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Sample records for generates distinct nurf

  1. Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators

    PubMed Central

    Kwon, So Yeon; Grisan, Valentina; Jang, Boyun; Herbert, John; Badenhorst, Paul

    2016-01-01

    NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx)) has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions. PMID:27046080

  2. Functional Interactions between NURF and Ctcf Regulate Gene Expression

    PubMed Central

    Qiu, Zhijun; Song, Carolyn; Malakouti, Navid; Murray, Daniel; Hariz, Aymen; Zimmerman, Mark; Gygax, Derek; Alhazmi, Aiman

    2014-01-01

    Gene expression frequently requires chromatin-remodeling complexes, and it is assumed that these complexes have common gene targets across cell types. Contrary to this belief, we show by genome-wide expression profiling that Bptf, an essential and unique subunit of the nucleosome-remodeling factor (NURF), predominantly regulates the expression of a unique set of genes between diverse cell types. Coincident with its functions in gene expression, we observed that Bptf is also important for regulating nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin. NURF function at Ctcf binding sites could be direct, because Bptf occupies Ctcf binding sites in vivo and has physical interactions with CTCF and the cohesin subunit SA2. Assays of several Ctcf binding sites using reporter assays showed that their regulatory activity requires Bptf in two different cell types. Focused studies at H2-K1 showed that Bptf regulates the ability of Klf4 to bind near an upstream Ctcf site, possibly influencing gene expression. In combination, these studies demonstrate that gene expression as regulated by NURF occurs partly through physical and functional interactions with the ubiquitous and multivalent factors Ctcf and cohesin. PMID:25348714

  3. The ISWI-containing NURF complex regulates the output of the canonical Wingless pathway.

    PubMed

    Song, Haiyun; Spichiger-Haeusermann, Chloe; Basler, Konrad

    2009-10-01

    Wingless (Wg) signalling regulates the expression of its target genes through Pangolin, Armadillo and their interacting co-factors. In a genetic screen for Wg signalling components, we found that imitation switch (ISWI), a chromatin-remodelling ATPase, had a positive role in transducing the canonical Wg signal, promoting the expression of the Wg target senseless. ISWI is found in several chromatin-remodelling complexes, including nucleosome remodelling factor (NURF). The effect of interfering with the function of other components of the NURF complex in vivo mimics that of ISWI. The NURF complex is also required for the efficient expression of other Wg target genes. Armadillo interacts directly with the NURF complex in vitro and recruits it to Wg targets in cultured cells. Together, our results suggest that the ISWI-containing NURF complex functions as a co-activator of Armadillo to promote Wg-mediated transcription.

  4. The ISWI-containing NURF complex regulates the output of the canonical Wingless pathway

    PubMed Central

    Song, Haiyun; Spichiger-Haeusermann, Chloe; Basler, Konrad

    2009-01-01

    Wingless (Wg) signalling regulates the expression of its target genes through Pangolin, Armadillo and their interacting co-factors. In a genetic screen for Wg signalling components, we found that imitation switch (ISWI), a chromatin-remodelling ATPase, had a positive role in transducing the canonical Wg signal, promoting the expression of the Wg target senseless. ISWI is found in several chromatin-remodelling complexes, including nucleosome remodelling factor (NURF). The effect of interfering with the function of other components of the NURF complex in vivo mimics that of ISWI. The NURF complex is also required for the efficient expression of other Wg target genes. Armadillo interacts directly with the NURF complex in vitro and recruits it to Wg targets in cultured cells. Together, our results suggest that the ISWI-containing NURF complex functions as a co-activator of Armadillo to promote Wg-mediated transcription. PMID:19713963

  5. Familiarity, relative distinctiveness, and the generation effect.

    PubMed

    Peynircioğlu, Z F; Mungan, E

    1993-05-01

    In Experiment 1, psychology experts and novices showed generation effects with both psychology-related and other words. In Experiment 2, music experts who were sports novices and sports experts who were music novices showed a generation effect in a recognition test for all words regardless of domain (music or sports). Moreover, the effect was greater for words from the subjects' "nonexpertise" area. In Experiments 3A and 3B, music experts showed a greater generation effect for sports words than for music words in a free recall test but only when the sports and music words were studied together. These results are inconsistent with the semantic elaboration requirement for the generation effect that predicts less of an effect, if any, with less familiar materials. Rather, they provide evidence for the idea that the generation effect is influenced by relative distinctiveness of the to-be-remembered items.

  6. A Novel Algorithm for the Generation of Distinct Kinematic Chain

    NASA Astrophysics Data System (ADS)

    Medapati, Sreenivasa Reddy; Kuchibhotla, Mallikarjuna Rao; Annambhotla, Balaji Srinivasa Rao

    2016-07-01

    Generation of distinct kinematic chains is an important topic in the design of mechanisms for various industrial applications i.e., robotic manipulator, tractor, crane etc. Many researchers have intently focused on this area and explained various processes of generating distinct kinematic chains which are laborious and complex. It is desirable to enumerate the kinematic chains systematically to know the inherent characteristics of a chain related to its structure so that all the distinct chains can be analyzed in depth, prior to the selection of a chain for a purpose. This paper proposes a novel and simple method with set of rules defined to eliminate isomorphic kinematic chains generating distinct kinematic chains. Also, this method simplifies the process of generating distinct kinematic chains even at higher levels i.e., 10-link, 11-link with single and multiple degree of freedom.

  7. Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation

    PubMed Central

    Li, Ying; Schulz, Vincent P.; Deng, Changwang; Li, Guangyao; Shen, Yong; Tusi, Betsabeh K.; Ma, Gina; Stees, Jared; Qiu, Yi; Steiner, Laurie A.; Zhou, Lei; Zhao, Keji; Bungert, Jörg; Gallagher, Patrick G.; Huang, Suming

    2016-01-01

    The modulation of chromatin structure is a key step in transcription regulation in mammalian cells and eventually determines lineage commitment and differentiation. USF1/2, Setd1a and NURF complexes interact to regulate chromatin architecture in erythropoiesis, but the mechanistic basis for this regulation is hitherto unknown. Here we showed that Setd1a and NURF complexes bind to promoters to control chromatin structural alterations and gene activation in a cell context dependent manner. In human primary erythroid cells USF1/2, H3K4me3 and the NURF complex were significantly co-enriched at transcription start sites of erythroid genes, and their binding was associated with promoter/enhancer accessibility that resulted from nucleosome repositioning. Mice deficient for Setd1a, an H3K4 trimethylase, in the erythroid compartment exhibited reduced Ter119/CD71 positive erythroblasts, peripheral blood RBCs and hemoglobin levels. Loss of Setd1a led to a reduction of promoter-associated H3K4 methylation, inhibition of gene transcription and blockade of erythroid differentiation. This was associated with alterations in NURF complex occupancy at erythroid gene promoters and reduced chromatin accessibility. Setd1a deficiency caused decreased associations between enhancer and promoter looped interactions as well as reduced expression of erythroid genes such as the adult β-globin gene. These data indicate that Setd1a and NURF complexes are specifically targeted to and coordinately regulate erythroid promoter chromatin dynamics during erythroid lineage differentiation. PMID:27141965

  8. A functional insulator screen identifies NURF and dREAM components to be required for enhancer-blocking.

    PubMed

    Bohla, Dorte; Herold, Martin; Panzer, Imke; Buxa, Melanie K; Ali, Tamer; Demmers, Jeroen; Krüger, Marcus; Scharfe, Maren; Jarek, Michael; Bartkuhn, Marek; Renkawitz, Rainer

    2014-01-01

    Chromatin insulators of higher eukaryotes functionally divide the genome into active and inactive domains. Furthermore, insulators regulate enhancer/promoter communication, which is evident from the Drosophila bithorax locus in which a multitude of regulatory elements control segment specific gene activity. Centrosomal protein 190 (CP190) is targeted to insulators by CTCF or other insulator DNA-binding factors. Chromatin analyses revealed that insulators are characterized by open and nucleosome depleted regions. Here, we wanted to identify chromatin modification and remodelling factors required for an enhancer blocking function. We used the well-studied Fab-8 insulator of the bithorax locus to apply a genome-wide RNAi screen for factors that contribute to the enhancer blocking function of CTCF and CP190. Among 78 genes required for optimal Fab-8 mediated enhancer blocking, all four components of the NURF complex as well as several subunits of the dREAM complex were most evident. Mass spectrometric analyses of CTCF or CP190 bound proteins as well as immune precipitation confirmed NURF and dREAM binding. Both co-localise with most CP190 binding sites in the genome and chromatin immune precipitation showed that CP190 recruits NURF and dREAM. Nucleosome occupancy and histone H3 binding analyses revealed that CP190 mediated NURF binding results in nucleosomal depletion at CP190 binding sites. Thus, we conclude that CP190 binding to CTCF or to other DNA binding insulator factors mediates recruitment of NURF and dREAM. Furthermore, the enhancer blocking function of insulators is associated with nucleosomal depletion and requires NURF and dREAM.

  9. Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells.

    PubMed

    Koludrovic, Dana; Laurette, Patrick; Strub, Thomas; Keime, Céline; Le Coz, Madeleine; Coassolo, Sebastien; Mengus, Gabrielle; Larue, Lionel; Davidson, Irwin

    2015-10-01

    MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf-mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes.

  10. Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells

    PubMed Central

    Koludrovic, Dana; Laurette, Patrick; Strub, Thomas; Keime, Céline; Le Coz, Madeleine; Coassolo, Sebastien; Mengus, Gabrielle; Larue, Lionel; Davidson, Irwin

    2015-01-01

    MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf-mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes. PMID:26440048

  11. Net Generation or Digital Natives: Is There a Distinct New Generation Entering University?

    ERIC Educational Resources Information Center

    Jones, Chris; Ramanau, Ruslan; Cross, Simon; Healing, Graham

    2010-01-01

    This article reports key findings from the first phase of a research project investigating Net generation age students as they encounter e-learning at five universities in England. We take a critical view of the idea of a distinct generation which has been described using various terms including Net generation and Digital Natives and explore age…

  12. Net Generation or Digital Natives: Is There a Distinct New Generation Entering University?

    ERIC Educational Resources Information Center

    Jones, Chris; Ramanau, Ruslan; Cross, Simon; Healing, Graham

    2010-01-01

    This article reports key findings from the first phase of a research project investigating Net generation age students as they encounter e-learning at five universities in England. We take a critical view of the idea of a distinct generation which has been described using various terms including Net generation and Digital Natives and explore age…

  13. Selection on a Subunit of the NURF Chromatin Remodeler Modifies Life History Traits in a Domesticated Strain of Caenorhabditis elegans

    PubMed Central

    Large, Edward E.; Zhao, Yuehui; Long, Lijiang; Butcher, Rebecca A.; Andersen, Erik C.; McGrath, Patrick T.

    2016-01-01

    Evolutionary life history theory seeks to explain how reproductive and survival traits are shaped by selection through allocations of an individual’s resources to competing life functions. Although life-history traits evolve rapidly, little is known about the genetic and cellular mechanisms that control and couple these tradeoffs. Here, we find that two laboratory-adapted strains of C. elegans descended from a single common ancestor that lived in the 1950s have differences in a number of life-history traits, including reproductive timing, lifespan, dauer formation, growth rate, and offspring number. We identified a quantitative trait locus (QTL) of large effect that controls 24%–75% of the total trait variance in reproductive timing at various timepoints. Using CRISPR/Cas9-induced genome editing, we show this QTL is due in part to a 60 bp deletion in the 3’ end of the nurf-1 gene, which is orthologous to the human gene encoding the BPTF component of the NURF chromatin remodeling complex. Besides reproduction, nurf-1 also regulates growth rate, lifespan, and dauer formation. The fitness consequences of this deletion are environment specific—it increases fitness in the growth conditions where it was fixed but decreases fitness in alternative laboratory growth conditions. We propose that chromatin remodeling, acting through nurf-1, is a pleiotropic regulator of life history trade-offs underlying the evolution of multiple traits across different species. PMID:27467070

  14. Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation.

    PubMed

    Li, Ying; Schulz, Vincent P; Deng, Changwang; Li, Guangyao; Shen, Yong; Tusi, Betsabeh K; Ma, Gina; Stees, Jared; Qiu, Yi; Steiner, Laurie A; Zhou, Lei; Zhao, Keji; Bungert, Jörg; Gallagher, Patrick G; Huang, Suming

    2016-09-06

    The modulation of chromatin structure is a key step in transcription regulation in mammalian cells and eventually determines lineage commitment and differentiation. USF1/2, Setd1a and NURF complexes interact to regulate chromatin architecture in erythropoiesis, but the mechanistic basis for this regulation is hitherto unknown. Here we showed that Setd1a and NURF complexes bind to promoters to control chromatin structural alterations and gene activation in a cell context dependent manner. In human primary erythroid cells USF1/2, H3K4me3 and the NURF complex were significantly co-enriched at transcription start sites of erythroid genes, and their binding was associated with promoter/enhancer accessibility that resulted from nucleosome repositioning. Mice deficient for Setd1a, an H3K4 trimethylase, in the erythroid compartment exhibited reduced Ter119/CD71 positive erythroblasts, peripheral blood RBCs and hemoglobin levels. Loss of Setd1a led to a reduction of promoter-associated H3K4 methylation, inhibition of gene transcription and blockade of erythroid differentiation. This was associated with alterations in NURF complex occupancy at erythroid gene promoters and reduced chromatin accessibility. Setd1a deficiency caused decreased associations between enhancer and promoter looped interactions as well as reduced expression of erythroid genes such as the adult β-globin gene. These data indicate that Setd1a and NURF complexes are specifically targeted to and coordinately regulate erythroid promoter chromatin dynamics during erythroid lineage differentiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Epigenetic regulation of stem cell maintenance in the Drosophila testis via the nucleosome-remodeling factor NURF.

    PubMed

    Cherry, Christopher M; Matunis, Erika L

    2010-06-04

    Regulation of stem cells depends on both tissue-specific transcriptional regulators and changes in chromatin organization, yet the coordination of these events in endogenous niches is poorly understood. In the Drosophila testis, local JAK-STAT signaling maintains germline and somatic stem cells (GSCs and cyst progenitor cells, or CPCs) in a single niche. Here we show that epigenetic regulation via the nucleosome-remodeling factor (NURF) complex ensures GSC and CPC maintenance by positively regulating JAK-STAT signaling, thereby preventing premature differentiation. Conversely, NURF is not required in early differentiating daughter cells of either lineage. Because three additional ATP-dependent chromatin remodelers (ACF, CHRAC, and dMi-2/NuRD) are dispensable for stem cell maintenance in the testis, epigenetic regulation of stem cells within this niche may rely primarily on NURF. Thus, local signals cooperate with specific chromatin-remodeling complexes in intact niches to coordinately regulate a common set of target genes to prevent premature stem cell differentiation.

  16. Distinct EEG seizure patterns reflect different seizure generation mechanisms

    PubMed Central

    Salami, Pariya; Lévesque, Maxime; Gotman, Jean

    2015-01-01

    Low-voltage fast (LVF)- and hypersynchronous (HYP)-seizure onset patterns can be recognized in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples (80–200 Hz) and fast ripples (250–500 Hz) have been linked to each pattern, with ripples predominating during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the contribution of neural networks with distinct transmitter signaling characteristics. Here, we tested this hypothesis by analyzing the seizure activity induced with the K+ channel blocker 4-aminopyridine (4AP, 4–5 mg/kg ip), which enhances both glutamatergic and GABAergic transmission, or the GABAA receptor antagonist picrotoxin (3–5 mg/kg ip); rats were implanted with electrodes in the hippocampus, the entorhinal cortex, and the subiculum. We found that LVF onset occurred in 82% of 4AP-induced seizures whereas seizures after picrotoxin were always HYP. In addition, high-frequency oscillation analysis revealed that 4AP-induced LVF seizures were associated with higher ripple rates compared with fast ripples (P < 0.05), whereas picrotoxin-induced seizures contained higher rates of fast ripples compared with ripples (P < 0.05). These results support the hypothesis that two distinct patterns of seizure onset result from different pathophysiological mechanisms. PMID:25652916

  17. Overland flow generation in two lithologically distinct rainforest catchments

    USGS Publications Warehouse

    Godsey, S.; Elsenbeer, H.; Stallard, R.

    2004-01-01

    Streams on uniformly rainforest-covered, but lithologically very diverse Barro Colorado Island in central Panama?? show remarkable differences in their runoff response to rainfall. This lithological diversity is reflected in equally diverse soilscapes, and our objective was to test the hypothesis that contrasting runoff responses derive from soilscape features that control the generation of overland flow. We determined the soil saturated hydraulic conductivity (Ks) of two neighboring, but hydrologically contrasting catchments (Lutz Creek with a flashy and Conrad Trail with a delayed response to rainfall), and quantified the spatial and temporal frequency of overland flow occurrence. The median Ks values at a depth of 12.5 cm are large enough to rule out Hortonian overland flow, but a marked decrease in K s in Lutz Creek catchment at 30 cm suggests the formation of a perched water table and the generation saturation overland flow; the decrease in Ks in the Conrad Trail catchment is more gradual, and a perched water table is expected to form only at depths below 50 cm. In Lutz Creek, overland flow was generated frequently in time and space and regardless of topographic position, including near the interfluve, with very low thresholds of storm magnitude, duration, intensity and antecedent wetness, whereas in Conrad Trail, overland flow was generated much less frequently and then only locally. We conclude that soilscape features and microtopography are important controls of overland flow generation in these catchments. Our results contribute to the growing evidence that overland flow and forests are not a priori a contradiction in terms. ?? 2004 Elsevier B.V. All rights reserved.

  18. Overland flow generation in two lithologically distinct rainforest catchments

    NASA Astrophysics Data System (ADS)

    Godsey, S.; Elsenbeer, H.; Stallard, R.

    2004-08-01

    Streams on uniformly rainforest-covered, but lithologically very diverse Barro Colorado Island in central Panamá show remarkable differences in their runoff response to rainfall. This lithological diversity is reflected in equally diverse soilscapes, and our objective was to test the hypothesis that contrasting runoff responses derive from soilscape features that control the generation of overland flow. We determined the soil saturated hydraulic conductivity ( Ks) of two neighboring, but hydrologically contrasting catchments (Lutz Creek with a flashy and Conrad Trail with a delayed response to rainfall), and quantified the spatial and temporal frequency of overland flow occurrence. The median Ks values at a depth of 12.5 cm are large enough to rule out Hortonian overland flow, but a marked decrease in Ks in Lutz Creek catchment at 30 cm suggests the formation of a perched water table and the generation saturation overland flow; the decrease in Ks in the Conrad Trail catchment is more gradual, and a perched water table is expected to form only at depths below 50 cm. In Lutz Creek, overland flow was generated frequently in time and space and regardless of topographic position, including near the interfluve, with very low thresholds of storm magnitude, duration, intensity and antecedent wetness, whereas in Conrad Trail, overland flow was generated much less frequently and then only locally. We conclude that soilscape features and microtopography are important controls of overland flow generation in these catchments. Our results contribute to the growing evidence that overland flow and forests are not a priori a contradiction in terms.

  19. Exposure to bacterial endotoxin generates a distinct strain of α-synuclein fibril

    PubMed Central

    Kim, Changyoun; Lv, Guohua; Lee, Jun Sung; Jung, Byung Chul; Masuda-Suzukake, Masami; Hong, Chul-Suk; Valera, Elvira; Lee, He-Jin; Paik, Seung R.; Hasegawa, Masato; Masliah, Eliezer; Eliezer, David; Lee, Seung-Jae

    2016-01-01

    A single amyloidogenic protein is implicated in multiple neurological diseases and capable of generating a number of aggregate “strains” with distinct structures. Among the amyloidogenic proteins, α-synuclein generates multiple patterns of proteinopathies in a group of diseases, such as Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, the link between specific conformations and distinct pathologies, the key concept of the strain hypothesis, remains elusive. Here we show that in the presence of bacterial endotoxin, lipopolysaccharide (LPS), α-synuclein generated a self-renewable, structurally distinct fibril strain that consistently induced specific patterns of synucleinopathies in mice. These results suggest that amyloid fibrils with self-renewable structures cause distinct types of proteinopathies despite the identical primary structure and that exposure to exogenous pathogens may contribute to the diversity of synucleinopathies. PMID:27488222

  20. Chromatin-modifying complex component Nurf55/p55 associates with histones H3 and H4 and polycomb repressive complex 2 subunit Su(z)12 through partially overlapping binding sites.

    PubMed

    Nowak, Agnieszka J; Alfieri, Claudio; Stirnimann, Christian U; Rybin, Vladimir; Baudin, Florence; Ly-Hartig, Nga; Lindner, Doris; Müller, Christoph W

    2011-07-01

    Drosophila Nurf55 is a component of different chromatin-modifying complexes, including the PRC2 (Polycomb repressive complex 2). Based on the 1.75-Å crystal structure of Nurf55 bound to histone H4 helix 1, we analyzed interactions of Nurf55 (Nurf55 or p55 in fly and RbAp48/46 in human) with the N-terminal tail of histone H3, the first helix of histone H4, and an N-terminal fragment of the PRC2 subunit Su(z)12 using isothermal calorimetry and pulldown experiments. Site-directed mutagenesis identified the binding site of histone H3 at the top of the Nurf55 WD40 propeller. Unmodified or K9me3- or K27me3-containing H3 peptides were bound with similar affinities, whereas the affinity for K4me3-containing H3 peptides was reduced. Helix 1 of histone H4 and Su(z)12 bound to the edge of the β-propeller using overlapping binding sites. Our results show similarities in the recognition of histone H4 and Su(z)12 and identify Nurf55 as a versatile interactor that simultaneously contacts multiple partners.

  1. The Adjective Generation Technique (AGT) and the Trait-Anxiety, State-Anxiety Distinction.

    ERIC Educational Resources Information Center

    Allen, Bem P.

    Research involving Potkay and Allen's Adjective Generation Technique (AGT) is reviewed concerning the measurement of anxiety. In this paper, no distinction is made between state anxiety and trait anxiety. It is suggested that state and trait anxiety may be considered apart from behavioral consistency. The issue of dramaturgical quality is…

  2. Distinct molecular processes associated with isometric force generation and rapid tension recovery after quick release.

    PubMed Central

    Brenner, B; Chalovich, J M; Yu, L C

    1995-01-01

    It was proposed by Huxley and Simmons (Nature 1971, 233:533-538) that force-generating cross-bridges are attached to actin in several stable positions. In this concept, isometric force is generated by the same mechanism as the quick tension recovery after an abrupt release of length; i.e., when crossbridges proceed from the first postulated stable position to the second and/or subsequent positions, resulting in straining of the elastic elements within the cross-bridges. Therefore, isometric force is generated by cross-bridges in the second or even subsequent stable positions. However, through mechanical measurements of skinned rabbit psoas muscle fibers, we found that during isometric contraction only the first stable state is significantly occupied; i.e., isometric force is generated by cross-bridges in the first of the stable states. Thus, isometric force and the quick tension recovery appear to result from two distinctly different molecular processes. We propose that isometric force results from a structural change in the actomyosin complex associated with the transition from a weakly bound configuration to a strongly bound configuration before the reaction steps in the Huxley-Simmons model, whereas a major component of quick tension recovery originates from transitions among the subsequent strongly bound states. Mechanical, biochemical, and structural evidence for the two distinct processes is summarized and reviewed. PMID:7787051

  3. Distinct molecular processes associated with isometric force generation and rapid tension recovery after quick release.

    PubMed

    Brenner, B; Chalovich, J M; Yu, L C

    1995-04-01

    It was proposed by Huxley and Simmons (Nature 1971, 233:533-538) that force-generating cross-bridges are attached to actin in several stable positions. In this concept, isometric force is generated by the same mechanism as the quick tension recovery after an abrupt release of length; i.e., when crossbridges proceed from the first postulated stable position to the second and/or subsequent positions, resulting in straining of the elastic elements within the cross-bridges. Therefore, isometric force is generated by cross-bridges in the second or even subsequent stable positions. However, through mechanical measurements of skinned rabbit psoas muscle fibers, we found that during isometric contraction only the first stable state is significantly occupied; i.e., isometric force is generated by cross-bridges in the first of the stable states. Thus, isometric force and the quick tension recovery appear to result from two distinctly different molecular processes. We propose that isometric force results from a structural change in the actomyosin complex associated with the transition from a weakly bound configuration to a strongly bound configuration before the reaction steps in the Huxley-Simmons model, whereas a major component of quick tension recovery originates from transitions among the subsequent strongly bound states. Mechanical, biochemical, and structural evidence for the two distinct processes is summarized and reviewed.

  4. Concurrent Vaccination with two distinct vaccine platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations

    PubMed Central

    Boehm, Amanda L.; Higgins, Jack; Franzusoff, Alex; Schlom, Jeffrey; Hodge, James W.

    2009-01-01

    Purpose Studies comparing two or more vaccine platforms have historically evaluated each platform based on its ability to induce an immune response and may conclude that one vaccine is more efficacious than the other(s), leading to a recommendation for development of the more effective vaccine for clinical studies. Alternatively, these studies have documented the advantages of a diversified prime and boost regimen due to amplification of the antigen-specific T-cell population. We hypothesize here that two vaccine platforms targeting the same antigen might induce shared and distinct antigen-specific T-cell populations, and examined the possibility that two distinct vaccines could be used concomitantly. Experimental design Using recombinant poxvirus and yeast vaccines, we compared the T-cell populations induced by these two platforms in terms of serum cytokine response, T-cell gene expression, T-cell receptor phenotype, antigen-specific cytokine expression, T-cell avidity, and T-cell antigen-specific tumor cell lysis. Results These studies demonstrate for the first time that vaccination with a recombinant poxvirus platform (rV/F-CEA/TRICOM) or a heat-killed yeast vaccine platform (yeast-CEA) elicits T-cell populations with both shared and unique phenotypic and functional characteristics. Furthermore, both the antigen and the vector play a role in the induction of distinct T-cell populations. Conclusions In this study, we demonstrate that concurrent administration of two vaccines targeting the same antigen induces a more diverse T-cell population that leads to enhanced antitumor efficacy. These studies provide the rationale for future clinical studies investigating concurrent administration of vaccine platforms targeting a single antigen to enhance the antigen-specific immune response. PMID:19756595

  5. Generation of a Functionally Distinct Rhizopus oryzae Lipase through Protein Folding Memory.

    PubMed

    Satomura, Atsushi; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2015-01-01

    Rhizopus oryzae lipase (ROL) has a propeptide at its N-terminus that functions as an intramolecular chaperone and facilitates the folding of mature ROL (mROL). In this study, we successfully generated a functionally distinct imprinted mROL (mROLimp) through protein folding memory using a mutated propeptide. The mutated propeptide left its structural memory on mROL and produced mROLimp that exhibited different substrate specificities compared with mROLWT (prepared from the wild type propeptide), although the amino acid sequences of both mROLs were the same. mROLimp showed a preference for substrates with medium chain-length acyl groups and, noticeably, recognized a peptidase-specific substrate. In addition, ROLimp was more stable than mROLWT. These results strongly suggest that proteins with identical amino acid sequences can fold into different conformations and that mutations in intramolecular chaperones can dynamically induce changes in enzymatic activity.

  6. Generating Tonal Distinctions in Mandarin Chinese Using an Electrolarynx with Preprogrammed Tone Patterns

    PubMed Central

    Guo, Liana; Nagle, Kathy; Heaton, James T.

    2016-01-01

    An electrolarynx (EL) is a valuable rehabilitative option for individuals who have undergone laryngectomy, but current monotone ELs do not support controlled variations in fundamental frequency for producing tonal languages. The present study examined the production and perception of Mandarin Chinese using a customized hand-held EL driven by computer software to generate tonal distinctions (tonal EL). Four native Mandarin speakers were trained to articulate their speech coincidentally with preprogrammed tonal patterns in order to produce mono- and di-syllabic words with a monotone EL and tonal EL. Three native Mandarin speakers later transcribed and rated the speech samples for intelligibility and acceptability. Results indicated that words produced using the tonal EL were significantly more intelligible and acceptable than those produced using the monotone EL. PMID:26951783

  7. Generating Tonal Distinctions in Mandarin Chinese Using an Electrolarynx with Preprogrammed Tone Patterns.

    PubMed

    Guo, Liana; Nagle, Kathy; Heaton, James T

    2016-04-01

    An electrolarynx (EL) is a valuable rehabilitative option for individuals who have undergone laryngectomy, but current monotone ELs do not support controlled variations in fundamental frequency for producing tonal languages. The present study examined the production and perception of Mandarin Chinese using a customized hand-held EL driven by computer software to generate tonal distinctions (tonal EL). Four native Mandarin speakers were trained to articulate their speech coincidentally with preprogrammed tonal patterns in order to produce mono- and di-syllabic words with a monotone EL and tonal EL. Three native Mandarin speakers later transcribed and rated the speech samples for intelligibility and acceptability. Results indicated that words produced using the tonal EL were significantly more intelligible and acceptable than those produced using the monotone EL.

  8. Sequential generation of two distinct synapse-driven network patterns in developing neocortex.

    PubMed

    Allène, Camille; Cattani, Adriano; Ackman, James B; Bonifazi, Paolo; Aniksztejn, Laurent; Ben-Ari, Yehezkel; Cossart, Rosa

    2008-11-26

    Developing cortical networks generate a variety of coherent activity patterns that participate in circuit refinement. Early network oscillations (ENOs) are the dominant network pattern in the rodent neocortex for a short period after birth. These large-scale calcium waves were shown to be largely driven by glutamatergic synapses albeit GABA is a major excitatory neurotransmitter in the cortex at such early stages, mediating synapse-driven giant depolarizing potentials (GDPs) in the hippocampus. Using functional multineuron calcium imaging together with single-cell and field potential recordings to clarify distinct network dynamics in rat cortical slices, we now report that the developing somatosensory cortex generates first ENOs then GDPs, both patterns coexisting for a restricted time period. These patterns markedly differ by their developmental profile, dynamics, and mechanisms: ENOs are generated before cortical GDPs (cGDPs) by the activation of glutamatergic synapses mostly through NMDARs; cENOs are low-frequency oscillations (approximately 0.01 Hz) displaying slow kinetics and gradually involving the entire network. At the end of the first postnatal week, GABA-driven cortical GDPs can be reliably monitored; cGDPs are recurrent oscillations (approximately 0.1 Hz) that repetitively synchronize localized neuronal assemblies. Contrary to cGDPs, cENOs were unexpectedly facilitated by short anoxic conditions suggesting a contribution of glutamate accumulation to their generation. In keeping with this, alterations of extracellular glutamate levels significantly affected cENOs, which are blocked by an enzymatic glutamate scavenger. Moreover, we show that a tonic glutamate current contributes to the neuronal membrane excitability when cENOs dominate network patterns. Therefore, cENOs and cGDPs are two separate aspects of neocortical network maturation that may be differentially engaged in physiological and pathological processes.

  9. Distinct IFT mechanisms contribute to the generation of ciliary structural diversity in C. elegans.

    PubMed

    Mukhopadhyay, Saikat; Lu, Yun; Qin, Hongmin; Lanjuin, Anne; Shaham, Shai; Sengupta, Piali

    2007-06-20

    Individual cell types can elaborate morphologically diverse cilia. Cilia are assembled via intraflagellar transport (IFT) of ciliary precursors; however, the mechanisms that generate ciliary diversity are unknown. Here, we examine IFT in the structurally distinct cilia of the ASH/ASI and the AWB chemosensory neurons in Caenorhabditis elegans, enabling us to compare IFT in specific cilia types. We show that unlike in the ASH/ASI cilia, the OSM-3 kinesin moves independently of the kinesin-II motor in the AWB cilia. Although OSM-3 is essential to extend the distal segments of the ASH/ASI cilia, it is not required to build the AWB distal segments. Mutations in the fkh-2 forkhead domain gene result in AWB-specific defects in ciliary morphology, and FKH-2 regulates kinesin-II subunit gene expression specifically in AWB. Our results suggest that cell-specific regulation of IFT contributes to the generation of ciliary diversity, and provide insights into the networks coupling the acquisition of ciliary specializations with other aspects of cell fate.

  10. Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems

    NASA Astrophysics Data System (ADS)

    Hook, Vivian; Bandeira, Nuno

    2015-12-01

    Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human

  11. Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems.

    PubMed

    Hook, Vivian; Bandeira, Nuno

    2015-12-01

    Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human

  12. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues.

    PubMed

    Tremblay, Kimberly D; Zaret, Kenneth S

    2005-04-01

    The location and movement of mammalian gut tissue progenitors, prior to the expression of tissue-specific genes, has been unknown, but this knowledge is essential to identify transitions that lead to cell type specification. To address this, we used vital dyes to label exposed anterior endoderm cells of early somite stage mouse embryos, cultured the embryos into the tissue bud phase of development, and determined the tissue fate of the dye labeled cells. This approach was performed at three embryonic stages that are prior to, or coincident with, foregut tissue patterning (1-3 somites, 4-6 somites, and 7-10 somites). Short-term labeling experiments tracked the movement of tissue progenitor cells during foregut closure. Surprisingly, we found that two distinct types of endoderm-progenitor cells, lateral and medial, arising from three spatially separated embryonic domains, converge to generate the epithelial cells of the liver bud. Whereas the lateral endoderm-progenitors give rise to descendants that are constrained in tissue fate and position along the anterior-posterior axis of the gut, the medial gut endoderm-progenitors give rise to descendants that stream along the anterior-posterior axis at the ventral midline and contribute to multiple gut tissues. The fate map reveals extensive morphogenetic movement of progenitors prior to tissue specification, it permits a detailed analysis of endoderm tissue patterning, and it illustrates that diverse progenitor domains can give rise to individual tissue cell types.

  13. Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes

    PubMed Central

    Lee, Michael; Hills, Mark; Conomos, Dimitri; Stutz, Michael D.; Dagg, Rebecca A.; Lau, Loretta M.S.; Reddel, Roger R.; Pickett, Hilda A.

    2014-01-01

    Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during telomerase- and ALT-mediated telomere lengthening. Telomerase-mediated telomere extension resulted in biased repeat synthesis of variant repeats that differed from the canonical sequence at positions 1 and 3, but not at positions 2, 4, 5 or 6. This indicates that telomerase is most likely an error-prone reverse transcriptase that misincorporates nucleotides at specific positions on the telomerase RNA template. In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines. This is consistent with variant repeats spreading from proximal telomeric regions throughout telomeres in a stochastic manner by recombination-mediated templating of DNA synthesis. The presence of unexpectedly large numbers of variant repeats in cells utilizing either telomere maintenance mechanism suggests a conserved role for variant sequences at human telomeres. PMID:24225324

  14. Identification of distinct antibody epitopes and mimotopes from a peptide array of 5520 randomly generated sequences.

    PubMed

    Reineke, Ulrich; Ivascu, Claudia; Schlief, Marén; Landgraf, Christiane; Gericke, Seike; Zahn, Grit; Herzel, Hanspeter; Volkmer-Engert, Rudolf; Schneider-Mergener, Jens

    2002-09-01

    We used a relatively small library of 5520 randomly generated single 15-mer peptides prepared by SPOT synthesis as an array of 28.5x19.0 cm to identify epitopes for three distinct monoclonal antibodies, namely anti-p24 (human immunodeficiency virus (HIV)-1) monoclonal anibody (mab) CB4-1, anti-interleukin-10 (IL-10) mab CB/RS/13, and anti-transforming growth factor alpha (TGFalpha) mab Tab2. Initially identified peptide ligands mostly had very low affinities for the antibodies with dissociation constants around 10(-4) M. Subsequent identification of residues critical for the antibody interactions involved complete L-amino acid substitutional analyses. Several substitutions resulted in analogs with dissociation constants in the low micromolar and high nanomolar range. Specifically binding peptides with key residue patterns matching the wild-type epitopes were identified for all three antibodies. In addition, for antibody CB4-1 mimotopes that showed no homology to the known epitope were selected. Our results suggest that a very limited library diversity, although far from covering the entire sequence repertoire, can suffice to rapidly and economically select peptidic antibody epitopes and mimotopes.

  15. Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

    DOE PAGES

    Guo, Chun -Jun; Sun, Wei -Wen; Bruno, Kenneth S.; ...

    2015-07-13

    In secondary metabolite biosynthesis, core synthetic genes such as polyketide synthase genes usually encode proteins that generate various backbone precursors. These precursors are modified by other tailoring enzymes to yield a large variety of different secondary metabolites. The number of core synthesis genes in a given species correlates, therefore, with the number of types of secondary metabolites the organism can produce. In our study, heterologous expression of all the A. terreus NRPSlike genes showed that two NRPS-like proteins, encoded by atmelA and apvA, release the same natural product, aspulvinone E. In hyphae this compound is converted to aspulvinones whereas inmore » conidia it is converted to melanin. The genes are expressed in different tissues and this spatial control is probably regulated by their own specific promoters. Comparative genomics indicates that atmelA and apvA might share a same ancestral gene and the gene apvA is located in a highly conserved region in Aspergillus species that contains genes coding for life-essential proteins. Our data reveal the first case in secondary metabolite biosynthesis in which the tissue specific production of a single compound directs it into two separate pathways, producing distinct compounds with different functions. Our data also reveal that a single trans-prenyltransferase, AbpB, prenylates two substrates, aspulvinones and butyrolactones, revealing that genes outside of contiguous secondary metabolism gene clusters can modify more than one compound thereby expanding metabolite diversity. Our study raises the possibility of incorporation of spatial, cell-type specificity in expression of secondary metabolites of biological interest and provides new insight into designing and reconstituting their biosynthetic pathways.« less

  16. Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

    SciTech Connect

    Guo, Chun -Jun; Sun, Wei -Wen; Bruno, Kenneth S.; Oakley, Berl R.; Keller, Nancy P.; Wang, Clay C. C.

    2015-07-13

    In secondary metabolite biosynthesis, core synthetic genes such as polyketide synthase genes usually encode proteins that generate various backbone precursors. These precursors are modified by other tailoring enzymes to yield a large variety of different secondary metabolites. The number of core synthesis genes in a given species correlates, therefore, with the number of types of secondary metabolites the organism can produce. In our study, heterologous expression of all the A. terreus NRPSlike genes showed that two NRPS-like proteins, encoded by atmelA and apvA, release the same natural product, aspulvinone E. In hyphae this compound is converted to aspulvinones whereas in conidia it is converted to melanin. The genes are expressed in different tissues and this spatial control is probably regulated by their own specific promoters. Comparative genomics indicates that atmelA and apvA might share a same ancestral gene and the gene apvA is located in a highly conserved region in Aspergillus species that contains genes coding for life-essential proteins. Our data reveal the first case in secondary metabolite biosynthesis in which the tissue specific production of a single compound directs it into two separate pathways, producing distinct compounds with different functions. Our data also reveal that a single trans-prenyltransferase, AbpB, prenylates two substrates, aspulvinones and butyrolactones, revealing that genes outside of contiguous secondary metabolism gene clusters can modify more than one compound thereby expanding metabolite diversity. Our study raises the possibility of incorporation of spatial, cell-type specificity in expression of secondary metabolites of biological interest and provides new insight into designing and reconstituting their biosynthetic pathways.

  17. Divergence in a master variator generates distinct phenotypes and transcriptional responses

    PubMed Central

    Gallagher, Jennifer E.G.; Zheng, Wei; Rong, Xiaoqing; Miranda, Noraliz; Lin, Zhixiang; Dunn, Barbara; Zhao, Hongyu; Snyder, Michael P.

    2014-01-01

    Genetic basis of phenotypic differences in individuals is an important area in biology and personalized medicine. Analysis of divergent Saccharomyces cerevisiae strains grown under different conditions revealed extensive variation in response to both drugs (e.g., 4-nitroquinoline 1-oxide [4NQO]) and different carbon sources. Differences in 4NQO resistance were due to amino acid variation in the transcription factor Yrr1. Yrr1YJM789 conferred 4NQO resistance but caused slower growth on glycerol, and vice versa with Yrr1S96, indicating that alleles of Yrr1 confer distinct phenotypes. The binding targets of Yrr1 alleles from diverse yeast strains varied considerably among different strains grown under the same conditions as well as for the same strain under different conditions, indicating that distinct molecular programs are conferred by the different Yrr1 alleles. Our results demonstrate that genetic variations in one important control gene (YRR1), lead to distinct regulatory programs and phenotypes in individuals. We term these polymorphic control genes “master variators.” PMID:24532717

  18. Distinct rhythm generators for inspiration and expiration in the juvenile rat

    PubMed Central

    Janczewski, Wiktor A; Feldman, Jack L

    2006-01-01

    Inspiration and active expiration are commonly viewed as antagonistic phases of a unitary oscillator that generates respiratory rhythm. This view conflicts with observations we report here in juvenile rats, where by administration of fentanyl, a selective μ-opiate agonist, and induction of lung reflexes, we separately manipulated the frequency of inspirations and expirations. Moreover, completely transecting the brainstem at the caudal end of the facial nucleus abolished active expirations, while rhythmic inspirations continued. We hypothesize that inspiration and expiration are generated by coupled, anatomically separate rhythm generators, one generating active expiration located close to the facial nucleus in the region of the retrotrapezoid nucleus/parafacial respiratory group, the other generating inspiration located more caudally in the preBötzinger Complex. PMID:16293645

  19. Optical Generation And Spatially Distinct Interferometric Detection Of Ultrahigh Frequency Surface Acoustic Waves

    SciTech Connect

    David H. Hurley

    2006-05-01

    Generation and interferometric detection of 22 GHz surface acoustic waves (SAWs) using two laterally separated absorption gratings on a Si substrate are presented. Optical phase sensitive detection of SAWs is demonstrated using a modified Sagnac interferometer. The reflection characteristics of the suboptical wavelength grating necessitate the use of only linear polarization. This is accomplished by employing a Faraday rotator to ensure path reversal of the reference and signal pulses. The enhanced sensitivity of the interferometer is exploited to measure the acoustic disturbance on an identical absorption grating at a distance of ~4.5 µm from the generation site.

  20. Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation.

    PubMed

    Foudi, Adlen; Kramer, Daniel J; Qin, Jinzhong; Ye, Denise; Behlich, Anna-Sophie; Mordecai, Scott; Preffer, Frederic I; Amzallag, Arnaud; Ramaswamy, Sridhar; Hochedlinger, Konrad; Orkin, Stuart H; Hock, Hanno

    2014-05-05

    The zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b's adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow. We reveal strict, lineage-intrinsic requirements for continuous adult Gfi-1b expression at two distinct critical stages of erythropoiesis and megakaryopoiesis. Induced disruption of Gfi-1b was lethal within 3 wk with severely reduced hemoglobin levels and platelet counts. The erythroid lineage was arrested early in bipotential progenitors, which did not give rise to mature erythroid cells in vitro or in vivo. Yet Gfi-1b(-/-) progenitors had initiated the erythroid program as they expressed many lineage-restricted genes, including Klf1/Eklf and Erythropoietin receptor. In contrast, the megakaryocytic lineage developed beyond the progenitor stage in Gfi-1b's absence and was arrested at the promegakaryocyte stage, after nuclear polyploidization, but before cytoplasmic maturation. Genome-wide analyses revealed that Gfi-1b directly regulates a wide spectrum of megakaryocytic and erythroid genes, predominantly repressing their expression. Together our study establishes Gfi-1b as a master transcriptional repressor of adult erythropoiesis and thrombopoiesis.

