation and property optimization of domains and domain boundaries in functional materials.
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Molecular basis for TPR domain-mediated regulation of protein phosphatase 5.
Yang, Jing; Roe, S Mark; Cliff, Matthew J; Williams, Mark A; Ladbury, John E; Cohen, Patricia T W; Barford, David
2005-01-12
Protein phosphatase 5 (Ppp5) is a serine/threonine protein phosphatase comprising a regulatory tetratricopeptide repeat (TPR) domain N-terminal to its phosphatase domain. Ppp5 functions in signalling pathways that control cellular responses to stress, glucocorticoids and DNA damage. Its phosphatase activity is suppressed by an autoinhibited conformation maintained by the TPR domain and a C-terminal subdomain. By interacting with the TPR domain, heat shock protein 90 (Hsp90) and fatty acids including arachidonic acid stimulate phosphatase activity. Here, we describe the structure of the autoinhibited state of Ppp5, revealing mechanisms of TPR-mediated phosphatase inhibition and Hsp90- and arachidonic acid-induced stimulation of phosphatase activity. The TPR domain engages with the catalytic channel of the phosphatase domain, restricting access to the catalytic site. This autoinhibited conformation of Ppp5 is stabilised by the C-terminal alphaJ helix that contacts a region of the Hsp90-binding groove on the TPR domain. Hsp90 activates Ppp5 by disrupting TPR-phosphatase domain interactions, permitting substrate access to the constitutively active phosphatase domain, whereas arachidonic acid prompts an alternate conformation of the TPR domain, destabilising the TPR-phosphatase domain interface.
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Interface conditions for domain decomposition with radical grid refinement
NASA Technical Reports Server (NTRS)
Scroggs, Jeffrey S.
1991-01-01
Interface conditions for coupling the domains in a physically motivated domain decomposition method are discussed. The domain decomposition is based on an asymptotic-induced method for the numerical solution of hyperbolic conservation laws with small viscosity. The method consists of multiple stages. The first stage is to obtain a first approximation using a first-order method, such as the Godunov scheme. Subsequent stages of the method involve solving internal-layer problem via a domain decomposition. The method is derived and justified via singular perturbation techniques.
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Domain Specific Language Support for Exascale
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mellor-Crummey, John
A multi-institutional project known as D-TEC (short for “Domain- specific Technology for Exascale Computing”) set out to explore technologies to support the construction of Domain Specific Languages (DSLs) to map application programs to exascale architectures. DSLs employ automated code transformation to shift the burden of delivering portable performance from application programmers to compilers. Two chief properties contribute: DSLs permit expression at a high level of abstraction so that a programmer’s intent is clear to a compiler and DSL implementations encapsulate human domain-specific optimization knowledge so that a compiler can be smart enough to achieve good results on specific hardware. Domainmore » specificity is what makes these properties possible in a programming language. If leveraging domain specificity is the key to keep exascale software tractable, a corollary is that many different DSLs will be needed to encompass the full range of exascale computing applications; moreover, a single application may well need to use several different DSLs in conjunction. As a result, developing a general toolkit for building domain-specific languages was a key goal for the D-TEC project. Different aspects of the D-TEC research portfolio were the focus of work at each of the partner institutions in the multi-institutional project. D-TEC research and development work at Rice University focused on on three principal topics: understanding how to automate the tuning of code for complex architectures, research and development of the Rosebud DSL engine, and compiler technology to support complex execution platforms. This report provides a summary of the research and development work on the D-TEC project at Rice University.« less