  1. Building the central complex in Drosophila: the generation and development of distinct neural subsets.

    PubMed

    Young, J M; Armstrong, J D

    2010-05-01

    The distinctive midline neuropil, the central complex (CX), is one of the most prominent features of the insect brain. We investigated the development of the four CX structures and several sets of CX neurons in the Drosophila brain using immunostaining for two cell adhesion molecules, DN-cadherin and Echinoid, and a set of seven enhancer trap lines. Our results showed that the CX is first identifiable in the third instar larva and that it elaborates over the first 48 hours of metamorphosis. The first identifiable structures to appear in their immature form are the protocerebral bridge and fan-shaped body, which are present in the brain of the third instar larva, followed by the noduli (from P12h), and finally the ellipsoid body (from P24h). We observed that neurons are added incrementally to the developing CX structure, with sets of small-field neurons projecting to the CX prior to the large-field neurons. The small-field neurons first project to the developing fan-shaped body, before arborizing or extending to the other structures. We found evidence to suggest that small-field neurons exist in sets of 16 and that they originate from eight common clusters of perikarya in the cortex, suggesting a common origin. We also identified a novel set of pontine neurons that connect contralateral segments in the fan-shaped body.

  2. Distinct biological events generated by ECM proteolysis by two homologous collagenases.

    PubMed

    Solomonov, Inna; Zehorai, Eldar; Talmi-Frank, Dalit; Wolf, Sharon G; Shainskaya, Alla; Zhuravlev, Alina; Kartvelishvily, Elena; Visse, Robert; Levin, Yishai; Kampf, Nir; Jaitin, Diego Adhemar; David, Eyal; Amit, Ido; Nagase, Hideaki; Sagi, Irit

    2016-09-27

    It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior.

  3. Distinct biological events generated by ECM proteolysis by two homologous collagenases

    PubMed Central

    Solomonov, Inna; Zehorai, Eldar; Talmi-Frank, Dalit; Shainskaya, Alla; Zhuravlev, Alina; Kartvelishvily, Elena; Visse, Robert; Levin, Yishai; Kampf, Nir; Jaitin, Diego Adhemar; David, Eyal; Amit, Ido; Nagase, Hideaki; Sagi, Irit

    2016-01-01

    It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM–cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior. PMID:27630193

  4. Enteroendocrine cells are generated from stem cells through a distinct progenitor in the adult Drosophila posterior midgut

    PubMed Central

    Zeng, Xiankun; Hou, Steven X.

    2015-01-01

    Functional mature cells are continually replenished by stem cells to maintain tissue homoeostasis. In the adult Drosophila posterior midgut, both terminally differentiated enterocyte (EC) and enteroendocrine (EE) cells are generated from an intestinal stem cell (ISC). However, it is not clear how the two differentiated cells are generated from the ISC. In this study, we found that only ECs are generated through the Su(H)GBE+ immature progenitor enteroblasts (EBs), whereas EEs are generated from ISCs through a distinct progenitor pre-EE by a novel lineage-tracing system. EEs can be generated from ISCs in three ways: an ISC becoming an EE, an ISC becoming a new ISC and an EE through asymmetric division, or an ISC becoming two EEs through symmetric division. We further identified that the transcriptional factor Prospero (Pros) regulates ISC commitment to EEs. Our data provide direct evidence that different differentiated cells are generated by different modes of stem cell lineage specification within the same tissues. PMID:25670791

  5. Enteroendocrine cells are generated from stem cells through a distinct progenitor in the adult Drosophila posterior midgut.

    PubMed

    Zeng, Xiankun; Hou, Steven X

    2015-02-15

    Functional mature cells are continually replenished by stem cells to maintain tissue homoeostasis. In the adult Drosophila posterior midgut, both terminally differentiated enterocyte (EC) and enteroendocrine (EE) cells are generated from an intestinal stem cell (ISC). However, it is not clear how the two differentiated cells are generated from the ISC. In this study, we found that only ECs are generated through the Su(H)GBE(+) immature progenitor enteroblasts (EBs), whereas EEs are generated from ISCs through a distinct progenitor pre-EE by a novel lineage-tracing system. EEs can be generated from ISCs in three ways: an ISC becoming an EE, an ISC becoming a new ISC and an EE through asymmetric division, or an ISC becoming two EEs through symmetric division. We further identified that the transcriptional factor Prospero (Pros) regulates ISC commitment to EEs. Our data provide direct evidence that different differentiated cells are generated by different modes of stem cell lineage specification within the same tissues. © 2015. Published by The Company of Biologists Ltd.

  6. Phage display and hybridoma generation of antibodies to human CXCR2 yields antibodies with distinct mechanisms and epitopes.

    PubMed

    Rossant, Christine J; Carroll, Danielle; Huang, Ling; Elvin, John; Neal, Frances; Walker, Edward; Benschop, Joris J; Kim, Eldar E; Barry, Simon T; Vaughan, Tristan J

    2014-01-01

    Generation of functional antibodies against integral membrane proteins such as the G-protein coupled receptor CXCR2 is technically challenging for several reasons, including limited epitope accessibility, the requirement for a lipid environment to maintain structure and their existence in dynamic conformational states. Antibodies to human CXCR2 were generated by immunization in vivo and by in vitro selection methods. Whole cell immunization of transgenic mice and screening of phage display libraries using CXCR2 magnetic proteoliposomes resulted in the isolation of antibodies with distinct modes of action. The hybridoma-derived antibody fully inhibited IL-8 and Gro-α responses in calcium flux and β-arrestin recruitment assays. The phage-display derived antibodies were allosteric antagonists that showed ligand dependent differences in functional assays. The hybridoma and phage display antibodies did not cross-compete in epitope competition assays and mapping using linear and CLIPS peptides confirmed that they recognized distinct epitopes of human CXCR2. This illustrates the benefits of using parallel antibody isolation approaches with different antigen presentation methods to successfully generate functionally and mechanistically diverse antagonistic antibodies to human CXCR2. The method is likely to be broadly applicable to other complex membrane proteins.

  7. Placental leucine aminopeptidase efficiently generates mature antigenic peptides in vitro but in patterns distinct from endoplasmic reticulum aminopeptidase 1.

    PubMed

    Georgiadou, Dimitra; Hearn, Arron; Evnouchidou, Irini; Chroni, Angeliki; Leondiadis, Leondios; York, Ian A; Rock, Kenneth L; Stratikos, Efstratios

    2010-08-01

    All three members of the oxytocinase subfamily of M1 aminopeptidases, endoplasmic reticulum aminopeptidase 1 (ERAP1), ERAP2, and placental leucine aminopeptidase (PLAP), also known as insulin-regulated aminopeptidase, have been implicated in the generation of MHC class I-presented peptides. ERAP1 and 2 trim peptides in the endoplasmic reticulum for direct presentation, whereas PLAP has been recently implicated in cross-presentation. The best characterized member of the family, ERAP1, has unique enzymatic properties that fit well with its role in Ag processing. ERAP1 can trim a large variety of long peptide sequences and efficiently accumulate mature antigenic epitopes of 8-9 aa long. In this study, we evaluate the ability of PLAP to process antigenic peptide precursors in vitro and compare it with ERAP1. We find that, similar to ERAP1, PLAP can trim a variety of long peptide sequences efficiently and, in most cases, accumulates appreciable amounts of correct length mature antigenic epitope. Again, similar to ERAP1, PLAP continued trimming some of the epitopes tested and accumulated smaller products effectively destroying the epitope. However, the intermediate accumulation properties of ERAP1 and PLAP are distinct and epitope dependent, suggesting that these two enzymes may impose different selective pressures on epitope generation. Overall, although PLAP has the necessary enzymatic properties to participate in generating or destroying MHC class I-presented peptides, its trimming behavior is distinct from that of ERAP1, something that supports a separate role for these two enzymes in Ag processing.

  8. Phage display and hybridoma generation of antibodies to human CXCR2 yields antibodies with distinct mechanisms and epitopes

    PubMed Central

    Rossant, Christine J; Carroll, Danielle; Huang, Ling; Elvin, John; Neal, Frances; Walker, Edward; Benschop, Joris J; Kim, Eldar E; Barry, Simon T; Vaughan, Tristan J

    2014-01-01

    Generation of functional antibodies against integral membrane proteins such as the G-protein coupled receptor CXCR2 is technically challenging for several reasons, including limited epitope accessibility, the requirement for a lipid environment to maintain structure and their existence in dynamic conformational states. Antibodies to human CXCR2 were generated by immunization in vivo and by in vitro selection methods. Whole cell immunization of transgenic mice and screening of phage display libraries using CXCR2 magnetic proteoliposomes resulted in the isolation of antibodies with distinct modes of action. The hybridoma-derived antibody fully inhibited IL-8 and Gro-α responses in calcium flux and β-arrestin recruitment assays. The phage-display derived antibodies were allosteric antagonists that showed ligand dependent differences in functional assays. The hybridoma and phage display antibodies did not cross-compete in epitope competition assays and mapping using linear and CLIPS peptides confirmed that they recognized distinct epitopes of human CXCR2. This illustrates the benefits of using parallel antibody isolation approaches with different antigen presentation methods to successfully generate functionally and mechanistically diverse antagonistic antibodies to human CXCR2. The method is likely to be broadly applicable to other complex membrane proteins. PMID:25484064

  9. Generation of functionally distinct isoforms of PTBP3 by alternative splicing and translation initiation

    PubMed Central

    Tan, Lit-Yeen; Whitfield, Peter; Llorian, Miriam; Monzon-Casanova, Elisa; Diaz-Munoz, Manuel D.; Turner, Martin; Smith, Christopher W.J.

    2015-01-01

    Polypyrimidine tract binding protein (PTBP1) is a widely expressed RNA binding protein that acts as a regulator of alternative splicing and of cytoplasmic mRNA functions. Vertebrates contain two closely-related paralogs with >75% amino acid sequence identity. Early replacement of PTBP1 by PTBP2 during neuronal differentiation causes a concerted set of splicing changes. By comparison, very little is known about the molecular functions or physiological roles of PTBP3, although its expression and conservation throughout the vertebrates suggest a role in haematopoietic cells. To begin to understand its functions we have characterized the mRNA and protein isoform repertoire of PTBP3. Combinatorial alternative splicing events at the 5′ end of the gene allow for the generation of eight mRNA and three major protein isoforms. Individual mRNAs generate up to three protein isoforms via alternative translation initiation by re-initiation and leaky scanning using downstream AUG codons. The N-terminally truncated PTBP3 isoforms lack nuclear localization signals and/or most of the RRM1 domain and vary in their RNA binding properties and nuclear/cytoplasmic distribution, suggesting that PTBP3 may have major post-transcriptional cytoplasmic roles. Our findings set the stage for understanding the non-redundant physiological roles of PTBP3. PMID:25940628

  10. Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells

    PubMed Central

    Funahashi, Satomi; Okazaki, Yasumasa; Ito, Daiki; Asakawa, Atsushi; Nagai, Hirotaka; Tajima, Masafumi; Toyokuni, Shinya

    2015-01-01

    Asbestos exposure is considered a social burden by causing mesothelioma. Despite the use of synthetic materials, multi-walled carbon nanotubes (MWCNTs) are similar in dimension to asbestos and produce mesothelioma in animals. The role of inflammatory cells in mesothelial carcinogenesis remains unclear. Here, we evaluated the differences in inflammatory cell responses following exposure to these fibrous materials using a luminometer and L-012 (8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H) dione) to detect reactive oxygen species (ROS). Rat peripheral blood or RAW264.7 cells were used to assess the effects on neutrophils and macrophages, respectively. Crocidolite and amosite induced significant ROS generation by neutrophils with a peak at 10 min, whereas that of chrysotile was ~25% of the crocidolite/amosite response. MWCNTs with different diameters (~15, 50, 115 and 145 nm) and different carcinogenicity did not induce significant ROS in peripheral blood. However, the MWCNTs induced a comparable amount of ROS in RAW264.7 cells to that following asbestos treatment. The peaks for MWCNTs (0.5–1.5 h) were observed earlier than those for asbestos (1–5 h). Apocynin and superoxide dismutase significantly inhibited ROS generation for each fiber, suggesting an involvement of NADPH oxidase and superoxide. Thus, asbestos and MWCNTs induce different oxidative responses in inflammatory cells, indicating the importance of mesothelial cell evaluation for carcinogenesis. PMID:25759516

  11. Multichannel recordings of the human brainstem frequency-following response: scalp topography, source generators, and distinctions from the transient ABR.

    PubMed

    Bidelman, Gavin M

    2015-05-01

    Brainstem frequency-following responses (FFRs) probe the neural transcription of speech/music, auditory disorders, and plasticity in subcortical auditory function. Despite clinical and empirical interest, the response's neural basis remains poorly understood. The current study aimed to more fully characterize functional properties of the human FFR (topography, source locations, generation). Speech-evoked FFRs were recorded using a high-density (64 channel) electrode montage. Source dipole modeling and 3-channel Lissajous analysis was used to localize the most likely FFR generators and their orientation trajectories. Additionally, transient auditory brainstem responses (ABRs), recorded in the same listeners, were used to predict FFRs and test the long-held assumption that the sustained potential reflects a series of overlapping onset responses. Results showed that FFRs were maximal at frontocentral scalp locations with obliquely oriented sources from putative generators in the midbrain (i.e., upper brainstem). Comparisons between derived and actual recordings revealed the FFR is not a series of repeated ABR wavelets and thus, represents a functionally distinct brainstem response. FFRs recorded at temporal electrode sites showed larger amplitudes and contained higher frequency components than vertex channels (Fz, Cz) suggesting that FFRs measured near the mastoid are generated more peripherally (auditory nerve) than measurements at frontocentral scalp locations. Furthermore, this reveals the importance of choice in reference electrode location for FFR interpretation. Our findings provide non-invasive evidence that (i) FFRs reflect sustained neural activity whose sources are consistent with rostral brainstem generators and (ii) FFRs are functionally distinct from the onset ABR response. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Dual Processing of FAT1 Cadherin Protein by Human Melanoma Cells Generates Distinct Protein Products*

    PubMed Central

    Sadeqzadeh, Elham; de Bock, Charles E.; Zhang, Xu Dong; Shipman, Kristy L.; Scott, Naomi M.; Song, Chaojun; Yeadon, Trina; Oliveira, Camila S.; Jin, Boquan; Hersey, Peter; Boyd, Andrew W.; Burns, Gordon F.; Thorne, Rick F.

    2011-01-01

    The giant cadherin FAT1 is one of four vertebrate orthologues of the Drosophila tumor suppressor fat. It engages in several functions, including cell polarity and migration, and in Hippo signaling during development. Homozygous deletions in oral cancer suggest that FAT1 may play a tumor suppressor role, although overexpression of FAT1 has been reported in some other cancers. Here we show using Northern blotting that human melanoma cell lines variably but universally express FAT1 and less commonly FAT2, FAT3, and FAT4. Both normal melanocytes and keratinocytes also express comparable FAT1 mRNA relative to melanoma cells. Analysis of the protein processing of FAT1 in keratinocytes revealed that, like Drosophila FAT, human FAT1 is cleaved into a non-covalent heterodimer before achieving cell surface expression. The use of inhibitors also established that such cleavage requires the proprotein convertase furin. However, in melanoma cells, the non-cleaved proform of FAT1 is also expressed at the cell surface together with the furin-cleaved heterodimer. Moreover, furin-independent processing generates a potentially functional proteolytic product in melanoma cells, a persistent 65-kDa membrane-bound cytoplasmic fragment no longer in association with the extracellular fragment. In vitro localization studies of FAT1 showed that melanoma cells display high levels of cytosolic FAT1 protein, whereas keratinocytes, despite comparable FAT1 expression levels, exhibited mainly cell-cell junctional staining. Such differences in protein distribution appear to reconcile with the different protein products generated by dual FAT1 processing. We suggest that the uncleaved FAT1 could promote altered signaling, and the novel products of alternate processing provide a dominant negative function in melanoma. PMID:21680732

  13. Escherichia coli Quorum-Sensing EDF, A Peptide Generated by Novel Multiple Distinct Mechanisms and Regulated by trans-Translation.

    PubMed

    Kumar, Sathish; Kolodkin-Gal, Ilana; Vesper, Oliver; Alam, Nawsad; Schueler-Furman, Ora; Moll, Isabella; Engelberg-Kulka, Hanna

    2016-01-26

    Eshcerichia coli mazEF is a stress-induced toxin-antitoxin module mediating cell death and requiring a quorum-sensing (QS) extracellular death factor (EDF), the pentapeptide NNWNN. Here we uncovered several distinct molecular mechanisms involved in its generation from the zwf mRNA encoding glucose-6-phosphate dehydrogenase. In particular, we show that, under stress conditions, the endoribonuclease MazF cleaves specific ACA sites, thereby generating a leaderless zwf mRNA which is truncated 30 codons after the EDF-encoding region. Since the nascent ribosome peptide exit tunnel can accommodate up to 40 amino acids, this arrangement allows the localization of the EDF residues inside the tunnel when the ribosome is stalled at the truncation site. Moreover, ribosome stalling activates the trans-translation system, which provides a means for the involvement of ClpPX in EDF generation. Furthermore, the trans-translation is described as a regulatory system that attenuated the generation of EDF, leading to low levels of EDF in the single cell. Therefore, the threshold EDF molecule concentration required is achieved only by the whole population, as expected for QS. Bacteria communicate with one another via quorum-sensing (QS) signal molecules. QS provides a mechanism for bacteria to monitor each other's presence and to modulate gene expression in response to population density. Previously, we added E. coli pentapeptide EDF to this list of QS molecules. We showed that, under stress conditions, the induced MazF, an endoribonuclease cleaving at ACA sites, generates EDF from zwf. Here we studied the mechanism of EDF generation and asked whether it is related to EDF density dependency. We illustrated that, under stress conditions, multiple distinct complex mechanisms are involved in EDF generation. This includes formation of leaderless truncated zwf mRNA by MazF, configuration of a length corresponding to the nascent ribosome peptide exit tunnel, rescue performed by the trans

  14. Mission Immiscible: Distinct subduction components generate two primary magmas of Pagan Volcano, Mariana arc

    NASA Astrophysics Data System (ADS)

    Tamura, Y.; Ishizuka, O.; Stern, R. J.; Nunokawa, A.; Shukuno, H.; Kawabata, H.; Hirahara, Y.; Chang, Q.; Miyazaki, T.; Kimura, J.; Embley, R. W.; Bloomer, S. H.; Tatsumi, Y.

    2012-12-01

    such higher pressures, hydrous fluid and sediment melt could mix into a uniform supercritical fluid, with different proportions yield distinct NWR1 COB and POB (Tamura et al., 2011). In conclusion, Pagan COB1 is enriched in aqueous fluid component and COB2 is enriched in sediment melt component. Why and how do these different primary magmas form in the same volcano? Hydrous fluid could not be miscible with sediment melt in the depth of the subducting slab below the volcanic front, which might have resulted in two neighboring, but completely different primary magmas.

  15. Distinct types of translation termination generate substrates for ribosome-associated quality control

    PubMed Central

    Shcherbik, Natalia; Chernova, Tatiana A.; Chernoff, Yury O.; Pestov, Dimitri G.

    2016-01-01

    Cotranslational degradation of polypeptide nascent chains plays a critical role in quality control of protein synthesis and the rescue of stalled ribosomes. In eukaryotes, ribosome stalling triggers release of 60S subunits with attached nascent polypeptides, which undergo ubiquitination by the E3 ligase Ltn1 and proteasomal degradation facilitated by the ATPase Cdc48. However, the identity of factors acting upstream in this process is less clear. Here, we examined how the canonical release factors Sup45–Sup35 (eRF1–eRF3) and their paralogs Dom34-Hbs1 affect the total population of ubiquitinated nascent chains associated with yeast ribosomes. We found that the availability of the functional release factor complex Sup45–Sup35 strongly influences the amount of ubiquitinated polypeptides associated with 60S ribosomal subunits, while Dom34-Hbs1 generate 60S-associated peptidyl-tRNAs that constitute a relatively minor fraction of Ltn1 substrates. These results uncover two separate pathways that target nascent polypeptides for Ltn1-Cdc48-mediated degradation and suggest that in addition to canonical termination on stop codons, eukaryotic release factors contribute to cotranslational protein quality control. PMID:27325745

  16. Bottom-up and top-down processes in emotion generation: common and distinct neural mechanisms.

    PubMed

    Ochsner, Kevin N; Ray, Rebecca R; Hughes, Brent; McRae, Kateri; Cooper, Jeffrey C; Weber, Jochen; Gabrieli, John D E; Gross, James J

    2009-11-01

    Emotions are generally thought to arise through the interaction of bottom-up and top-down processes. However, prior work has not delineated their relative contributions. In a sample of 20 females, we used functional magnetic resonance imaging to compare the neural correlates of negative emotions generated by the bottom-up perception of aversive images and by the top-down interpretation of neutral images as aversive. We found that (a) both types of responses activated the amygdala, although bottom-up responses did so more strongly; (b) bottom-up responses activated systems for attending to and encoding perceptual and affective stimulus properties, whereas top-down responses activated prefrontal regions that represent high-level cognitive interpretations; and (c) self-reported affect correlated with activity in the amygdala during bottom-up responding and with activity in the medial prefrontal cortex during top-down responding. These findings provide a neural foundation for emotion theories that posit multiple kinds of appraisal processes and help to clarify mechanisms underlying clinically relevant forms of emotion dysregulation.

  17. mTOR has distinct functions in generating versus sustaining humoral immunity

    PubMed Central

    Jones, Derek D.; Gaudette, Brian T.; Wilmore, Joel R.; Chernova, Irene; Bortnick, Alexandra; Weiss, Brendan M.; Allman, David

    2016-01-01

    Little is known about the role of mTOR signaling in plasma cell differentiation and function. Furthermore, for reasons not understood, mTOR inhibition reverses antibody-associated disease in a murine model of systemic lupus erythematosus. Here, we have demonstrated that induced B lineage–specific deletion of the gene encoding RAPTOR, an essential signaling adaptor for rapamycin-sensitive mTOR complex 1 (mTORC1), abrogated the generation of antibody-secreting plasma cells in mice. Acute treatment with rapamycin recapitulated the effects of RAPTOR deficiency, and both strategies led to the ablation of newly formed plasma cells in the spleen and bone marrow while also obliterating preexisting germinal centers. Surprisingly, although perturbing mTOR activity caused a profound decline in serum antibodies that were specific for exogenous antigen or DNA, frequencies of long-lived bone marrow plasma cells were unaffected. Instead, mTORC1 inhibition led to decreased expression of immunoglobulin-binding protein (BiP) and other factors needed for robust protein synthesis. Consequently, blockade of antibody synthesis was rapidly reversed after termination of rapamycin treatment. We conclude that mTOR signaling plays critical but diverse roles in early and late phases of antibody responses and plasma cell differentiation. PMID:27760048

  18. Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species.

    PubMed

    Jackson, Andrew P; Berry, Andrew; Aslett, Martin; Allison, Harriet C; Burton, Peter; Vavrova-Anderson, Jana; Brown, Robert; Browne, Hilary; Corton, Nicola; Hauser, Heidi; Gamble, John; Gilderthorp, Ruth; Marcello, Lucio; McQuillan, Jacqueline; Otto, Thomas D; Quail, Michael A; Sanders, Mandy J; van Tonder, Andries; Ginger, Michael L; Field, Mark C; Barry, J David; Hertz-Fowler, Christiane; Berriman, Matthew

    2012-02-28

    Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections.

  19. Distinct types of translation termination generate substrates for ribosome-associated quality control.

    PubMed

    Shcherbik, Natalia; Chernova, Tatiana A; Chernoff, Yury O; Pestov, Dimitri G

    2016-08-19

    Cotranslational degradation of polypeptide nascent chains plays a critical role in quality control of protein synthesis and the rescue of stalled ribosomes. In eukaryotes, ribosome stalling triggers release of 60S subunits with attached nascent polypeptides, which undergo ubiquitination by the E3 ligase Ltn1 and proteasomal degradation facilitated by the ATPase Cdc48. However, the identity of factors acting upstream in this process is less clear. Here, we examined how the canonical release factors Sup45-Sup35 (eRF1-eRF3) and their paralogs Dom34-Hbs1 affect the total population of ubiquitinated nascent chains associated with yeast ribosomes. We found that the availability of the functional release factor complex Sup45-Sup35 strongly influences the amount of ubiquitinated polypeptides associated with 60S ribosomal subunits, while Dom34-Hbs1 generate 60S-associated peptidyl-tRNAs that constitute a relatively minor fraction of Ltn1 substrates. These results uncover two separate pathways that target nascent polypeptides for Ltn1-Cdc48-mediated degradation and suggest that in addition to canonical termination on stop codons, eukaryotic release factors contribute to cotranslational protein quality control.

  20. Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

    SciTech Connect

    Guo, Chun-Jun; Sun, Wei-Wen; Bruno, Kenneth S.; Oakley, Berl R.; Keller, Nancy P.; Wang, Clay C.

    2015-07-13

    In secondary metabolite biosynthesis, core synthetic genes such as polyketide synthase genes or non-ribosomal peptide synthase genes usually encode proteins that generate various backbone precursors. These precursors are modified by other tailoring enzymes to yield a large variety of different secondary metabolites. The number of core synthesis genes in a given species correlates, therefore, with the number of types of secondary metabolites the organism can produce. In our study, heterologous expression of all the A. terreus NRPS-like genes showed that two NRPS-like proteins, encoded by atmelA and apvA, release the same natural product, aspulvinone E. More interestingly, further experiments revealed that the aspulvinone E produced by two different genes accumulates in different fungal compartments. And this spatial control of aspulvinone E production is likely to be regulated by their own specific promoters. Comparative genomics indicates that atmelA and apvA might share a same ancestral gene and the gene apvA is inserted in a highly conserved region in Aspergillus species that contains genes coding for life-essential proteins. The study also identified one trans-prenyltransferase AbpB which is capable of prenylating two different substrates aspulvinones and butyrolactones. In total, our study shows the first example in which the locally distribution of the same natural product could lead to its incorporation into different SM pathways.

  1. Be together, not the same: Spatiotemporal organization of different cilia types generates distinct transport functions

    NASA Astrophysics Data System (ADS)

    Nawroth, Janna; Guo, Hanliang; Ruby, Edward; Dabiri, John; McFall-Ngai, Margaret; Kanso, Eva

    2016-11-01

    Motile cilia are microscopic, hair-like structures on the cell surface that can sense and propel the extracellular fluid environment. Cilia are often thought to be limited to stereotypic morphologies, beat kinematics and non-discriminatory clearance functions, but we find that the spatiotemporal organization of different cilia types and beat behaviors can generate complex flow patterns and transport functions. Here, we present a case study in the Hawaiian bobtail squid where collective ciliary activity and resulting flow fields help recruit symbiont bacteria to the animal host. In particular, we demonstrate empirically and computationally how the squid's internal cilia act like a microfluidic device that actively filters the water for potential bacterial candidates and also provides a sheltered zone allowing for accumulation of mucus and bacteria into a biofilm. Moreover, in this sheltered zone, different cilia-driven flows enhance diffusion of biochemical signals, which could accelerate specific bacteria-host recognition. These results suggest that studying cilia activity on the population level might reveal a diverse range of biological transport and sensing functions. Moreover, understanding cilia as functional building blocks could inspire the design of ciliated robots and devices.

  2. Escherichia coli Quorum-Sensing EDF, A Peptide Generated by Novel Multiple Distinct Mechanisms and Regulated by trans-Translation

    PubMed Central

    Kumar, Sathish; Kolodkin-Gal, Ilana; Vesper, Oliver; Alam, Nawsad; Schueler-Furman, Ora; Moll, Isabella

    2016-01-01

    ABSTRACT Eshcerichia coli mazEF is a stress-induced toxin-antitoxin module mediating cell death and requiring a quorum-sensing (QS) extracellular death factor (EDF), the pentapeptide NNWNN. Here we uncovered several distinct molecular mechanisms involved in its generation from the zwf mRNA encoding glucose-6-phosphate dehydrogenase. In particular, we show that, under stress conditions, the endoribonuclease MazF cleaves specific ACA sites, thereby generating a leaderless zwf mRNA which is truncated 30 codons after the EDF-encoding region. Since the nascent ribosome peptide exit tunnel can accommodate up to 40 amino acids, this arrangement allows the localization of the EDF residues inside the tunnel when the ribosome is stalled at the truncation site. Moreover, ribosome stalling activates the trans-translation system, which provides a means for the involvement of ClpPX in EDF generation. Furthermore, the trans-translation is described as a regulatory system that attenuated the generation of EDF, leading to low levels of EDF in the single cell. Therefore, the threshold EDF molecule concentration required is achieved only by the whole population, as expected for QS. PMID:26814184

  3. Role of the cytokine environment and cytokine receptor expression on the generation of functionally distinct dendritic cells from human monocytes.

    PubMed

    Conti, Lucia; Cardone, Marco; Varano, Barbara; Puddu, Patrizia; Belardelli, Filippo; Gessani, Sandra

    2008-03-01

    Myeloid dendritic cells (DC) and macrophages evolve from a common precursor. However, factors controlling monocyte differentiation toward DC or macrophages are poorly defined. We report that the surface density of the GM-CSF receptor (GM-CSFR) alpha subunit in human peripheral blood monocytes varies among donors. Although no correlation was found between the extent of GM-CSFR and monocyte differentiation into DC driven by GM-CSF and IL-4, GM-CSFR expression strongly influenced the generation of CD1a(+) dendritic-like cells in the absence of IL-4. CD1a(+) cells generated in the presence of GM-CSF express CD40, CD80, MHC class I and II, DC-SIGN, MR, CCR5, and partially retain CD14 expression. Interestingly, they spontaneously induce the expansion of CD4(+) and CD8(+) allogeneic T lymphocytes producing IFN-gamma, and migrate toward CCL4 and CCL19. Upon stimulation with TLR ligands, they acquire the phenotypic features of mature DC. In contrast, the allostimulatory capacity is not further increased upon LPS activation. However, by blocking LPS-induced IL-10, a higher T cell proliferative response and IL-12 production were observed. Interestingly, IL-23 secretion was not affected by endogenous IL-10. These results highlight the importance of GM-CSFR expression in monocytes for cytokine-induced DC generation and point to GM-CSF as a direct player in the generation of functionally distinct DC.

  4. The hippocampal CA3 region can generate two distinct types of sharp wave-ripple complexes, in vitro.

    PubMed

    Hofer, Katharina T; Kandrács, Ágnes; Ulbert, István; Pál, Ildikó; Szabó, Csilla; Héja, László; Wittner, Lucia

    2015-02-01

    Hippocampal sharp wave-ripples (SPW-Rs) occur during slow wave sleep and behavioral immobility and are thought to play an important role in memory formation. We investigated the cellular and network properties of SPW-Rs with simultaneous laminar multielectrode and intracellular recordings in a rat hippocampal slice model, using physiological bathing medium. Spontaneous SPW-Rs were generated in the dentate gyrus (DG), CA3, and CA1 regions. These events were characterized by a local field potential gradient (LFPg) transient, increased fast oscillatory activity and increased multiple unit activity (MUA). Two types of SPW-Rs were distinguished in the CA3 region based on their different LFPg and current source density (CSD) pattern. Type 1 (T1) displayed negative LFPg transient in the pyramidal cell layer, and the associated CSD sink was confined to the proximal dendrites. Type 2 (T2) SPW-Rs were characterized by positive LFPg transient in the cell layer, and showed CSD sinks involving both the apical and basal dendrites. In both types, consistent with the somatic CSD source, only a small subset of CA3 pyramidal cells fired, most pyramidal cells were hyperpolarized, while most interneurons increased firing rate before the LFPg peak. Different neuronal populations, with different proportions of pyramidal cells and distinct subsets of interneurons were activated during T1 and T2 SPW-Rs. Activation of specific inhibitory cell subsets-with the possible leading role of perisomatic interneurons-seems to be crucial to synchronize distinct ensembles of CA3 pyramidal cells finally resulting in the expression of different SPW-R activities. This suggests that the hippocampus can generate dynamic changes in its activity stemming from the same excitatory and inhibitory circuits, and so, might provide the cellular and network basis for an input-specific and activity-dependent information transmission.

  5. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

    SciTech Connect

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu; Abu Lila, Amr S.; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2014-05-15

    anti-PEG IgMs were generated against distinct PEGylated materials. • In vivo cross-reactivity to the immunized materials was limited. • Although in vitro cross-reactivity of generated monoclonal IgMs has been confirmed.

  6. Linking structure and function in food webs: maximization of different ecological functions generates distinct food web structures.

    PubMed

    Yen, Jian D L; Cabral, Reniel B; Cantor, Mauricio; Hatton, Ian; Kortsch, Susanne; Patrício, Joana; Yamamichi, Masato

    2016-03-01

    Trophic interactions are central to ecosystem functioning, but the link between food web structure and ecosystem functioning remains obscure. Regularities (i.e. consistent patterns) in food web structure suggest the possibility of regularities in ecosystem functioning, which might be used to relate structure to function. We introduce a novel, genetic algorithm approach to simulate food webs with maximized throughput (a proxy for ecosystem functioning) and compare the structure of these simulated food webs to real empirical food webs using common metrics of food web structure. We repeat this analysis using robustness to secondary extinctions (a proxy for ecosystem resilience) instead of throughput to determine the relative contributions of ecosystem functioning and ecosystem resilience to food web structure. Simulated food webs that maximized robustness were similar to real food webs when connectance (i.e. levels of interaction across the food web) was high, but this result did not extend to food webs with low connectance. Simulated food webs that maximized throughput or a combination of throughput and robustness were not similar to any real food webs. Simulated maximum-throughput food webs differed markedly from maximum-robustness food webs, which suggests that maximizing different ecological functions can generate distinct food web structures. Based on our results, food web structure would appear to have a stronger relationship with ecosystem resilience than with ecosystem throughput. Our genetic algorithm approach is general and is well suited to large, realistically complex food webs. Genetic algorithms can incorporate constraints on structure and can generate outputs that can be compared directly to empirical data. Our method can be used to explore a range of maximization or minimization hypotheses, providing new perspectives on the links between structure and function in ecological systems.

  7. Two functionally distinct domains generated by in vivo cleavage of Nup145p: a novel biogenesis pathway for nucleoporins.

    PubMed Central

    Teixeira, M T; Siniossoglou, S; Podtelejnikov, S; Bénichou, J C; Mann, M; Dujon, B; Hurt, E; Fabre, E

    1997-01-01

    Nup145p is an essential yeast nucleoporin involved in nuclear export of polyadenylated RNAs. We demonstrate here that Nup145p is cleaved in vivo to yield two functionally distinct domains: a carboxy-terminal domain (C-Nup145p) which is located at the nuclear pore complex (NPC) and assembles into the Nup84p complex, and a GLFG-containing amino-terminal domain (N-Nup145p) which is not part of this complex. Whereas the essential C-Nup145p accomplishes the functions required for efficient mRNA export and normal NPC distribution, N-Nup145p, which is homologous to the GLFG-containing nucleoporins Nup100p and Nup116p, is not necessary for cell growth. However, the N-Nup145p becomes essential in a nup188 mutant background. Strikingly, generation of a free N-domain is a prerequisite for complementation of this peculiar synthetic lethal mutant. These data suggest that N- and C-domains of Nup145p perform independent functions, and that the in vivo cleavage observed is of functional importance. PMID:9305650

  8. Two distinct extracellular RNA signatures released by a single cell type identified by microarray and next-generation sequencing

    PubMed Central

    Lässer, Cecilia; Shelke, Ganesh Vilas; Yeri, Ashish; Kim, Dae-Kyum; Crescitelli, Rossella; Raimondo, Stefania; Sjöstrand, Margareta; Gho, Yong Song; Van Keuren Jensen, Kendall; Lötvall, Jan

    2017-01-01

    ABSTRACT Cells secrete extracellular RNA (exRNA) to their surrounding environment and exRNA has been found in many body fluids such as blood, breast milk and cerebrospinal fluid. However, there are conflicting results regarding the nature of exRNA. Here, we have separated 2 distinct exRNA profiles released by mast cells, here termed high-density (HD) and low-density (LD) exRNA. The exRNA in both fractions was characterized by microarray and next-generation sequencing. Both exRNA fractions contained mRNA and miRNA, and the mRNAs in the LD exRNA correlated closely with the cellular mRNA, whereas the HD mRNA did not. Furthermore, the HD exRNA was enriched in lincRNA, antisense RNA, vault RNA, snoRNA, and snRNA with little or no evidence of full-length 18S and 28S rRNA. The LD exRNA was enriched in mitochondrial rRNA, mitochondrial tRNA, tRNA, piRNA, Y RNA, and full-length 18S and 28S rRNA. The proteomes of the HD and LD exRNA-containing fractions were determined with LC-MS/MS and analyzed with Gene Ontology term finder, which showed that both proteomes were associated with the term extracellular vesicles and electron microscopy suggests that at least a part of the exRNA is associated with exosome-like extracellular vesicles. Additionally, the proteins in the HD fractions tended to be associated with the nucleus and ribosomes, whereas the LD fraction proteome tended to be associated with the mitochondrion. We show that the 2 exRNA signatures released by a single cell type can be separated by floatation on a density gradient. These results show that cells can release multiple types of exRNA with substantial differences in RNA species content. This is important for any future studies determining the nature and function of exRNA released from different cells under different conditions. PMID:27791479

  9. Human Recombinant Cytochrome P450 Enzymes Display Distinct Hydrogen Peroxide Generating Activities During Substrate Independent NADPH Oxidase Reactions

    PubMed Central

    Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-01-01

    Microsomal enzymes generate H2O2 in the presence of NADPH. In this reaction, referred to as “oxidase” activity, H2O2 is generated directly or indirectly via the formation of superoxide anion. In the presence of redox active transition metals, H2O2 can form highly toxic hydroxyl radicals and, depending on the “oxidase” activity of individual cytochrome P450 isoenzymes, this can compromise cellular functioning and contribute to tissue injury. In the present studies, we compared the initial rates of H2O2 generating activity of microsomal preparations containing various human recombinant cytochromes P450s. In the absence of cytochrome P450s the human recombinant NADPH cytochrome P450 reductase (CPR) generated low, but detectable amounts of H2O2 (∼0.04 nmol H2O2/min/100 units of reductase). Significantly greater activity was detected in preparations containing individual cytochrome P450s coexpressed with CPR (from 6.0 nmol H2O2/min/nmol P450 to 0.2 nmol/min/nmol P450); CYP1A1 was the most active, followed by CYP2D6, CYP3A4, CYP2E1, CYP4A11, CYP1A2, and CYP2C subfamily enzymes. H2O2 generating activity of the cytochrome P450s was independent of the ratio of CYP/CPR. Thus, similar H2O2 generating activity was noted with the same cytochrome P450s (CYP3A4, CYP2E1, and CYP2C9) expressed at or near the ratio of CYP/CPR in human liver microsomes (5–7), and when CPR was present in excess (CYP/CPR = 0.2–0.3). Because CYP3A4/5/7 represent up to 40% of total cytochrome P450 in the liver, these data indicate that these enzymes are the major source of H2O2 in human liver microsomes. PMID:25061110

  10. Distinct mechanisms of modulation in a neuronal oscillator generate different social signals in the electric fish Hypopomus.

    PubMed

    Kawasaki, M; Heiligenberg, W

    1989-10-01

    The medullary pacemaker nucleus of the gymnotiform electric fish, Hypopomus, is a relatively simple neuronal oscillator which contains pacemaker cells and relay cells. The pacemaker cells generate a regular discharge cycle and drive the relay cells which trigger pulse-like electric organ discharges (EODs). The diencephalic prepacemaker nucleus (PPN) projects to the pacemaker nucleus and modulates its activity to generate a variety of specific discharge patterns which serve as communicatory signals (Figs. 2 and 3). While inducing such signals by microiontophoresis of L-glutamate to the region of the PPN (Fig. 4) of curarized animals, we monitored the activity of neurons in the pacemaker nucleus intracellularly. We found that pacemaker cells and relay cells were affected differently in a manner specific to the type of EOD modulation (Figs. 5-10). The normal sequence of pacemaker cell and relay cell firing was maintained during gradual rises and falls in discharge rate. Both types of cells ceased to fire during interruptions following a decline in discharge rate. During sudden interruptions, however, relay cells were steadily depolarized, while pacemaker cells continued to fire regularly. Short and rapid barrages of EODs, called "chirps", were generated through direct and synchronous activation of the relay cells whose action potentials invaded pacemaker cells antidromically and interfered with their otherwise regular firing pattern.

  11. Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells.

    PubMed

    Eroglu, Emrah; Hallström, Seth; Bischof, Helmut; Opelt, Marissa; Schmidt, Kurt; Mayer, Bernd; Waldeck-Weiermair, Markus; Graier, Wolfgang F; Malli, Roland

    2017-09-04

    The members of the nitric oxide synthase (NOS) family, eNOS, nNOS and iNOS, are well-characterized enzymes. However, due to the lack of suitable direct NO sensors, little is known about the kinetic properties of cellular NO generation by the different nitric oxide synthase isoenzymes. Very recently, we developed a novel class of fluorescent protein-based NO-probes, the geNOps, which allow real-time measurement of cellular NO generation and fluctuation. By applying these genetic NO biosensors to nNOS-, eNOS- and iNOS-expressing HEK293 cells we were able to characterize the respective NO dynamics in single cells that exhibited identical Ca(2+) signaling as comparable activator of nNOS and eNOS. Our data demonstrate that upon Ca(2+) mobilization nNOS-derived NO signals occur instantly and strictly follow the Ca(2+) elevation while NO release by eNOS occurs gradually and sustained. To detect high NO levels in cells expressing iNOS, a new ratiometric probe based on two fluorescent proteins was developed. This novel geNOp variant allows the measurement of the high NO levels in cells expressing iNOS. Moreover, we used this probe to study the L-arginine-dependency of NO generation by iNOS on the level of single cells. Our experiments highlight that the geNOps technology is suitable to detect obvious differences in the kinetics, amplitude and substrate-dependence of cellular NO signals-derived from all three nitric oxide synthase isoforms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Vaccine adjuvants aluminum and monophosphoryl lipid A provide distinct signals to generate protective cytotoxic memory CD8 T cells

    PubMed Central

    MacLeod, Megan K. L.; McKee, Amy S.; David, Alexandria; Wang, Jieru; Mason, Robert; Kappler, John W.; Marrack, Philippa

    2011-01-01

    Vaccines can greatly reduce the spread of and deaths from many infectious diseases. However, many infections have no successful vaccines. Better understanding of the generation of protective CD8 memory T cells by vaccination is essential for the rational design of new vaccines that aim to prime cellular immune responses. Here we demonstrate that the combination of two adjuvants that are currently licensed for use in humans can be used to prime long-lived memory CD8 T cells that protect mice from viral challenge. The universally used adjuvant, aluminum salts, primed long-lived memory CD8 T cells; however, effective cytotoxic T-cell differentiation occurred only in the presence of an additional adjuvant, monophosphoryl lipid A (MPL). MPL-induced IL-6 was required for cytotoxic differentiation. The IL-6 acted by inducing granzyme B production and reducing expression of inhibitory molecule PD1 on the surface of the primed CD8 T cells. CD8 memory T cells generated by antigen delivered with both aluminum salts and MPL provided significant protection from influenza A challenge. These adjuvants could be used in human vaccines to prime protective memory CD8 T cells. PMID:21518876

  13. Human pluripotent stem cells differentiated in fully defined medium generate hematopoietic CD34- and CD34+ progenitors with distinct characteristics.

    PubMed

    Chicha, Laurie; Feki, Anis; Boni, Alessandro; Irion, Olivier; Hovatta, Outi; Jaconi, Marisa

    2011-02-25

    Differentiation of pluripotent stem cells in vitro provides a powerful means to investigate early developmental fates, including hematopoiesis. In particular, the use of a fully defined medium (FDM) would avoid biases induced by unidentified factors contained in serum, and would also allow key molecular mediators involved in such a process to be identified. Our goal was to induce in vitro, the differentiation of human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) into morphologically and phenotypically mature leukocytes and erythrocytes, in the complete absence of serum and feeder cells. ESC and iPSC were sequentially induced in liquid cultures for 4 days with bone morphogenic protein-4, and for 4 days with FLT3-ligand, stem cell factor, thrombopoietin and vascular endothelium growth factor. Cell differentiation status was investigated by both mRNA expression and FACS expression profiles. Cells were further sorted and assayed for their hematopoietic properties in colony-forming unit (CFU) assays. In liquid cultures, cells progressively down-modulated Oct-4 expression while a sizeable cell fraction expressed CD34 de novo. SCL/Tal1 and Runx1 transcripts were exclusively detected in CD34(+) cells. In clonal assays, both ESC and iPSC-derived cells generated CFU, albeit with a 150-fold lower efficacy than cord blood (CB) CD34(+) cells. ESC-derived CD34(+) cells generated myeloid and fully hemoglobinized erythroid cells whereas CD34(-) cells almost exclusively generated small erythroid colonies. Both ESC and iPSC-derived erythroid cells expressed embryonic and fetal globins but were unable to synthesize adult β-globin in contrast with CB cells, suggesting that they had differentiated from primitive rather than from definitive hematopoietic progenitors. Short-term, animal protein-free culture conditions are sufficient to sustain the differentiation of human ESC and iPSC into primitive hematopoietic progenitors, which, in turn, produce more mature

  14. Cell cycle arrest during S or M phase generates polarized growth via distinct signals in Candida albicans.

    PubMed

    Bachewich, Catherine; Nantel, Andre; Whiteway, Malcolm

    2005-08-01

    Treatments that perturb DNA synthesis or mitosis will activate checkpoints that prevent cell cycle progression and cell proliferation. In yeast-form cells of the fungal pathogen Candida albicans, exposure to hydroxyurea (HU) or shutting off expression of the polo-like kinase CaCDC5 blocked nuclear division and spindle elongation, but activated a highly polarized growth mode. We have used transcription profiling both to characterize the initiation and progression of this polar growth pattern and to determine how cell elongation may be linked to the cell cycle in C. albicans. Different gene expression patterns during early stages of cell elongation support the concept that CaCdc5p-depleted and HU-exposed cells were blocked at different stages of the cell cycle, and suggest that different signals may generate the common polarized growth phenotype. Consistent with this, BUB2 expression was modulated in CaCdc5p-depleted cells, and absence of BUB2 prevented the maintenance of cell polarization, resulting in multibudded, pseudohyphal cells with constrictions. In contrast, HU-induced filaments did not modulate or require BUB2, but were dependent on the GTPase Ras1p. However, at later stages of cell elongation, transcription profiles were more similar, and comparisons with serum-induced hyphae revealed that the cell cycle-arrested filaments expressed several targets of the hyphal signalling pathways. Thus, arresting the yeast cell cycle in S or M phase generates a polarized growth pattern through different mechanisms in C. albicans, and maintenance of the polar growth mode can ultimately lead to the expression of hyphal-associated cell wall and virulence-related factors, in the absence of any external stimuli.

  15. Two pathways of activation of the superoxide-generating NADPH oxidase of phagocytes in vitro--distinctive effects of inhibitors.

    PubMed

    Sigal, Natalia; Gorzalczany, Yara; Pick, Edgar

    2003-06-01

    The NADPH oxidase complex of phagocytes comprises a membrane-associated flavocytochrome b559, and 4 cytosolic components: p47phox, p67phox, p40phox, and the small GTPase Rac. Activation of the oxidase in vivo is the result of assembly of the cytosolic components with cytochrome b559 and is mimicked in vitro by a cell-free system consisting of membranes, p47phox, p67phox, nonprenylated or prenylated Rac, and an anionic amphiphile as activator (defined as "p47phox and amphiphile-dependent" or canonical pathway). We reported that prenylated Rac1 is capable of activating the NADPH oxidase in vitro in the absence of p47phox and amphiphile (defined as "p47phox and amphiphile-independent" pathway). We now demonstrate that the 2 pathways exhibit distinctive susceptibilities to inhibitors: 1) The anionic amphiphile lithium dodecyl sulfate, an activator of the canonical pathway, has the opposite effect (inhibition) on oxidase activation by prenylated Rac and p67phox; 2) GDP and, paradoxically, GTP (but not GMP, ATP, ADP, and AMP) prevent oxidase activation by the p47phox and amphiphile-independent pathway but do not affect activation by the canonical pathway; 3) The Rac-binding domain of p21-activated kinase is a potent inhibitor of activation by the p47phox and amphiphile-independent pathway while exerting a milder inhibitory effect on the canonical pathway; 4) The C-terminal polybasic Rac1 peptide 177-191 and the cationic antibiotic neomycin sulfate inhibit activation by the canonical pathway but do not affect activation by the p47phox and amphiphile-independent pathway; 5) Binding of prenylated Rac1 to membrane-mimicking phospholipid vesicles is, nevertheless, enhanced when these contain negatively charged lipids. It is proposed that preferential inhibition of oxidase activation, via the p47phox and amphiphile-independent pathway, is a reflection of interference by the inhibitors with Rac-dependent recruitment of p67phox to the membrane.

  16. Predicting memory benefits in the production effect: the use and misuse of self-generated distinctive cues when making judgments of learning.

    PubMed

    Castel, Alan D; Rhodes, Matthew G; Friedman, Michael C

    2013-01-01

    The production effect occurs when reading a word aloud leads to better memory for the item, relative to words that are read silently. In the present study, we assessed the degree to which judgments of learning (JOLs) are sensitive to the production effect, to determine whether people are aware of how distinctive cues can enhance memory. If the act of saying a word aloud is used as a cue for later memorability, then JOLs should be sensitive to production. Experiment 1 demonstrated that this was the case, as participants provided higher JOLs for produced items than for those read silently. This pattern of JOLs was also evident when participants silently mouthed words (Exp. 2). In Experiment 3, participants instead made a nonunique response as the production component (saying "yes" instead of the word itself). JOLs were still higher under production, although memory performance did not differ from that in a silent condition. The results suggest that the presence of both specific and nonspecific self-generated cues is used to make metacognitive judgments, likely due to the high accessibility of this information, but that participants are not precisely aware of how distinctiveness enhances encoding and retrieval. Such findings have implications for how distinctiveness is perceived by learners and for what cues would appropriately be incorporated when predicting future memory performance.

  17. Osmotic stress- and indole-3-butyric acid-induced NO generation are partially distinct processes in root growth and development in Pisum sativum.

    PubMed

    Kolbert, Zsuzsanna; Bartha, Bernadett; Erdei, László

    2008-06-01

    In this work, the effects of osmotic stress and exogenous auxin (indole-3-butyric acid, IBA) on root morphology and nitric oxide (NO) generation in roots were compared in pea plants. Five-day-old plants were treated with 0, 10(-3), 10(-4), 10(-5), 10(-6), 10(-7), 10(-8) or 10(-9) M IBA or with PEG 6000 at concentrations that determined 0, 50, 100, 200 or 400 mOsm in the medium, during 5 days. NO generation was examined by in situ and in vivo fluorescence method. Increasing concentrations of PEG as well as IBA resulted in shortening of primary root (PR), enhancement of lateral root (LR) number and significant increase of NO generation. Time-dependent investigations revealed that in the case of IBA treatments, the LR number increased in parallel with an intensified NO generation, while elongation of PR was not followed by changes in NO levels. Under osmotic stress, the time curve of NO development was distinct compared with that of IBA-treated roots, because significantly, the appearance of lateral initials was preceded by a transient burst of NO. This early phase of NO generation under osmotic stress was clearly distinguishable from that which accompanied LR initiation. It is concluded that osmotic stress and the presence of exogenous auxin resulted in partly similar root architecture but different time courses of NO synthesis. We suppose that the early phase of NO generation may fulfill a role in the osmotic stress-induced signalization process leading to the modification of root morphology.

  18. Through which looking glass? Distinct sources of public regard and self-esteem among first- and second-generation immigrants of color.

    PubMed

    Perkins, Krystal; Wiley, Shaun; Deaux, Kay

    2014-04-01

    How we think other people see us has long been believed to influence how we see ourselves, a phenomenon known as reflected appraisal. Among members of ethnic minority groups and immigrant groups, however, inconsistent patterns have been found. This study examined how immigrants' views of their ethnic group and of themselves are tied the appraisals of specific others. We hypothesized that members of the heritage culture and of White Americans are implicated in the reflected appraisal process to differing degrees. Moreover, we hypothesized that immigrants (first-generation) and the children of immigrants (second-generation) are affected differently by the appraisals of White Americans and heritage culture members. Results showed that perceived appraisal by members of the heritage culture was linked to how immigrants felt about their group and to their personal self-esteem. Perceived appraisal of White Americans was not related to how immigrants felt about their group and was only weakly related to personal self-esteem. The results highlight the distinction between public regard from the heritage culture and from White Americans and underscore the importance of the former for immigrants' private regard and self-esteem.

  19. Cortical Divergent Projections in Mice Originate from Two Sequentially Generated, Distinct Populations of Excitatory Cortical Neurons with Different Initial Axonal Outgrowth Characteristics.

    PubMed

    Hatanaka, Yumiko; Namikawa, Tomohiro; Yamauchi, Kenta; Kawaguchi, Yasuo

    2016-05-01

    Excitatory cortical neurons project to various subcortical and intracortical regions, and exhibit diversity in their axonal connections. Although this diversity may develop from primary axons, how many types of axons initially occur remains unknown. Using a sparse-labeling in utero electroporation method, we investigated the axonal outgrowth of these neurons in mice and correlated the data with axonal projections in adults. Examination of lateral cortex neurons labeled during the main period of cortical neurogenesis (E11.5-E15.5) indicated that axonal outgrowth commonly occurs in the intermediate zone. Conversely, the axonal direction varied; neurons labeled before E12.5 and the earliest cortical plate neurons labeled at E12.5 projected laterally, whereas neurons labeled thereafter projected medially. The expression of Ctip2 and Satb2 and the layer destinations of these neurons support the view that lateral and medial projection neurons are groups of prospective subcortical and callosal projection neurons, respectively. Consistently, birthdating experiments demonstrated that presumptive lateral projection neurons were generated earlier than medial projection neurons, even within the same layer. These results suggest that the divergent axonal connections of excitatory cortical neurons begin from two types of primary axons, which originate from two sequentially generated distinct subpopulations: early-born lateral (subcortical) and later-born medial (callosal) projection neuron groups.

  20. Regulation of PURA gene transcription by three promoters generating distinctly spliced 5-prime leaders: a novel means of fine control over tissue specificity and viral signals

    PubMed Central

    2010-01-01

    Background Purα is an evolutionarily conserved cellular protein participating in processes of DNA replication, transcription, and RNA transport; all involving binding to nucleic acids and altering conformation and physical positioning. The distinct but related roles of Purα suggest a need for expression regulated differently depending on intracellular and external signals. Results Here we report that human PURA (hPURA) transcription is regulated from three distinct and widely-separated transcription start sites (TSS). Each of these TSS is strongly homologous to a similar site in mouse chromosomal DNA. Transcripts from TSS I and II are characterized by the presence of large and overlapping 5'-UTR introns terminated at the same splice receptor site. Transfection of lung carcinoma cells with wild-type or mutated hPURA 5' upstream sequences identifies different regulatory elements. TSS III, located within 80 bp of the translational start codon, is upregulated by E2F1, CAAT and NF-Y binding elements. Transcription at TSS II is downregulated through the presence of adjacent consensus binding elements for interferon regulatory factors (IRFs). Chromatin immunoprecipitation reveals that IRF-3 protein binds hPURA promoter sequences at TSS II in vivo. By co-transfecting hPURA reporter plasmids with expression plasmids for IRF proteins we demonstrate that several IRFs, including IRF-3, down-regulate PURA transcription. Infection of NIH 3T3 cells with mouse cytomegalovirus results in a rapid decrease in levels of mPURA mRNA and Purα protein. The viral infection alters the degree of splicing of the 5'-UTR introns of TSS II transcripts. Conclusions Results provide evidence for a novel mechanism of transcriptional control by multiple promoters used differently in various tissues and cells. Viral infection alters not only the use of PURA promoters but also the generation of different non-coding RNAs from 5'-UTRs of the resulting transcripts. PMID:21062477

  1. The differential expression of low-threshold K+ currents generates distinct firing patterns in different subtypes of adult mouse trigeminal ganglion neurones.

    PubMed

    Catacuzzeno, Luigi; Fioretti, Bernard; Pietrobon, Daniela; Franciolini, Fabio

    2008-11-01

    In adult mouse trigeminal ganglion (TG) neurones we identified three neuronal subpopulations, defined in terms of their firing response to protracted depolarizations, namely MF neurones, characterized by a multiple tonic firing; DMF neurones, characterized by a delay before the beginning of repetitive firing; and SS neurones, characterized by a strongly adapting response. The three subpopulations also differed in several other properties important for defining their functional role in vivo, namely soma size, action potential (AP) shape and capsaicin sensitivity. MF neurones had small soma, markedly long AP and mostly responded to capsaicin, properties typical of a subgroup of C-type nociceptors. SS neurones had large soma, short AP duration and were mostly capsaicin insensitive, suggesting that most of them have functions other than nociception. DMF neurones were all capsaicin insensitive, had a small soma size and intermediate AP duration, making them functionally distinct from both MF and SS neurones. We investigated the ionic basis underlying the delay to the generation of the first AP of DMF neurones, and the strong adaptation of SS neurones. We found that the expression of a fast-inactivating, 4-AP- and CP-339,818-sensitive K+ current (I(A)) in DMF neurones plays a critical role in the generation of the delay, whereas a DTX-sensitive K+ current (I(DTX)) selectively expressed in SS neurones appeared to be determinant for their strong firing adaptation. A minimal theoretical model of TG neuronal excitability confirmed that I(A) and I(DTX) have properties congruent with their suggested role.

  2. Non-esterified fatty acids generate distinct low-molecular weight amyloid-β (Aβ42) oligomers along pathway different from fibril formation.

    PubMed

    Kumar, Amit; Bullard, Rebekah L; Patel, Pritesh; Paslay, Lea C; Singh, Dipti; Bienkiewicz, Ewa A; Morgan, Sarah E; Rangachari, Vijayaraghavan

    2011-04-19

    Amyloid-β (Aβ) peptide aggregation is known to play a central role in the etiology of Alzheimer's disease (AD). Among various aggregates, low-molecular weight soluble oligomers of Aβ are increasingly believed to be the primary neurotoxic agents responsible for memory impairment. Anionic interfaces are known to influence the Aβ aggregation process significantly. Here, we report the effects of interfaces formed by medium-chain (C9-C12), saturated non-esterified fatty acids (NEFAs) on Aβ42 aggregation. NEFAs uniquely affected Aβ42 aggregation rates that depended on both the ratio of Aβ:NEFA as well the critical micelle concentration (CMC) of the NEFAs. More importantly, irrespective of the kind of NEFA used, we observed that two distinct oligomers, 12-18 mers and 4-5 mers were formed via different pathway of aggregation under specific experimental conditions: (i) 12-18 mers were generated near the CMC in which NEFAs augment the rate of Aβ42 aggregation towards fibril formation, and, (ii) 4-5 mers were formed above the CMC, where NEFAs inhibit fibril formation. The data indicated that both 12-18 mers and 4-5 mers are formed along an alternate pathway called 'off-pathway' that did not result in fibril formation and yet have subtle structural and morphological differences that distinguish their bulk molecular behavior. These observations, (i) reflect the possible mechanism of Aβ aggregation in physiological lipid-rich environments, and (ii) reiterate the fact that all oligomeric forms of Aβ need not be obligatory intermediates of the fibril formation pathway.

  3. Targeted next-generation sequencing and non-coding RNA expression analysis of clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes.

    PubMed

    Lawrie, Charles H; Larrea, Erika; Larrinaga, Gorka; Goicoechea, Ibai; Arestin, María; Fernandez-Mercado, Marta; Hes, Ondrej; Cáceres, Francisco; Manterola, Lorea; López, José I

    2014-01-01

    Clear cell tubulopapillary renal cell carcinoma (CCPRCC) is a recently described rare renal malignancy that displays characteristic gross, microscopic and immunohistochemical differences from other renal tumour types. However, CCPRCC remains a very poorly understood entity. We therefore sought to elucidate some of the molecular mechanisms involved in this neoplasm by carrying out targeted next-generation sequencing (NGS) to identify associated mutations, and in addition examined the expression of non-coding (nc) RNAs. We identified multiple somatic mutations in CCPRCC cases, including a recurrent [3/14 cases (21%)] non-synonymous T992I mutation in the MET proto-oncogene, a gene associated with epithelial-to-mesenchymal transition (EMT). Using a microarray approach, we found that the expression of mature (n = 1105) and pre-miRNAs (n = 1105), as well as snoRNA and scaRNAs (n = 2214), in CCPRCC cases differed from that of clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) tumours. Surprisingly, and unlike other renal tumour subtypes, we found that all five members of the miR-200 family were over-expressed in CCPRCC cases. As these miRNAs are intimately involved with EMT, we stained CCPRCC cases for E-cadherin, vimentin and β-catenin and found that the tumour cells of all cases were positive for all three markers, a combination rarely reported in other renal tumours that could have diagnostic implications. Taken together with the mutational analysis, these data suggest that EMT in CCPRCC tumour cells is incomplete or blocked, consistent with the indolent clinical course typical of this malignancy. In summary, as well as describing a novel pathological mechanism in renal carcinomas, this study adds to the mounting evidence that CCPRCC should be formally considered a distinct entity. Microarray data have been deposited in the GEO database [GEO accession number (GSE51554)]. Copyright © 2013 Pathological Society of Great Britain and Ireland

  4. Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics.

    PubMed

    N'diaye, Marie; Warnecke, Andreas; Flytzani, Sevasti; Abdelmagid, Nada; Ruhrmann, Sabrina; Olsson, Tomas; Jagodic, Maja; Harris, Robert A; Guerreiro-Cacais, Andre Ortlieb

    2016-03-01

    Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells . GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3(+) regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3

  5. Generations.

    PubMed

    Chambers, David W

    2005-01-01

    Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession.

  6. The HIR corepressor complex binds to nucleosomes generating a distinct protein/DNA complex resistant to remodeling by SWI/SNF

    PubMed Central

    Prochasson, Philippe; Florens, Laurence; Swanson, Selene K.; Washburn, Michael P.; Workman, Jerry L.

    2005-01-01

    The histone regulatory (HIR) and histone promoter control (HPC) repressor proteins regulate three of the four histone gene loci during the Saccharomyces cerevisiae cell cycle. Here, we demonstrate that Hir1, Hir2, Hir3, and Hpc2 proteins form a stable HIR repressor complex. The HIR complex promotes histone deposition onto DNA in vitro and constitutes a novel nucleosome assembly complex. The HIR complex stably binds to DNA and nucleosomes. Furthermore, HIR complex binding to nucleosomes forms a distinct protein/DNA complex resistant to remodeling by SWI/SNF. Thus, the HIR complex is a novel nucleosome assembly complex which functions with SWI/SNF to regulate transcription. PMID:16264190

  7. In Arabidopsis thaliana distinct alleles encoding mitochondrial RNA PROCESSING FACTOR 4 support the generation of additional 5' termini of ccmB transcripts.

    PubMed

    Stoll, Katrin; Jonietz, Christian; Schleicher, Sarah; des Francs-Small, Catherine Colas; Small, Ian; Binder, Stefan

    2017-04-01

    In plant mitochondria, the 5' ends of many transcripts are generated post-transcriptionally. We show that the pentatricopeptide repeat (PPR) protein RNA PROCESSING FACTOR 4 (RPF4) supports the generation of extra 5' ends of ccmB transcripts in Landsberg erecta (Ler) and a number of other Arabidopsis thaliana ecotypes. RPF4 was identified in Ler applying a forward genetic approach supported by complementation studies of ecotype Columbia (Col), which generates the Ler-type extra ccmB 5' termini only after the introduction of the RPF4 allele from Ler. Studies with chimeric RPF4 proteins composed of various parts of the RPF4 proteins from Ler and Col identified differences in the N-terminal and central PPR motifs that explain ecotype-specific variations in ccmB processing. These results fit well with binding site predictions in ccmB transcripts based on the known determinants of nucleotide base recognition by PPR motifs.

  8. An alternative splicing event which occurs in mouse pachytene spermatocytes generates a form of DNA ligase III with distinct biochemical properties that may function in meiotic recombination.

    PubMed Central

    Mackey, Z B; Ramos, W; Levin, D S; Walter, C A; McCarrey, J R; Tomkinson, A E

    1997-01-01

    Three mammalian genes encoding DNA ligases have been identified. However, the role of each of these enzymes in mammalian DNA metabolism has not been established. In this study, we show that two forms of mammalian DNA ligase III, alpha and beta, are produced by a conserved tissue-specific alternative splicing mechanism involving exons encoding the C termini of the polypeptides. DNA ligase III-alpha cDNA, which encodes a 103-kDa polypeptide, is expressed in all tissues and cells, whereas DNA ligase III-beta cDNA, which encodes a 96-kDa polypeptide, is expressed only in the testis. During male germ cell differentiation, elevated expression of DNA ligase III-beta mRNA is restricted, beginning only in the latter stages of meiotic prophase and ending in the round spermatid stage. In 96-kDa DNA ligase III-beta, the C-terminal 77 amino acids of DNA ligase III-alpha are replaced by a different 17- to 18-amino acid sequence. As reported previously, the 103-kDa DNA ligase III-alpha interacts with the DNA strand break repair protein encoded by the human XRCC1 gene. In contrast, the 96-kDa DNA ligase III-beta does not interact with XRCC1, indicating that DNA ligase III-beta may play a role in cellular functions distinct from the DNA repair pathways involving the DNA ligase III-alpha x XRCC1 complex. The distinct biochemical properties of DNA ligase III-beta, in combination with the tissue- and cell-type-specific expression of DNA ligase III-beta mRNA, suggest that this form of DNA ligase III is specifically involved in the completion of homologous recombination events that occur during meiotic prophase. PMID:9001252

  9. Reversible linkage of two distinct small molecule inhibitors of Myc generates a dimeric inhibitor with improved potency that is active in myc over-expressing cancer cell lines.

    PubMed

    Wanner, Jutta; Romashko, Darlene; Werner, Douglas S; May, Earl W; Peng, Yue; Schulz, Ryan; Foreman, Kenneth W; Russo, Suzanne; Arnold, Lee D; Pingle, Maneesh; Bergstrom, Donald E; Barany, Francis; Thomson, Stuart

    2015-01-01

    We describe the successful application of a novel approach for generating dimeric Myc inhibitors by modifying and reversibly linking two previously described small molecules. We synthesized two directed libraries of monomers, each comprised of a ligand, a connector, and a bioorthogonal linker element, to identify the optimal dimer configuration required to inhibit Myc. We identified combinations of monomers, termed self-assembling dimeric inhibitors, which displayed synergistic inhibition of Myc-dependent cell growth. We confirmed that these dimeric inhibitors directly bind to Myc blocking its interaction with Max and affect transcription of MYC dependent genes. Control combinations that are unable to form a dimer do not show any synergistic effects in these assays. Collectively, these data validate our new approach to generate more potent and selective inhibitors of Myc by self-assembly from smaller, lower affinity components. This approach provides an opportunity for developing novel therapeutics against Myc and other challenging protein:protein interaction (PPI) target classes.

  10. Reversible Linkage of Two Distinct Small Molecule Inhibitors of Myc Generates a Dimeric Inhibitor with Improved Potency That Is Active in Myc Over-Expressing Cancer Cell Lines

    PubMed Central

    Wanner, Jutta; Romashko, Darlene; Werner, Douglas S.; May, Earl W.; Peng, Yue; Schulz, Ryan; Foreman, Kenneth W.; Russo, Suzanne; Arnold, Lee D.; Pingle, Maneesh; Bergstrom, Donald E.; Barany, Francis; Thomson, Stuart

    2015-01-01

    We describe the successful application of a novel approach for generating dimeric Myc inhibitors by modifying and reversibly linking two previously described small molecules. We synthesized two directed libraries of monomers, each comprised of a ligand, a connector, and a bioorthogonal linker element, to identify the optimal dimer configuration required to inhibit Myc. We identified combinations of monomers, termed self-assembling dimeric inhibitors, which displayed synergistic inhibition of Myc-dependent cell growth. We confirmed that these dimeric inhibitors directly bind to Myc blocking its interaction with Max and affect transcription of MYC dependent genes. Control combinations that are unable to form a dimer do not show any synergistic effects in these assays. Collectively, these data validate our new approach to generate more potent and selective inhibitors of Myc by self-assembly from smaller, lower affinity components. This approach provides an opportunity for developing novel therapeutics against Myc and other challenging protein:protein interaction (PPI) target classes. PMID:25875098

  11. Phenotypic diversification in vivo: Pseudomonas aeruginosa gacS- strains generate small colony variants in vivo that are distinct from in vitro variants.

    PubMed

    Nelson, Lisa K; Stanton, M Mark; Elphinstone, Robyn E A; Helwerda, Janessa; Turner, Raymond J; Ceri, Howard

    2010-12-01

    Pseudomonas aeruginosa has long been known to produce phenotypic variants during chronic mucosal surface infections. These variants are thought to be generated to ensure bacterial survival against the diverse challenges in the mucosal environment. Studies have begun to elucidate the mechanisms by which these variants emerge in vitro; however, too little information exists on phenotypic variation in vivo to draw any links between variants generated in vitro and in vivo. Consequently, in this study, the P. aeruginosa gacS gene, which has previously been linked to the generation of small colony variants (SCVs) in vitro, was studied in an in vivo mucosal surface infection model. More specifically, the rat prostate served as a model mucosal surface to test for the appearance of SCVs in vivo following infections with P. aeruginosa gacS(-) strains. As in in vitro studies, deletion of the gacS gene led to SCV production in vivo. The appearance of these in vivo SCVs was important for the sustainability of a chronic infection. In the subset of rats in which P. aeruginosa gacS(-) did not convert to SCVs, clearance of the bacteria took place and healing of the tissue ensued. When comparing the SCVs that arose at the mucosal surface (MS-SCVs) with in vitro SCVs (IV-SCVs) from the same gacS(-) parent, some differences between the phenotypic variants were observed. Whereas both MS-SCVs and IV-SCVs formed dense biofilms, MS-SCVs exhibited a less diverse resistance profile to antimicrobial agents than IV-SCVs. Additionally, MS-SCVs were better suited to initiate an infection in the rat model than IV-SCVs. Together, these observations suggest that phenotypic variation in vivo can be important for maintenance of infection, and that in vivo variants may differ from in vitro variants generated from the same genetic parent.

  12. Processing of lysozyme at distinct loops by pepsin: a novel action for generating multiple antimicrobial peptide motifs in the newborn stomach.

    PubMed

    Ibrahim, Hisham R; Inazaki, Daisuke; Abdou, Adham; Aoki, Takayoshi; Kim, Mujo

    2005-10-30

    C-type lysozyme (cLZ) is an antimicrobial enzyme that plays a major defense role in many human secretions. Recently, we have identified a helix-loop-helix antimicrobial peptide fragment of cLZ. This finding suggests that processing by coexisting proteases might be a relevant physiological process for generating peptides that contribute to the in vivo mucosal defense role of cLZ. In this study, we found that pepsin, under condition relevant to the newborn stomach (pH 4.0), generated various peptides from cLZ with potent bactericidal activity against several strains of Gram-negative and Gram-positive bacteria. Microsequencing and mass spectral analysis revealed that pepsin cleavage occurred at conserved loops within the alpha-domain of cLZ. We found that the bactericidal domain, which was isolated by gel filtration and reversed-phase HPLC, contains two cationic alpha-helical peptides generated from a helix-loop-helix domain (residues 1-38 of cLZ) by nicking at leucine17. A third peptide consisting of an alpha-helix (residues 18-38) and a two-stranded beta-sheet (residues 39-56) structure was also identified. These peptides share structural motifs commonly found in different innate immune defenses. Functional cellular studies with outer membrane-, cytoplasmic membrane vitality- and redox-specific fluorescence dyes revealed that the lethal effect of the isolated antimicrobial peptides is due to membrane permeabilization and inhibition of redox-driven bacterial respiration. The results provide the first demonstration that pepsin can fine-tune the antimicrobial potency of cLZ by generating multiple antimicrobial peptide motifs, delineating a new molecular switch of cLZ in the mucosal defense systems. Finally, this finding offers a new strategy for the design of antibiotic peptide drugs with potential use in the treatment of infectious diseases.

  13. Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide.

    PubMed

    Chaves, Guilherme Maranhão; da Silva, Walicyranison Plinio

    2012-12-01

    To cope with oxidative stress, Candida albicans possesses several enzymes involved in a number of biological processes, including superoxide dismutases (Sods) and glutaredoxins (Grxs). The resistance of C. albicans to reactive oxygen species is thought to act as a virulence factor. Genes such as SOD1 and GRX2, which encode for a Sod and Grx, respectively, in C. albicans are widely recognised to be important for pathogenesis. We generated a double mutant, Δgrx2/sod1, for both genes. This strain is very defective in hyphae formation and is susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, the double null mutant was susceptible to menadione and resistant to diamide. The reintegration of the SOD1 gene in the null mutant led to recovery in resistance to menadione, whereas reintegration of the GRX2 gene made the null mutant sensitive to diamide. Despite having two different roles in the responses to oxidative stress generated by chemical compounds, GRX2 and SOD1 are important for C. albicans pathogenesis because the double mutant Δgrx2/sod1 was very susceptible to neutrophil killing and was defective in hyphae formation in addition to having a lower virulence in an animal model of systemic infection.

  14. Parallel-Distinct Structures of Internal World and External Reality: Disavowing and Re-Claiming the Self-Identity in the Aftermath of Trauma-Generated Dissociation

    PubMed Central

    Şar, Vedat

    2017-01-01

    The nature of consciousness and the autonomy of the individual's mind have been a focus of interest throughout the past century and inspired many theories and models. Revival of studies on psychological trauma and dissociation, which remained outside mainstream psychiatry, psychology, and psychoanalysis for the most part of the past century, has provided a new opportunity to revisit this intellectual and scientific endeavor. This paper attempts to integrate a series of empirical and theoretical studies on psychological consequences of developmental traumatization, which may yield further insight into factors which threaten the integrity of human consciousness. The paper proposes that an individual's experience of distorted reality and betrayal precipitates a cyclical dynamic between the individual and the external world by disrupting the developmental function of mutuality which is essential for maintenance of the integrity of the internal world while this inner world is in turn regulated vis-à-vis external reality. Dissociation -the common factor in all types of post-traumatic syndromes- is facilitated by violation of boundaries by relational omission and intrusion as represented by distinct effects and consequences of childhood neglect and abuse. Recent research conducted on clinical and non-clinical populations shows both bimodal (undermodulation and overmodulation) and bipolar (intrusion and avoidance) neurobiological and phenomenological characteristics of post-traumatic response. These seem to reflect “parallel-distinct structures” that control separate networks covering sensori-motor and cognitive-emotional systems. This understanding provides a conceptual framework to assist explanation of diverse post-traumatic mental trajectories which culminate in a common final pathway comprised of partly overlapping clinical syndromes such as complex PTSD, dissociative depression, dissociative identity disorder (DID), or “borderline” phenomena. Of crucial

  15. Parallel-Distinct Structures of Internal World and External Reality: Disavowing and Re-Claiming the Self-Identity in the Aftermath of Trauma-Generated Dissociation.

    PubMed

    Şar, Vedat

    2017-01-01

    The nature of consciousness and the autonomy of the individual's mind have been a focus of interest throughout the past century and inspired many theories and models. Revival of studies on psychological trauma and dissociation, which remained outside mainstream psychiatry, psychology, and psychoanalysis for the most part of the past century, has provided a new opportunity to revisit this intellectual and scientific endeavor. This paper attempts to integrate a series of empirical and theoretical studies on psychological consequences of developmental traumatization, which may yield further insight into factors which threaten the integrity of human consciousness. The paper proposes that an individual's experience of distorted reality and betrayal precipitates a cyclical dynamic between the individual and the external world by disrupting the developmental function of mutuality which is essential for maintenance of the integrity of the internal world while this inner world is in turn regulated vis-à-vis external reality. Dissociation -the common factor in all types of post-traumatic syndromes- is facilitated by violation of boundaries by relational omission and intrusion as represented by distinct effects and consequences of childhood neglect and abuse. Recent research conducted on clinical and non-clinical populations shows both bimodal (undermodulation and overmodulation) and bipolar (intrusion and avoidance) neurobiological and phenomenological characteristics of post-traumatic response. These seem to reflect "parallel-distinct structures" that control separate networks covering sensori-motor and cognitive-emotional systems. This understanding provides a conceptual framework to assist explanation of diverse post-traumatic mental trajectories which culminate in a common final pathway comprised of partly overlapping clinical syndromes such as complex PTSD, dissociative depression, dissociative identity disorder (DID), or "borderline" phenomena. Of crucial theoretical

  16. Distinct transduction profiles in the CNS via three injection routes of AAV9 and the application to generation of a neurodegenerative mouse model

    PubMed Central

    Huda, Fathul; Konno, Ayumu; Matsuzaki, Yasunori; Goenawan, Hanna; Miyake, Koichi; Shimada, Takashi; Hirai, Hirokazu

    2014-01-01

    Using single-stranded adeno-associated virus serotype 9 (ssAAV9) vectors containing the neuron-specific synapsin-I promoter, we examined whether different administration routes (direct cerebellar cortical (DC), intrathecal (IT) and intravenous (IV) injections) could elicit specific transduction profiles in the CNS. The DC injection route robustly and exclusively transduced the whole cerebellum, whereas the IT injection route primarily transduced the cerebellar lobules 9 and 10 close to the injection site and the spinal cord. An IV injection in neonatal mice weakly and homogenously transduced broad CNS areas. In the cerebellar cortex, the DC and IT injection routes transduced all neuron types, whereas the IV injection route primarily transduced Purkinje cells. To verify the usefulness of this method, we generated a mouse model of spinocerebellar ataxia type 1 (SCA1). Mice that received a DC injection of the ssAAV9 vector expressing mutant ATXN1, a protein responsible for SCA1, showed the intranuclear aggregation of mutant ATXN1 in Purkinje cells, significant atrophy of the Purkinje cell dendrites and progressive motor deficits, which are characteristics of SCA1. Thus, ssAAV9-mediated transduction areas, levels, and cell types change depending on the route of injection. Moreover, this approach can be used for the generation of different mouse models of CNS/neurodegenerative diseases. PMID:26015973

  17. Generation of isotopically and compositionally distinct water during thermochemical sulfate reduction (TSR) in carbonate reservoirs: Triassic Feixianguan Formation, Sichuan Basin, China

    NASA Astrophysics Data System (ADS)

    Jiang, Lei; Worden, Richard H.; Cai, Chunfang

    2015-09-01

    Thermochemical sulfate reduction (TSR), the reaction of petroleum with anhydrite in reservoirs resulting in the growth of calcite and the accumulation of H2S, has been documented in the Feixianguan Formation dolomite reservoir in the Sichuan Basin, China. Fluid inclusion salinity and homogenization temperature data have shown that TSR results in a decrease in salinity from a pre-TSR value of 25 wt.% down to 5 wt.% as a result of water created as a byproduct of progressive TSR. We have studied the isotopic character of the water that resulted from TSR in the Feixianguan Formation by analyzing the oxygen isotopes of TSR calcite and determining the oxygen isotopes of the water in equilibrium with the TSR calcite at the temperatures determined by aqueous fluid inclusion analysis. We have compared these TSR-waters to water that would have been in equilibrium with the bulk rock, also at the temperatures determined by aqueous fluid inclusion analysis. We have found that the TSR-waters are relatively depleted in oxygen isotopes (by up to 8‰ compared to what would be expected at equilibrium between the bulk rock and water) since this type of water was specifically derived from anhydrite. The generation of relatively large volumes of low salinity, low δ18O water associated with advanced TSR in the Feixianguan Formation has also been reported in the Permian Khuff Formation in Abu Dhabi and from sour Devonian fields in the Western Canada Basin. This suggests that TSR-derived water may be a common phenomenon, the effects of which on mesogenetic secondary porosity and reservoir quality have previously been underappreciated.

  18. Electrochemically-induced TCNQ/Mn[TCNQ]2(H2O)2 (TCNQ = 7,7,8,8-tetracyanoquinodimethane) solid-solid interconversion: two voltammetrically distinct processes that allow selective generation of nanofiber or nanorod network morphologies.

    PubMed

    Nafady, Ayman; Bond, Alan M; O'Mullane, Anthony P

    2009-10-05

    Unlike the case with other divalent transition metal M[TCNQ](2)(H(2)O)(2) (M = Fe, Co, Ni) analogues, the electrochemically induced solid-solid phase interconversion of TCNQ microcrystals (TCNQ = 7,7,8,8-tetracyanoquinodimethane) to Mn[TCNQ](2)(H(2)O)(2) occurs via two voltammetrically distinct, time dependent processes that generate the coordination polymer in nanofiber or rod-like morphologies. Careful manipulation of the voltammetric scan rate, electrolysis time, Mn(2+)((aq)) concentration, and the method of electrode modification with solid TCNQ allows selective generation of either morphology. Detailed ex situ spectroscopic (IR, Raman), scanning electron microscopy (SEM), and X-ray powder diffraction (XRD) characterization clearly establish that differences in the electrochemically synthesized Mn-TCNQ material are confined to morphology. Generation of the nanofiber form is proposed to take place rapidly via formation and reduction of a Mn-stabilized anionic dimer intermediate, [(Mn(2+))(TCNQ-TCNQ)(2)(*-)], formed as a result of radical-substrate coupling between TCNQ(*-) and neutral TCNQ, accompanied by ingress of Mn(2+) ions from the aqueous solution at the triple phase TCNQ/electrode/electrolyte boundary. In contrast, formation of the nanorod form is much slower and is postulated to arise from disproportionation of the [(Mn(2+))(TCNQ-TCNQ)(*-)(2)] intermediate. Thus, identification of the time dependent pathways via the solid-solid state electrochemical approach allows the crystal size of the Mn[TCNQ](2)(H(2)O)(2) material to be tuned and provides new mechanistic insights into the formation of different morphologies.

  19. Endopeptidase Cleavage Generates a Functionally Distinct Isoform of C1q/Tumor Necrosis Factor-related Protein-12 (CTRP12) with an Altered Oligomeric State and Signaling Specificity*

    PubMed Central

    Wei, Zhikui; Lei, Xia; Seldin, Marcus M.; Wong, G. William

    2012-01-01

    Adipose tissue-derived adipokines are an important class of secreted metabolic regulators that mediate tissue cross-talk to control systemic energy balance. We recently described C1q/TNF-related protein-12 (CTRP12), a novel insulin-sensitizing adipokine that regulates glucose metabolism in liver and adipose tissue. However, the biochemical properties of CTRP12 and its naturally occurring cleaved isoform have not been characterized. Here, we show that CTRP12 is a secreted hormone subjected to multiple functionally relevant posttranslational modifications at highly conserved residues. For example, Asn39 is glycosylated, whereas Cys85 mediates the assembly of higher order oligomeric structure. Endopeptidase cleavage at Lys91 generates a cleaved globular gCTRP12 isoform, the expression of which is increased by insulin. PCSK3/furin was identified as the major proprotein convertase expressed by adipocytes that mediates the endogenous cleavage of CTRP12. Cleavage at Lys91 is context-dependent: mutation of the charged Arg93 to Ala on the P2′ position enhanced cleavage, and triple mutations (K90A/K91A/R93A) abolished cleavage. Importantly, the two isoforms of CTRP12 differ in oligomeric structures and are functionally distinct. The full-length protein forms trimers and larger complexes, and the cleaved isoform consisted of predominantly dimers. Whereas full-length fCTRP12 strongly activated Akt signaling in H4IIE hepatocytes and 3T3-L1 adipocytes, gCTRP12 preferentially activated MAP kinase (ERK1/2 and p38 MAPK) signaling. Further, only fCTRP12 improved insulin-stimulated glucose uptake in adipocytes. These results reveal a novel mechanism controlling signaling specificity and function of a hormone via cleavage-dependent alteration in oligomeric state. PMID:22942287

  20. Social conformity despite individual preferences for distinctiveness.

    PubMed

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  1. Social conformity despite individual preferences for distinctiveness

    PubMed Central

    Smaldino, Paul E.; Epstein, Joshua M.

    2015-01-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity. PMID:26064615

  2. Distinct functions for ERKs?

    PubMed Central

    Lloyd, Alison C

    2006-01-01

    The Ras/Raf/MEK/ERK signaling pathway is one of the best understood signal routes in cells. Recent studies add complexity to this cascade by indicating that the two ERK kinases, ERK1 (p44ERK1) and ERK2 (p42ERK2), may have distinct functions. PMID:16879721

  3. Touch communicates distinct emotions.

    PubMed

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. (c) 2006 APA, all rights reserved

  4. Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts.

    PubMed

    Bhasin, Shalender; Pencina, Michael; Jasuja, Guneet Kaur; Travison, Thomas G; Coviello, Andrea; Orwoll, Eric; Wang, Patty Y; Nielson, Carrie; Wu, Frederick; Tajar, Abdelouahid; Labrie, Fernand; Vesper, Hubert; Zhang, Anqi; Ulloor, Jagadish; Singh, Ravinder; D'Agostino, Ralph; Vasan, Ramachandran S

    2011-08-01

    Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

  5. Distinct signaling pathways leading to the induction of human β-defensin 2 by stimulating an electrolyticaly-generated acid functional water and double strand RNA in oral epithelial cells.

    PubMed

    Gojoubori, Takahiro; Nishio, Yukina; Asano, Masatake; Nishida, Tetsuya; Komiyama, Kazuo; Ito, Koichi

    2014-04-01

    Defensins, a major family of cationic antimicrobial peptides, play important roles in innate immunity. In the present study, we investigated whether double-stranded RNA (dsRNA), a by-product of RNA virus replication, can induce human β-defensins-2 (hBD-2) expression in oral epithelial cells (OECs). We also examined the hBD-2-inducible activity of acid-electrolyzed functional water (FW). The results indicated that both dsRNA- and FW-induced hBD-2 expression in OECs. The induction efficiency was much higher for FW than for dsRNA. FW-induced production of hBD-2 was clearly observed by immunofluorescence staining. A luciferase assay was performed with 1.2 kb of the 5'-untranslated region (5'-UTR) of the hBD-2 gene. The results indicated that the nuclear factor-kappa B (NF-κB)-binding site proximal to the translation initiation site was indispensable for dsRNA-stimulated hBD-2 expression, but not in the case of FW. Moreover, FW-stimulated hBD-2 expression did not depend on NF-κB activity; instead, FW inhibited NF-κB activity. Pretreatment of the cells with specific inhibitors against NF-κB further confirmed NF-κB-independent hBD-2 induction by FW. In analogy to the results for intestinal epithelial cells (IECs), the dsRNA signal, but not FW, was sensed by toll-like receptor 3 (TLR3) in OECs. These results suggested that hBD-2 expression induced by dsRNA and FW is regulated by distinct mechanisms in OECs.

  6. Visualization of Ins(1,4,5)P3 dynamics in living cells: two distinct pathways for Ins(1,4,5)P3 generation following mechanical stimulation of HSY-EA1 cells.

    PubMed

    Nezu, Akihiro; Tanimura, Akihiko; Morita, Takao; Tojyo, Yosuke

    2010-07-01

    In the present study, the contribution of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] generation on the mechanical-stimulation-induced Ca(2+) response was investigated in HSY-EA1 cells. Mechanical stimulation induced a local increase in the cytosolic concentration of Ins(1,4,5)P(3) ([IP(3)](i)), as indicated by the Ins(1,4,5)P(3) biosensor LIBRAvIII. The area of this increase expanded like an intracellular Ins(1,4,5)P(3) wave as [IP(3)](i) increased in the stimulated region. A small transient [IP(3)](i) increase was subsequently seen in neighboring cells. The phospholipase C inhibitor U-73122 abolished these Ins(1,4,5)P(3) responses and resultant Ca(2+) releases. The purinergic receptor blocker suramin completely blocked increases in [IP(3)](1) and the Ca(2+) release in neighboring cells, but failed to attenuate the responses in mechanically stimulated cells. These results indicate that generation of Ins(1,4,5)P(3) in response to mechanical stimulation is primarily independent of extracellular ATP. The speed of the mechanical-stimulation-induced [IP(3)](i) increase was much more rapid than that induced by a supramaximal concentration of ATP (1 mM). The contribution of the Ins(1,4,5)P(3)-induced Ca(2+) release was larger than that of Ca(2+) entry in the Ca(2+) response to mechanical stimulation in HSY-EA1 cells.

  7. Foundations of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Baltaxe, Christiane A. M.

    This treatise on the theoretical and historical foundations of distinctive feature theory traces the evolution of the distinctive features concept in the context of related notions current in linguistic theory, discusses the evolution of individual distinctive features, and criticizes certain acoustic and perceptual correlates attributed to these…

  8. Foundations of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Baltaxe, Christiane A. M.

    This treatise on the theoretical and historical foundations of distinctive feature theory traces the evolution of the distinctive features concept in the context of related notions current in linguistic theory, discusses the evolution of individual distinctive features, and criticizes certain acoustic and perceptual correlates attributed to these…

  9. A distinctly disorganised dwarf

    NASA Image and Video Library

    2016-03-28

    Despite being less famous than their elliptical and spiral galactic cousins, irregular dwarf galaxies, such as the one captured in this NASA/ESA Hubble Space Telescope image, are actually one of the most common types of galaxy in the Universe. Known as UGC 4459, this dwarf galaxy is located approximately 11 million light-years away in the constellation of Ursa Major (The Great Bear), a constellation that is also home to the Pinwheel Galaxy (M101), the Owl Nebula (M97), Messier 81, Messier 82 and several other galaxies all part of the M81 group. UGC 4459’s diffused and disorganised appearance is characteristic of an irregular dwarf galaxy. Lacking a distinctive structure or shape, irregular dwarf galaxies are often chaotic in appearance, with neither a nuclear bulge — a huge, tightly packed central group of stars — nor any trace of spiral arms — regions of stars extending from the centre of the galaxy. Astronomers suspect that some irregular dwarf galaxies were once spiral or elliptical galaxies, but were later deformed by the gravitational pull of nearby objects. Rich with young blue stars and older red stars, UGC 4459 has a stellar population of several billion. Though seemingly impressive, this is small when compared to the 200 to 400 billion stars in the Milky Way! Observations with Hubble have shown that because of their low masses, star formation is very low compared to larger galaxies. Only very little of their original gas has been turned into stars. Thus, these small galaxies are interesting to study to better understand primordial environments and the star formation process.

  10. Cfr and RlmN Contain a Single [4Fe-4S] Cluster, which Directs Two Distinct Reactivities for S-Adenosylmethionine: Methyl Transfer by SN2 Displacement and Radical Generation

    PubMed Central

    Grove, Tyler L.; Radle, Matthew I.; Krebs, Carsten; Booker, Squire J.

    2012-01-01

    The radical SAM (RS) proteins RlmN and Cfr catalyze methylation of carbons 2 and 8, respectively, of adenosine 2503 in 23S rRNA. Both reactions are similar in scope, entailing the synthesis of a methyl group partially derived from S-adenosylmethionine (SAM) onto electrophilic sp2-hybridized carbon atoms via the intermediacy of a protein S-methylcysteinyl (mCys) residue. Both proteins contain five conserved Cys residues, each of which is required for turnover. Three cysteines lie in a canonical RS CxxxCxxC motif and coordinate a [4Fe–4S]-cluster cofactor. The remaining two cysteines are at opposite ends of the polypeptide. Herein we show that each protein contains only the one “radical SAM” [4Fe–4S] cluster, and that the two remaining conserved cysteines do not coordinate additional iron-containing species. In addition, we show that while wild-type RlmN bears the C355 mCys residue in its as-isolated state, RlmN that is either engineered to lack the [4Fe–4S] cluster by substitution of the coordinating cysteines, or isolated from Escherichia coli cultured under iron-limiting conditions, does not bear a C355 mCys residue. Reconstitution of the [4Fe–4S] cluster on wild-type apo RlmN followed by addition of SAM results in rapid production of S-adenosylhomocysteine (SAH) and the mCys residue, while treatment of apo RlmN with SAM affords no observable reaction. These results indicate that in Cfr and RlmN, SAM bound to the unique iron of the [4Fe–4S] cluster displays two reactivities. It serves to methylate C355 of RlmN (C338 of Cfr), or it serves to generate the 5’-deoxyadenosyl 5’-radical, required for substrate-dependent methyl synthase activity. PMID:21916495

  11. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation.

    PubMed

    Grove, Tyler L; Radle, Matthew I; Krebs, Carsten; Booker, Squire J

    2011-12-14

    The radical SAM (RS) proteins RlmN and Cfr catalyze methylation of carbons 2 and 8, respectively, of adenosine 2503 in 23S rRNA. Both reactions are similar in scope, entailing the synthesis of a methyl group partially derived from S-adenosylmethionine (SAM) onto electrophilic sp(2)-hybridized carbon atoms via the intermediacy of a protein S-methylcysteinyl (mCys) residue. Both proteins contain five conserved Cys residues, each required for turnover. Three cysteines lie in a canonical RS CxxxCxxC motif and coordinate a [4Fe-4S]-cluster cofactor; the remaining two are at opposite ends of the polypeptide. Here we show that each protein contains only the one "radical SAM" [4Fe-4S] cluster and the two remaining conserved cysteines do not coordinate additional iron-containing species. In addition, we show that, while wild-type RlmN bears the C355 mCys residue in its as-isolated state, RlmN that is either engineered to lack the [4Fe-4S] cluster by substitution of the coordinating cysteines or isolated from Escherichia coli cultured under iron-limiting conditions does not bear a C355 mCys residue. Reconstitution of the [4Fe-4S] cluster on wild-type apo RlmN followed by addition of SAM results in rapid production of S-adenosylhomocysteine (SAH) and the mCys residue, while treatment of apo RlmN with SAM affords no observable reaction. These results indicate that in Cfr and RlmN, SAM bound to the unique iron of the [4Fe-4S] cluster displays two reactivities. It serves to methylate C355 of RlmN (C338 of Cfr), or to generate the 5'-deoxyadenosyl 5'-radical, required for substrate-dependent methyl synthase activity. © 2011 American Chemical Society

  12. Development of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Meyer, Peggy L.

    Since the beginning of man's awareness of his language capabilities and language structure, he has assumed that speech is composed of discrete entities. The linguist attempts to establish a model of the workings of these distinctive sounds in a language. Utilizing an historical basis for discussion, this general survey of the distinctive feature…

  13. Counselor Identity: Conformity or Distinction?

    ERIC Educational Resources Information Center

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  14. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

    Two experiments were carried out to study the role of gender category in evaluations of face distinctiveness. In Experiment 1, participants had to evaluate the distinctiveness and the femininity-masculinity of real or artificial composite faces. The composite faces were created by blending either faces of the same gender (sexed composite faces,…

  15. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

    Two experiments were carried out to study the role of gender category in evaluations of face distinctiveness. In Experiment 1, participants had to evaluate the distinctiveness and the femininity-masculinity of real or artificial composite faces. The composite faces were created by blending either faces of the same gender (sexed composite faces,…

  16. Optimal Distinctiveness Signals Membership Trust.

    PubMed

    Leonardelli, Geoffrey J; Loyd, Denise Lewin

    2016-07-01

    According to optimal distinctiveness theory, sufficiently small minority groups are associated with greater membership trust, even among members otherwise unknown, because the groups are seen as optimally distinctive. This article elaborates on the prediction's motivational and cognitive processes and tests whether sufficiently small minorities (defined by relative size; for example, 20%) are associated with greater membership trust relative to mere minorities (45%), and whether such trust is a function of optimal distinctiveness. Two experiments, examining observers' perceptions of minority and majority groups and using minimal groups and (in Experiment 2) a trust game, revealed greater membership trust in minorities than majorities. In Experiment 2, participants also preferred joining minorities over more powerful majorities. Both effects occurred only when minorities were 20% rather than 45%. In both studies, perceptions of optimal distinctiveness mediated effects. Discussion focuses on the value of relative size and optimal distinctiveness, and when membership trust manifests.

  17. Window generator

    NASA Astrophysics Data System (ADS)

    Johnson, William K.; May, Roger A.

    1989-03-01

    The present invention relates generally to video target recognition systems and more specifically to a window generator which receives a field of video data and applies an identification code to rectangular subregions to identify distinct target areas within a given background area. The present invention comprises a window generator which provides a 6 bit target identification number for up to 63 target areas and one background area in a frame of serially scanned data. The window generator receives a field of video data from an image data source. This video data consists of digitized frames of serially scanned data similar to a conventional television screen image, which is divided horizontally in pixels, and vertically in lines. The window generator permits any given frame to be subdivided into specific rectangular subregions, which may be located anywhere on the video picture. By allowing statistics to be collected on the individual subregions (or target areas) the window generator permits local processing of video data within the specified target areas as opposed to processing of video data over the entire video field. One embodiment of the window generator is composed of: a microprocessor, a random access memory (RAM), a comparator, a line memory, two counters, an OR gate, a frame initialization circuit, and a buffer. These elements function as described below.

  18. Neurobehavioral perspectives on the distinction between fear and anxiety

    PubMed Central

    Perusini, Jennifer N.

    2015-01-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action. PMID:26286652

  19. Gingival Tissue Transcriptomes Identify Distinct Periodontitis Phenotypes

    PubMed Central

    Kebschull, M.; Demmer, R.T.; Grün, B.; Guarnieri, P.; Pavlidis, P.; Papapanou, P.N.

    2014-01-01

    The currently recognized principal forms of periodontitis—chronic and aggressive—lack an unequivocal, pathobiology-based foundation. We explored whether gingival tissue transcriptomes can serve as the basis for an alternative classification of periodontitis. We used cross-sectional whole-genome gene expression data from 241 gingival tissue biopsies obtained from sites with periodontal pathology in 120 systemically healthy nonsmokers with periodontitis, with available data on clinical periodontal status, subgingival microbial profiles, and serum IgG antibodies to periodontal microbiota. Adjusted model-based clustering of transcriptomic data using finite mixtures generated two distinct clusters of patients that did not align with the current classification of chronic and aggressive periodontitis. Differential expression profiles primarily related to cell proliferation in cluster 1 and to lymphocyte activation and unfolded protein responses in cluster 2. Patients in the two clusters did not differ with respect to age but presented with distinct phenotypes (statistically significantly different whole-mouth clinical measures of extent/severity, subgingival microbial burden by several species, and selected serum antibody responses). Patients in cluster 2 showed more extensive/severe disease and were more often male. The findings suggest that distinct gene expression signatures in pathologic gingival tissues translate into phenotypic differences and can provide a basis for a novel classification. PMID:24646639

  20. Crossing the Generational Divide: Supporting Generational Differences at Work

    ERIC Educational Resources Information Center

    Berl, Patricia Scallan

    2006-01-01

    Differences in attitudes and behaviors, regularly exhibited between youth and their elders, are frequently referred to as the "generation gap". On the job, these generational distinctions are becoming increasingly complex as "multi-generation gaps" emerge, with three or more generations defining roles and expectations, each vying for positions in…

  1. Acute jejunoileitis. A distinct entity?

    PubMed

    Levine, J; Schmidt, M H; Burrell, M I; Hopkins, M S

    1992-01-01

    A 44-year-old man with acute jejunoileitis of unknown etiology developed small bowel obstruction. Intermittent abdominal pain, bloody diarrhea, ascites, and leukocytosis were prominent features. All stool cultures were negative. On steroid treatment, symptoms and radiographic features completely resolved. We suggest, in agreement with an earlier report, that acute jejunoileitis may be regarded as a distinct clinical entity.

  2. China English: Its Distinctive Features

    ERIC Educational Resources Information Center

    Yang, Wei-dong; Dai, Wei-ping

    2011-01-01

    This paper attempts to expound that China English boasting its own distinctive features on the levels of phonology, words, sentences and discourse has been playing an irreplaceable role in intercultural activities, though still in its infancy and in the process of developing and perfecting itself, and it now makes every effort to move towards…

  3. Distinctiveness Maps for Image Matching

    NASA Technical Reports Server (NTRS)

    Manduchi, Roberto; Tomasi, Carlo

    2000-01-01

    Stereo correspondence is hard because different image features can look alike. We propose a measure for the ambiguity of image points that allows matching distinctive points first and breaks down the matching task into smaller and separate subproblems. Experiments with an algorithm based on this measure demonstrate the ensuing efficiency and low likelihood of incorrect matches.

  4. Educational Psychology: The Distinctive Contribution

    ERIC Educational Resources Information Center

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  5. Educational Psychology: The Distinctive Contribution

    ERIC Educational Resources Information Center

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  6. Grima: A Distinct Emotion Concept?

    PubMed Central

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M.; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as ‘grima’ with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of ‘grima’ was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as ‘grima’, whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers. PMID:28217102

  7. Grima: A Distinct Emotion Concept?

    PubMed

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as 'grima' with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of 'grima' was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as 'grima', whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers.

  8. BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

    PubMed Central

    Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Çuburu, Nicolas

    2013-01-01

    BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. PMID:23843634

  9. Distinctive features in speech pathology: phonology or phonemics?

    PubMed

    Parker, F

    1976-02-01

    Distinctive feature is not a unique concept within linguistic theory. It has two distinct bases: phonemic theory and generative theory. Phonemic theory assumes a direct correspondence between distinctive features (the elements of phonemes) and the speech signal. Although this assumption can be shown to be incorrect, it seems to be the one most widely held in speech science. Generative theory, on the other hand, assumes no such direct relation and consequently can account for certain linguistic phenomena that phonemic theory cannot. This theory then seems to be preferable to phonemic theory for a featural analysis of misarticulation. However, there is a problem. Chomsky and Halle's system (generative theory) as it stands does not deal with the link between what it conceives to be the lowest level of linguistic structure (the phonetic matrix) and speech production. Therefore, Chomsky and Halle's distinctive features cannot be applied fruitfully to all instances of misarticulation. The discrepancy that exists between phonological structure and the speech signal must be accounted for in a theory of speech production. This can be accomplished by recognizing a production matrix below the phonetic matrix, where segments are described in terms of production features. The crucial point is that no one-to-one relationship necessarily exists between distinctive features and production features.

  10. Nonlinear behavior of the tarka flute's distinctive sounds

    NASA Astrophysics Data System (ADS)

    Gérard, Arnaud; Yapu-Quispe, Luis; Sakuma, Sachiko; Ghezzi, Flavio; Ramírez-Ávila, Gonzalo Marcelo

    2016-09-01

    The Andean tarka flute generates multiphonic sounds. Using spectral techniques, we verify two distinctive musical behaviors and the nonlinear nature of the tarka. Through nonlinear time series analysis, we determine chaotic and hyperchaotic behavior. Experimentally, we observe that by increasing the blow pressure on different fingerings, peculiar changes from linear to nonlinear patterns are produced, leading ultimately to quenching.

  11. Nonlinear behavior of the tarka flute's distinctive sounds.

    PubMed

    Gérard, Arnaud; Yapu-Quispe, Luis; Sakuma, Sachiko; Ghezzi, Flavio; Ramírez-Ávila, Gonzalo Marcelo

    2016-09-01

    The Andean tarka flute generates multiphonic sounds. Using spectral techniques, we verify two distinctive musical behaviors and the nonlinear nature of the tarka. Through nonlinear time series analysis, we determine chaotic and hyperchaotic behavior. Experimentally, we observe that by increasing the blow pressure on different fingerings, peculiar changes from linear to nonlinear patterns are produced, leading ultimately to quenching.

  12. Critical Pedagogy, Rituals of Distinction, and True Professionalism

    ERIC Educational Resources Information Center

    Nodoushan, Mohammad Ali Salmani; Pashapour, Arezou

    2016-01-01

    The current study sought to critically address the practice of rituals of distinction in nation-wide educational milieus to see if such practices can produce generations of underdeveloped and deprived learners. Data were collected over a course of two years from North Korea, Pakistan, Zimbabwe, Venezuela, and Somalia. A total of 419 teachers,…

  13. Magnetic mirror fusion systems: Characteristics and distinctive features

    SciTech Connect

    Post, R.F.

    1987-08-10

    A tutorial account is given of the main characteristics and distinctive features of conceptual magnetic fusion systems employing the magnetic mirror principle. These features are related to the potential advantages that mirror-based fusion systems may exhibit for the generation of economic fusion power.

  14. Distinct responses to reduplicated chromosomes require distinct Mad2 responses.

    PubMed

    Stormo, Benjamin M; Fox, Donald T

    2016-05-09

    Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2's control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention.

  15. Dementia: Continuum or Distinct Entity?

    PubMed Central

    Walters, Glenn D.

    2009-01-01

    The latent structure of dementia was examined in a group of 10,775 older adults with indicators derived from a neuropsychological test battery. Subjecting these data to taxometric analysis using mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode) produced results more consistent with dementia as a dimensional (lying along a continuum) than categorical (representing a distinct entity) construct. A second study conducted on a group of 2375 21-to-64-year olds produced similar results. These findings denote that dementia, as measured by deficits in episodic memory, attention/concentration, executive function, and language, differs quantitatively rather than qualitatively from the cognitive status of non-demented adults. The implications of these results for classification, assessment, etiology, and prevention are discussed. PMID:20677881

  16. Distinct responses to reduplicated chromosomes require distinct Mad2 responses

    PubMed Central

    Stormo, Benjamin M; Fox, Donald T

    2016-01-01

    Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2’s control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention. DOI: http://dx.doi.org/10.7554/eLife.15204.001 PMID:27159240

  17. Identifying distinct thermal components of a creek

    NASA Astrophysics Data System (ADS)

    Boughton, David A.; Hatch, Christine; Mora, Ethan

    2012-09-01

    Statistical and heat budget methods for analyzing temperature dynamics of creeks are limited by the ability to resolve thermal processes and fine-grained thermal structures, respectively. Here we describe a hybrid method that identifies distinct thermal components in a stream's heat budget using only temperature data and an algorithm that employs mutual information to "unmix" signals in the temperature data. Spatial resolution is limited only by the number of temperature-logging sensors, which can be quite high for distributed-temperature sensors. Process resolution is at the level of thermal components, defined as distinct collections of heat flux elements sharing coordinated (nonindependent) dynamics. Inference can be used to relate thermal components to meteorological forcing and structural heterogeneity in the fluvial system and to suggest novel hypotheses for further testing with targeted heat budget studies. Applying the method to a small, arid-land creek produced two novel hypotheses: (1) lateral conduction of heat from adjacent dry land (bed, terraces) appeared to cause a substantial heating of the stream, augmented by off-channel flow paths, and (2) riparian vegetation was associated with a subtraction of heat from the stream at a rate proportionate to solar insolation, exceeding the maximum decoupling effect of shade by at least 2°C at midday, and suggesting upwelling heat flux from water to tree canopy proportional to sunlight. The method appears useful for generating new hypotheses, for selecting informative sites for detailed heat budgets, for determining the dimensionality of heat budgets in natural streams, and more broadly for associating thermal components to fluvial structure and processes.

  18. Anticancer Properties of Distinct Antimalarial Drug Classes

    PubMed Central

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  19. Penoscrotal porokeratosis: A distinct entity

    PubMed Central

    Joshi, Rajiv; Jadhav, Yatin

    2015-01-01

    A 26-year-old man presented with five months history of redness associated with itching and burning over the scrotum and shaft of the penis with a persistent rash on those sites. There had been no response to topical steroid and antifungal creams. Clinical examination revealed a large well-circumscribed erythematous plaque with a thready raised border with a tiny groove at its summit that involved almost two-thirds of the ventral part of the shaft of the penis. Ill-defined erythema with a granular surface was seen over the anterior scrotal skin. A 4 mm punch biopsy of the plaque on the penile shaft revealed multiple cornoid lamellae located adjacent to one another. The patient was treated with topical emollients. Follow up after four months revealed almost complete resolution of the plaque on the penile shaft. Penoscrotal porokeratosis appears to be a distinct entity in the family of porokeratotic diseases, described only in young males in their twenties with involvement of the penile shaft and anterior scrotum with severe burning and itching and histologically associated with multiple cornoid lamellae. It may represent an unusual epidermal porokeratotic reaction pattern and may be a self-resolving condition. PMID:26500866

  20. The distinctiveness heuristic in false recognition and false recall.

    PubMed

    McCabe, David P; Smith, Anderson D

    2006-07-01

    The effects of generative processing on false recognition and recall were examined in four experiments using the Deese-Roediger-McDermott false memory paradigm (Deese, 1959; Roediger & McDermott, 1995). In each experiment, a Generate condition in which subjects generated studied words from audio anagrams was compared to a Control condition in which subjects simply listened to studied words presented normally. Rates of false recognition and false recall were lower for critical lures associated with generated lists, than for critical lures associated with control lists, but only in between-subjects designs. False recall and recognition did not differ when generate and control conditions were manipulated within-subjects. This pattern of results is consistent with the distinctiveness heuristic (Schacter, Israel, & Racine, 1999), a metamemorial decision-based strategy whereby global changes in decision criteria lead to reductions of false memories. This retrieval-based monitoring mechanism appears to operate in a similar fashion in reducing false recognition and false recall.

  1. Cardiolipin: characterization of distinct oxidized molecular species

    PubMed Central

    Kim, Junhwan; Minkler, Paul E.; Salomon, Robert G.; Anderson, Vernon E.; Hoppel, Charles L.

    2011-01-01

    Cardiolipin (CL) is a phospholipid predominantly found in the mitochondrial inner membrane and is associated structurally with individual complexes of the electron transport chain (ETC). Because the ETC is the major mitochondrial reactive oxygen species (ROS)-generating site, the proximity to the ETC and bisallylic methylenes of the PUFA chains of CL make it a likely target of ROS in the mitochondrial inner membrane. Oxidized cellular CL products, uniquely derived from ROS-induced autoxidation, could serve as biomarkers for the presence of the ROS and could help in the understanding of the mechanism of oxidative stress. Because major CL species have four unsaturated acyl chains, whereas other phospholipids usually have only one in the sn-2 position, characterization of oxidized CL is highly challenging. In the current study, we exposed CL, under aerobic conditions, to singlet oxygen (1O2), the radical initiator 2,2′-azobis(2-methylpropionamidine) dihydrochloride, or room air, and the oxidized CL species were characterized by HPLC-tandem mass spectrometry (MS/MS). Our reverse-phase ion-pair HPLC-MS/MS method can characterize the major and minor oxidized CL species by detecting distinctive fragment ions associated with specific oxidized species. The HPLC-MS/MS results show that monohydroperoxides and bis monohydroperoxides were generated under all three conditions. However, significant amounts of CL dihydroperoxides were produced only by 1O2-mediated oxidation. These products were barely detectable from radical oxidation either in a liposome bilayer or in thin film. These observations are only possible due to the chromatographic separation of the different oxidized species. PMID:20858593

  2. Teaching Millennials and Generation Z: Bridging the Generational Divide.

    PubMed

    Shatto, Bobbi; Erwin, Kelly

    2017-02-01

    Most undergraduate students today are part of the millennial generation. However, the next wave of students-Generation Z-are just beginning to enter universities. Although these groups share many similarities, they each have unique characteristics that create challenges in the classroom. Incorporating technology, engaging students with adaptive learning activities, and understanding basic generational differences are ways to limit the effects of generational conflict while keeping both millennials and Generation Z students engaged in learning. It is important to understand basic differences and distinctions across generations for developing pedagogy that reaches these unique student populations.

  3. Distinct requirements for Wntless in habenular development

    PubMed Central

    Akitake, Courtney M.; Fortuno, Lea; Gamse, Joshua; Moens, Cecilia; Halpern, Marnie E.

    2015-01-01

    Secreted Wnt proteins play pivotal roles in development, including regulation of cell proliferation, differentiation, progenitor maintenance and tissue patterning. The transmembrane protein Wntless (Wls) is necessary for secretion of most Wnts and essential for effective Wnt signaling. During a mutagenesis screen to identify genes important for development of the habenular nuclei in the dorsal forebrain, we isolated a mutation in the sole wls gene of zebrafish and confirmed its identity with a second, independent allele. Early embryonic development appears normal in homozygous wls mutants, but they later lack the ventral habenular nuclei, form smaller dorsal habenulae and otic vesicles, have truncated jaw and fin cartilages and lack swim bladders. Activation of a reporter for β-catenin-dependent transcription is decreased in wls mutants, indicative of impaired signaling by the canonical Wnt pathway, and expression of Wnt-responsive genes is reduced in the dorsal diencephalon. Wnt signaling was previously implicated in patterning of the zebrafish brain and in the generation of left–right (L–R) differences between the bilaterally paired dorsal habenular nuclei. Outside of the epithalamic region, development of the brain is largely normal in wls mutants and, despite their reduced size, the dorsal habenulae retain L–R asymmetry. We find that homozygous wls mutants show a reduction in two cell populations that contribute to the presumptive dorsal habenulae. The results support distinct temporal requirements for Wls in habenular development and reveal a new role for Wnt signaling in the regulation of dorsal habenular progenitors. PMID:26116173

  4. Distinct requirements for Wntless in habenular development.

    PubMed

    Kuan, Yung-Shu; Roberson, Sara; Akitake, Courtney M; Fortuno, Lea; Gamse, Joshua; Moens, Cecilia; Halpern, Marnie E

    2015-10-15

    Secreted Wnt proteins play pivotal roles in development, including regulation of cell proliferation, differentiation, progenitor maintenance and tissue patterning. The transmembrane protein Wntless (Wls) is necessary for secretion of most Wnts and essential for effective Wnt signaling. During a mutagenesis screen to identify genes important for development of the habenular nuclei in the dorsal forebrain, we isolated a mutation in the sole wls gene of zebrafish and confirmed its identity with a second, independent allele. Early embryonic development appears normal in homozygous wls mutants, but they later lack the ventral habenular nuclei, form smaller dorsal habenulae and otic vesicles, have truncated jaw and fin cartilages and lack swim bladders. Activation of a reporter for β-catenin-dependent transcription is decreased in wls mutants, indicative of impaired signaling by the canonical Wnt pathway, and expression of Wnt-responsive genes is reduced in the dorsal diencephalon. Wnt signaling was previously implicated in patterning of the zebrafish brain and in the generation of left-right (L-R) differences between the bilaterally paired dorsal habenular nuclei. Outside of the epithalamic region, development of the brain is largely normal in wls mutants and, despite their reduced size, the dorsal habenulae retain L-R asymmetry. We find that homozygous wls mutants show a reduction in two cell populations that contribute to the presumptive dorsal habenulae. The results support distinct temporal requirements for Wls in habenular development and reveal a new role for Wnt signaling in the regulation of dorsal habenular progenitors.

  5. Pit- and trench-forming osteoclasts: a distinction that matters.

    PubMed

    Merrild, Ditte Mh; Pirapaharan, Dinisha C; Andreasen, Christina M; Kjærsgaard-Andersen, Per; Møller, Anaïs Mj; Ding, Ming; Delaissé, Jean-Marie; Søe, Kent

    2015-01-01

    Osteoclasts (OCs) seeded on bone slices either drill round pits or dig long trenches. Whereas pits correspond to intermittent resorption, trenches correspond to continuous and faster resorption and require a distinct assembly of the resorption apparatus. It is unknown whether the distinction between pits and trenches has any biological relevance. Using OCs prepared from different blood donors, we found that female OCs achieved increased resorption mainly through pit formation, whereas male OCs did so through trench formation. Trench formation went along with high collagenolytic activity and high cathepsin K (CatK) expression, thereby allowing deeper demineralization. A specific CatK inhibitor abrogated the generation of trenches, while still allowing the generation of pits. OCs obtained from bone marrow were more prone to generate trenches than those obtained from blood. Scanning electron microscopy of bone surfaces eroded in vivo showed trenches and pits of similar size as those made by OCs in culture. We conclude that the distinction between trench- and pit-forming OCs is relevant to the differences among OCs from different skeletal sites, different individuals, including gender, and results from differences in collagenolytic power. This indicates a biological relevance and highlights the importance of discriminating between pits and trenches when assessing resorption.

  6. Pit- and trench-forming osteoclasts: a distinction that matters

    PubMed Central

    Merrild, Ditte MH; Pirapaharan, Dinisha C; Andreasen, Christina M; Kjærsgaard-Andersen, Per; Møller, Anaïs MJ; Ding, Ming; Delaissé, Jean-Marie; Søe, Kent

    2015-01-01

    Osteoclasts (OCs) seeded on bone slices either drill round pits or dig long trenches. Whereas pits correspond to intermittent resorption, trenches correspond to continuous and faster resorption and require a distinct assembly of the resorption apparatus. It is unknown whether the distinction between pits and trenches has any biological relevance. Using OCs prepared from different blood donors, we found that female OCs achieved increased resorption mainly through pit formation, whereas male OCs did so through trench formation. Trench formation went along with high collagenolytic activity and high cathepsin K (CatK) expression, thereby allowing deeper demineralization. A specific CatK inhibitor abrogated the generation of trenches, while still allowing the generation of pits. OCs obtained from bone marrow were more prone to generate trenches than those obtained from blood. Scanning electron microscopy of bone surfaces eroded in vivo showed trenches and pits of similar size as those made by OCs in culture. We conclude that the distinction between trench- and pit-forming OCs is relevant to the differences among OCs from different skeletal sites, different individuals, including gender, and results from differences in collagenolytic power. This indicates a biological relevance and highlights the importance of discriminating between pits and trenches when assessing resorption. PMID:26664853

  7. Computer-Generated Feedback on Student Writing

    ERIC Educational Resources Information Center

    Ware, Paige

    2011-01-01

    A distinction must be made between "computer-generated scoring" and "computer-generated feedback". Computer-generated scoring refers to the provision of automated scores derived from mathematical models built on organizational, syntactic, and mechanical aspects of writing. In contrast, computer-generated feedback, the focus of this article, refers…

  8. Computer-Generated Feedback on Student Writing

    ERIC Educational Resources Information Center

    Ware, Paige

    2011-01-01

    A distinction must be made between "computer-generated scoring" and "computer-generated feedback". Computer-generated scoring refers to the provision of automated scores derived from mathematical models built on organizational, syntactic, and mechanical aspects of writing. In contrast, computer-generated feedback, the focus of this article, refers…

  9. Teenage Drinking, Symbolic Capital and Distinction

    ERIC Educational Resources Information Center

    Jarvinen, Margaretha; Gundelach, Peter

    2007-01-01

    This article analyses alcohol-related lifestyles among Danish teenagers. Building on Bourdieu's reasoning on symbolic capital and distinction, we analyse three interrelated themes. First, we show that alcohol-related variables (drinking patterns, drinking debut, experience of intoxication, etc.) can be used to identify some very distinctive life…

  10. Evidence for a Distinct Kind of Noun.

    ERIC Educational Resources Information Center

    Soja, Nancy N.

    1994-01-01

    Examined the spontaneous speech of four children and their parents for use of determiners with NP-type nouns and count nouns. Found that the parents made a clear distinction between the two kinds of nouns, omitting determiners with the NP-type nouns but not with the count nouns. The children all made the same distinction by four years of age. (HTH)

  11. Triton College: One Institution's Search for Distinctiveness.

    ERIC Educational Resources Information Center

    Townsend, Barbara K.; Catanzaro, James L.

    1989-01-01

    Recounts Triton College's efforts to identify its distinctive elements. Reviews empirical evidence showing that Triton's school schedule, curricular offerings, and continuing education and support services are distinctive among local colleges. Discusses students' and staff members' perceptions of Triton. Considers the value of the research to the…

  12. 14 CFR 1252.411 - Age distinctions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Age distinctions. 1252.411 Section 1252.411 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF AGE IN... Procedures § 1252.411 Age distinctions. There are no Federal statutes or regulations containing...

  13. 14 CFR 1252.411 - Age distinctions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Age distinctions. 1252.411 Section 1252.411 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF AGE IN... Procedures § 1252.411 Age distinctions. There are no Federal statutes or regulations containing...

  14. 14 CFR 1252.411 - Age distinctions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Age distinctions. 1252.411 Section 1252.411 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF AGE IN... Procedures § 1252.411 Age distinctions. There are no Federal statutes or regulations containing...

  15. 14 CFR 1252.411 - Age distinctions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Age distinctions. 1252.411 Section 1252.411 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF AGE IN... Procedures § 1252.411 Age distinctions. There are no Federal statutes or regulations containing...

  16. Killing and letting die: a defensible distinction.

    PubMed

    Cartwright, W

    1996-04-01

    The distinction between killing and letting die is investigated and clarified. It is then argued that in most cases, though not in all, it is worse to kill than to let die. In euthanasia the significance of the distinction is diminished, but still important.

  17. Molecular basis for DPY-30 association to COMPASS-like and NURF complexes.

    PubMed

    Tremblay, Véronique; Zhang, Pamela; Chaturvedi, Chandra-Prakash; Thornton, Janet; Brunzelle, Joseph S; Skiniotis, Georgios; Shilatifard, Ali; Brand, Marjorie; Couture, Jean-François

    2014-12-02

    DPY-30 is a subunit of mammalian COMPASS-like complexes (complex of proteins associated with Set1) and regulates global histone H3 Lys-4 trimethylation. Here we report structural evidence showing that the incorporation of DPY-30 into COMPASS-like complexes is mediated by several hydrophobic interactions between an amphipathic α helix located on the C terminus of COMPASS subunit ASH2L and the inner surface of the DPY-30 dimerization/docking (D/D) module. Mutations impairing the interaction between ASH2L and DPY-30 result in a loss of histone H3K4me3 at the β locus control region and cause a delay in erythroid cell terminal differentiation. Using overlay assays, we defined a consensus sequence for DPY-30 binding proteins and found that DPY-30 interacts with BAP18, a subunit of the nucleosome remodeling factor complex. Overall, our results indicate that the ASH2L/DPY-30 complex is important for cell differentiation and provide insights into the ability of DPY-30 to associate with functionally divergent multisubunit complexes.

  18. Generational diversity.

    PubMed

    Kramer, Linda W

    2010-01-01

    Generational diversity has proven challenges for nurse leaders, and generational values may influence ideas about work and career planning. This article discusses generational gaps, influencing factors and support, and the various generational groups present in today's workplace as well as the consequences of need addressing these issues. The article ends with a discussion of possible solutions.

  19. Visual distinctiveness can enhance recency effects.

    PubMed

    Bornstein, B H; Neely, C B; LeCompte, D C

    1995-05-01

    Experimental efforts to meliorate the modality effect have included attempts to make the visual stimulus more distinctive. McDowd and Madigan (1991) failed to find an enhanced recency effect in serial recall when the last item was made more distinct in terms of its color. In an attempt to extend this finding, three experiments were conducted in which visual distinctiveness was manipulated in a different manner, by combining the dimensions of physical size and coloration (i.e., whether the stimuli were solid or outlined in relief). Contrary to previous findings, recency was enhanced when the size and coloration of the last item differed from the other items in the list, regardless of whether the "distinctive" item was larger or smaller than the remaining items. The findings are considered in light of other research that has failed to obtain a similar enhanced recency effect, and their implications for current theories of the modality effect are discussed.

  20. Validity of Sensory Systems as Distinct Constructs

    PubMed Central

    Su, Chia-Ting

    2014-01-01

    This study investigated the validity of sensory systems as distinct measurable constructs as part of a larger project examining Ayres’s theory of sensory integration. Confirmatory factor analysis (CFA) was conducted to test whether sensory questionnaire items represent distinct sensory system constructs. Data were obtained from clinical records of two age groups, 2- to 5-yr-olds (n = 231) and 6- to 10-yr-olds (n = 223). With each group, we tested several CFA models for goodness of fit with the data. The accepted model was identical for each group and indicated that tactile, vestibular–proprioceptive, visual, and auditory systems form distinct, valid factors that are not age dependent. In contrast, alternative models that grouped items according to sensory processing problems (e.g., over- or underresponsiveness within or across sensory systems) did not yield valid factors. Results indicate that distinct sensory system constructs can be measured validly using questionnaire data. PMID:25184467

  1. Strategy, Distinctive Competence, and Organizational Performance.

    ERIC Educational Resources Information Center

    Snow, Charles C.; Hrebiniak, Lawrence G.

    1980-01-01

    Focuses on the perceptions of top managers in four industries (plastics, semiconductors, automotives, and air transportation) who examined relationships among strategy, distinctive competence, and organizational performance. (Author/IRT)

  2. Visual Support System for Report Distinctiveness Evaluation

    NASA Astrophysics Data System (ADS)

    Sunayama, Wataru; Kawaguchi, Toshiaki

    In recent years, as the Internet has grown, electronic reports have come to be used in educational organizations such as universities. Though reports written by hand must be evaluated by hand except for stereotype descriptions or numerical answers, electronic reports can be rated by computer. There are two major criteria in rating reports, correctness and distinctiveness. Correctness is rated by absolute criteria and distinctiveness is rated by relative criteria. Relative evaluation is difficult because raters should memorize all contents of submitted reports to provide objective rates. In addition, electronic data are easily copied or exchanged by students. This paper presents a report evaluation support system with which raters can compare each report and give objective rates for distinctiveness. This system evaluates each report by objective similarity criteria and visualizes them in a two-dimensional interface as the calculated distinctiveness order. Experimental results show the system is valid and effective for estimating associations between reports.

  3. Neuroimaging distinction between neurological and psychiatric disorders†

    PubMed Central

    Crossley, Nicolas A.; Scott, Jessica; Ellison-Wright, Ian; Mechelli, Andrea

    2015-01-01

    Background It is unclear to what extent the traditional distinction between neurological and psychiatric disorders reflects biological differences. Aims To examine neuroimaging evidence for the distinction between neurological and psychiatric disorders. Method We performed an activation likelihood estimation meta-analysis on voxel-based morphometry studies reporting decreased grey matter in 14 neurological and 10 psychiatric disorders, and compared the regional and network-level alterations for these two classes of disease. In addition, we estimated neuroanatomical heterogeneity within and between the two classes. Results Basal ganglia, insula, sensorimotor and temporal cortex showed greater impairment in neurological disorders; whereas cingulate, medial frontal, superior frontal and occipital cortex showed greater impairment in psychiatric disorders. The two classes of disorders affected distinct functional networks. Similarity within classes was higher than between classes; furthermore, similarity within class was higher for neurological than psychiatric disorders. Conclusions From a neuroimaging perspective, neurological and psychiatric disorders represent two distinct classes of disorders. PMID:26045351

  4. Hemispheric lateralization of semantic feature distinctiveness.

    PubMed

    Reilly, M; Machado, N; Blumstein, S E

    2015-08-01

    Recent models of semantic memory propose that the semantic representation of concepts is based, in part, on a network of features. In this view, a feature that is distinctive for an object (a zebra has stripes) is processed differently from a feature that is shared across many objects (a zebra has four legs). The goal of this paper is to determine whether there are hemispheric differences in such processing. In a feature verification task, participants responded 'yes' or 'no' following concepts which were presented to a single visual field (left or right) paired with a shared or distinctive feature. Both hemispheres showed faster reaction times to shared features than to distinctive features, although right hemisphere responses were significantly slower overall and particularly in the processing of distinctive features. These findings support models of semantic processing in which the dominant left hemisphere more efficiently performs highly discriminating 'fine' encoding, in contrast to the right hemisphere which performs less discriminating 'coarse' encoding.

  5. Strategy, Distinctive Competence, and Organizational Performance.

    ERIC Educational Resources Information Center

    Snow, Charles C.; Hrebiniak, Lawrence G.

    1980-01-01

    Focuses on the perceptions of top managers in four industries (plastics, semiconductors, automotives, and air transportation) who examined relationships among strategy, distinctive competence, and organizational performance. (Author/IRT)

  6. Chaplain Ministry to the Millennial Generation

    DTIC Science & Technology

    2006-01-09

    results in a younger generation replacing it. As a result, basic attitudes and behaviors change with differing generations. These shifts in...based upon perceived generational beliefs and attitudes . Additionally, American businesses and college campuses repeatedly base their marketing and...that, it is necessary to explore this group’s distinctive characteristics, attitudes and beliefs. Demography Annual birth rates in the United States

  7. Distinct photoresponse in graphene induced by laser irradiation

    SciTech Connect

    Wang, Wen Hui; Nan, Hai Yan; Liu, Qi; Ni, Zhen Hua; Liang, Zheng; Yu, Zhi Hao; Liu, Feng Yuan; Wang, Xin Ran; Hu, Wei Da; Zhang, Wei

    2015-01-12

    The graphene-based photodetector with tunable p-p{sup +}-p junctions was fabricated through a simple laser irradiation process. Distinct photoresponse was observed at the graphene (G)-laser irradiated graphene (LIG) junction by scanning photocurrent measurements, and its magnitude can be modulated as a result of a positive correlation between the photocurrent and doping concentration in LIG region. Detailed investigation suggests that the photo-thermoelectric effect, instead of the photovoltaic effect, dominates the photocurrent generation at the G-LIG junctions. Such a simple and low-cost technique offers an alternative way for the fabrication of graphene-based optoelectronic devices.

  8. Distinct photoresponse in graphene induced by laser irradiation

    NASA Astrophysics Data System (ADS)

    Wang, Wen Hui; Nan, Hai Yan; Liu, Qi; Liang, Zheng; Yu, Zhi Hao; Liu, Feng Yuan; Hu, Wei Da; Zhang, Wei; Wang, Xin Ran; Ni, Zhen Hua

    2015-01-01

    The graphene-based photodetector with tunable p-p+-p junctions was fabricated through a simple laser irradiation process. Distinct photoresponse was observed at the graphene (G)-laser irradiated graphene (LIG) junction by scanning photocurrent measurements, and its magnitude can be modulated as a result of a positive correlation between the photocurrent and doping concentration in LIG region. Detailed investigation suggests that the photo-thermoelectric effect, instead of the photovoltaic effect, dominates the photocurrent generation at the G-LIG junctions. Such a simple and low-cost technique offers an alternative way for the fabrication of graphene-based optoelectronic devices.

  9. Distinctions between transgenerational and non-transgenerational epimutations.

    PubMed

    McCarrey, John R

    2014-12-01

    Recent studies have described numerous environmentally-induced disruptions of the epigenome (epimutations) in mammals. While some of these appear to be corrected by normal germline-specific epigenetic reprogramming and are therefore not transmitted transgenerationally, others are not corrected and are transmitted over multiple subsequent generations. The mechanism(s) that distinguish transgenerational and non-transgenerational epimutations have not been delineated. This review examines several potential molecular and developmental distinctions between transgenerational and non-transgenerational epimutations in the context of the likelihood that any of these may or may not contribute to transgenerational inheritance of epimutations.

  10. Cluster modified projective synchronization between networks with distinct topologies

    NASA Astrophysics Data System (ADS)

    Vahedi, Shahed; Noorani, Mohd Salmi Md

    2016-02-01

    Cluster modified projective synchronization (CMPS) between two topologically distinct community networks is studied in this paper. Each cluster here has a unique dynamics at least with respect to the parameter sets. Using an adaptive feedback control gain and a matrix scaling factor, we show that CMPS between two community networks can be realized with considering minimum assumptions and imposing just few restrictions on the configuration set. We use Lyapunov stability theory for the proof and employ computer simulation to confirm our result on randomly generated community networks. Simulations also show the possibility of having hybrid synchronization between the two networks.

  11. Instant Generation

    ERIC Educational Resources Information Center

    Loveland, Elaina

    2017-01-01

    Generation Z students (born between 1995-2010) have replaced millennials on college campuses. Generation Z students are entrepreneurial, desire practical skills with their education, and are concerned about the cost of college. This article presents what need to be known about this new generation of students.

  12. Pesticide Registration: Clarification for Ion Generating Equipment

    EPA Pesticide Factsheets

    EPA issued a Federal Register Notice that clarifies the Agency's position on the distinction between devices and pesticides with regard to ion-generating equipment and explains why such equipment will now be regulated as a pesticide.

  13. Wind Generators

    NASA Technical Reports Server (NTRS)

    1989-01-01

    When Enerpro, Inc. president, Frank J. Bourbeau, attempted to file a patent on a system for synchronizing a wind generator to the electric utility grid, he discovered Marshall Space Flight Center's Frank Nola's power factor controller. Bourbeau advanced the technology and received a NASA license and a patent for his Auto Synchronous Controller (ASC). The ASC reduces generator "inrush current," which occurs when large generators are abruptly brought on line. It controls voltage so the generator is smoothly connected to the utility grid when it reaches its synchronous speed, protecting the components from inrush current damage. Generator efficiency is also increased in light winds by applying lower than rated voltage. Wind energy is utilized to drive turbines to generate electricity for utility companies.

  14. Differential effects of distinct bacterial biofilms in a cave environment.

    PubMed

    Portillo, Maria C; Gonzalez, Juan M

    2010-06-01

    Current microbial surveys using molecular methods provide us with critical information on the major components of natural bacterial communities. However, limited investigation has been performed on the influence of bacterial metabolism on the environment. In this study, we analyzed the pH generated by distinct bacterial communities in a cave environment. Different bacterial biofilms developing on the walls of the cave were visually distinguished by their colorations (e.g., white, yellow, and gray) and mineral depositions, and previous studies have reported on their bacterial diversity and distribution. Using pH microelectrodes, we carried out in situ measurements and were able to detect differences among these bacterial biofilms. White biofilms and carbonate depositions resulted in alkaline pH values. Gray biofilms also increased the pH although these values remained lower than in white biofilms. A combination of gray-white biofilms resulted in alkaline pH values with highest values at the white edge of the colonies. Yellow biofilms generated a slightly acid pH. These results suggest that different bacterial communities can lead to distinct effects on their environment, for instance, precipitation or dissolution of carbonates in caves. These results add information about metabolic response to current knowledge from bacterial diversity surveys, providing information on the interaction between complex bacterial communities and the geological substrate.

  15. Chemical transformations that yield compounds with distinct activity profiles.

    PubMed

    Hu, Ye; Bajorath, Jürgen

    2011-07-14

    We have systematically searched for chemical changes that generate compounds with distinct biological activity profiles. For this purpose, activity profiles were generated for ∼42000 compounds active against human targets. Unique activity profiles involving multiple target proteins were determined, and all possible matched molecular pairs (MMPs) were identified for compounds representing these profiles. An MMP is defined as a pair of compounds that are distinguished from each other only at a single site such as an R group or ring system. For example, in an MMP, a hydroxyl group might be replaced by a halogen atom or a benzene ring by an amide group. From ∼37500 MMPs, more than 300 nonredundant chemical transformations were isolated that yielded compounds with distinct activity profiles. None of these transformations was found in pairs of compounds with overlapping activity profiles. These transformations were ranked according to the number of MMPs, the number of activity profiles, and the total number of targets that they covered. In many instances, prioritized transformations involved ring systems of varying complexity. All transformations that were found to switch activity profiles are provided to enable further analysis and aid in compound design efforts.

  16. Rainfall generation

    NASA Astrophysics Data System (ADS)

    Sharma, Ashish; Mehrotra, Raj

    This chapter presents an overview of methods for stochastic generation of rainfall at annual to subdaily time scales, at single- to multiple-point locations, and in a changing climatic regime. Stochastic rainfall generators are used to provide inputs for risk assessment of natural or engineering systems that can undergo failure under sustained (high or low) extremes. As a result, generation of rainfall has evolved to provide options that adequately represent such conditions, leading to sequences that exhibit low-frequency variability of a nature similar to the observed rainfall. The chapter consists of three key sections: the first two outlining approaches for rainfall generation using endogenous predictor variables and the third highlighting approaches for generation using exogenous predictors often simulated to represent future climatic conditions. The first section presents approaches for generation of annual and seasonal rainfall and daily rainfall, both at single-point locations and multiple sites, with an emphasis on alternatives that ensure appropriate representation of low-frequency variability in the generated rainfall sequences. The second section highlights advancements in the subdaily rainfall generation procedures including commonly used approaches for daily to subdaily rainfall generation. The final section (generation using exogenous predictors) presents a range of alternatives for stochastic downscaling of rainfall for climate change impact assessments of natural and engineering systems. We conclude the chapter by outlining some of the key challenges that remain to be addressed, especially in generation under climate change conditions, with an emphasis on the importance of incorporating uncertainty present in both measurements and models, in the rainfall sequences that are generated.

  17. Generation X

    DTIC Science & Technology

    2007-11-02

    service or government agency. STRATEGY RESEARCH PROJECT GENERATION X BY LIEUTENANT COLONEL NEIL YAMASHIRO United States Army National Guard CVI...WAR COLLEGE, CARLISLE BARRACKS, PA 17013-5050 ■"""" mimmm n USAWC STRATEGY RESEARCH PROJECT Generation X by LTC Neil Yamashiro COL Paul...is unlimited. 11 ABSTRACT AUTHOR: LTC Neil Yamashiro TITLE: Generation X FORMAT: Strategy Research Project DATE: 7 April 1998 PAGES: 26

  18. Knowledge Affords Distinctive Processing in Memory

    ERIC Educational Resources Information Center

    Hunt, R. Reed; Rawson, Katherine A.

    2011-01-01

    The effect of knowledge on memory generally is processing. However, both conceptual and empirical reasons exist to suspect that the organizational account is incomplete. Recently a revised version of that account has been proposed under the rubric of distinctiveness theory (Rawson & Van Overschelde, 2008). The goal of the experiments reported…

  19. Distinctiveness of Saudi Arabian EFL Learners

    ERIC Educational Resources Information Center

    Habbash, Manssour; Idapalapati, Srinivasa Rao

    2016-01-01

    In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs…

  20. Issues in Conducting Linkages between Distinct Tests

    ERIC Educational Resources Information Center

    Pommerich, Mary; Hanson, Bradley A.; Harris, Deborah J.; Sconing, James A.

    2004-01-01

    Educational measurement practitioners are often asked to link scores on tests that are built to different content specifications. The goal in linking distinct tests is often similar to that for equating scores across different forms of the same test: to provide a set of comparable scores across the two measures. Traditional equating methods can be…

  1. The Cosmology Distinction Course for Gifted Students.

    ERIC Educational Resources Information Center

    Hollow, Robert

    1995-01-01

    Describes the Cosmology Distinction Course for gifted students completing their Higher School Certificate, which seeks to provide a challenging and stimulating broadly based one-year course that goes beyond the normal confines of traditional matriculation subjects. Presents a course outline, details on assessment, and reflections upon the first…

  2. Indopithecus giganteus distinct from Sivapithecus indicus

    USGS Publications Warehouse

    Madden, C.T.; Lewis, G.E.

    1980-01-01

    The very large Eurasian Miocene ape Indopithecus giganteus is distinct from contemporanious Sivapithecus (non-Dryopithecus)indicus. The probabilities that length and width for the only specimen of I. giganteus could be sampled from populations similar or identical to those of S. indicus are less than six chances in 100,000 for both parameters. ?? 1980 Japan Monkey Centre.

  3. The Distinctive Difficulties of Disagreeable Youth

    ERIC Educational Resources Information Center

    Laursen, Brett; Hafen, Christopher A.; Rubin, Kenneth H.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda

    2010-01-01

    This study examines whether disagreeable youth are distinct from aggressive youth, victimized youth, and withdrawn youth. Young adolescents (120 girls and 104 boys, M = 13.59 years old) completed personality and adjustment inventories. Aggression, withdrawal, and victimization scores were derived from peer nominations (N = 807). Cluster analyses…

  4. Hemispheric lateralization of semantic feature distinctiveness

    PubMed Central

    Reilly, M.; Machado, N.; Blumstein, S. E.

    2015-01-01

    Recent models of semantic memory propose that the semantic representation of concepts is based, in part, on a network of features. In this view, a feature that is distinctive for an object (a zebra has stripes) is processed differently from a feature that is shared across many objects (a zebra has four legs). The goal of this paper is to determine whether there are hemispheric differences in such processing. In a feature verification task, participants responded ‘yes’ or ‘no’ following concepts which were presented to a single visual field (left or right) paired with a shared or distinctive feature. Both hemispheres showed faster reaction times to shared features than to distinctive features, although right hemisphere responses were significantly slower overall and particularly in the processing of distinctive features. These findings support models of semantic processing in which the dominant left hemisphere more efficiently performs highly discriminating ‘fine’ encoding, in contrast to the right hemisphere which performs less discriminating ‘coarse’ encoding. PMID:26022059

  5. Toward a Distinctive Christian Undergraduate Management Program

    ERIC Educational Resources Information Center

    Smith, Thomas M.; VanderVeen, Steve

    2008-01-01

    We motivate and develop a theoretical framework for creating a distinctive Christian undergraduate management program that is directed toward providing (a) the necessary intellectual characteristics to do "well" and (b) the necessary emotional characteristics to do "good." This framework consists of seven propositions that connect the learning…

  6. Vestibular thalamus: Two distinct graviceptive pathways.

    PubMed

    Baier, Bernhard; Conrad, Julian; Stephan, Thomas; Kirsch, Valerie; Vogt, Thomas; Wilting, Janine; Müller-Forell, Wibke; Dieterich, Marianne

    2016-01-12

    To determine whether there are distinct thalamic regions statistically associated with either contraversive or ipsiversive disturbance of verticality perception measured by subjective visual vertical (SVV). We used modern statistical lesion behavior mapping on a sample of 37 stroke patients with isolated thalamic lesions to clarify which thalamic regions are involved in graviceptive otolith processing and whether there are distinct regions associated with contraversive or ipsiversive SVV deviation. We found 2 distinct systems of graviceptive processing within the thalamus. Contraversive tilt of SVV was associated with lesions to the nuclei dorsomedialis, intralamellaris, centrales thalami, posterior thalami, ventrooralis internus, ventrointermedii, ventrocaudales and superior parts of the nuclei parafascicularis thalami. The regions associated with ipsiversive tilt of SVV were located in more inferior regions, involving structures such as the nuclei endymalis thalami, inferior parts of the nuclei parafascicularis thalami, and also small parts of the junction zone of the nuclei ruber tegmenti and brachium conjunctivum. Our data indicate that there are 2 anatomically distinct graviceptive signal processing mechanisms within the vestibular network in humans that lead, when damaged, to a vestibular tone imbalance either to the contraversive or to the ipsiversive side. © 2015 American Academy of Neurology.

  7. Issues in Conducting Linkages between Distinct Tests

    ERIC Educational Resources Information Center

    Pommerich, Mary; Hanson, Bradley A.; Harris, Deborah J.; Sconing, James A.

    2004-01-01

    Educational measurement practitioners are often asked to link scores on tests that are built to different content specifications. The goal in linking distinct tests is often similar to that for equating scores across different forms of the same test: to provide a set of comparable scores across the two measures. Traditional equating methods can be…

  8. The Cosmology Distinction Course for gifted students

    NASA Astrophysics Data System (ADS)

    Hollow, R.

    1995-05-01

    The Cosmology Distinction Course is an innovative subject introduced in 1994 for gifted students completing their Higher School Certificate (HSC) in New South Wales, Australia. It seeks to provide a challenging and stimulating, broadly based one year course that goes beyond the normal confines of traditional matriculation subjects. Provided free of charge it is taught via distance learning mode and includes a residential component.

  9. The Distinctive Difficulties of Disagreeable Youth

    ERIC Educational Resources Information Center

    Laursen, Brett; Hafen, Christopher A.; Rubin, Kenneth H.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda

    2010-01-01

    This study examines whether disagreeable youth are distinct from aggressive youth, victimized youth, and withdrawn youth. Young adolescents (120 girls and 104 boys, M = 13.59 years old) completed personality and adjustment inventories. Aggression, withdrawal, and victimization scores were derived from peer nominations (N = 807). Cluster analyses…

  10. Collegiate Educators: From Novice to Distinction

    ERIC Educational Resources Information Center

    Wise, Kimberly Ashton

    2013-01-01

    The purpose of this phenomenological study was to explore reflective practices of lived experiences of collegiate educators as they progressed from novice to distinction. Specifically, this study investigated how a phenomenon connects to consciousness from lived experiences of teachers who proceeded from novice to a distinguished collegiate…

  11. Teacher Preparation for Distinctive Evangelical Schools

    ERIC Educational Resources Information Center

    Stoner, Thomas Stephen

    2012-01-01

    In the current atmosphere of expanding school choice, evangelical Christian schools provide a distinctive alternative consistent with deeply held beliefs of what is required for human flourishing, and represent a significant resource for parents seeking education based on a perspective diverging from those promoted by popular culture and public…

  12. Generative Semantics

    ERIC Educational Resources Information Center

    Bagha, Karim Nazari

    2011-01-01

    Generative semantics is (or perhaps was) a research program within linguistics, initiated by the work of George Lakoff, John R. Ross, Paul Postal and later McCawley. The approach developed out of transformational generative grammar in the mid 1960s, but stood largely in opposition to work by Noam Chomsky and his students. The nature and genesis of…

  13. Generative Semantics.

    ERIC Educational Resources Information Center

    King, Margaret

    The first section of this paper deals with the attempts within the framework of transformational grammar to make semantics a systematic part of linguistic description, and outlines the characteristics of the generative semantics position. The second section takes a critical look at generative semantics in its later manifestations, and makes a case…

  14. Radionuclide Generators

    NASA Astrophysics Data System (ADS)

    Rösch, F.; Knapp, F. F. (Russ)

    Radionuclide generator systems continue to play a key role in providing both diagnostic and therapeutic radionuclides for various applications in nuclear medicine, oncology, and interventional cardiology. Although many parent/daughter pairs have been evaluated as radionuclide generator systems, there are a relatively small number of generators, which are currently in routine clinical and research use. Essentially every conceivable approach has been used for parent/separation strategies, including sublimation, thermochromatographic separation, solvent extraction, and adsorptive column chromatography. The most widely used radionuclide generator for clinical applications is the 99Mo/99mTc generator system, but recent years have seen an enormous increase in the use of generators to provide therapeutic radionuclides, which has paralleled the development of complementary technologies for targeting agents for therapy and in the general increased interest in the use of unsealed therapeutic radioactive sources. More recently, use of the 68Ge/68Ga generator is showing great potential as a source of positron-emitting 68Ga for positron emission tomography (PET)/CT imaging. Key advantages for the use of radionuclide generators include reasonable costs, the convenience of obtaining the desired daughter radionuclide on demand, and availability of the daughter radionuclide in high specific activity, no-carrier added form.

  15. Energy generator

    SciTech Connect

    Krisko, P.

    1989-08-01

    The patent describes a power booster. It comprises: at least one pendulum means suspended at one end to oscillate about the point of suspension; power generating means; mass means connected to one end of the pendulum means; spring means disposed in operative cooperation with the mass means to impart energy into the pendulum means and assist the pendulum means in oscillating about the point of suspension; and energy transfer linkage means between the pendulum means and the power generating means for transferring energy between the pendulum means and the power generating means.

  16. Different Functions of Phylogenetically Distinct Bacterial Complex I Isozymes

    PubMed Central

    Spero, Melanie A.; Brickner, Joshua R.; Mollet, Jordan T.; Pisithkul, Tippapha; Amador-Noguez, Daniel

    2016-01-01

    ABSTRACT NADH:quinone oxidoreductase (complex I) is a bioenergetic enzyme that transfers electrons from NADH to quinone, conserving the energy of this reaction by contributing to the proton motive force. While the importance of NADH oxidation to mitochondrial aerobic respiration is well documented, the contribution of complex I to bacterial electron transport chains has been tested in only a few species. Here, we analyze the function of two phylogenetically distinct complex I isozymes in Rhodobacter sphaeroides, an alphaproteobacterium that contains well-characterized electron transport chains. We found that R. sphaeroides complex I activity is important for aerobic respiration and required for anaerobic dimethyl sulfoxide (DMSO) respiration (in the absence of light), photoautotrophic growth, and photoheterotrophic growth (in the absence of an external electron acceptor). Our data also provide insight into the functions of the phylogenetically distinct R. sphaeroides complex I enzymes (complex IA and complex IE) in maintaining a cellular redox state during photoheterotrophic growth. We propose that the function of each isozyme during photoheterotrophic growth is either NADH synthesis (complex IA) or NADH oxidation (complex IE). The canonical alphaproteobacterial complex I isozyme (complex IA) was also shown to be important for routing electrons to nitrogenase-mediated H2 production, while the horizontally acquired enzyme (complex IE) was dispensable in this process. Unlike the singular role of complex I in mitochondria, we predict that the phylogenetically distinct complex I enzymes found across bacterial species have evolved to enhance the functions of their respective electron transport chains. IMPORTANCE Cells use a proton motive force (PMF), NADH, and ATP to support numerous processes. In mitochondria, complex I uses NADH oxidation to generate a PMF, which can drive ATP synthesis. This study analyzed the function of complex I in bacteria, which contain more

  17. Detection of antigenically distinct rotaviruses from infants.

    PubMed Central

    Dimitrov, D H; Estes, M K; Rangelova, S M; Shindarov, L M; Melnick, J L; Graham, D Y

    1983-01-01

    Antigenically distinct rotaviruses, i.e., viruses morphologically identical to conventional rotaviruses by electron microscopy, yet lacking the common group antigen(s) detected by an enzyme-linked immunosorbent assay, were found in 2 of 51 fecal samples from Bulgarian infants with rotavirus gastroenteritis. These antigenically distinct viruses contained 11 segments of double-stranded RNA, but they demonstrated a unique RNA migration profile after electrophoresis of the genome RNA in polyacrylamide gels. This report confirms the presence of a new group of rotaviruses in humans. The significance of these viruses is currently unknown, and specific diagnostic tests must be developed for epidemiological studies to determine their role as human and veterinary pathogens and to evaluate their impact on proposed vaccine development programs. Images PMID:6307873

  18. Thermally distinct ejecta blankets from Martian craters

    NASA Astrophysics Data System (ADS)

    Betts, B. H.; Murray, B. C.

    1993-06-01

    A study of Martian ejecta blankets is carried out using the high-resolution thermal IR/visible data from the Termoskan instrument aboard Phobos '88 mission. It is found that approximately 100 craters within the Termoskan data have an ejecta blanket distinct in the thermal infrared (EDITH). These features are examined by (1) a systematic examination of all Termoskan data using high-resolution image processing; (2) a study of the systematics of the data by compiling and analyzing a data base consisting of geographic, geologic, and mormphologic parameters for a significant fraction of the EDITH and nearby non-EDITH; and (3) qualitative and quantitative analyses of localized regions of interest. It is noted that thermally distinct ejecta blankets are excellent locations for future landers and remote sensing because of relatively dust-free surface exposures of material excavated from depth.

  19. Distinct Presentations of Hernia of Umbilical Cord

    PubMed Central

    Mirza, Bilal; Ali, Waqas

    2016-01-01

    Hernia of umbilical cord is a well-known entity which presents with herniation of small bowel into the proximal part of umbilical cord. It has very good prognosis after surgical repair. Occasionally, it can have distinct presentations and varied malformations at the umbilicus which have bearing on the course of treatment and final outcome. Herein, we describe various presentations and malformations associated with hernia of umbilical cord. Embryological extrapolation is attempted for the malformations at umbilicus. PMID:27896161

  20. Distinct Presentations of Hernia of Umbilical Cord.

    PubMed

    Mirza, Bilal; Ali, Waqas

    2016-01-01

    Hernia of umbilical cord is a well-known entity which presents with herniation of small bowel into the proximal part of umbilical cord. It has very good prognosis after surgical repair. Occasionally, it can have distinct presentations and varied malformations at the umbilicus which have bearing on the course of treatment and final outcome. Herein, we describe various presentations and malformations associated with hernia of umbilical cord. Embryological extrapolation is attempted for the malformations at umbilicus.

  1. Army nurses in wartime: distinction and pride.

    PubMed

    Higgins, L P

    1996-08-01

    Nurses have served with distinction in wartime since Florence Nightingale went to the Crimea. Women often accompanied their husbands to battle during the Revolutionary and Civil Wars, caring for the sick and wounded. Although not officially given officer status until 1920, Army nurses served in the Spanish-American War and World War I. As officers, thousands of nurses served in subsequent wars, distinguishing themselves by their heroism, devotion to duty, and sheer tenacity of spirit.

  2. Generation Wrecked.

    ERIC Educational Resources Information Center

    Watson, Noshua

    2002-01-01

    Young adults in Generation X are facing financial problems. Because of their college and credit card debt, many in worse financial shape than anyone since the Depression and have little or no retirement savings. (JOW)

  3. Generation Wrecked.

    ERIC Educational Resources Information Center

    Watson, Noshua

    2002-01-01

    Young adults in Generation X are facing financial problems. Because of their college and credit card debt, many in worse financial shape than anyone since the Depression and have little or no retirement savings. (JOW)

  4. Hydrogen generator

    SciTech Connect

    Adlhart, O. J.

    1985-04-23

    This disclosure relates to a replaceable cartridge hydrogen generator of the type which relies at least partially on the process of anodic corrosion to produce hydrogen. A drum contains a plurality of the cartridges.

  5. The directionality of distinctively mathematical explanations.

    PubMed

    Craver, Carl F; Povich, Mark

    2017-06-01

    In "What Makes a Scientific Explanation Distinctively Mathematical?" (2013b), Lange uses several compelling examples to argue that certain explanations for natural phenomena appeal primarily to mathematical, rather than natural, facts. In such explanations, the core explanatory facts are modally stronger than facts about causation, regularity, and other natural relations. We show that Lange's account of distinctively mathematical explanation is flawed in that it fails to account for the implicit directionality in each of his examples. This inadequacy is remediable in each case by appeal to ontic facts that account for why the explanation is acceptable in one direction and unacceptable in the other direction. The mathematics involved in these examples cannot play this crucial normative role. While Lange's examples fail to demonstrate the existence of distinctively mathematical explanations, they help to emphasize that many superficially natural scientific explanations rely for their explanatory force on relations of stronger-than-natural necessity. These are not opposing kinds of scientific explanations; they are different aspects of scientific explanation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Development of individually distinct recognition cues.

    PubMed

    Mateo, Jill M

    2006-11-01

    Despite extensive research on the functions of kin recognition, little is known about ontogenetic changes in the cues mediating such recognition. In Belding's ground squirrels, Spermophilus beldingi, secretions from oral glands are both individually distinct and kin distinct, and function in social recognition across many contexts. Behavioral studies of recognition and kin preferences suggest that these cues may change across development, particularly around the time of weaning and emergence from natal burrows (around 25 days of age). I used an habituation-discrimination task with captive S. beldingi, presenting subjects with odors collected from a pair of pups at several ages across early development. I found that at 21 days of age, but not at 7 or 14, young produce detectable odors. Odors are not individually distinct, however, until 28 days of age, after young have emerged from their burrows and begun foraging. In addition, an individual's odor continues to develop after emergence: odors produced by an individual at 20 and 40 days of age are perceived as dissimilar, yet odors produced at 28 and 40 days are treated as similar. Developmental changes in odors provide a proximate explanation for why S. beldingi littermate preferences are not consolidated until after natal emergence, and demonstrate that conspecifics must update their recognition templates as young develop. (c) 2006 Wiley Periodicals, Inc.

  7. Quantum information sharing between topologically distinct platforms

    NASA Astrophysics Data System (ADS)

    Hou, Chang-Yu; Refael, Gil; Shtengel, Kirill

    2016-12-01

    Can topological quantum entanglement between anyons in one topological medium "stray" into a different, topologically distinct medium? In other words, can quantum information encoded nonlocally in the combined state of non-Abelian anyons be shared between two distinct topological media? For one-dimensional topological superconductors with Majorana bound states at the end of system, the quantum information store in those Majorana bound states can be transfered by directly coupling nearby Majorana bound states. However, coupling of two one-dimensional Majorana states will produce a gap, indicating that distinct topological regions of one-dimensional wires unite into a single topological region through the information transfer process. In this paper, we consider a setup with two two-dimensional p -wave superconductors of opposite chirality adjacent to each other. Even two comoving chiral modes at the domain wall between them cannot be gapped through interactions; we demonstrate that information encoded in the fermionic parity of two Majorana zero modes, originally within the same superconducting domain, can be shared between the domains or moved entirely from one domain to another provided that vortices can tunnel between them in a controlled fashion.

  8. Multifunctional pattern-generating circuits.

    PubMed

    Briggman, K L; Kristan, W B

    2008-01-01

    The ability of distinct anatomical circuits to generate multiple behavioral patterns is widespread among vertebrate and invertebrate species. These multifunctional neuronal circuits are the result of multistable neural dynamics and modular organization. The evidence suggests multifunctional circuits can be classified by distinct architectures, yet the activity patterns of individual neurons involved in more than one behavior can vary dramatically. Several mechanisms, including sensory input, the parallel activity of projection neurons, neuromodulation, and biomechanics, are responsible for the switching between patterns. Recent advances in both analytical and experimental tools have aided the study of these complex circuits.

  9. Hydrogen Generator

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A unit for producing hydrogen on site is used by a New Jersey Electric Company. The hydrogen is used as a coolant for the station's large generator; on-site production eliminates the need for weekly hydrogen deliveries. High purity hydrogen is generated by water electrolysis. The electrolyte is solid plastic and the control system is electronic. The technology was originally developed for the Gemini spacecraft.

  10. Methane generator

    SciTech Connect

    Whiteside, C.H.

    1984-03-27

    A biogas generator is disclosed which includes a medium conducive to the growing of plants that are floating and of the family that includes water hyacinths, lily pads, and elodea; a conveyor for transferring the free floating plants from the growing area to a decomposition area including a canopy adapted to entrain therewithin biogas given off by decomposing plants constrained thereunder, and an instrumentality for scavenging the biogas generated therein to a remote area for subsequent use and or compression.

  11. Insects Use Two Distinct Classes of Steps during Unrestrained Locomotion

    PubMed Central

    Theunissen, Leslie M.; Dürr, Volker

    2013-01-01

    Background Adaptive, context-dependent control of locomotion requires modulation of centrally generated rhythmic motor patterns through peripheral control loops and postural reflexes. Thus assuming that the modulation of rhythmic motor patterns accounts for much of the behavioural variability observed in legged locomotion, investigating behavioural variability is a key to the understanding of context-dependent control mechanisms in locomotion. To date, the variability of unrestrained locomotion is poorly understood, and virtually nothing is known about the features that characterise the natural statistics of legged locomotion. In this study, we quantify the natural variability of hexapedal walking and climbing in insects, drawing from a database of several thousand steps recorded over two hours of walking time. Results We show that the range of step length used by unrestrained climbing stick insects is large, showing that step length can be changed substantially for adaptive locomotion. Step length distributions were always bimodal, irrespective of leg type and walking condition, suggesting the presence of two distinct classes of steps: short and long steps. Probability density of step length was well-described by a gamma distribution for short steps, and a logistic distribution for long steps. Major coefficients of these distributions remained largely unaffected by walking conditions. Short and long steps differed concerning their spatial occurrence on the walking substrate, their timing within the step sequence, and their prevalent swing direction. Finally, ablation of structures that serve to improve foothold increased the ratio of short to long steps, indicating a corrective function of short steps. Conclusions Statistical and functional differences suggest that short and long steps are physiologically distinct classes of leg movements that likely reflect distinct control mechanisms at work. PMID:24376877

  12. Methane Seep Carbonates Host Distinct, Diverse, and Dynamic Microbial Assemblages

    PubMed Central

    Pasulka, Alexis L.; Marlow, Jeffrey J.; Grupe, Benjamin M.; Levin, Lisa A.

    2015-01-01

    ABSTRACT Marine methane seeps are globally distributed geologic features in which reduced fluids, including methane, are advected upward from the subsurface. As a result of alkalinity generation during sulfate-coupled methane oxidation, authigenic carbonates form slabs, nodules, and extensive pavements. These carbonates shape the landscape within methane seeps, persist long after methane flux is diminished, and in some cases are incorporated into the geologic record. In this study, microbial assemblages from 134 native and experimental samples across 5,500 km, representing a range of habitat substrates (carbonate nodules and slabs, sediment, bottom water, and wood) and seepage conditions (active and low activity), were analyzed to address two fundamental questions of seep microbial ecology: (i) whether carbonates host distinct microbial assemblages and (ii) how sensitive microbial assemblages are to habitat substrate type and temporal shifts in methane seepage flux. Through massively parallel 16S rRNA gene sequencing and statistical analysis, native carbonates are shown to be reservoirs of distinct and highly diverse seep microbial assemblages. Unique coupled transplantation and colonization experiments on the seafloor demonstrated that carbonate-associated microbial assemblages are resilient to seep quiescence and reactive to seep activation over 13 months. Various rates of response to simulated seep quiescence and activation are observed among similar phylogenies (e.g., Chloroflexi operational taxonomic units) and similar metabolisms (e.g., putative S oxidizers), demonstrating the wide range of microbial sensitivity to changes in seepage flux. These results imply that carbonates do not passively record a time-integrated history of seep microorganisms but rather host distinct, diverse, and dynamic microbial assemblages. PMID:26695630

  13. Identification of New and Distinctive Exposures from Little Cigars

    PubMed Central

    Klupinski, Theodore P.; Strozier, Erich D.; Friedenberg, David A.; Brinkman, Marielle C.; Gordon, Sydney M.; Clark, Pamela I.

    2016-01-01

    Little cigar mainstream smoke is less well-characterized than cigarette mainstream smoke in terms of chemical composition. This study compared four popular little cigar products against four popular cigarette products to determine compounds that are either unique to or more abundant in little cigars. These compounds are categorized as new or distinctive exposures, respectively. Total particulate matter samples collected from machine-generated mainstream smoke were extracted with methylene chloride, and the extracts were analyzed using two-dimensional gas chromatography–time-of-flight mass spectrometry. The data were evaluated using novel data-processing algorithms that account for characteristics specific to the selected analytical technique and variability associated with replicate sample analyses. Among more than 25 000 components detected across the complete data set, ambrox was confirmed as a new exposure, and 3-methylbutanenitrile and 4-methylimidazole were confirmed as distinctive exposures. Concentrations of these compounds for the little cigar mainstream smoke were estimated at approximately 0.4, 0.7, and 12 μg/rod, respectively. In achieving these results, this study has demonstrated the capability of a powerful analytical approach to identify previously uncharacterized tobacco-related exposures from little cigars. The same approach could also be applied to other samples to characterize constituents associated with tobacco product classes or specific tobacco products of interest. Such analyses are critical in identifying tobacco-related exposures that may affect public health. PMID:26605856

  14. Distinct Phyllosphere Bacterial Communities on Arabidopsis Wax Mutant Leaves

    PubMed Central

    Reisberg, Eva E.; Hildebrandt, Ulrich; Riederer, Markus; Hentschel, Ute

    2013-01-01

    The phyllosphere of plants is inhabited by diverse microorganisms, however, the factors shaping their community composition are not fully elucidated. The plant cuticle represents the initial contact surface between microorganisms and the plant. We thus aimed to investigate whether mutations in the cuticular wax biosynthesis would affect the diversity of the phyllosphere microbiota. A set of four Arabidopsis thaliana eceriferum mutants (cer1, cer6, cer9, cer16) and their respective wild type (Landsberg erecta) were subjected to an outdoor growth period and analysed towards this purpose. The chemical distinctness of the mutant wax phenotypes was confirmed by gas chromatographic measurements. Next generation amplicon pyrosequencing of the bacterial communities showed distinct community patterns. This observation was supported by denaturing gradient gel electrophoresis experiments. Microbial community analyses revealed bacterial phylotypes that were ubiquitously present on all plant lines (termed “core” community) while others were positively or negatively affected by the wax mutant phenotype (termed “plant line-specific“ community). We conclude from this study that plant cuticular wax composition can affect the community composition of phyllosphere bacteria. PMID:24223831

  15. Identification of New and Distinctive Exposures from Little Cigars.

    PubMed

    Klupinski, Theodore P; Strozier, Erich D; Friedenberg, David A; Brinkman, Marielle C; Gordon, Sydney M; Clark, Pamela I

    2016-02-15

    Little cigar mainstream smoke is less well-characterized than cigarette mainstream smoke in terms of chemical composition. This study compared four popular little cigar products against four popular cigarette products to determine compounds that are either unique to or more abundant in little cigars. These compounds are categorized as new or distinctive exposures, respectively. Total particulate matter samples collected from machine-generated mainstream smoke were extracted with methylene chloride, and the extracts were analyzed using two-dimensional gas chromatography-time-of-flight mass spectrometry. The data were evaluated using novel data-processing algorithms that account for characteristics specific to the selected analytical technique and variability associated with replicate sample analyses. Among more than 25 000 components detected across the complete data set, ambrox was confirmed as a new exposure, and 3-methylbutanenitrile and 4-methylimidazole were confirmed as distinctive exposures. Concentrations of these compounds for the little cigar mainstream smoke were estimated at approximately 0.4, 0.7, and 12 μg/rod, respectively. In achieving these results, this study has demonstrated the capability of a powerful analytical approach to identify previously uncharacterized tobacco-related exposures from little cigars. The same approach could also be applied to other samples to characterize constituents associated with tobacco product classes or specific tobacco products of interest. Such analyses are critical in identifying tobacco-related exposures that may affect public health.

  16. Chemical distinctions between Stradivari’s maple and modern tonewood

    PubMed Central

    Li, Guo-Chian; Huang, Shing-Jong; Jhu, Chang-Ruei; Chung, Jen-Hsuan; Wang, Bo Y.; Hsu, Chia-Shuo; Brandmair, Brigitte; Chung, Dai-Ting; Chen, Hao Ming; Chan, Jerry Chun Chung

    2017-01-01

    Violins made by Antonio Stradivari are renowned for having been the preferred instruments of many leading violinists for over two centuries. There have been long-standing questions about whether wood used by Stradivari possessed unique properties compared with modern tonewood for violin making. Analyses of maple samples removed from four Stradivari and a Guarneri instrument revealed highly distinct organic and inorganic compositions compared with modern maples. By solid-state 13C NMR spectroscopy, we observed that about one-third of hemicellulose had decomposed after three centuries, accompanied by signs of lignin oxidation. No apparent changes in cellulose were detected by NMR and synchrotron X-ray diffraction. By thermogravimetric analysis, historical maples exhibited reduced equilibrium moisture content. In differential scanning calorimetry measurements, only maples from Stradivari violins, but not his cellos, exhibited unusual thermooxidation patterns distinct from natural wood. Elemental analyses by inductively coupled plasma mass spectrometry suggested that Stradivari’s maples were treated with complex mineral preservatives containing Al, Ca, Cu, Na, K, and Zn. This type of chemical seasoning was an unusual practice, unknown to later generations of violin makers. In their current state, maples in Stradivari violins have very different chemical properties compared with their modern counterparts, likely due to the combined effects of aging, chemical treatments, and vibrations. These findings may inspire further chemical experimentation with tonewood processing for instrument making in the 21st century. PMID:27994135

  17. Subsarcolemmal and interfibrillar mitochondria display distinct superoxide production profiles.

    PubMed

    Crochemore, C; Mekki, M; Corbière, C; Karoui, A; Noël, R; Vendeville, C; Vaugeois, J-M; Monteil, C

    2015-03-01

    Cardiac subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) subpopulations display distinct biochemical, morphological, and functional characteristics. Moreover, they appear to be differently influenced during cardiac pathologies or toxic injuries. Although mitochondrial reactive oxygen species seem to play a critical role in cardiac function and diseases, limited information exists about the superoxide production characteristics of these mitochondrial subpopulations. In this work, using direct measurement of superoxide by electron paramagnetic resonance, we showed that differences in superoxide production profiles were present between cardiac IFM and SSM, in terms of intensity and major sites of superoxide generation. In SSM incubated with glutamate plus malate as substrates, the total observed superoxide levels were significantly higher than those observed with IFM, with an important contribution of the NADH-oxidizing site of complex I (site If) and the quinol-oxidizing site of complex III (site IIIQ0). In both IFM and SSM, succinate leads to similar rates of total superoxide levels with a substantial role for contribution of reverse electron transfer. Finally, using two spin probes with different membrane permeabilities, our data on complex III showed direct intra- and extra-mitochondrial superoxide release whereas complex I- and II-dependent superoxide were exclusively released inside the mitochondria, confirming previous studies. Feasibility of this approach to measure intra- and extra-mitochondrial superoxide levels and to characterize distinct superoxide production profiles of cardiac IFM and SSM has been demonstrated.

  18. Two Distinct Moral Mechanisms for Ascribing and Denying Intentionality.

    PubMed

    Ngo, Lawrence; Kelly, Meagan; Coutlee, Christopher G; Carter, R McKell; Sinnott-Armstrong, Walter; Huettel, Scott A

    2015-12-04

    Philosophers and legal scholars have long theorized about how intentionality serves as a critical input for morality and culpability, but the emerging field of experimental philosophy has revealed a puzzling asymmetry. People judge actions leading to negative consequences as being more intentional than those leading to positive ones. The implications of this asymmetry remain unclear because there is no consensus regarding the underlying mechanism. Based on converging behavioral and neural evidence, we demonstrate that there is no single underlying mechanism. Instead, two distinct mechanisms together generate the asymmetry. Emotion drives ascriptions of intentionality for negative consequences, while the consideration of statistical norms leads to the denial of intentionality for positive consequences. We employ this novel two-mechanism model to illustrate that morality can paradoxically shape judgments of intentionality. This is consequential for mens rea in legal practice and arguments in moral philosophy pertaining to terror bombing, abortion, and euthanasia among others.

  19. The picture superiority effect: support for the distinctiveness model.

    PubMed

    Mintzer, M Z; Snodgrass, J G

    1999-01-01

    The form change paradigm was used to explore the basis for the picture superiority effect. Recognition memory for studied pictures and words was tested in their study form or the alternate form. Form change cost was defined as the difference between recognition performance for same and different form items. Based on the results of Experiment 1 and previous studies, it was difficult to determine the relative cost for studied pictures and words due to a reversal of the mirror effect. We hypothesized that the reversed mirror effect results from subjects' basing their recognition decisions on their assumptions about the study form. Experiments 2 and 3 confirmed this hypothesis and generated a method for evaluating the relative cost for pictures and words despite the reversed mirror effect. More cost was observed for pictures than words, supporting the distinctiveness model of the picture superiority effect.

  20. Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks.

    PubMed

    Benevento, Marco; Tonge, Peter D; Puri, Mira C; Hussein, Samer M I; Cloonan, Nicole; Wood, David L; Grimmond, Sean M; Nagy, Andras; Munoz, Javier; Heck, Albert J R

    2014-12-10

    The ectopic expression of Oct4, Klf4, c-Myc and Sox2 (OKMS) transcription factors allows reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). The reprogramming process, which involves a complex network of molecular events, is not yet fully characterized. Here we perform a quantitative mass spectrometry-based analysis to probe in-depth dynamic proteome changes during somatic cell reprogramming. Our data reveal defined waves of proteome resetting, with the first wave occurring 48 h after the activation of the reprogramming transgenes and involving specific biological processes linked to the c-Myc transcriptional network. A second wave of proteome reorganization occurs in a later stage of reprogramming, where we characterize the proteome of two distinct pluripotent cellular populations. In addition, the overlay of our proteome resource with parallel generated -omics data is explored to identify post-transcriptionally regulated proteins involved in key steps during reprogramming.

  1. Distinct mechanisms and timing of language recovery after stroke

    PubMed Central

    Jarso, Samson; Li, Muwei; Faria, Andreia; Davis, Cameron; Leigh, Richard; Sebastian, Rajani; Tsapkini, Kyrana; Mori, Susumu; Hillis, Argye E.

    2014-01-01

    The “language network” is remarkably stable across language tasks but changes in response to injury to specific components or in response to “disconnection” of input to one component. We investigated network changes during language recovery, hypothesizing that language recovery takes place through distinct mechanisms: (a) reperfusion; (b) recovery from diaschisis; (c) recovery from structural disconnection; and (d) “reorganization” of language, whereby various components assume function of a damaged component. We also tested the hypothesis that “reorganization” depends on: the language task, level of performance, size and site of stroke, and time post onset. We tested these hypotheses in five participants who had structural, perfusion, and functional imaging utilizing spelling, reading, word generation, and picture naming tasks at acute and subsequent stages after ischaemic stroke. These cases illustrate different mechanisms of aphasia recovery or illustrate that reorganization of language acutely depends on individual variables in addition to size and site of stroke. PMID:24472056

  2. Two Distinct Moral Mechanisms for Ascribing and Denying Intentionality

    PubMed Central

    Ngo, Lawrence; Kelly, Meagan; Coutlee, Christopher G.; Carter, R. McKell; Sinnott-Armstrong, Walter; Huettel, Scott A.

    2015-01-01

    Philosophers and legal scholars have long theorized about how intentionality serves as a critical input for morality and culpability, but the emerging field of experimental philosophy has revealed a puzzling asymmetry. People judge actions leading to negative consequences as being more intentional than those leading to positive ones. The implications of this asymmetry remain unclear because there is no consensus regarding the underlying mechanism. Based on converging behavioral and neural evidence, we demonstrate that there is no single underlying mechanism. Instead, two distinct mechanisms together generate the asymmetry. Emotion drives ascriptions of intentionality for negative consequences, while the consideration of statistical norms leads to the denial of intentionality for positive consequences. We employ this novel two-mechanism model to illustrate that morality can paradoxically shape judgments of intentionality. This is consequential for mens rea in legal practice and arguments in moral philosophy pertaining to terror bombing, abortion, and euthanasia among others. PMID:26634909

  3. Microwave generator

    DOEpatents

    Kwan, T.J.T.; Snell, C.M.

    1987-03-31

    A microwave generator is provided for generating microwaves substantially from virtual cathode oscillation. Electrons are emitted from a cathode and accelerated to an anode which is spaced apart from the cathode. The anode has an annular slit there through effective to form the virtual cathode. The anode is at least one range thickness relative to electrons reflecting from the virtual cathode. A magnet is provided to produce an optimum magnetic field having the field strength effective to form an annular beam from the emitted electrons in substantial alignment with the annular anode slit. The magnetic field, however, does permit the reflected electrons to axially diverge from the annular beam. The reflected electrons are absorbed by the anode in returning to the real cathode, such that substantially no reflexing electrons occur. The resulting microwaves are produced with a single dominant mode and are substantially monochromatic relative to conventional virtual cathode microwave generators. 6 figs.

  4. PULSE GENERATOR

    DOEpatents

    Roeschke, C.W.

    1957-09-24

    An improvement in pulse generators is described by which there are produced pulses of a duration from about 1 to 10 microseconds with a truly flat top and extremely rapid rise and fall. The pulses are produced by triggering from a separate input or by modifying the current to operate as a free-running pulse generator. In its broad aspect, the disclosed pulse generator comprises a first tube with an anode capacitor and grid circuit which controls the firing; a second tube series connected in the cathode circuit of the first tube such that discharge of the first tube places a voltage across it as the leading edge of the desired pulse; and an integrator circuit from the plate across the grid of the second tube to control the discharge time of the second tube, determining the pulse length.

  5. Hydrogen Generator

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Another spinoff from spacecraft fuel cell technology is the portable hydrogen generator shown. Developed by General Electric Company, it is an aid to safer operation of systems that use hydrogen-for example, gas chromatographs, used in laboratory analysis of gases. or flame ionization detectors used as $ollution monitors. The generator eliminates the need for high-pressure hydrogen storage bottles, which can be a safety hazard, in laboratories, hospitals and industrial plants. The unit supplies high-purity hydrogen by means of an electrochemical process which separates the hydrogen and oxygen in distilled water. The oxygen is vented away and the hydrogen gas is stored within the unit for use as needed. GE's Aircraft Equipment Division is producing about 1,000 of the generators annually.

  6. Distinctiveness in the face of gene flow: hybridization between specialist and generalist gartersnakes.

    PubMed

    Fitzpatrick, Benjamin M; Placyk, John S; Niemiller, Matthew L; Casper, Gary S; Burghardt, Gordon M

    2008-09-01

    Patterns of divergence and polymorphism across hybrid zones can provide important clues as to their origin and maintenance. Unimodal hybrid zones or hybrid swarms are composed predominantly of recombinant individuals whose genomes are patchworks of alleles derived from each parental lineage. In contrast, bimodal hybrid zones contain few identifiable hybrids; most individuals fall within distinct genetic clusters. Distinguishing between hybrid swarms and bimodal hybrid zones can be important for taxonomic and conservation decisions regarding the status and value of hybrid populations. In addition, the causes of bimodality are important in understanding the generation and maintenance of biological diversity. For example, are distinct clusters mostly reproductively isolated and co-adapted gene complexes, or can distinctiveness be maintained by a few 'genomic islands' despite rampant gene flow across much of the genome? Here we focus on three patterns of distinctiveness in the face of gene flow between gartersnake taxa in the Great Lakes region of North America. Bimodality, the persistence of distinct clusters of genotypes, requires strong barriers to gene flow and supports recognition of distinct specialist (Thamnophis butleri) and generalist (Thamnophis radix) taxa. Concordance of DNA-based clusters with morphometrics supports the hypothesis that trophic morphology is a key component of divergence. Finally, disparity in the level of differentiation across molecular markers (amplified fragment length polymorphisms) indicates that distinctiveness is maintained by strong selection on a few traits despite high gene flow currently or in the recent past.

  7. Why have the peninsular "negritos" remained distinct?

    PubMed

    Benjamin, Geoffrey

    2013-01-01

    The primary focus of this article is on the so-called negritos of Peninsular Malaysia and southern Thailand, but attention is also paid to other parts of Southeast Asia. I present a survey of current views on the "negrito" phenotype--is it single or many? If the phenotype is many (as now seems likely), it must have resulted from parallel evolution in the several different regions where it has been claimed to exist. This would suggest (contrary to certain views that have been expressed on the basis of very partial genetic data) that the phenotype originated recently and by biologically well-authenticated processes from within the neighboring populations. Whole-genome and physical-anthropological research currently support this view. Regardless of whether the negrito phenotype is ancient or recent-and to the extent that it retains any valid biological reality (which is worth questioning)-explanations are still needed for its continued distinctiveness. In the Malay Peninsula, a distinctive "Semang" societal pattern followed by most, but not all, so-called negritos may have been responsible for this by shaping familial, breeding, and demographic patterns to suit the two main modes of environmental appropriation that they have followed, probably for some millennia: nomadic foraging in the forest, and facultative dependence on exchange or labor relations with neighboring populations. The known distribution of "negritos" in the Malay Peninsula is limited to areas within relatively easy reach of archaeologically authenticated premodern transpeninsular trading and portage routes, as well as of other non-negrito, Aslian-speaking populations engaged in swidden farming. This suggests that their continued distinctiveness has resulted from a wish to maintain a complementary advantage vis-à-vis other, less specialized populations. Nevertheless, a significant degree of discordance exists between the associated linguistic, societal-tradition, and biological patterns which suggests

  8. Generational mentoring.

    PubMed

    Stewart, Della W

    2006-01-01

    Healthcare organizations struggle with the best way to integrate new staff members, including novice and experienced nurses returning to practice, into the organization. One way of accomplishing this integration is mentoring. Mentoring is a process of guiding the development of another person. The methods used to mentor staff members can be influenced by the generation to which they belong. Each generation typically experiences different events that shape their expectations and responses. Consideration of the influence of these events can improve the effectiveness of the mentoring process.

  9. Hydrogen generator

    SciTech Connect

    Hansen, J.R.

    1984-06-19

    A hydrogen generator decomposes water into hydrogen and oxygen, and includes an induction coil which is electrically heated to a temperature sufficient to decompose water passing therethrough. A generator coil is connected in communicating relation to the induction coil, and is positioned in a fire resistant crucible containing ferrous oxide pellets. Oxygen and hydrogen produced by decomposition of water pass through the ferrous oxide pellets where the oxygen reacts with the ferrous oxide and the hydrogen is burned to produce heat for heating a building, such as a conventional home.

  10. Solar Generator

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The Vanguard I dish-Stirling module program, initiated in 1982, produced the Vanguard I module, a commercial prototype erected by the Advanco Corporation. The module, which automatically tracks the sun, combines JPL mirrored concentrator technology, an advanced Stirling Solar II engine/generator, a low cost microprocessor-controlled parabolic dish. Vanguard I has a 28% sunlight to electricity conversion efficiency. If tests continue to prove the system effective, Advanco will construct a generating plant to sell electricity to local utilities. An agreement has also been signed with McDonnell Douglas to manufacture a similar module.

  11. Visual Distinctness Determined by Partially Invariant Features

    DTIC Science & Technology

    2000-03-01

    DISTINCTNESS DETERMINED BY PARTIALLY INVARIANT FEATURES. J.A. Garcia, J. Fdez-Valdivia Departamento de Ciencias de la Computacion e I.A. Univ. de Granada...E.T.S. de Ingenieria Informatica. 18071 Granada. Spain E-mail: jagsadecsai.ugr.es, J.Fdez-Valdivia@decsai.ugr.es Xose R. Fdez-Vidal Departamento de... Fisica Aplicada. Univ. de Santiago de Compostela. Facultad de Fisica . 15706 Santiago de Compostela. Spain E-mail: faxose@usc.es Rosa Rodriguez-Sanchez

  12. Distinct Turbulence Saturation Regimes in Stellarators

    NASA Astrophysics Data System (ADS)

    Plunk, G. G.; Xanthopoulos, P.; Helander, P.

    2017-03-01

    In the complex 3D magnetic fields of stellarators, ion-temperature-gradient turbulence is shown to have two distinct saturation regimes, as revealed by petascale numerical simulations and explained by a simple turbulence theory. The first regime is marked by strong zonal flows and matches previous observations in tokamaks. The newly observed second regime, in contrast, exhibits small-scale quasi-two-dimensional turbulence, negligible zonal flows, and, surprisingly, a weaker heat flux scaling. Our findings suggest that key details of the magnetic geometry control turbulence in stellarators.

  13. Catatonia in autism: a distinct subtype?

    PubMed

    Ghaziuddin, M; Quinlan, P; Ghaziuddin, N

    2005-01-01

    Catatonia is a life-threatening disorder characterized by motor abnormalities, mutism, and disturbances of behaviour, which is increasingly being diagnosed in persons with autism. In this report, we describe the presentation and course of catatonia in an adolescent with autism who responded to electroconvulsive therapy (ECT). The illness started with depressive symptoms, but the predominant feature was one of extreme obsessive slowing and immobility. We propose that catatonia should be ruled out as a cause of regression sometimes seen in adolescents with autism, and that catatonia of autism may index a distinct subtype with a particularly poor outcome.

  14. Euthanasia and the active-passive distinction.

    PubMed

    Reichenbach, Bruce R

    1987-01-01

    The author examines various claimed differences between active and passive euthanasia and, if there are differences, whether they are morally significant. He refutes arguments based on acting vs. not acting, intention, double effect, cause of death, and natural law theory. Reichenbach proposes that the most helpful distinction is the one between intentional killing (active euthanasia) and appropriate treatment for the dying or terminally ill (passive euthanasia). Significant moral difference, however, rests on the contention that intentional killing is always wrong and that, all else being equal, dying by natural means is intrinsically good, whereas dying by unnatural means is not.

  15. Generation Next

    ERIC Educational Resources Information Center

    Hawkins, B. Denise

    2010-01-01

    There is a shortage of accounting professors with Ph.D.s who can prepare the next generation. To help reverse the faculty deficit, the American Institute of Certified Public Accountants (CPAs) has created the new Accounting Doctoral Scholars program by pooling more than $17 million and soliciting commitments from more than 70 of the nation's…

  16. Generation Next

    ERIC Educational Resources Information Center

    Hawkins, B. Denise

    2010-01-01

    There is a shortage of accounting professors with Ph.D.s who can prepare the next generation. To help reverse the faculty deficit, the American Institute of Certified Public Accountants (CPAs) has created the new Accounting Doctoral Scholars program by pooling more than $17 million and soliciting commitments from more than 70 of the nation's…

  17. Generational Myth

    ERIC Educational Resources Information Center

    Vaidhyanathan, Siva

    2008-01-01

    College students in America are not as "digital" as one might wish to pretend. And even at elite universities, many are not rich enough. All the mystical talk about a generational shift and all the claims that kids won't read books are not true. In this article, the author challenges the notion of "digital natives." The author argues that the term…

  18. Generative Contexts

    NASA Astrophysics Data System (ADS)

    Lyles, Dan Allen

    Educational research has identified how science, technology, engineering, and mathematics (STEM) practice and education have underperforming metrics in racial and gender diversity, despite decades of intervention. These disparities are part of the construction of a culture of science that is alienating to these populations. Recent studies in a social science framework described as "Generative Justice" have suggested that the context of social and scientific practice might be modified to bring about more just and equitable relations among the disenfranchised by circulating the value they and their non-human allies create back to them in unalienated forms. What is not known are the underlying principles of social and material space that makes a system more or less generative. I employ an autoethnographic method at four sites: a high school science class; a farm committed to "Black and Brown liberation"; a summer program geared towards youth environmental mapping; and a summer workshop for Harlem middle school students. My findings suggest that by identifying instances where material affinity, participatory voice, and creative solidarity are mutually reinforcing, it is possible to create educational contexts that generate unalienated value, and circulate it back to the producers themselves. This cycle of generation may help explain how to create systems of justice that strengthen and grow themselves through successive iterations. The problem of lack of diversity in STEM may be addressed not merely by recruiting the best and the brightest from underrepresented populations, but by changing the context of STEM education to provide tools for its own systematic restructuring.

  19. Methane Seep Carbonates Host Distinct, Diverse, and Dynamic Microbial Assemblages.

    PubMed

    Case, David H; Pasulka, Alexis L; Marlow, Jeffrey J; Grupe, Benjamin M; Levin, Lisa A; Orphan, Victoria J

    2015-12-22

    Marine methane seeps are globally distributed geologic features in which reduced fluids, including methane, are advected upward from the subsurface. As a result of alkalinity generation during sulfate-coupled methane oxidation, authigenic carbonates form slabs, nodules, and extensive pavements. These carbonates shape the landscape within methane seeps, persist long after methane flux is diminished, and in some cases are incorporated into the geologic record. In this study, microbial assemblages from 134 native and experimental samples across 5,500 km, representing a range of habitat substrates (carbonate nodules and slabs, sediment, bottom water, and wood) and seepage conditions (active and low activity), were analyzed to address two fundamental questions of seep microbial ecology: (i) whether carbonates host distinct microbial assemblages and (ii) how sensitive microbial assemblages are to habitat substrate type and temporal shifts in methane seepage flux. Through massively parallel 16S rRNA gene sequencing and statistical analysis, native carbonates are shown to be reservoirs of distinct and highly diverse seep microbial assemblages. Unique coupled transplantation and colonization experiments on the seafloor demonstrated that carbonate-associated microbial assemblages are resilient to seep quiescence and reactive to seep activation over 13 months. Various rates of response to simulated seep quiescence and activation are observed among similar phylogenies (e.g., Chloroflexi operational taxonomic units) and similar metabolisms (e.g., putative S oxidizers), demonstrating the wide range of microbial sensitivity to changes in seepage flux. These results imply that carbonates do not passively record a time-integrated history of seep microorganisms but rather host distinct, diverse, and dynamic microbial assemblages. Since their discovery in 1984, the global distribution and importance of marine methane seeps have become increasingly clear. Much of our understanding of

  20. Distinct types of eigenvector localization in networks

    PubMed Central

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q−γ, localization occurs on the largest hub if γ > 5/2; for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix. PMID:26754565

  1. Distinct developmental profiles in typical speech acquisition

    PubMed Central

    Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Abdi, Hervé; Rusiewicz, Heather Leavy; Venkatesh, Lakshmi; Moore, Christopher A.

    2012-01-01

    Three- to five-year-old children produce speech that is characterized by a high level of variability within and across individuals. This variability, which is manifest in speech movements, acoustics, and overt behaviors, can be input to subgroup discovery methods to identify cohesive subgroups of speakers or to reveal distinct developmental pathways or profiles. This investigation characterized three distinct groups of typically developing children and provided normative benchmarks for speech development. These speech development profiles, identified among 63 typically developing preschool-aged speakers (ages 36–59 mo), were derived from the children's performance on multiple measures. These profiles were obtained by submitting to a k-means cluster analysis of 72 measures that composed three levels of speech analysis: behavioral (e.g., task accuracy, percentage of consonants correct), acoustic (e.g., syllable duration, syllable stress), and kinematic (e.g., variability of movements of the upper lip, lower lip, and jaw). Two of the discovered group profiles were distinguished by measures of variability but not by phonemic accuracy; the third group of children was characterized by their relatively low phonemic accuracy but not by an increase in measures of variability. Analyses revealed that of the original 72 measures, 8 key measures were sufficient to best distinguish the 3 profile groups. PMID:22357794

  2. Distinct developmental profiles in typical speech acquisition.

    PubMed

    Vick, Jennell C; Campbell, Thomas F; Shriberg, Lawrence D; Green, Jordan R; Abdi, Hervé; Rusiewicz, Heather Leavy; Venkatesh, Lakshmi; Moore, Christopher A

    2012-05-01

    Three- to five-year-old children produce speech that is characterized by a high level of variability within and across individuals. This variability, which is manifest in speech movements, acoustics, and overt behaviors, can be input to subgroup discovery methods to identify cohesive subgroups of speakers or to reveal distinct developmental pathways or profiles. This investigation characterized three distinct groups of typically developing children and provided normative benchmarks for speech development. These speech development profiles, identified among 63 typically developing preschool-aged speakers (ages 36-59 mo), were derived from the children's performance on multiple measures. These profiles were obtained by submitting to a k-means cluster analysis of 72 measures that composed three levels of speech analysis: behavioral (e.g., task accuracy, percentage of consonants correct), acoustic (e.g., syllable duration, syllable stress), and kinematic (e.g., variability of movements of the upper lip, lower lip, and jaw). Two of the discovered group profiles were distinguished by measures of variability but not by phonemic accuracy; the third group of children was characterized by their relatively low phonemic accuracy but not by an increase in measures of variability. Analyses revealed that of the original 72 measures, 8 key measures were sufficient to best distinguish the 3 profile groups.

  3. Nora's lesion, a distinct radiological entity?

    PubMed

    Dhondt, E; Oudenhoven, L; Khan, S; Kroon, H M; Hogendoorn, P C; Nieborg, A; Bloem, J L; De Schepper, A

    2006-07-01

    To describe the radiological findings of "Bizarre parosteal osteochondromatous proliferation"(BPOP)-otherwise known as Nora's lesion, to describe the natural evolution of BPOP and to assess radiologically if BPOP is indeed part of a spectrum of reactive lesions including florid reactive periostitis and turret exostosis. Four experienced musculoskeletal radiologists studied plain radiographs and other imaging documents of histologically-proven Nora's lesions, looking for soft-tissue changes, periosteal reaction/calcification and calcified/ossified pseudotumours, and compared those findings with findings on pathology reviewed by a peer group of pathologists. Twenty-four Nora's lesions originating from a series of 200 consecutive, histologically-verified bone (pseudo)tumours of the hand, seen by the "Netherlands Committee on Bone Tumours" for review and second opinion. Nora's lesions have a recognised presentation on radiographs without specific MR characteristics. Natural evolution could be assessed retrospectively in four cases. Recurrent lesions were seen in seven cases and are difficult to differentiate from primary lesions. Nora's lesion, defined as a "well-marginated mass of heterotopic mineralization arising from the periosteal aspect of an intact cortex, without medullary changes" has a distinct radiological presentation and is part of a spectrum of reactive lesions which includes florid reactive periostitis and turret exostosis. As it has a distinct radiological appearance, differential diagnosis of malignant lesions such as osteosarcoma and chondrosarcoma should be clear. It does not require immediate biopsy unless the natural evolution is unspecific.

  4. The neural signatures of distinct psychopathic traits.

    PubMed

    Carré, Justin M; Hyde, Luke W; Neumann, Craig S; Viding, Essi; Hariri, Ahmad R

    2013-01-01

    Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward-related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy.

  5. Distinctive Solvation Patterns Make Renal Osmolytes Diverse

    PubMed Central

    Jackson-Atogi, Ruby; Sinha, Prem Kumar; Rösgen, Jörg

    2013-01-01

    The kidney uses mixtures of five osmolytes to counter the stress induced by high urea and NaCl concentrations. The individual roles of most of the osmolytes are unclear, and three of the five have not yet been thermodynamically characterized. Here, we report partial molar volumes and activity coefficients of glycerophosphocholine (GPC), taurine, and myo-inositol. We derive their solvation behavior from the experimental data using Kirkwood-Buff theory. We also provide their solubility data, including solubility data for scyllo-inositol. It turns out that renal osmolytes fall into three distinct classes with respect to their solvation. Trimethyl-amines (GPC and glycine-betaine) are characterized by strong hard-sphere-like self-exclusion; urea, taurine, and myo-inositol have a tendency toward self-association; sorbitol and most other nonrenal osmolytes have a relatively constant, intermediate solvation that has components of both exclusion and association. The data presented here show that renal osmolytes are quite diverse with respect to their solvation patterns, and they can be further differentiated based on observations from experiments examining their effect on macromolecules. It is expected, based on the available surface groups, that each renal osmolyte has distinct effects on various classes of biomolecules. This likely allows the kidney to use specific combinations of osmolytes independently to fine-tune the chemical activities of several types of molecules. PMID:24209862

  6. Visually distinct patterns with matching subband statistics.

    PubMed

    Gluckman, Joshua

    2005-02-01

    A commonly used representation of a visual pattern is a statistical distribution measured from the output of a bank of filters (Gaussian, Laplacian, Gabor, etc.). Both marginal and joint distributions of filter responses have been advocated and effectively used for a variety of vision tasks, including texture classification, texture synthesis, object detection, and image retrieval. This paper examines the ability of these representations to discriminate between an arbitrary pair of visual stimuli. Examples of patterns are derived that provably possess the same marginal and joint statistical properties, yet are "visually distinct." This is accomplished by showing sufficient conditions for matching the first k moments of the marginal distributions of a pair of images. Then, given a set of filters, we show how to match the marginal statistics of the subband images formed through convolution with the filter set. Next, joint statistics are examined and images with similar joint distributions of subband responses are shown. Finally, distinct periodic patterns are derived that possess approximately the same subband statistics for any arbitrary filter set.

  7. IVUS coronary volume alignment for distinct phases

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica Mitiko Soares; Lemos, Pedro Alves; Furuie, Sergio Shiguemi

    2009-02-01

    Image-based intravascular ultrasound (IVUS) cardiac phase detection allows coronary volume reconstruction in different phases. Consecutive volumes are not necessarily spatially aligned due to longitudinal movement of the catheter. Besides ordinary pullback velocity, there is a relative longitudinal movement of the heart vessel walls and the transducer, due to myocardial contraction. In this manuscript, we aim to spatially align cardiac phase coronary IVUS volumes. In addition, we want to investigate this non-linear longitudinal catheter movement. With this purpose, we have analyzed 120 simulated IVUS images and 10 real IVUS pullbacks. We implemented the following methodology. Firstly, we built IVUS volume for each distinct phase. Secondly, each IVUS volume was transformed into a parametric signal of average frame intensity. We have used these signals to make correlation in space with a reference one. Then we estimated the spatial distance between the distinct IVUS volumes and the reference. We have tested in simulated images and real examinations. We have also observed similar pattern in real IVUS examinations. This spatial alignment method is feasible and useful as a step towards dynamic studies of IVUS examination.

  8. Distinct immunosuppressive effect by Isodon serra extracts.

    PubMed

    Zhang, Yan; Liu, Jianwen; Jia, Wei; Zhao, Aihua; Li, Ting

    2005-12-01

    Distinct effect of ent-Kaurene Diterpenoids from Isodon serra on abnormal proliferation of murine lymphocytes was examined with MTT assay and Flow Cytometry Analyses (FCAS). After choosing the most appropriate monomer from these Diterpenoids, we introduced mouse tumescence model to investigate whether it could impact cytokine production in vivo with ELISA assay. The result of MTT assay showed that four ent-Kaurene Diterpenoids could effectively suppress the murine splenic T lymphocytes overproduction stimulated by Concanavalin A, while inhibitive effect was softer on normal sleep lymphocytes than the stimulated ones. Among four ent-Kaurene Diterpenoids, Enmein was the most sensitive one with IC50/EC50 equaling to 1.55. This inhibitive activity was due to interfering DNA replication in G1-S stage and to regulating cell cycle according to flow cytometry analyses (FCAS) result. Xylene-induced mouse tumescence model result further suggested that Enmein depressed the murine ear swelling extent and the level of Interleukin-2 in blood serum in a dose-dependent manner. In conclusion, it demonstrated that four ent-Kaurene Diterpenoids from I. serra had distinct immunosuppressive effect in vitro and in vivo systems, which primarily differentiated Enmein from the others. The experimental results provided insight into a potential immunosuppressive action of Enmein as a promising drug, though profound mechanism remained to be further studied.

  9. Alternative applications for distinct RNA sequencing strategies

    PubMed Central

    Han, Leng; Vickers, Kasey C.; Samuels, David C.

    2015-01-01

    Recent advances in RNA library preparation methods, platform accessibility and cost efficiency have allowed high-throughput RNA sequencing (RNAseq) to replace conventional hybridization microarray platforms as the method of choice for mRNA profiling and transcriptome analyses. RNAseq is a powerful technique to profile both long and short RNA expression, and the depth of information gained from distinct RNAseq methods is striking and facilitates discovery. In addition to expression analysis, distinct RNAseq approaches also allow investigators the ability to assess transcriptional elongation, DNA variance and exogenous RNA content. Here we review the current state of the art in transcriptome sequencing and address epigenetic regulation, quantification of transcription activation, RNAseq output and a diverse set of applications for RNAseq data. We detail how RNAseq can be used to identify allele-specific expression, single-nucleotide polymorphisms and somatic mutations and discuss the benefits and limitations of using RNAseq to monitor DNA characteristics. Moreover, we highlight the power of combining RNA- and DNAseq methods for genomic analysis. In summary, RNAseq provides the opportunity to gain greater insight into transcriptional regulation and output than simply miRNA and mRNA profiling. PMID:25246237

  10. The Cosmology Distinction Course in NSW

    NASA Astrophysics Data System (ADS)

    Hollow, Robert P.; McAdam, W. B.; O'Byrne, J.; White, Graeme L.; Holmes, R.; Webb, J. K.; Allen, L. R.; Zealey, W. J.; Hafner, R.

    1994-04-01

    The Cosmology Distinction Course is a new one-year course to be introduced for Year 12 candidates in the 1994 Higher School Certificate (HSC) examinations in NSW. It is one of three challenging courses of study that will enrich the HSC for talented students who accelerate and complete part of the HSC one year early. The courses will be taught through distance learning and will include residential seminars. They will be implemented on behalf of the Board of Studies by Charles Sturt University and the University of New England. The Cosmology Course is organized into nine modules of course work covering historical and social aspects of cosmology, observational techniques, key observatons and the various models developed--Newtonian, de Sitter, Friedmann, Lemaitre, steady-state, quasi-steady-state and big bang. Assessment will be through assignments, exams and a major project. As the first Distinction Course in a scientific area, the Cosmology Course represents an exciting and important educational initiative that needs the cooperation of NSW astronomers and, in return, promises to benefit the astronomical and general scientific community in Australia.

  11. Submersible Generator for Marine Hydrokinetics

    SciTech Connect

    Cinq-Mars, Robert S; Burke, Timothy; Irish, James; Gustafson, Brian; Kirtley, James; Alawa, Aiman

    2011-09-01

    A submersible generator was designed as a distinct and critical subassembly of marine hydrokinetics systems, specifically tidal and stream energy conversion. The generator is designed to work with both vertical and horizontal axis turbines. The final product is a high-pole-count, radial-flux, permanent magnet, rim mounted generator, initially rated at twenty kilowatts in a two-meter-per-second flow, and designed to leverage established and simple manufacturing processes. The generator was designed to work with a 3 meter by 7 meter Gorlov Helical Turbine or a marine hydrokinetic version of the FloDesign wind turbine. The team consisted of experienced motor/generator design engineers with cooperation from major US component suppliers (magnetics, coil winding and electrical steel laminations). Support for this effort was provided by Lucid Energy Technologies and FloDesign, Inc. The following tasks were completed: Identified the conditions and requirements for MHK generators. Defined a methodology for sizing and rating MHK systems. Selected an MHK generator topology and form factor. Completed electromechanical design of submersible generator capable of coupling to multiple turbine styles. Investigated MHK generator manufacturing requirements. Reviewed cost implications and financial viability. Completed final reporting and deliverables

  12. Characterizing Drug Non-Users as Distinctive in Prevention Messages: Implications of Optimal Distinctiveness Theory

    PubMed Central

    Comello, Maria Leonora G.

    2011-01-01

    Optimal Distinctiveness Theory posits that highly valued groups are those that can simultaneously satisfy needs to belong and to be different. The success of drug-prevention messages with a social-identity theme should therefore depend on the extent to which the group is portrayed as capable of meeting these needs. Specifically, messages that portray non-users as a large and undifferentiated majority may not be as successful as messages that emphasize uniqueness of non-users. This prediction was examined using marijuana prevention messages that depicted non-users as a distinctive or a majority group. Distinctiveness characterization lowered behavioral willingness to use marijuana among non-users (Experiment 1) and served as a source of identity threat (contingent on gender) among users (Experiment 2). PMID:21409672

  13. Splinter generator

    NASA Astrophysics Data System (ADS)

    Held, Manfred

    A splinter generator was designed, built and tested for the study of the synergistic effects in shooting at target structures with splinter-effect ammunition. The design of the generator and the test stand are described. Due to the possibility to correlate the positions of the hit encounters on the target plate, the angle of jump in elevation and azimuthal direction and hence the real paths between the detonation of the bursting charge and the X-ray flash pictures could be determined. This allows a precise determination of the velocities of the single splinters. In spite of the large scattering of the splinter penetration depths in the soft-iron target plate, a correlation between impact speed and working depth was deduced.

  14. Magnetocumulative generator

    DOEpatents

    Pettibone, J.S.; Wheeler, P.C.

    1981-06-08

    An improved magnetocumulative generator is described that is useful for producing magnetic fields of very high energy content over large spatial volumes. The polar directed pleated magnetocumulative generator has a housing providing a housing chamber with an electrically conducting surface. The chamber forms a coaxial system having a small radius portion and a large radius portion. When a magnetic field is injected into the chamber, from an external source, most of the magnetic flux associated therewith positions itself in the small radius portion. The propagation of an explosive detonation through high-explosive layers disposed adjacent to the housing causes a phased closure of the chamber which sweeps most of the magnetic flux into the large radius portion of the coaxial system. The energy content of the magnetic field is greatly increased by flux stretching as well as by flux compression. The energy enhanced magnetic field is utilized within the housing chamber itself.

  15. Cluster generator

    DOEpatents

    Donchev, Todor I.; Petrov, Ivan G.

    2011-05-31

    Described herein is an apparatus and a method for producing atom clusters based on a gas discharge within a hollow cathode. The hollow cathode includes one or more walls. The one or more walls define a sputtering chamber within the hollow cathode and include a material to be sputtered. A hollow anode is positioned at an end of the sputtering chamber, and atom clusters are formed when a gas discharge is generated between the hollow anode and the hollow cathode.

  16. PLASMA GENERATOR

    DOEpatents

    Foster, J.S. Jr.

    1958-03-11

    This patent describes apparatus for producing an electricity neutral ionized gas discharge, termed a plasma, substantially free from contamination with neutral gas particles. The plasma generator of the present invention comprises a plasma chamber wherein gas introduced into the chamber is ionized by a radiofrequency source. A magnetic field is used to focus the plasma in line with an exit. This magnetic field cooperates with a differential pressure created across the exit to draw a uniform and uncontaminated plasma from the plasma chamber.

  17. Photon generator

    DOEpatents

    Srinivasan-Rao, Triveni

    2002-01-01

    A photon generator includes an electron gun for emitting an electron beam, a laser for emitting a laser beam, and an interaction ring wherein the laser beam repetitively collides with the electron beam for emitting a high energy photon beam therefrom in the exemplary form of x-rays. The interaction ring is a closed loop, sized and configured for circulating the electron beam with a period substantially equal to the period of the laser beam pulses for effecting repetitive collisions.

  18. Thermoelectric generator

    DOEpatents

    Pryslak, N.E.

    1974-02-26

    A thermoelectric generator having a rigid coupling or stack'' between the heat source and the hot strap joining the thermoelements is described. The stack includes a member of an insulating material, such as ceramic, for electrically isolating the thermoelements from the heat source, and a pair of members of a ductile material, such as gold, one each on each side of the insulating member, to absorb thermal differential expansion stresses in the stack. (Official Gazette)

  19. Electric generator

    DOEpatents

    Foster, Jr., John S.; Wilson, James R.; McDonald, Jr., Charles A.

    1983-01-01

    1. In an electrical energy generator, the combination comprising a first elongated annular electrical current conductor having at least one bare surface extending longitudinally and facing radially inwards therein, a second elongated annular electrical current conductor disposed coaxially within said first conductor and having an outer bare surface area extending longitudinally and facing said bare surface of said first conductor, the contiguous coaxial areas of said first and second conductors defining an inductive element, means for applying an electrical current to at least one of said conductors for generating a magnetic field encompassing said inductive element, and explosive charge means disposed concentrically with respect to said conductors including at least the area of said inductive element, said explosive charge means including means disposed to initiate an explosive wave front in said explosive advancing longitudinally along said inductive element, said wave front being effective to progressively deform at least one of said conductors to bring said bare surfaces thereof into electrically conductive contact to progressively reduce the inductance of the inductive element defined by said conductors and transferring explosive energy to said magnetic field effective to generate an electrical potential between undeformed portions of said conductors ahead of said explosive wave front.

  20. Lipedema: a clinical entity distinct from lymphedema.

    PubMed

    Rudkin, G H; Miller, T A

    1994-11-01

    In a review of 250 cases of lymphedema of the lower extremity, 9 patients were noted to share unique similarities in their history and physical findings. Although these patients had mild swelling in their pretibial areas and were all referred with a diagnosis of lymphedema of the legs, their findings differed significantly from the usual patient with either congenital or acquired lymphedema. Notably, the lower extremity swelling was always bilateral and symmetrical in nature and never involved the feet. Skin changes characteristic of lymphedema were not found, and consistent fat pads were present anterior to the lateral malleoli in each patient. These findings are representative of a clinical entity known as lipedema, which is distinct from lymphedema and for which treatment may be different.

  1. Distinct patterns of seasonal Greenland glacier velocity.

    PubMed

    Moon, Twila; Joughin, Ian; Smith, Ben; van den Broeke, Michiel R; van de Berg, Willem Jan; Noël, Brice; Usher, Mika

    2014-10-28

    Predicting Greenland Ice Sheet mass loss due to ice dynamics requires a complete understanding of spatiotemporal velocity fluctuations and related control mechanisms. We present a 5 year record of seasonal velocity measurements for 55 marine-terminating glaciers distributed around the ice sheet margin, along with ice-front position and runoff data sets for each glacier. Among glaciers with substantial speed variations, we find three distinct seasonal velocity patterns. One pattern indicates relatively high glacier sensitivity to ice-front position. The other two patterns are more prevalent and appear to be meltwater controlled. These patterns reveal differences in which some subglacial systems likely transition seasonally from inefficient, distributed hydrologic networks to efficient, channelized drainage, while others do not. The difference may be determined by meltwater availability, which in some regions may be influenced by perennial firn aquifers. Our results highlight the need to understand subglacial meltwater availability on an ice sheet-wide scale to predict future dynamic changes.

  2. Qualitative and Quantitative Distinctions in Personality Disorder

    PubMed Central

    Wright, Aidan G. C.

    2011-01-01

    The “categorical-dimensional debate” has catalyzed a wealth of empirical advances in the study of personality pathology. However, this debate is merely one articulation of a broader conceptual question regarding whether to define and describe psychopathology as a quantitatively extreme expression of normal functioning or as qualitatively distinct in its process. In this paper I argue that dynamic models of personality (e.g., object-relations, cognitive-affective processing system) offer the conceptual scaffolding to reconcile these seemingly incompatible approaches to characterizing the relationship between normal and pathological personality. I propose that advances in personality assessment that sample behavior and experiences intensively provide the empirical techniques, whereas interpersonal theory offers an integrative theoretical framework, for accomplishing this goal. PMID:22804676

  3. Two distinct mechanisms of fibroblast adhesion

    NASA Astrophysics Data System (ADS)

    Harper, P. A.; Juliano, R. L.

    1981-03-01

    The adhesion of cells to the connective tissue matrix is commonly thought to be governed by fibronectin, a pericellular glycoprotein with binding sites for cell surfaces, collagen and glycosaminoglycans. Here we report evidence that Chinese hamster ovary (CHO) cells possess an alternative mechanism for adhesion which is independent of fibronectin. Cells of a variant CHO clone called ADVF11 are defective in their ability to adhere to fibronectin-coated substrata, but can adhere to a substratum coated with SAM (substrate-attached material), a pericellular material produced by fibroblasts. The adhesion of wild-type CHO cells to fibronectin-coated substrata and adhesion of ADVF11 cells to SAM-coated substrata are differentially sensitive to proteolytic treatment. This suggests that there are two distinct adhesion mechanisms for CHO cells, only one of which is dependent on fibronectin.

  4. Hereditary gingival fibromatosis with distinctive facies.

    PubMed

    Prasad, Sunkara Shree Ramalinga; Radharani, Chitturi; Sinha, Soumya; Kumar, Sv Kiran

    2012-11-01

    Hereditary gingival enlargement also known as gingivitis or familial elephantiasis is a rare type of gingival enlargement. It appears as an isolated autosomal dominant disorder or maybe associated with other conditions. Oral manifestations may vary from minimal involvement of only tuberosity area and the buccal gingiva around the lower molars to a generalized enlargement inhibiting eruption of the teeth. This paper discusses the case of a 13-year-old female patient with distinctive facial characteristics who presented to the department with a chief complaint of swollen gums since 1 year. She had severe diffuse gingival enlargement of the maxilla and mandible. Diagnosis was made based upon clinical examination and family history. Quadrant wise internal bevel gingivectomy procedure was done for the patient to restore her functional and esthetic needs.

  5. Three Distinct Glutamate Decarboxylase Genes in Vertebrates

    PubMed Central

    Grone, Brian P.; Maruska, Karen P.

    2016-01-01

    Gamma-aminobutyric acid (GABA) is a widely conserved signaling molecule that in animals has been adapted as a neurotransmitter. GABA is synthesized from the amino acid glutamate by the action of glutamate decarboxylases (GADs). Two vertebrate genes, GAD1 and GAD2, encode distinct GAD proteins: GAD67 and GAD65, respectively. We have identified a third vertebrate GAD gene, GAD3. This gene is conserved in fishes as well as tetrapods. We analyzed protein sequence, gene structure, synteny, and phylogenetics to identify GAD3 as a homolog of GAD1 and GAD2. Interestingly, we found that GAD3 was lost in the hominid lineage. Because of the importance of GABA as a neurotransmitter, GAD3 may play important roles in vertebrate nervous systems. PMID:27461130

  6. Socioeconomic Distinction, Cultural Tastes, and Cigarette Smoking.

    PubMed

    Pampel, Fred C

    2006-03-01

    OBJECTIVES: The inverse relationship between socioeconomic status (SES) and smoking is typically seen in terms of the greater economic and social resources of advantaged groups, but it may also relate to cultural resources. This study aims to test theories of symbolic distinction by examining relationships between smoking and ostensibly unrelated cultural preferences. METHODS: Using the 1993 General Social Survey, ordinal logistic regression models, and a three-category dependent variable (never, former, and current smoker), the analysis estimates relationships of musical likes and dislikes with smoking while controlling for SES and social strain. RESULTS: Preferences for classical music are associated with lower smoking, while preferences for bluegrass, jazz, and heavy metal music are associated with higher smoking. CONCLUSIONS: The results suggest that SES groups may use smoking, like other cultural tastes, to distinguish their lifestyles from those of others.

  7. Socioeconomic Distinction, Cultural Tastes, and Cigarette Smoking*

    PubMed Central

    Pampel, Fred C.

    2011-01-01

    Objectives The inverse relationship between socioeconomic status (SES) and smoking is typically seen in terms of the greater economic and social resources of advantaged groups, but it may also relate to cultural resources. This study aims to test theories of symbolic distinction by examining relationships between smoking and ostensibly unrelated cultural preferences. Methods Using the 1993 General Social Survey, ordinal logistic regression models, and a three-category dependent variable (never, former, and current smoker), the analysis estimates relationships of musical likes and dislikes with smoking while controlling for SES and social strain. Results Preferences for classical music are associated with lower smoking, while preferences for bluegrass, jazz, and heavy metal music are associated with higher smoking. Conclusions The results suggest that SES groups may use smoking, like other cultural tastes, to distinguish their lifestyles from those of others. PMID:21874073

  8. Lakshmi Planum: A distinctive highland volcanic province

    NASA Technical Reports Server (NTRS)

    Roberts, Kari M.; Head, James W.

    1989-01-01

    Lakshmi Planum, a broad smooth plain located in western Ishtar Terra and containing two large oval depressions (Colette and Sacajawea), has been interpreted as a highland plain of volcanic origin. Lakshmi is situated 3 to 5 km above the mean planetary radius and is surrounded on all sides by bands of mountains interpreted to be of compressional tectonic origin. Four primary characteristics distinguish Lakshmi from other volcanic regions known on the planet, such as Beta Regio: (1) high altitude, (2) plateau-like nature, (3) the presence of very large, low volcanic constructs with distinctive central calderas, and (4) its compressional tectonic surroundings. Building on the previous work of Pronin, the objective is to establish the detailed nature of the volcanic deposits on Lakshmi, interpret eruption styles and conditions, sketch out an eruption history, and determine the relationship between volcanism and the tectonic environment of the region.

  9. Independent Optical Excitation of Distinct Neural Populations

    PubMed Central

    Klapoetke, Nathan C; Murata, Yasunobu; Kim, Sung Soo; Pulver, Stefan R.; Birdsey-Benson, Amanda; Cho, Yong Ku; Morimoto, Tania K; Chuong, Amy S; Carpenter, Eric J; Tian, Zhijian; Wang, Jun; Xie, Yinlong; Yan, Zhixiang; Zhang, Yong; Chow, Brian Y; Surek, Barbara; Melkonian, Michael; Jayaraman, Vivek; Constantine-Paton, Martha; Wong, Gane Ka-Shu; Boyden, Edward S

    2014-01-01

    Optogenetic tools enable the causal examination of how specific cell types contribute to brain circuit functions. A long-standing question is whether it is possible to independently activate two distinct neural populations in mammalian brain tissue. Such a capability would enable the examination of how different synapses or pathways interact to support computation. Here we report two new channelrhodopsins, Chronos and Chrimson, obtained through the de novo sequencing and physiological characterization of opsins from over 100 species of algae. Chrimson is 45 nm red-shifted relative to any previous channelrhodopsin, important for scenarios where red light would be preferred; we show minimal visual system mediated behavioral artifact in optogenetically stimulated Drosophila. Chronos has faster kinetics than any previous channelrhodopsin, yet is effectively more light-sensitive. Together, these two reagents enable crosstalk-free two-color activation of neural spiking and downstream synaptic transmission in independent neural populations in mouse brain slice. PMID:24509633

  10. ngravs: Distinct gravitational interactions in GADGET-2

    NASA Astrophysics Data System (ADS)

    Croker, K. A. S.

    2016-10-01

    We discuss an extension of the massively parallel cosmological simulation code GADGET-2, which now enables investigation of multiple and distinct gravitational force laws, provided they are dominated by a constant scaling of the Newtonian force. In addition to simplifying investigations of a universally modified force law, the ngravs extension provides a foundation for state-of-the-art collisionless cosmological simulations of exotic gravitational scenarios. We briefly review the algorithms used by GADGET-2, and present our extension to multiple gravities, highlighting additional features that facilitate consideration of exotic force laws. We discuss the accuracy and performance of the ngravs extension, both internally and with an unaltered GADGET-2, in the relevant operational modes. The ngravs extension is publicly released to the research community.

  11. Opioid receptors: distinct roles in mood disorders

    PubMed Central

    Lutz, Pierre-Eric; Kieffer, Brigitte L.

    2012-01-01

    The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention. Accumulating evidence from animal research reveal that mu, delta and kappa opioid receptors (MORs, DORs and KORs, respectively) exert highly distinct controls over mood-related processes. DOR agonists and KOR antagonists have promising antidepressant potential, whereas the risk-benefit ratio of currently available MOR agonists as antidepressants remain difficult to evaluate, in addition to their inherent abuse liability. At present, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address delta and kappa receptor function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment and social behaviors. PMID:23219016

  12. Mushrooms—Biologically Distinct and Nutritionally Unique

    PubMed Central

    Feeney, Mary Jo; Miller, Amy Myrdal; Roupas, Peter

    2014-01-01

    Mushrooms are fungi, biologically distinct from plant- and animal-derived foods (fruits, vegetables, grains, dairy, protein [meat, fish, poultry, legumes, nuts, and seeds]) that comprise the US Department of Agriculture food patterns operationalized by consumer-focused MyPlate messages. Although mushrooms provide nutrients found in these food groups, they also have a unique nutrient profile. Classified into food grouping systems by their use as a vegetable, mushrooms’ increasing use in main entrées in plant-based diets is growing, supporting consumers’ efforts to follow dietary guidance recommendations. Mushrooms’ nutrient and culinary characteristics suggest it may be time to reevaluate food groupings and health benefits in the context of 3 separate food kingdoms: plants/botany, animals/zoology, and fungi/mycology. PMID:25435595

  13. Entrepreneurship research in Spain: developments and distinctiveness.

    PubMed

    Sánchez, José C; Gutiérrez, Andrea

    2011-08-01

    This article presents a review of research on entrepreneurship in Spain, paying particular attention to its beginnings, nature and main focus of interest. We have developed a database based on the review of 471 works produced between 1977 and 2009, including articles published in national and international journals and dissertations (read in Spain) that allowed us to extract the following results. There is a preference for qualitative methods, conceptual contributions and the entrepreneurial process as the privileged research theme. There is also a strong focus of interest on micro and small enterprises. These characteristics of Spanish research in areas of entrepreneurship can make a distinctive contribution to international research. However, the dissemination of knowledge and inadequate strategies for international publication limit the diffusion of Spanish research in entrepreneurship. Lastly, we discuss the implications for future research.

  14. The distinction between transudates and exudates.

    PubMed

    Gonlugur, Ugur; Gonlugur, Tanseli Efeoglu

    2005-12-01

    The first step in the diagnosis of pleural effusions is the distinction between exudates and transudates. The aim of this study was to evaluate the usefulness of various parameters for the differentiation of pleural exudates and transudates. We recorded clinical characteristics, final diagnoses, and measured pleural fluid and serum levels of albumin, protein, LDH, cholesterol, and bilirubin of 381 consecutive patients with pleural effusion. Seventy-one (23%) pleural effusions were transudates and 236 were exudates. As a single criterion, the pleural fluid to serum albumin ratio >0.5 was the most accurate parameter (88.4%). An albumin gradient of 12 g/l had an accuracy of 75% in the whole population but it detected 96% of transudative effusions in patients treated with diuretics. Light's criteria and abbreviated Light's criteria had similar accuracies, 87.8% vs. 88.2%, respectively. In conclusions, different alternatives can be used instead of Light's criteria.

  15. Postpartum period: three distinct but continuous phases

    PubMed Central

    Romano, Mattea; Cacciatore, Alessandra; Giordano, Rosalba; La Rosa, Beatrice

    2010-01-01

    Postpartum period is distinct in three phases. The third phase is the delayed postpartum period, which can last up to 6 months. Some changes to the genitourinary system are much longer in resolving, and some may never fully revert to the prepregnant state. A burgeoning volume of literature on pelvic floor support implicates childbirth as the initiation of a whole host of conditions including stress urinary incontinence, incontinence of flatus or feces, uterine prolapse, cystocele, and rectocele. The duration and severity of these conditions affect many variables, including the patientʼs intrinsic collagen support, the size of the infant, the route of delivery, and the degree of perineal trauma occurring either naturally (lacerations) or iatrogenically (episiotomy). PMID:22439056

  16. Neuropsychological evidence for three distinct motion mechanisms

    PubMed Central

    Vaina, Lucia M.; Dumoulin, Serge O.

    2012-01-01

    We describe psychophysical performance of two stroke patients with lesions in distinct cortical regions in the left hemisphere. Both patients were selectively impaired on direction discrimination in several local and global second-order but not first-order motion tasks. However, only patient FD was impaired on a specific bi-stable motion task where the direction of motion is biased by object similarity. We suggest that this bi-stable motion task may be mediated by a high-level attention or position based mechanism indicating a separate neurological substrate for a high-level attention or position-based mechanism. Therefore, these results provide evidence for the existence of at least three motion mechanisms in the human visual system: a low-level first-and second-order motion mechanism and a high-level attention or position-based mechanism. PMID:21440602

  17. Oxytocin and vasopressin: distinct receptors in myometrium

    SciTech Connect

    Guillon, G.; Balestre, M.N.; Roberts, J.M.; Bottari, S.P.

    1987-06-01

    The binding characteristics of (/sup 3/H)oxytocin (( /sup 3/H)OT) and (/sup 3/H)lysine vasopressin (( /sup 3/H)LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas (/sup 3/H)OT was found to bind to a single class of sites with high affinity (Kd, 1.5 +/- 0.4 (+/- SEM) nM) and low capacity (maximum binding (Bmax), 34 +/- 6 fmol/mg protein), (/sup 3/H)LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for (/sup 3/H)OT and (/sup 3/H)LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for (/sup 3/H)LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.

  18. The pursuit of optimal distinctiveness and consumer preferences.

    PubMed

    He, Lingnan; Cong, Feng; Liu, Yanping; Zhou, Xinyue

    2010-10-01

    This article investigates the effect of optimal distinctiveness on consumer product consumption. The authors argue that consumers acquire and display material possessions to restore their optimal levels of distinctiveness. Results showed that placing consumers in a state of low distinctiveness increased desire to acquire distinctive products, whereas perceptions of high distinctiveness reduced desire to acquire such products. Consumers' desire for distinctiveness-related products held true for various consumer choices, including willingness to pay more for limited-edition products and preference for unpopular gifts. This finding has implications for understanding consumer choice in expressing identity.

  19. Piezoelectrostatic generator

    NASA Technical Reports Server (NTRS)

    Robertson, Glen A. (Inventor)

    1990-01-01

    A piezoelectrostatic generator includes a plurality of elongated piezoelectric elements having first and second ends, with the first ends fixedly mounted in a cylindrical housing and the second extending radially inwardly toward an axis. A shaft movable along the axis is connected to the inner ends of the elements to produce bending forces in piezoelectric strips within the elements. Each element includes a pair of strips mounted in surface contact and in electrical series to produce a potential upon bending. Electrodes spaced from the strips by a solid dielectric material act as capacitor plates to collect the potential charge.

  20. Smoke generator

    NASA Technical Reports Server (NTRS)

    Rogers, J. R. (Inventor)

    1976-01-01

    A smoke generator is disclosed which is particularly suitable for mounting on the wing tips of an aircraft and for conducting airflow studies. The device includes a network of thermally insulated tubes for carrying a fluid which is used to produce smoke. The fluid, which need not be combustible, is heated above its vaporization temperature by electric current which is passed through the fluid conduit tubes, so that the tubes serve both as fluid conduits and resistance heating elements. Fluid supply and monitoring systems and electrical control systems are also disclosed.

  1. HEAT GENERATION

    DOEpatents

    Imhoff, D.H.; Harker, W.H.

    1963-12-01

    Heat is generated by the utilization of high energy neutrons produced as by nuclear reactions between hydrogen isotopes in a blanket zone containing lithium, a neutron moderator, and uranium and/or thorium effective to achieve multtplicatton of the high energy neutron. The rnultiplied and moderated neutrons produced react further with lithium-6 to produce tritium in the blanket. Thermal neutron fissionable materials are also produced and consumed in situ in the blanket zone. The heat produced by the aggregate of the various nuclear reactions is then withdrawn from the blanket zone to be used or otherwise disposed externally. (AEC)

  2. Tide generator

    SciTech Connect

    Feltenberger, B.D.

    1981-06-16

    A tidewater power system consisting of a high tide reservoir and a low tide reservoir. The high tide reservoir has an inlet adapted to be supported at high tide level and an outlet with a water wheel and generator between the outlet of the high tide reservoir and the low tide reservoir. The low tide reservoir has an outlet at the low tide level. The outlet from the high tide reservoir is adjustable to control the flow rate and the high tide reservoir can be closed at high tide to retain water for use over a period of time.

  3. Loading and pre-loading processes generate a distinct siRNA population in Tetrahymena.

    PubMed

    Mochizuki, Kazufumi; Kurth, Henriette M

    2013-07-05

    The various properties of small RNAs, such as length, terminal nucleotide, thermodynamic asymmetry and duplex mismatches, can impact their sorting into different Argonaute proteins in diverse eukaryotes. The developmentally regulated 26- to 32-nt siRNAs (scnRNAs) are loaded to the Argonaute protein Twi1p and display a strong bias for uracil at the 5' end. In this study, we used deep sequencing to analyze loaded and unloaded populations of scnRNAs. We show that the size of the scnRNA is determined during a pre-loading process, whereas their 5' uracil bias is attributed to both pre-loading and loading processes. We also demonstrate that scnRNAs have a strong bias for adenine at the third base from the 3' terminus, suggesting that most scnRNAs are direct Dicer products. Furthermore, we show that the thermodynamic asymmetry of the scnRNA duplex does not affect the guide and passenger strand decision. Finally, we show that scnRNAs frequently have templated uracil at the last base without a strong bias for adenine at the second base indicating non-sequential production of scnRNAs from substrates. These findings provide a biochemical basis for the varying attributes of scnRNAs, which should help improve our understanding of the production and turnover of scnRNAs in vivo. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.

    PubMed

    Zuena, Anna Rita; Mairesse, Jerome; Casolini, Paola; Cinque, Carlo; Alemà, Giovanni Sebastiano; Morley-Fletcher, Sara; Chiodi, Valentina; Spagnoli, Luigi Giusto; Gradini, Roberto; Catalani, Assia; Nicoletti, Ferdinando; Maccari, Stefania

    2008-05-14

    Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS ("PRS rats") showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.

  5. Gene conversion variations generate structurally distinct pilin polypeptides in Neisseria gonorrhoeae.

    PubMed

    Swanson, J; Robbins, K; Barrera, O; Koomey, J M

    1987-04-01

    Pilus+ to pilus- phenotype change occurs in Neisseria gonorrhoeae through gene conversion of the gonococcus' complete, expressed pilin gene by nucleotides homologous to the pilS1 copy 5 partial pilin gene; assembly missense pilin is synthesized but pili are not. Reversion to pilus+ occurs by a subsequent recombinational event that replaces the complete pilin gene's pilS1 copy 5-like sequence with nucleotides from a different partial gene to effect expression of an orthodox (i.e., pilus producing) pilin. Sibling pilus+ revertants of common parentage can carry different sequences in their expressed pilin genes because they have undergone nonidentical gene conversion events such as recombinations with sequences from different partial genes, or recombinations with different length nucleotide stretches of the same partial gene; either can yield structurally and antigenically variant pilin polypeptides.

  6. Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks.

    PubMed

    Chopin, Michaël; Seillet, Cyril; Chevrier, Stéphane; Wu, Li; Wang, Hongsheng; Morse, Herbert C; Belz, Gabrielle T; Nutt, Stephen L

    2013-12-16

    Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation remain sparse. We addressed the function of a group of key DC transcription factors-PU.1, ID2, IRF4, and IRF8-in the establishment of the LC network. We show that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow-derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-β responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements in a TGF-β-dependent manner, whereas ectopic expression of RUNX3 rescued LC differentiation in the absence of PU.1 and promoted LC differentiation from PU.1-sufficient progenitors. These findings highlight the dual molecular network underlying LC differentiation, and show the central role of PU.1 in these processes.

  7. Distinct binding of BRCA2 BRC repeats to RAD51 generates differential DNA damage sensitivity

    PubMed Central

    Chatterjee, Gouri; Jimenez-Sainz, Judit; Presti, Thomas; Nguyen, Tiffany; Jensen, Ryan B.

    2016-01-01

    BRCA2 is a multi-faceted protein critical for the proper regulation of homology-directed repair of DNA double-strand breaks. Elucidating the mechanistic features of BRCA2 is crucial for understanding homologous recombination and how patient-derived mutations impact future cancer risk. Eight centrally located BRC repeats in BRCA2 mediate binding and regulation of RAD51 on resected DNA substrates. Herein, we dissect the biochemical and cellular features of the BRC repeats tethered to the DNA binding domain of BRCA2. To understand how the BRC repeats and isolated domains of BRCA2 contribute to RAD51 binding, we analyzed both the biochemical and cellular properties of these proteins. In contrast to the individual BRC repeat units, we find that the BRC5–8 region potentiates RAD51-mediated DNA strand pairing and provides complementation functions exceeding those of BRC repeats 1–4. Furthermore, BRC5–8 can efficiently repair nuclease-induced DNA double-strand breaks and accelerate the assembly of RAD51 repair complexes upon DNA damage. These findings highlight the importance of the BRC5–8 domain in stabilizing the RAD51 filament and promoting homology-directed repair under conditions of cellular DNA damage. PMID:27084934

  8. Prenatal Restraint Stress Generates Two Distinct Behavioral and Neurochemical Profiles in Male and Female Rats

    PubMed Central

    Casolini, Paola; Cinque, Carlo; Alemà, Giovanni Sebastiano; Morley-Fletcher, Sara; Chiodi, Valentina; Spagnoli, Luigi Giusto; Gradini, Roberto; Catalani, Assia; Nicoletti, Ferdinando; Maccari, Stefania

    2008-01-01

    Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS (“PRS rats”) showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females. PMID:18478112

  9. Alternative mRNA splicing generates two distinct ADAM12 prodomain variants.

    PubMed

    Duhachek-Muggy, Sara; Li, Hui; Qi, Yue; Zolkiewska, Anna

    2013-01-01

    Human ADAM12, transcript variant 1 (later on referred to as Var-1b), present in publicly available databases contains the sequence 5'-GTAATTCTG-3' at the nucleotide positions 340-348 of the coding region, at the 3' end of exon 4. The translation product of this variant, ADAM12-Lb, includes the three amino acid motif (114)VIL(116) in the prodomain. This motif is not conserved in ADAM12 from different species and is not present in other human ADAMs. Currently, it is not clear whether a shorter variant, Var-1a, encoding the protein version without the (114)VIL(116) motif, ADAM12-La, is expressed in human. In this work, we have established that human mammary epithelial cells and breast cancer cells express both Var-1a and Var-1b transcripts. Importantly, the proteolytic processing and intracellular trafficking of the corresponding ADAM12-La and ADAM12-Lb proteins are different. While ADAM12-La is cleaved and trafficked to the cell surface in a manner similar to ADAM12 in other species, ADAM12-Lb is retained in the ER and is not proteolytically processed. Furthermore, the relative abundance of ADAM12-La and ADAM12-Lb proteins detected in several breast cancer cell lines varies significantly. We conclude that the canonical form of transmembrane ADAM12 is represented by Var-1a/ADAM12-La, rather than Var-1b/ADAM12-Lb currently featured in major sequence databases.

  10. Loading and pre-loading processes generate a distinct siRNA population in Tetrahymena

    SciTech Connect

    Mochizuki, Kazufumi Kurth, Henriette M.

    2013-07-05

    Highlights: •The Tetrahymena Argonaute protein Twi1p binds to ∼28–30-nt siRNAs called scnRNAs. •The size of scnRNAs is determined during a pre-loading process. •The 5′ uracil bias of scnRNAs is attributed to pre-loading and loading processes. •The thermodynamic asymmetry of scnRNA duplex doesnot affect the guide strand decision. •scnRNAs may be produced non-sequentially from dsRNA substrates by Dicer. -- Abstract: The various properties of small RNAs, such as length, terminal nucleotide, thermodynamic asymmetry and duplex mismatches, can impact their sorting into different Argonaute proteins in diverse eukaryotes. The developmentally regulated 26- to 32-nt siRNAs (scnRNAs) are loaded to the Argonaute protein Twi1p and display a strong bias for uracil at the 5′ end. In this study, we used deep sequencing to analyze loaded and unloaded populations of scnRNAs. We show that the size of the scnRNA is determined during a pre-loading process, whereas their 5′ uracil bias is attributed to both pre-loading and loading processes. We also demonstrate that scnRNAs have a strong bias for adenine at the third base from the 3′ terminus, suggesting that most scnRNAs are direct Dicer products. Furthermore, we show that the thermodynamic asymmetry of the scnRNA duplex does not affect the guide and passenger strand decision. Finally, we show that scnRNAs frequently have templated uracil at the last base without a strong bias for adenine at the second base indicating non-sequential production of scnRNAs from substrates. These findings provide a biochemical basis for the varying attributes of scnRNAs, which should help improve our understanding of the production and turnover of scnRNAs in vivo.

  11. Magnetocumulative generator

    DOEpatents

    Pettibone, Joseph S.; Wheeler, Paul C.

    1983-01-01

    An improved magnetocumulative generator is described that is useful for producing magnetic fields of very high energy content over large spatial volumes. The polar directed pleated magnetocumulative generator has a housing (100, 101, 102, 103, 104, 105) providing a housing chamber (106) with an electrically conducting surface. The chamber (106) forms a coaxial system having a small radius portion and a large radius portion. When a magnetic field is injected into the chamber (106), from an external source, most of the magnetic flux associated therewith positions itself in the small radius portion. The propagation of an explosive detonation through high-explosive layers (107, 108) disposed adjacent to the housing causes a phased closure of the chamber (106) which sweeps most of the magnetic flux into the large radius portion of the coaxial system. The energy content of the magnetic field is greatly increased by flux stretching as well as by flux compression. The energy enhanced magnetic field is utilized within the housing chamber itself.

  12. A Search for Institutional Distinctiveness: Overview of Process and Possibilities.

    ERIC Educational Resources Information Center

    Townsend, Barbara K.

    1989-01-01

    Provides an overview of the process by which community college practitioners can research their institution's distinctive elements and features. Explains the use of information on institutional distinctiveness in program development, marketing, and college planning. (DMM)

  13. Yeast cells can access distinct quiescent states.

    PubMed

    Klosinska, Maja M; Crutchfield, Christopher A; Bradley, Patrick H; Rabinowitz, Joshua D; Broach, James R

    2011-02-15

    We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth. In contrast, the metabolic changes that occur upon starvation and the genetic requirements for surviving starvation differ significantly depending on the nutrient for which the cell is starved. The genes needed by cells to survive starvation do not overlap the genes that are induced upon starvation. We conclude that cells do not access a unique and discrete G(0) state, but rather are programmed, when nutrients are scarce, to prepare for a range of possible future stressors. Moreover, these survival strategies are not unique to quiescence, but are engaged by the cell in proportion to nutrient scarcity.

  14. China's distinctive engagement in global health.

    PubMed

    Liu, Peilong; Guo, Yan; Qian, Xu; Tang, Shenglan; Li, Zhihui; Chen, Lincoln

    2014-08-30

    China has made rapid progress in four key domains of global health. China's health aid deploys medical teams, constructs facilities, donates drugs and equipment, trains personnel, and supports malaria control mainly in Africa and Asia. Prompted by the severe acute respiratory syndrome (SARS) outbreak in 2003, China has prioritised the control of cross-border transmission of infectious diseases and other health-related risks. In governance, China has joined UN and related international bodies and has begun to contribute to pooled multilateral funds. China is both a knowledge producer and sharer, offering lessons based on its health accomplishments, traditional Chinese medicine, and research and development investment in drug discovery. Global health capacity is being developed in medical universities in China, which also train foreign medical students. China's approach to global health is distinctive; different from other countries; and based on its unique history, comparative strength, and policies driven by several governmental ministries. The scope and depth of China's global engagement are likely to grow and reshape the contours of global health. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Reservoir floodplains support distinct fish assemblages

    USGS Publications Warehouse

    Miranda, Leandro E.; Wigen, S. L.; Dagel, Jonah D.

    2014-01-01

    Reservoirs constructed on floodplain rivers are unique because the upper reaches of the impoundment may include extensive floodplain environments. Moreover, reservoirs that experience large periodic water level fluctuations as part of their operational objectives seasonally inundate and dewater floodplains in their upper reaches, partly mimicking natural inundations of river floodplains. In four flood control reservoirs in Mississippi, USA, we explored the dynamics of connectivity between reservoirs and adjacent floodplains and the characteristics of fish assemblages that develop in reservoir floodplains relative to those that develop in reservoir bays. Although fish species richness in floodplains and bays were similar, species composition differed. Floodplains emphasized fish species largely associated with backwater shallow environments, often resistant to harsh environmental conditions. Conversely, dominant species in bays represented mainly generalists that benefit from the continuous connectivity between the bay and the main reservoir. Floodplains in the study reservoirs provided desirable vegetated habitats at lower water level elevations, earlier in the year, and more frequently than in bays. Inundating dense vegetation in bays requires raising reservoir water levels above the levels required to reach floodplains. Therefore, aside from promoting distinct fish assemblages within reservoirs and helping promote diversity in regulated rivers, reservoir floodplains are valued because they can provide suitable vegetated habitats for fish species at elevations below the normal pool, precluding the need to annually flood upland vegetation that would inevitably be impaired by regular flooding. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  16. Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles

    PubMed Central

    Hu, Shijia; Parker, Joel; Divaris, Kimon; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50–80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human “dentome”) for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment. PMID:27491308

  17. Morphologically and Functionally Distinct Lipid Droplet Subpopulations

    PubMed Central

    Zhang, Shuyan; Wang, Yang; Cui, Liujuan; Deng, Yaqin; Xu, Shimeng; Yu, Jinhai; Cichello, Simon; Serrero, Ginette; Ying, Yunshu; Liu, Pingsheng

    2016-01-01

    Lipid droplet (LD), a multi-functional organelle, is often found to associate with other cellular membranous structures and vary in size in a given cell, which may be related to their functional diversity. Here we established a method to separate LD subpopulations from isolated CHO K2 LDs into three different size categories. The subpopulation with smallest LDs was nearly free of ER and other membranous structures while those with larger LDs contained intact ER. These distinct subpopulations of LDs differed in their protein composition and ability to recruit proteins. This method was also applicable to LDs obtained from other sources, such as Huh7 cells, mouse liver and brown adipose tissue, et al. We developed an in vitro assay requiring only isolated LDs, Coenzyme A, and ATP to drive lipid synthesis. The LD subpopulation nearly depleted of ER was able to incorporate fatty acids into triacylglycerol and phospholipids. Together, our data demonstrate that LDs in a given cell are heterogeneous in size and function, and suggest that LDs are one of cellular lipid synthetic organelles. PMID:27386790

  18. Modeling the distinct phases of skill acquisition.

    PubMed

    Tenison, Caitlin; Anderson, John R

    2016-05-01

    A focus of early mathematics education is to build fluency through practice. Several models of skill acquisition have sought to explain the increase in fluency because of practice by modeling both the learning mechanisms driving this speedup and the changes in cognitive processes involved in executing the skill (such as transitioning from calculation to retrieval). In the current study, we use hidden Markov modeling to identify transitions in the learning process. This method accounts for the gradual speedup in problem solving and also uncovers abrupt changes in reaction time, which reflect changes in the cognitive processes that participants are using to solve math problems. We find that as participants practice solving math problems they transition through 3 distinct learning states. Each learning state shows some speedup with practice, but the major speedups are produced by transitions between learning states. In examining and comparing the behavioral and neurological profiles of each of these states, we find parallels with the 3 phases of skill acquisition proposed by Fitts and Posner (1967): a cognitive, an associative, and an autonomous phase. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. Are empathy and concern psychologically distinct?

    PubMed

    Jordan, Matthew R; Amir, Dorsa; Bloom, Paul

    2016-12-01

    Researchers have long been interested in the relationship between feeling what you believe others feel-often described as empathy-and caring about the welfare of others-often described as compassion or concern. Many propose that empathy is a prerequisite for concern and is therefore the ultimate motivator of prosocial actions. To assess this hypothesis, the authors developed the Empathy Index, which consists of 2 novel scales, and explored their relationship to a measure of concern as well as to measures of cooperative and altruistic behavior. A series of factor analyses reveal that empathy and concern consistently load on different factors. Furthermore, they show that empathy and concern motivate different behaviors: concern for others is a uniquely positive predictor of prosocial action whereas empathy is either not predictive or negatively predictive of prosocial actions. Together these studies suggest that empathy and concern are psychologically distinct and empathy plays a more limited role in our moral lives than many believe. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. Distinct patterns of seasonal Greenland glacier velocity

    PubMed Central

    Moon, Twila; Joughin, Ian; Smith, Ben; van den Broeke, Michiel R; van de Berg, Willem Jan; Noël, Brice; Usher, Mika

    2014-01-01

    Predicting Greenland Ice Sheet mass loss due to ice dynamics requires a complete understanding of spatiotemporal velocity fluctuations and related control mechanisms. We present a 5 year record of seasonal velocity measurements for 55 marine-terminating glaciers distributed around the ice sheet margin, along with ice-front position and runoff data sets for each glacier. Among glaciers with substantial speed variations, we find three distinct seasonal velocity patterns. One pattern indicates relatively high glacier sensitivity to ice-front position. The other two patterns are more prevalent and appear to be meltwater controlled. These patterns reveal differences in which some subglacial systems likely transition seasonally from inefficient, distributed hydrologic networks to efficient, channelized drainage, while others do not. The difference may be determined by meltwater availability, which in some regions may be influenced by perennial firn aquifers. Our results highlight the need to understand subglacial meltwater availability on an ice sheet-wide scale to predict future dynamic changes. Key Points First multi-region seasonal velocity measurements show regional differences Seasonal velocity fluctuations on most glaciers appear meltwater controlled Seasonal development of efficient subglacial drainage geographically divided PMID:25821275

  1. Medical student empathy: interpersonal distinctions and correlates.

    PubMed

    Jordan, Kevin D; Foster, Penni Smith

    2016-12-01

    Attention to interpersonal behaviors, communication, and relational factors is taking on increasing importance in medical education. Medical student empathy is one aspect of the physician-patient relationship that is often involved in beneficial interactions leading to improved clinical outcomes and patient satisfaction. As an interpersonal quality, empathy is a social behavior well-suited to be examined from an interpersonal perspective. The present study used the interpersonal theory of clinical, personality, and social psychology to examine the construct of empathy and theorize about likely interpersonal correlates. One hundred and sixty-three students from an academic health center in the southeastern United States participated in this study. The medical student version of the Jefferson Scale of Empathy was used to assess empathy and its factors: Perspective taking, compassionate care, and walking in the patient's shoes. Interpersonal assessments included the International Personality Item Pool-Interpersonal Circumplex, the Interpersonal Support Evaluation List, and the UCLA Loneliness Scale. Distinct interpersonal styles and correlates emerged among empathy and its factors. While all factors of empathy were related to interpersonal warmth, perspective taking and compassionate care were also associated with submissiveness. Of note, only walking in the patient's shoes was correlated with both social support and less loneliness. These findings are discussed in light of interpersonal theory with particular attention paid to the implications for medical education and professional development.

  2. HYSTERESIS BETWEEN DISTINCT MODES OF TURBULENT DYNAMOS

    SciTech Connect

    Karak, Bidya Binay; Brandenburg, Axel; Kitchatinov, Leonid L.

    2015-04-20

    Nonlinear mean-field models of the solar dynamo show long-term variability, which may be relevant to different states of activity inferred from long-term radiocarbon data. This paper is aimed at probing the dynamo hysteresis predicted by the recent mean-field models of Kitchatinov and Olemskoy with direct numerical simulations. We perform three-dimensional (3D) simulations of large-scale dynamos in a shearing box with helically forced turbulence. As an initial condition, we either take a weak random magnetic field or we start from a snapshot of an earlier simulation. Two quasi-stable states are found to coexist in a certain range of parameters close to the onset of the large-scale dynamo. The simulations converge to one of these states depending on the initial conditions. When either the fractional helicity or the magnetic Prandtl number is increased between successive runs above the critical value for onset of the dynamo, the field strength jumps to a finite value. However, when the fractional helicity or the magnetic Prandtl number is then decreased again, the field strength stays at a similar value (strong field branch) even below the original onset. We also observe intermittent decaying phases away from the strong field branch close to the point where large-scale dynamo action is just possible. The dynamo hysteresis seen previously in mean-field models is thus reproduced by 3D simulations. Its possible relation to distinct modes of solar activity such as grand minima is discussed.

  3. Is fibromyalgia a distinct clinical syndrome?

    PubMed

    Rau, C L; Russell, I J

    2000-01-01

    The validity of the fibromyalgia syndrome (FMS) as a distinct clinical entity has been challenged for several reasons. Many skeptics express concern about the subjective nature of chronic pain, the subjectivity of the tender point (TeP) examination, the lack of a gold standard laboratory test, and the absence of a clear pathogenic mechanism by which to define FMS. Another expressed concern has been the relative nature of the pain-distress relationship in the rheumatology clinic. The apparently continuous relationship between TePs and somatic distress across a variety of clinical disorders is said to argue against FMS as a separate clinical disorder. The most aggressive challenges of the FMS concept have been from legal defenses of insurance carriers motivated by economic concerns. Other forms of critique have presented as psychiatric dogma, uninformed posturing, suspicion of malingering, ignorance of nociceptive physiology, and occasionally have resulted from honest misunderstanding. It is not likely that a few paragraphs of data and logic will cause an unbeliever to change an ingrained opinion. Therefore, this review describes the clinical manifestations of FMS, responds to some of the theoretic arguments against it, and discusses some possible pathophysiologic mechanisms by which FMS may develop and persist as a unique syndrome.

  4. Distinct vascular conduction with cortical spreading depression.

    PubMed

    Brennan, Kevin C; Beltrán-Parrazal, Luis; López-Valdés, Hector E; Theriot, Jeremy; Toga, Arthur W; Charles, Andrew C

    2007-06-01

    Cortical spreading depression (CSD) is associated with significant vasodilatation and vasoconstriction, but the relationship between the cortical parenchymal and vascular phenomena remains poorly understood. We used optical intrinsic signal (OIS) imaging and electrophysiology to simultaneously examine the vascular and parenchymal changes that occur with CSD in anesthetized mice and rats. CSD was associated with a propagated multiphasic change in optical reflectance, with correlated negative DC shift in field potential. Dilatation of cortical surface arterioles propagated with a significantly greater intrinsic velocity than the parenchymal CSD wavefront measured by OIS and electrophysiology. Dilatation traveled in a circuitous pattern along individual arterioles, indicating specific vascular conduction as opposed to concentric propagation of a parenchymal signal. Arteriolar dilatation propagated into areas beyond the spread of parenchymal OIS and electrophysiological changes of CSD. Conversely, vasomotor activity could be experimentally dissociated from the parenchymal CSD wave. Frequent repetitive CSD evoked by continuous stimulation was associated with a reduced or absent arteriolar response despite preserved parenchymal OIS and electrophysiological changes. Similarly, dimethylsulfoxide at high concentrations (10%) inhibited arteriolar reactivity despite preserved parenchymal OIS and electrophysiological changes. These results suggest a mechanism, intrinsic to the vasculature, for propagation of vasodilatation associated with CSD. Distinct vascular conduction could be important for the pathogenesis of conditions that involve CSD, including migraine, stroke, and traumatic brain injury.

  5. Distinctive features of internally driven magnetotail reconnection

    NASA Astrophysics Data System (ADS)

    Sitnov, M. I.; Merkin, V. G.; Pritchett, P. L.; Swisdak, M.

    2017-04-01

    Onset of reconnection in a tail-like equilibrium with a finite Bz magnetic field component is studied using 3-D explicit particle-in-cell simulations. Due to a region of a tailward Bz gradient the onset develops spontaneously as the magnetic flux release instability with dominant earthward ion flows. The instability drives the change of magnetic field topology internally, without any external forcing. The distinctive features of this regime are: previously unreported Hall magnetic field patterns; energy conversion near the dipolarization front prior to the X line formation; asymmetry of the energy conversion, plasma heating, and anisotropy relative to the X line, with regions of ion and electron heating out of phase both along and across the tail. These features distinguish the internally driven reconnection regime from similar processes in antiparallel magnetic field configurations as well as interchange and externally driven magnetotail reconnection regimes and can be used to identify the different regimes in upcoming Magnetospheric Multiscale (MMS) mission tail season observations.

  6. Vestibular stimulation leads to distinct hemodynamic patterning

    NASA Technical Reports Server (NTRS)

    Kerman, I. A.; Emanuel, B. A.; Yates, B. J.

    2000-01-01

    Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 +/- 2 mmHg (mean +/- SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 +/- 4% decrease in vascular resistance or 36 +/- 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 +/- 6% and conductance decrease of 11 +/- 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 +/- 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

  7. PLASMA GENERATOR

    DOEpatents

    Wilcox, J.M.; Baker, W.R.

    1963-09-17

    This invention is a magnetohydrodynamic device for generating a highly ionized ion-electron plasma at a region remote from electrodes and structural members, thus avoiding contamination of the plasma. The apparatus utilizes a closed, gas-filled, cylindrical housing in which an axially directed magnetic field is provided. At one end of the housing, a short cylindrical electrode is disposed coaxially around a short axial inner electrode. A radial electrical discharge is caused to occur between the inner and outer electrodes, creating a rotating hydromagnetic ionization wave that propagates aiong the magnetic field lines toward the opposite end of the housing. A shorting switch connected between the electrodes prevents the wave from striking the opposite end of the housing. (AEC)

  8. Triboelectric generator

    DOEpatents

    Wang, Zhong L; Fan, Fengru; Lin, Long; Zhu, Guang; Pan, Caofeng; Zhou, Yusheng

    2015-11-03

    A generator includes a thin first contact charging layer and a thin second contact charging layer. The thin first contact charging layer includes a first material that has a first rating on a triboelectric series. The thin first contact charging layer has a first side with a first conductive electrode applied thereto and an opposite second side. The thin second contact charging layer includes a second material that has a second rating on a triboelectric series that is more negative than the first rating. The thin first contact charging layer has a first side with a first conductive electrode applied thereto and an opposite second side. The thin second contact charging layer is disposed adjacent to the first contact charging layer so that the second side of the second contact charging layer is in contact with the second side of the first contact charging layer.

  9. Single cell sequencing: a distinct new field.

    PubMed

    Wang, Jian; Song, Yuanlin

    2017-12-01

    Single cell sequencing (SCS) has become a new approach to study biological heterogeneity. The advancement in technologies for single cell isolation, amplification of genome/transcriptome and next-generation sequencing enables SCS to reveal the inherent properties of a single cell from the large scale of the genome, transcriptome or epigenome at high resolution. Recently, SCS has been widely applied in various clinical and research fields, such as cancer biology and oncology, immunology, microbiology, neurobiology and prenatal diagnosis. In this review, we will discuss the development of SCS methods and focus on the latest clinical and research applications of SCS.

  10. Next-Generation Sequencing.

    PubMed

    Le Gallo, Matthieu; Lozy, Fred; Bell, Daphne W

    2017-01-01

    Endometrial cancers are the most frequently diagnosed gynecological malignancy and were expected to be the seventh leading cause of cancer death among American women in 2015. The majority of endometrial cancers are of serous or endometrioid histology. Most human tumors, including endometrial tumors, are driven by the acquisition of pathogenic mutations in cancer genes. Thus, the identification of somatic mutations within tumor genomes is an entry point toward cancer gene discovery. However, efforts to pinpoint somatic mutations in human cancers have, until recently, relied on high-throughput sequencing of single genes or gene families using Sanger sequencing. Although this approach has been fruitful, the cost and throughput of Sanger sequencing generally prohibits systematic sequencing of the ~22,000 genes that make up the exome. The recent development of next-generation sequencing technologies changed this paradigm by providing the capability to rapidly sequence exomes, transcriptomes, and genomes at relatively low cost. Remarkably, the application of this technology to catalog the mutational landscapes of endometrial tumor exomes, transcriptomes, and genomes has revealed, for the first time, that serous and endometrioid endometrial cancers can be classified into four distinct molecular subgroups. In this chapter, we overview the characteristic genomic features of each subgroup and discuss the known and putative cancer genes that have emerged from next-generation sequencing of endometrial carcinomas.

  11. Two distinct neural mechanisms underlying indirect reciprocity.

    PubMed

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  12. Distinct Genetic Alterations in Colorectal Cancer

    PubMed Central

    Ashktorab, Hassan; Schäffer, Alejandro A.; Daremipouran, Mohammad; Smoot, Duane T.; Lee, Edward; Brim, Hassan

    2010-01-01

    Background Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. Methodology/Principal Findings We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. Conclusions/Significance Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs. PMID:20126641

  13. A distinct break between butane and pentane.

    PubMed

    Uchibayashi, M

    1999-01-01

    In organic chemistry, hydrocarbon compounds with one to four carbon atoms are given individual names such as methane, ethane, propane and butane, whereas those with five carbons or more are named by the serial Greco-Roman numerals like pentane pente, 5), hexane hex, 6 (and heptane hepta, 7). The author points out a distinct conceptual break between the numbers four and five. There have been arguments that primitive cultures had numerals only up to four, and a quantum mental leap was required to cross the boundary after four. Linguistic discussions are made to substantiate the break by scrutinizing the spellings of the numbers "five", "eight" and "nine" of the proto-Indo-European language. In ancient Roman times, 1 (children's ages were counted by winters up to four and by years from five on, 2 (the first four calender months had real names and after four they were called by serial numbers, (3) children up to the fourth were given individual names but from the fifth child on they were named by serial number words, and (4) the words of the number of times had a sharp break between four and five. In various Indo-European languages long ago, the numbers one through four were inflected adjectives, while the numbers beyond four were non-inflectable. All the above observations indicate an existence of a conceptual break after the number four. The author concludes that the notion of such break latently survived in peoples' minds for a long time and came to light when naming of the hydrocarbons was attempted in the 19th century.

  14. Two distinct neural mechanisms underlying indirect reciprocity

    PubMed Central

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-01-01

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards. PMID:24591599

  15. Photostability and photodegradation pathways of distinctive pesticides.

    PubMed

    Kiss, Attila; Virág, Diána

    2009-01-01

    Transformation of pesticides in the environment is a highly complex process affected by different factors. Biological and physical-chemical factors may play a role in the degradation to variable extent. Photodecomposition might be regarded as one of the most crucial factors affecting the fate of pesticides. Therefore, our study focused on revealing specific details of the photolytic degradation of pesticides. The toxicity of the examined pesticides is well known; however, little information is available regarding their natural degradation processes. More detailed examinations are required to reveal the exact mechanism of the pesticide decomposition and the biological impacts of the degradates. Significance of this study is enhanced by the fact that decomposition of pesticides may result in the formation of toxic degradation products. The photolytic degradation of frequently applied pesticides (e.g., acetochlor, simazine, chlorpyrifos, and carbendazim) with different chemical structures was investigated. An immersible ultraviolet light source was applied to induce photodegradation. The degradation processes were followed by thin-layer chromatography and gas chromatography/mass spectrometry techniques. Electron ionization mass spectrometry was used to identify the degradation species. Detailed mechanisms of photolytic transformation were established by identification of each degradate. The photolytic degradation of pesticides of distinctive chemical character exhibited markedly different photodecomposition mechanisms. At least four degradation species were detected and identified in each case. Loss of alkyl, chloro, and hydroxyl groups as well as cleavage of alkyloxy, amide, amino-alkyl, and ester bonds might be regarded as typical decomposition patterns. Deamination and ring opening might be observed at the last stages of decomposition.

  16. Municipal Solid Waste Landfills Harbor Distinct Microbiomes.

    PubMed

    Stamps, Blake W; Lyles, Christopher N; Suflita, Joseph M; Masoner, Jason R; Cozzarelli, Isabelle M; Kolpin, Dana W; Stevenson, Bradley S

    2016-01-01

    Landfills are the final repository for most of the discarded material from human society and its "built environments." Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2) and a complex mixture of soluble chemical compounds in leachate. Characterization of "landfill microbiomes" and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity.

  17. Municipal solid waste landfills harbor distinct microbiomes

    USGS Publications Warehouse

    Stamps, Blake W.; Lyles, Christopher N.; Suflita, Joseph M.; Masoner, Jason R.; Cozzarelli, Isabelle M.; Kolpin, Dana W.; Stevenson, Bradley S.

    2016-01-01

    Landfills are the final repository for most of the discarded material from human society and its “built environments.” Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2) and a complex mixture of soluble chemical compounds in leachate. Characterization of “landfill microbiomes” and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity.

  18. Municipal Solid Waste Landfills Harbor Distinct Microbiomes

    PubMed Central

    Stamps, Blake W.; Lyles, Christopher N.; Suflita, Joseph M.; Masoner, Jason R.; Cozzarelli, Isabelle M.; Kolpin, Dana W.; Stevenson, Bradley S.

    2016-01-01

    Landfills are the final repository for most of the discarded material from human society and its “built environments.” Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2) and a complex mixture of soluble chemical compounds in leachate. Characterization of “landfill microbiomes” and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity. PMID:27148222

  19. Structurally divergent human T cell receptor. gamma. proteins encoded by distinct C. gamma. genes

    SciTech Connect

    Krangel, M.S.; Band, H.; Hata, S.; McLean, J.; Brenner, M.B.

    1987-07-03

    The human T cell receptor (TCR) ..gamma.. polypeptide occurs in structurally distinct forms on certain peripheral blood T lymphocytes. Complementary DNA clones representing the transcripts of functionally rearranged TCR ..gamma.. genes in these cells have been analyzed. The expression of a disulfide-linked and a nondisulfide-linked form of TCR ..gamma.. correlates with the use of the C..gamma..1 and C..gamma..2 constant-region gene segments, respectively. Variability in TCR ..gamma.. polypeptide and disulfide linkage is determined by the number of copies and the sequence of a repeated segment of the constant region. Thus, C..gamma..1 and C..gamma..2 are used to generate structurally distinct, yet functional, T3-associated receptor complexes on peripheral blood lymphocytes. Tryptic peptide mapping suggests that the T3-associated TCR ..gamma.. and delta peptides in the nondisulfide-linked form are distinct.

  20. Independent control of gamma and theta activity by distinct interneuron networks in the olfactory bulb

    PubMed Central

    Fukunaga, Izumi; Herb, Jan; Kollo, Mihaly; Boyden, Edward S; Schaefer, Andreas T

    2014-01-01

    Circuits in the brain possess a remarkable ability to orchestrate activities on different timescales, but how distinct circuits interact to sculpt diverse rhythms remains unresolved. The olfactory bulb is a classic example where slow, theta, and fast, gamma, rhythms coexist. Furthermore inhibitory interneurons generally implicated in rhythm generation are segregated into distinct layers, neatly separating local from global motifs. Here, combining intracellular recordings in vivo with circuit-specific optogenetic interference we dissect the contribution of inhibition to rhythmic activity in the mouse olfactory bulb. We found that the two inhibitory circuits control rhythms on distinct timescales: local, glomerular networks coordinate theta activity, regulating baseline and odor-evoked inhibition; granule cells orchestrate gamma synchrony and spike timing. Surprisingly, they did not contribute to baseline rhythms, or sniff-coupled odor-evoked inhibition despite their perceived dominance. Thus, activities on theta and gamma time scales are controlled by separate, dissociable inhibitory networks in the olfactory bulb. PMID:24997762

  1. Yours, Mine, Theirs: Multiple Generations in Today's Workplace

    ERIC Educational Resources Information Center

    Grotophorst, Julie

    2011-01-01

    For the first time in history, four distinct generations are sharing the same workspace. Veterans, Baby Boomers, Gen-Xers, and Generation Y (the Millennials) are all bringing very different life experiences, expectations, and value systems to the work table. How do leaders bridge the gap among these generations and provide common ground on which…

  2. Yours, Mine, Theirs: Multiple Generations in Today's Workplace

    ERIC Educational Resources Information Center

    Grotophorst, Julie

    2011-01-01

    For the first time in history, four distinct generations are sharing the same workspace. Veterans, Baby Boomers, Gen-Xers, and Generation Y (the Millennials) are all bringing very different life experiences, expectations, and value systems to the work table. How do leaders bridge the gap among these generations and provide common ground on which…

  3. Twentieth-Century Spanish Textbooks: A Generational Approach.

    ERIC Educational Resources Information Center

    Pardinas-Barnes, Patricia

    1998-01-01

    Examines the evolution of Spanish textbooks qualitatively using computerized pedagogical data. Results show distinct generational text style trends from 1860 to 1998 which chronicle a common engine of change and conflict in standardization movements and the production of generational text styles. Summarizes 20th-century textbook generations and…

  4. Distinct molecular profile of diffuse cerebellar gliomas.

    PubMed

    Nomura, Masashi; Mukasa, Akitake; Nagae, Genta; Yamamoto, Shogo; Tatsuno, Kenji; Ueda, Hiroki; Fukuda, Shiro; Umeda, Takayoshi; Suzuki, Tomonari; Otani, Ryohei; Kobayashi, Keiichi; Maruyama, Takashi; Tanaka, Shota; Takayanagi, Shunsaku; Nejo, Takahide; Takahashi, Satoshi; Ichimura, Koichi; Nakamura, Taishi; Muragaki, Yoshihiro; Narita, Yoshitaka; Nagane, Motoo; Ueki, Keisuke; Nishikawa, Ryo; Shibahara, Junji; Aburatani, Hiroyuki; Saito, Nobuhito

    2017-08-29

    Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation in SETD2 (n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive with H3F3A K27M mutation (n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function including TP53 mutation (n = 9), PPM1D mutation (n = 2), and a novel type of PPM1D fusion (n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those with H3F3A mutations were categorized in the "RTK I (PDGFRA)" group, and those DCGs had a gene expression signature that was highly associated with PDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brain regions, promoter methylation of transcription factors genes associated with glial development showed a characteristic pattern presumably reflecting their tumor origin. Notably, SOX10, a key transcription factor associated with oligodendroglial differentiation and PDGFRA regulation, was up-regulated in both DCG and H3 K27M-mutant diffuse midline glioma, suggesting their developmental and biological commonality. In contrast, SOX10 was silenced by promoter methylation in most cerebral gliomas. These

  5. Distinctive space weathering on Vesta from regolith mixing processes.

    PubMed

    Pieters, C M; Ammannito, E; Blewett, D T; Denevi, B W; De Sanctis, M C; Gaffey, M J; Le Corre, L; Li, J-Y; Marchi, S; McCord, T B; McFadden, L A; Mittlefehldt, D W; Nathues, A; Palmer, E; Reddy, V; Raymond, C A; Russell, C T

    2012-11-01

    The surface of the asteroid Vesta has prominent near-infrared absorption bands characteristic of a range of pyroxenes, confirming a direct link to the basaltic howardite-eucrite-diogenite class of meteorites. Processes active in the space environment produce 'space weathering' products that substantially weaken or mask such diagnostic absorption on airless bodies observed elsewhere, and it has long been a mystery why Vesta's absorption bands are so strong. Analyses of soil samples from both the Moon and the asteroid Itokawa determined that nanophase metallic particles (commonly nanophase iron) accumulate on the rims of regolith grains with time, accounting for an observed optical degradation. These nanophase particles, believed to be related to solar wind and micrometeoroid bombardment processes, leave unique spectroscopic signatures that can be measured remotely but require sufficient spatial resolution to discern the geologic context and history of the surface, which has not been achieved for Vesta until now. Here we report that Vesta shows its own form of space weathering, which is quite different from that of other airless bodies visited. No evidence is detected on Vesta for accumulation of lunar-like nanophase iron on regolith particles, even though distinct material exposed at several fresh craters becomes gradually masked and fades into the background as the craters age. Instead, spectroscopic data reveal that on Vesta a locally homogenized upper regolith is generated with time through small-scale mixing of diverse surface components.

  6. Microtubule depolymerization induces traction force increase through two distinct pathways

    PubMed Central

    Rape, Andrew; Guo, Wei-hui; Wang, Yu-li

    2011-01-01

    Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microscopy to cells cultured on micropatterned polyacrylamide hydrogels to obtain samples of homogeneous shape and size. Control cells and cells treated with a focal adhesion kinase (FAK) inhibitor showed similar increases in traction forces, indicating that the response is independent of FAK. Surprisingly, pharmacological inhibition of myosin II did not prevent the increase of residual traction forces upon nocodazole treatment. This increase was abolished upon pharmacological inhibition of FAK. These results suggest two distinct pathways for the regulation of traction forces. First, microtubule depolymerization activates a myosin-II-dependent mechanism through a FAK-independent pathway. Second, microtubule depolymerization also enhances traction forces through a myosin-II-independent, FAK-regulated pathway. Traction forces are therefore regulated by a complex network of complementary signals and force-generating mechanisms. PMID:22193960

  7. Related allopolyploids display distinct floral pigment profiles and transgressive pigments.

    PubMed

    McCarthy, Elizabeth W; Berardi, Andrea E; Smith, Stacey D; Litt, Amy

    2017-01-01

    Both polyploidy and shifts in floral color have marked angiosperm evolution. Here, we investigate the biochemical basis of the novel and diverse floral phenotypes seen in allopolyploids in Nicotiana (Solanaceae) and examine the extent to which the merging of distinct genomes alters flavonoid pigment production. We analyzed flavonol and anthocyanin pigments from Nicotiana allopolyploids of different ages (N. tabacum, 0.2 million years old; several species from Nicotiana section Repandae, 4.5 million years old; and five lines of first-generation synthetic N. tabacum) as well as their diploid progenitors. Allopolyploid floral pigment profiles tend not to overlap with their progenitors or related allopolyploids, and allopolyploids produce transgressive pigments that are not present in either progenitor. Differences in floral color among N. tabacum accessions seems mainly to be due to variation in cyanidin concentration, but changes in flavonol concentrations among accessions are also present. Competition for substrates within the flavonoid biosynthetic pathway to make either flavonols or anthocyanins may drive the differences seen among related allopolyploids. Some of the pigment differences observed in allopolyploids may be associated with making flowers more visible to nocturnal pollinators. © 2017 Botanical Society of America.

  8. Phosphorylation induces distinct alpha-synuclein strain formation

    PubMed Central

    Ma, Meng-Rong; Hu, Zhi-Wen; Zhao, Yu-Fen; Chen, Yong-Xiang; Li, Yan-Mei

    2016-01-01

    Synucleinopathies are a group of neurodegenerative diseases associated with alpha-synuclein (α-Syn) aggregation. Recently, increasing evidence has demonstrated the existence of different structural characteristics or ‘strains’ of α-Syn, supporting the concept that synucleinopathies share several common features with prion diseases and possibly explaining how a single protein results in different clinical phenotypes within synucleinopathies. In earlier studies, the different strains were generated through the regulation of solution conditions, temperature, or repetitive seeded fibrillization in vitro. Here, we synthesize homogeneous α-Syn phosphorylated at serine 129 (pS129 α-Syn), which is highly associated with the pathological changes, and demonstrate that phosphorylation at Ser129 induces α-Syn to form a distinct strain with different structures, propagation properties, and higher cytotoxicity compared with the wild-type α-Syn. The results are the first demonstration that post-translational modification of α-Syn can induce different strain formation, offering a new mechanism for strain formation. PMID:27853185

  9. Microtubule depolymerization induces traction force increase through two distinct pathways.

    PubMed

    Rape, Andrew; Guo, Wei-hui; Wang, Yu-li

    2011-12-15

    Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microscopy to cells cultured on micropatterned polyacrylamide hydrogels to obtain samples of homogeneous shape and size. Control cells and cells treated with a focal adhesion kinase (FAK) inhibitor showed similar increases in traction forces, indicating that the response is independent of FAK. Surprisingly, pharmacological inhibition of myosin II did not prevent the increase of residual traction forces upon nocodazole treatment. This increase was abolished upon pharmacological inhibition of FAK. These results suggest two distinct pathways for the regulation of traction forces. First, microtubule depolymerization activates a myosin-II-dependent mechanism through a FAK-independent pathway. Second, microtubule depolymerization also enhances traction forces through a myosin-II-independent, FAK-regulated pathway. Traction forces are therefore regulated by a complex network of complementary signals and force-generating mechanisms.

  10. Accurate three-dimensional documentation of distinct sites

    NASA Astrophysics Data System (ADS)

    Singh, Mahesh K.; Dutta, Ashish; Subramanian, Venkatesh K.

    2017-01-01

    One of the most critical aspects of documenting distinct sites is acquiring detailed and accurate range information. Several three-dimensional (3-D) acquisition techniques are available, but each has its own limitations. This paper presents a range data fusion method with the aim to enhance the descriptive contents of the entire 3-D reconstructed model. A kernel function is introduced for supervised classification of the range data using a kernelized support vector machine. The classification method is based on the local saliency features of the acquired range data. The range data acquired from heterogeneous range sensors are transformed into a defined common reference frame. Based on the segmentation criterion, the fusion of range data is performed by integrating finer regions of range data acquired from a laser range scanner with the coarser region of Kinect's range data. After fusion, the Delaunay triangulation algorithm is applied to generate the highly accurate, realistic 3-D model of the scene. Finally, experimental results show the robustness of the proposed approach.

  11. Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function.

    PubMed

    Mgbemena, Victoria E; Signer, Robert A J; Wijayatunge, Ranjula; Laxson, Travis; Morrison, Sean J; Ross, Theodora S

    2017-01-24

    BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here, we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1(F22-24/F22-24)) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs). Although mice homozygous for a huBRCA1 knockin allele (Brca1(BRCA1/BRCA1)) were normal, mice with a mutant huBRCA1/5382insC allele and a null allele (Mx1-Cre;Brca1(F22-24/5382insC)) had severe hematopoietic defects marked by a complete loss of hematopoietic stem and progenitor cells. Our data show that Brca1 is necessary for HSC maintenance and normal hematopoiesis and that distinct mutations lead to different degrees of hematopoietic dysfunction.

  12. Distinct and extinct: genetic differentiation of the Hawaiian eagle.

    PubMed

    Hailer, Frank; James, Helen F; Olson, Storrs L; Fleischer, Robert C

    2015-02-01

    Eagles currently occur in the Hawaiian Islands only as vagrants, but Quaternary bones of Haliaeetus eagles have been found on three of the major islands. A previous study of a ∼3500-year-old skeleton from Maui found its mtDNA more similar to White-tailed (H. albicilla) than to Bald (H. leucocephalus) Eagles, but low intraspecific resolution of the markers and lack of comparative data from mainland populations precluded assessment of whether the individual was part of the diversity found in Eurasia, or whether it represented an endemic Hawaiian lineage. Using ancient DNA techniques, we sequenced part of the rapidly evolving mtDNA control region from the same specimen, and compared it to published range-wide control region data from White-tailed Eagles and newly generated sequences from Bald Eagles. Phylogenetic analyses indicated that the Hawaiian eagle represents a distinct (>3% divergent) mtDNA lineage most closely related to those of extant White-tailed Eagles. Based on fossil calibration, we estimate that the Hawaiian mtDNA lineage diverged from mainland sequences around the Middle Pleistocene. Although not clearly differentiated morphologically from mainland forms, the Hawaiian eagle thus likely constituted an isolated, resident population in the Hawaiian archipelago for more than 100,000 years, where it was the largest terrestrial predator. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. A distinct lineage of influenza A virus from bats

    PubMed Central

    Tong, Suxiang; Li, Yan; Rivailler, Pierre; Conrardy, Christina; Castillo, Danilo A. Alvarez; Chen, Li-Mei; Recuenco, Sergio; Ellison, James A.; Davis, Charles T.; York, Ian A.; Turmelle, Amy S.; Moran, David; Rogers, Shannon; Shi, Mang; Tao, Ying; Weil, Michael R.; Tang, Kevin; Rowe, Lori A.; Sammons, Scott; Xu, Xiyan; Frace, Michael; Lindblade, Kim A.; Cox, Nancy J.; Anderson, Larry J.; Rupprecht, Charles E.; Donis, Ruben O.

    2012-01-01

    Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses. PMID:22371588

  14. Distinct Motivational Effects of Contingent and Noncontingent Rewards

    PubMed Central

    Manohar, Sanjay G.; Finzi, Rebecca Dawn; Drew, Daniel; Husain, Masud

    2017-01-01

    When rewards are available, people expend more energy, increasing their motivational vigor. In theory, incentives might drive behavior for two distinct reasons: First, they increase expected reward; second, they increase the difference in subjective value between successful and unsuccessful performance, which increases contingency—the degree to which action determines outcome. Previous studies of motivational vigor have never compared these directly. Here, we indexed motivational vigor by measuring the speed of eye movements toward a target after participants heard a cue indicating how outcomes would be determined. Eye movements were faster when the cue indicated that monetary rewards would be contingent on performance than when the cue indicated that rewards would be random. But even when the cue indicated that a reward was guaranteed regardless of speed, movement was still faster than when no reward was available. Motivation by contingent and certain rewards was uncorrelated across individuals, which suggests that there are two separable, independent components of motivation. Contingent motivation generated autonomic arousal, and unlike noncontingent motivation, was effective with penalties as well as rewards. PMID:28488927

  15. Establishment of photosynthesis is controlled by two distinct regulatory phases.

    PubMed

    Dubreuil, Carole; Jin, Xu; Barajas-López, Juan de Dios; Hewitt, Timothy Hewitt; Tanz, Sandra; Dobrenel, Thomas; Schröder, Wolfgang; Hanson, Johannes; Pesquet, Edouard; Grönlund, Andreas; Small, Ian D; Strand, Asa

    2017-06-16

    Chloroplasts develop from undifferentiated proplastids present in meristematic tissue. Chloroplast biogenesis is thus closely connected to leaf development, which restricts our ability to study the process of chloroplast biogenesis per se. As a consequence we know relatively little about the regulatory mechanisms behind the establishment of the photosynthetic reactions and how the activities of the two genomes involved are coordinated during chloroplast development. We developed a single-cell-based experimental system from Arabidopsis with high temporal resolution allowing for investigations of the transition from proplastids to functional chloroplasts. Using this unique cell line we could show that establishment of photosynthesis is dependent on a regulatory mechanism involving two distinct phases. The first phase is triggered by rapid light-induced changes in gene expression and the metabolome. The second phase is dependent on the activation of the chloroplast and generates massive changes in nuclear gene expression required for the transition to photosynthetically functional chloroplasts.. The second phase is also associated with a spatial transition of the chloroplasts from clusters around the nucleus to the final position at the cell cortex. Thus, establishment of photosynthesis is a two-phase process with a clear checkpoint associated with the second regulatory phase allowing coordination of the activities of the nuclear and plastid genomes. {copyright, serif} 2017 American Society of Plant Biologists. All rights reserved.

  16. Distinctive space weathering on Vesta from regolith mixing processes

    NASA Astrophysics Data System (ADS)

    Pieters, C. M.; Ammannito, E.; Blewett, D. T.; Denevi, B. W.; de Sanctis, M. C.; Gaffey, M. J.; Le Corre, L.; Li, J.-Y.; Marchi, S.; McCord, T. B.; McFadden, L. A.; Mittlefehldt, D. W.; Nathues, A.; Palmer, E.; Reddy, V.; Raymond, C. A.; Russell, C. T.

    2012-11-01

    The surface of the asteroid Vesta has prominent near-infrared absorption bands characteristic of a range of pyroxenes, confirming a direct link to the basaltic howardite-eucrite-diogenite class of meteorites. Processes active in the space environment produce `space weathering' products that substantially weaken or mask such diagnostic absorption on airless bodies observed elsewhere, and it has long been a mystery why Vesta's absorption bands are so strong. Analyses of soil samples from both the Moon and the asteroid Itokawa determined that nanophase metallic particles (commonly nanophase iron) accumulate on the rims of regolith grains with time, accounting for an observed optical degradation. These nanophase particles, believed to be related to solar wind and micrometeoroid bombardment processes, leave unique spectroscopic signatures that can be measured remotely but require sufficient spatial resolution to discern the geologic context and history of the surface, which has not been achieved for Vesta until now. Here we report that Vesta shows its own form of space weathering, which is quite different from that of other airless bodies visited. No evidence is detected on Vesta for accumulation of lunar-like nanophase iron on regolith particles, even though distinct material exposed at several fresh craters becomes gradually masked and fades into the background as the craters age. Instead, spectroscopic data reveal that on Vesta a locally homogenized upper regolith is generated with time through small-scale mixing of diverse surface components.

  17. Identification of two distinct Bacillus subtilis citrate synthase genes.

    PubMed

    Jin, S; Sonenshein, A L

    1994-08-01

    Two distinct Bacillus subtilis genes (citA and citZ) were found to encode citrate synthase isozymes that catalyze the first step of the Krebs cycle. The citA gene was cloned by genetic complementation of an Escherichia coli citrate synthase mutant strain (W620) and was in a monocistronic transcriptional unit. A divergently transcribed gene, citR, could encode a protein with strong similarity to the bacterial LysR family of regulatory proteins. A null mutation in citA had little effect on citrate synthase enzyme activity or sporulation. The residual citrate synthase activity was purified from a citA null mutant strain, and the partial amino acid sequence for the purified protein (CitZ) was determined. The citZ gene was cloned from B. subtilis chromosomal DNA by using a PCR-generated probe synthesized with oligonucleotide primers derived from the partial amino acid sequence of purified CitZ. The citZ gene proved to be the first gene in a tricistronic cluster that also included citC (coding for isocitrate dehydrogenase) and citH (coding for malate dehydrogenase). A mutation in citZ caused a substantial loss of citrate synthase enzyme activity, glutamate auxotrophy, and a defect in sporulation.

  18. Bacterial protease uses distinct thermodynamic signatures for substrate recognition.

    PubMed

    Bezerra, Gustavo Arruda; Ohara-Nemoto, Yuko; Cornaciu, Irina; Fedosyuk, Sofiya; Hoffmann, Guillaume; Round, Adam; Márquez, José A; Nemoto, Takayuki K; Djinović-Carugo, Kristina

    2017-06-06

    Porphyromonas gingivalis and Porphyromonas endodontalis are important bacteria related to periodontitis, the most common chronic inflammatory disease in humans worldwide. Its comorbidity with systemic diseases, such as type 2 diabetes, oral cancers and cardiovascular diseases, continues to generate considerable interest. Surprisingly, these two microorganisms do not ferment carbohydrates; rather they use proteinaceous substrates as carbon and energy sources. However, the underlying biochemical mechanisms of their energy metabolism remain unknown. Here, we show that dipeptidyl peptidase 11 (DPP11), a central metabolic enzyme in these bacteria, undergoes a conformational change upon peptide binding to distinguish substrates from end products. It binds substrates through an entropy-driven process and end products in an enthalpy-driven fashion. We show that increase in protein conformational entropy is the main-driving force for substrate binding via the unfolding of specific regions of the enzyme ("entropy reservoirs"). The relationship between our structural and thermodynamics data yields a distinct model for protein-protein interactions where protein conformational entropy modulates the binding free-energy. Further, our findings provide a framework for the structure-based design of specific DPP11 inhibitors.

  19. Distinct Trajectories in the Transition to Adulthood: Are Children of Immigrants Advantaged?

    PubMed Central

    Hao, Lingxin; Woo, Han Soo

    2015-01-01

    Studies on children of immigrants have generally ignored distinct developmental trajectories during adolescence and their role in the transition to adulthood. This study identifies distinct trajectories in cognitive, socio-behavioral, and psychological domains and estimates their consequences for young-adult. Drawing data from a nationally representative sample of 10,795 adolescents aged 13-17 who were followed up to ages 25-32, we use growth mixture modeling to test advantages for children of immigrants. The analysis shows a 1.5 generation advantage in academic achievement and school engagement, as well as a weaker second-generation advantage in academic achievement, but no disadvantage in depression for children of immigrants. In addition, we found that these results hold for children of Hispanic origin. Theoretical and policy implications are discussed. PMID:22966927

  20. Distinct trajectories in the transition to adulthood: are children of immigrants advantaged?

    PubMed

    Hao, Lingxin; Woo, Han S

    2012-01-01

    Studies on children of immigrants have generally ignored distinct developmental trajectories during adolescence and their role in the transition to adulthood. This study identifies distinct trajectories in cognitive, sociobehavioral, and psychological domains and estimates their consequences for young adults. Drawing data from a nationally representative sample of 10,795 adolescents aged 13-17 who were followed up to ages 25-32, the study uses growth mixture modeling to test advantages for children of immigrants. The analysis shows a 1.5-generation advantage in academic achievement and school engagement, as well as a weaker second-generation advantage in academic achievement, but no disadvantage in depression for children of immigrants. In addition, these results hold for children of Hispanic origin. Theoretical and policy implications are discussed.

  1. The production effect in memory: multiple species of distinctiveness

    PubMed Central

    Icht, Michal; Mama, Yaniv; Algom, Daniel

    2014-01-01

    The production effect is the difference in memory favoring words read aloud relative to words read silently during study. According to a currently popular explanation, the distinctiveness of aloud words relative to silent words at the time of encoding underlies the better memory for the former. This distinctiveness is attributable to the additional dimension(s) of encoding for the aloud items that can be subsequently used during retrieval. In this study we argue that encoding distinctiveness is not the sole source of distinctiveness and that, in fact, there is an independent source of distinctiveness, statistical distinctiveness, which may or may not work in harmony with encoding distinctiveness in influencing memory. Statistical distinctiveness refers to the relative size of a subset of items marked by a(ny) unique property. Silently read words can carry statistical distinctiveness if they form a salient minority on the background of a majority of vocalized words. We show that, when the two sources are placed in opposition, statistical distinctiveness modifies the PE in a profound way. PMID:25157237

  2. Similarities and distinctions of CIR and Sheath

    NASA Astrophysics Data System (ADS)

    Yermolaev, Yuri; Lodkina, Irina; Nikolaeva, Nadezhda; Yermolaev, Michael

    2016-04-01

    On the basis of OMNI data and our catalog of large scale solar wind (SW) streams during 1976-2000 [Yermolaev et al., 2009] we study the average temporal profiles for two types of compressed regions: CIR (corotating interaction region - compressed region before High Speed Stream (HSS)) and Sheath (compressed region before fast Interplanetary CMEs (ICMEs), including Magnetic Cloud (MC) and Ejecta). As have been shown by Nikolaeva et al, [2015], the efficiency of magnetic storm generation is ~50% higher for Sheath and CIR than for ICME (MC and Ejecta), i.e. reaction magnetosphere depends on type of driver. To take into account the different durations of SW types, we use the double superposed epoch analysis (DSEA) method: rescaling the duration of the interval for all types in such a manner that, respectively, beginning and end for all intervals of selected type coincide [Yermolaev et al., 2010; 2015]. Obtained data allows us to suggest that the formation of all types of compression regions has the same physical mechanism irrespective of piston (HSS or ICME) type and differences are connected with geometry and full jumps of speed in edges of compression regions. If making the natural assumption that the gradient of speed is directed approximately on normal to the piston, CIR has the largest angle between the gradient of speed and the direction of average SW speed, and ICME - the smallest angle. The work was supported by the Russian Foundation for Basic Research, projects 13-02-00158, 16-02-00125 and by Program of Presidium of the Russian Academy of Sciences. References: Nikolaeva, N. S. , Yu. I. Yermolaev, and I. G. Lodkina (2015), Modeling of the Corrected Dst* Index Temporal Profile on the Main Phase of the Magnetic Storms Generated by Different Types of Solar Wind, Cosmic Research, Vol. 53, No. 2, pp. 119-127. Yermolaev, Yu. I., N. S. Nikolaeva, I. G. Lodkina, and M. Yu. Yermolaev (2009), Catalog of Large-Scale Solar Wind Phenomena during 1976-2000, Cosmic Research

  3. Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages

    PubMed Central

    Piccinini, Anna M.; Zuliani-Alvarez, Lorena; Lim, Jenny M. P.; Midwood, Kim S.

    2017-01-01

    Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. The microbial product lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C are released during bacterial infection and tissue injury, respectively, and both activate Toll-like receptor 4 (TLR4). We found that these two TLR4 ligands stimulated distinct signaling pathways in macrophages, resulting in cells with divergent phenotypes. Although macrophages activated by LPS or tenascin-C displayed some common features, including activation of nuclear factor κB and mitogen-activated protein kinase signaling and cytokine synthesis, each ligand stimulated the production of different subsets of cytokines and generated different phosphoproteomic signatures. Moreover, tenascin-C promoted the generation of macrophages that exhibited increased synthesis and phosphorylation of extracellular matrix components, whereas LPS stimulated the production of macrophages that exhibited an enhanced capacity to degrade the matrix. These data reveal how the activation of one pattern recognition receptor by different microenvironmental cues generates macrophage with distinct phenotypes. PMID:27577261

  4. Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory

    PubMed Central

    Kaji, Tomohiro; Ishige, Akiko; Hikida, Masaki; Taka, Junko; Hijikata, Atsushi; Kubo, Masato; Nagashima, Takeshi; Takahashi, Yoshimasa; Kurosaki, Tomohiro; Okada, Mariko; Ohara, Osamu

    2012-01-01

    One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen. PMID:23027924

  5. Mechanistically Distinct Mouse Models for CRX-Associated Retinopathy

    PubMed Central

    Tran, Nicholas M.; Zhang, Alan; Zhang, Xiaodong; Huecker, Julie B.; Hennig, Anne K.; Chen, Shiming

    2014-01-01

    Cone-rod homeobox (CRX) protein is a “paired-like” homeodomain transcription factor that is essential for regulating rod and cone photoreceptor transcription. Mutations in human CRX are associated with the dominant retinopathies Retinitis Pigmentosa (RP), Cone-Rod Dystrophy (CoRD) and Leber Congenital Amaurosis (LCA), with variable severity. Heterozygous Crx Knock-Out (KO) mice (“+/−”) have normal vision as adults and fail to model the dominant human disease. To investigate how different mutant CRX proteins produce distinct disease pathologies, we generated two Crx Knock-IN (K-IN) mouse models: CrxE168d2 (“E168d2”) and CrxR90W (“R90W”). E168d2 mice carry a frameshift mutation in the CRX activation domain, Glu168del2, which is associated with severe dominant CoRD or LCA in humans. R90W mice carry a substitution mutation in the CRX homeodomain, Arg90Trp, which is associated with dominant mild late-onset CoRD and recessive LCA. As seen in human patients, heterozygous E168d2 (“E168d2/+”) but not R90W (“R90W/+”) mice show severely impaired retinal function, while mice homozygous for either mutation are blind and undergo rapid photoreceptor degeneration. E168d2/+ mice also display abnormal rod/cone morphology, greater impairment of CRX target gene expression than R90W/+ or +/− mice, and undergo progressive photoreceptor degeneration. Surprisingly, E168d2/+ mice express more mutant CRX protein than wild-type CRX. E168d2neo/+, a subline of E168d2 with reduced mutant allele expression, displays a much milder retinal phenotype, demonstrating the impact of Crx expression level on disease severity. Both CRX[E168d2] and CRX[R90W] proteins fail to activate transcription in vitro, but CRX[E168d2] interferes more strongly with the function of wild type (WT) CRX, supporting an antimorphic mechanism. E168d2 and R90W are mechanistically distinct mouse models for CRX-associated disease that will allow the elucidation of molecular mechanisms and testing of

  6. Some conceptual distinctions are more useful than others.

    PubMed

    de Shazer, S

    1982-03-01

    Useful distinctions in conceptual schemes lead to explanatory or descriptive metaphors that have a clear form. Muddles, on the other hand, are created when useful distinctions that could be drawn are not or when an unnecessary distinction is drawn. The field of family therapy, now involved in an explicit epistemological and paradigmatic shift, has various muddles of each kind. The purpose of this essay is to describe some of these muddles and to suggest that making a distinction between "the study of the family-as-a-system" and "the study of family-therapy-as-a-system" leads to some useful and clear metaphors.

  7. Distinct Dgrip84 isoforms correlate with distinct gamma-tubulins in Drosophila.

    PubMed

    Wiese, Christiane

    2008-01-01

    Gamma-tubulin is an indispensable component of the animal centrosome and is required for proper microtubule organization. Within the cell, gamma-tubulin exists in a multiprotein complex containing between two (some yeasts) and six or more (metazoa) additional highly conserved proteins named gamma ring proteins (Grips) or gamma complex proteins (GCPs). gamma-Tubulin containing complexes isolated from Xenopus eggs or Drosophila embryos appear ring-shaped and have therefore been named the gamma-tubulin ring complex (gammaTuRC). Curiously, many organisms (including humans) have two distinct gamma-tubulin genes. In Drosophila, where the two gamma-tubulin isotypes have been studied most extensively, the gamma-tubulin genes are developmentally regulated: the "maternal" gamma-tubulin isotype (named gammaTub37CD according to its location on the genetic map) is expressed in the ovary and is deposited in the egg, where it is thought to orchestrate the meiotic and early embryonic cleavages. The second gamma-tubulin isotype (gammaTub23C) is ubiquitously expressed and persists in most of the cells of the adult fly. In those rare cases where both gamma-tubulins coexist in the same cell, they show distinct subcellular distributions and cell-cycle-dependent changes: gammaTub37CD mainly localizes to the centrosome, where its levels vary only slightly with the cell cycle. In contrast, the level of gammaTub23C at the centrosome increases at the beginning of mitosis, and gammaTub23C also associates with spindle pole microtubules. Here, we show that gammaTub23C forms discrete complexes that closely resemble the complexes formed by gammaTub37CD. Surprisingly, however, gammaTub23C associates with a distinct, longer splice variant of Dgrip84. This may reflect a role for Dgrip84 in regulating the activity and/or the location of the gamma-tubulin complexes formed with gammaTub37CD and gammaTub23C.

  8. Distinct Dgrip84 Isoforms Correlate with Distinct γ-Tubulins in Drosophila

    PubMed Central

    2008-01-01

    γ-Tubulin is an indispensable component of the animal centrosome and is required for proper microtubule organization. Within the cell, γ-tubulin exists in a multiprotein complex containing between two (some yeasts) and six or more (metazoa) additional highly conserved proteins named gamma ring proteins (Grips) or gamma complex proteins (GCPs). γ-Tubulin containing complexes isolated from Xenopus eggs or Drosophila embryos appear ring-shaped and have therefore been named the γ-tubulin ring complex (γTuRC). Curiously, many organisms (including humans) have two distinct γ-tubulin genes. In Drosophila, where the two γ-tubulin isotypes have been studied most extensively, the γ-tubulin genes are developmentally regulated: the “maternal” γ-tubulin isotype (named γTub37CD according to its location on the genetic map) is expressed in the ovary and is deposited in the egg, where it is thought to orchestrate the meiotic and early embryonic cleavages. The second γ-tubulin isotype (γTub23C) is ubiquitously expressed and persists in most of the cells of the adult fly. In those rare cases where both γ-tubulins coexist in the same cell, they show distinct subcellular distributions and cell-cycle-dependent changes: γTub37CD mainly localizes to the centrosome, where its levels vary only slightly with the cell cycle. In contrast, the level of γTub23C at the centrosome increases at the beginning of mitosis, and γTub23C also associates with spindle pole microtubules. Here, we show that γTub23C forms discrete complexes that closely resemble the complexes formed by γTub37CD. Surprisingly, however, γTub23C associates with a distinct, longer splice variant of Dgrip84. This may reflect a role for Dgrip84 in regulating the activity and/or the location of the γ-tubulin complexes formed with γTub37CD and γTub23C. PMID:18003974

  9. Distinct Soil Bacterial Communities Revealed under a Diversely Managed Agroecosystem

    PubMed Central

    Shange, Raymon S.; Ankumah, Ramble O.; Ibekwe, Abasiofiok M.; Zabawa, Robert; Dowd, Scot E.

    2012-01-01

    Land-use change and management practices are normally enacted to manipulate environments to improve conditions that relate to production, remediation, and accommodation. However, their effect on the soil microbial community and their subsequent influence on soil function is still difficult to quantify. Recent applications of molecular techniques to soil biology, especially the use of 16S rRNA, are helping to bridge this gap. In this study, the influence of three land-use systems within a demonstration farm were evaluated with a view to further understand how these practices may impact observed soil bacterial communities. Replicate soil samples collected from the three land-use systems (grazed pine forest, cultivated crop, and grazed pasture) on a single soil type. High throughput 16S rRNA gene pyrosequencing was used to generate sequence datasets. The different land use systems showed distinction in the structure of their bacterial communities with respect to the differences detected in cluster analysis as well as diversity indices. Specific taxa, particularly Actinobacteria, Acidobacteria, and classes of Proteobacteria, showed significant shifts across the land-use strata. Families belonging to these taxa broke with notions of copio- and oligotrphy at the class level, as many of the less abundant groups of families of Actinobacteria showed a propensity for soil environments with reduced carbon/nutrient availability. Orders Actinomycetales and Solirubrobacterales showed their highest abundance in the heavily disturbed cultivated system despite the lowest soil organic carbon (SOC) values across the site. Selected soil properties ([SOC], total nitrogen [TN], soil texture, phosphodiesterase [PD], alkaline phosphatase [APA], acid phosphatase [ACP] activity, and pH) also differed significantly across land-use regimes, with SOM, PD, and pH showing variation consistent with shifts in community structure and composition. These results suggest that use of pyrosequencing

  10. Distinct frontal lobe morphology in girls and boys with ADHD.

    PubMed

    Dirlikov, Benjamin; Shiels Rosch, Keri; Crocetti, Deana; Denckla, Martha B; Mahone, E Mark; Mostofsky, Stewart H

    2015-01-01

    This study investigated whether frontal lobe cortical morphology differs for boys and girls with ADHD (ages 8-12 years) in comparison to typically developing (TD) peers. Participants included 226 children between the ages of 8-12 including 93 children with ADHD (29 girls) and 133 TD children (42 girls) for which 3T MPRAGE MRI scans were obtained. A fully automated frontal lobe atlas was used to generate functionally distinct frontal subdivisions, with surface area (SA) and cortical thickness (CT) assessed in each region. Analyses focused on overall diagnostic differences as well as examinations of the effect of diagnosis within boys and girls. Girls, but not boys, with ADHD showed overall reductions in total prefrontal cortex (PFC) SA. Localization revealed that girls showed widely distributed reductions in the bilateral dorsolateral PFC, left inferior lateral PFC, right medial PFC, right orbitofrontal cortex, and left anterior cingulate; and boys showed reduced SA only in the right anterior cingulate and left medial PFC. In contrast, boys, but not girls, with ADHD showed overall reductions in total premotor cortex (PMC) SA. Further localization revealed that in boys, premotor reductions were observed in bilateral lateral PMC regions; and in girls reductions were observed in bilateral supplementary motor complex. In line with diagnostic group differences, PMC and PFC SAs were inversely correlated with symptom severity in both girls and boys with ADHD. These results elucidate sex-based differences in cortical morphology of functional subdivisions of the frontal lobe and provide additional evidence of associations among SA and symptom severity in children with ADHD.

  11. Sustained attention and prediction: distinct brain maturation trajectories during adolescence

    PubMed Central

    Thillay, Alix; Roux, Sylvie; Gissot, Valérie; Carteau-Martin, Isabelle; Knight, Robert T.; Bonnet-Brilhault, Frédérique; Bidet-Caulet, Aurélie

    2015-01-01

    Adolescence is a key period for frontal cortex maturation necessary for the development of cognitive ability. Sustained attention and prediction are cognitive functions critical for optimizing sensory processing, and essential to efficiently adapt behaviors in an ever-changing world. The aim of the current study was to investigate the brain developmental trajectories of attentive and predictive processing through adolescence. We recorded EEG in 36 participants from the age of 12–24 years (three age groups: 12–14, 14–17, 18–24 years) to target development during early and late adolescence, and early adulthood. We chose a visual target detection task which loaded upon sustained attention, and we manipulated target predictability. Continued maturation of sustained attention after age 12 was evidenced by improved performance (hits, false alarms (FAs) and sensitivity) in a detection task, associated with a frontal shift in the scalp topographies of the Contingent Negative Variation (CNV) and P3 responses, with increasing age. No effect of age was observed on predictive processing, with all ages showing similar benefits in reaction time, increases in P3 amplitude (indexing predictive value encoding and memorization), increases in CNV amplitude (corresponding to prediction implementation) and reduction in target-P3 latency (reflecting successful prediction building and use), with increased predictive content. This suggests that adolescents extracted and used predictive information to generate predictions as well as adults. The present results show that predictive and attentive processing follow distinct brain developmental trajectories: prediction abilities seem mature by the age of 12 and sustained attention continues to improve after 12-years of age and is associated with maturational changes in the frontal cortices. PMID:26483653

  12. Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts distinctive features

    PubMed Central

    Malouf, Gabriel G; Tahara, Tomomitsu; Paradis, Valérie; Fabre, Monique; Guettier, Catherine; Yamazaki, Jumpei; Long, Hi; Lu, Yue; Raynal, Noël J-M; Jelinek, Jaroslav; Mouawad, Roger; Khayat, David; Brugières, Laurence; Raymond, Eric; Issa, Jean-Pierre J

    2015-01-01

    With the goal of studying epigenetic alterations in fibrolamellar hepatocellular carcinoma (FLC) and establish an associated DNA methylation signature, we analyzed LINE-1 methylation in a cohort of FLC and performed next-generation sequencing of DNA methylation in a training set of pure-FLCs and non-cirrhotic hepatocellular carcinomas (nc-HCC). DNA methylation was correlated with gene expression. Furthermore, we established and validated an epigenetic signature differentiating pure-FLC from other HCCs. LINE-1 methylation correlated with shorter recurrence-free survival and overall survival in resected pure-FLC patients. Unsupervised clustering using CG sites located in islands distinguished pure-FLC from nc-HCC. Major DNA methylation changes occurred outside promoters, mainly in gene bodies and intergenic regions located in the vicinity of liver developmental genes (i.e., SMARCA4 and RXRA). Partially methylated domains were more prone to DNA methylation changes. Furthermore, we identified several putative tumor suppressor genes (e.g., DLEU7) and oncogenes (e.g., DUSP4). While ∼70% of identified gene promoters gaining methylation were marked by bivalent histone marks (H3K4me3/H3K27me3) in embryonic stem cells, ∼70% of those losing methylation were marked by H3K4me3. Finally, we established a pure FLC DNA methylation signature and validated it in an independent dataset. Our analysis reveals a distinct epigenetic signature of pure FLC as compared to nc-HCC, with DNA methylation changes occurring in the vicinity of liver developmental genes. These data suggest new options for targeting FLC based on cancer epigenome aberrations. PMID:26224146

  13. Distinct soil bacterial communities revealed under a diversely managed agroecosystem.

    PubMed

    Shange, Raymon S; Ankumah, Ramble O; Ibekwe, Abasiofiok M; Zabawa, Robert; Dowd, Scot E

    2012-01-01

    Land-use change and management practices are normally enacted to manipulate environments to improve conditions that relate to production, remediation, and accommodation. However, their effect on the soil microbial community and their subsequent influence on soil function is still difficult to quantify. Recent applications of molecular techniques to soil biology, especially the use of 16S rRNA, are helping to bridge this gap. In this study, the influence of three land-use systems within a demonstration farm were evaluated with a view to further understand how these practices may impact observed soil bacterial communities. Replicate soil samples collected from the three land-use systems (grazed pine forest, cultivated crop, and grazed pasture) on a single soil type. High throughput 16S rRNA gene pyrosequencing was used to generate sequence datasets. The different land use systems showed distinction in the structure of their bacterial communities with respect to the differences detected in cluster analysis as well as diversity indices. Specific taxa, particularly Actinobacteria, Acidobacteria, and classes of Proteobacteria, showed significant shifts across the land-use strata. Families belonging to these taxa broke with notions of copio- and oligotrphy at the class level, as many of the less abundant groups of families of Actinobacteria showed a propensity for soil environments with reduced carbon/nutrient availability. Orders Actinomycetales and Solirubrobacterales showed their highest abundance in the heavily disturbed cultivated system despite the lowest soil organic carbon (SOC) values across the site. Selected soil properties ([SOC], total nitrogen [TN], soil texture, phosphodiesterase [PD], alkaline phosphatase [APA], acid phosphatase [ACP] activity, and pH) also differed significantly across land-use regimes, with SOM, PD, and pH showing variation consistent with shifts in community structure and composition. These results suggest that use of pyrosequencing

  14. Adenovirus Vectors Targeting Distinct Cell Types in the Retina

    PubMed Central

    Sweigard, J. Harry; Cashman, Siobhan M.

    2010-01-01

    Purpose. Gene therapy for a number of retinal diseases necessitates efficient transduction of photoreceptor cells. Whereas adenovirus (Ad) serotype 5 (Ad5) does not transduce photoreceptors efficiently, previous studies have demonstrated improved photoreceptor transduction by Ad5 pseudotyped with Ad35 (Ad5/F35) or Ad37 (Ad5/F37) fiber or by the deletion of the RGD domain in the Ad5 penton base (Ad5ΔRGD). However, each of these constructs contained a different transgene cassette, preventing the evaluation of the relative performance of these vectors, an important consideration before the use of these vectors in the clinic. The aim of this study was to evaluate these vectors in the retina and to attempt photoreceptor-specific transgene expression. Methods. Three Ad5-based vectors containing the same expression cassette were generated and injected into the subretinal space of adult mice. Eyes were analyzed for green fluorescence protein expression in flat-mounts, cross-sections, quantitative RT-PCR, and a modified stereological technique. A 257-bp fragment derived from the mouse opsin promoter was analyzed in the context of photoreceptor-specific transgene expression. Results. Each virus tested efficiently transduced the retinal pigment epithelium. The authors found no evidence that Ad5/F35 or Ad5/F37 transduced photoreceptors. Instead, they found that Ad5/F37 transduced Müller cells. Robust photoreceptor transduction by Ad5ΔRGD was detected. Photoreceptor-specific transgene expression from the 257-bp mouse opsin promoter in the context of Ad5ΔRGD vectors was found. Conclusions. Adenovirus vectors may be designed with tropism to distinct cell populations. Robust photoreceptor-specific transgene expression can be achieved in the context of Ad5ΔRGD vectors. PMID:19892875

  15. Listening and Questioning: The "Apophatic/Cataphatic" Distinction Revisited

    ERIC Educational Resources Information Center

    Waks, Leonard

    2007-01-01

    In an earlier article I drew a distinction between two general types of listening. In one the listener brings pre-determined categories to bear in extracting useful information from the speaker's utterance. In the other the listener suspends such categories to hear as much as possible in the utterance. This distinction has been challenged by…

  16. The Curious Case of Orthographic Distinctiveness: Disruption of Categorical Processing

    ERIC Educational Resources Information Center

    McDaniel, Mark A.; Cahill, Michael J.; Bugg, Julie M.

    2016-01-01

    How does orthographic distinctiveness affect recall of structured (categorized) word lists? On one theory, enhanced item-specific information (e.g., more distinct encoding) in concert with robust relational information (e.g., categorical information) optimally supports free recall. This predicts that for categorically structured lists,…

  17. The Curious Case of Orthographic Distinctiveness: Disruption of Categorical Processing

    ERIC Educational Resources Information Center

    McDaniel, Mark A.; Cahill, Michael J.; Bugg, Julie M.

    2016-01-01

    How does orthographic distinctiveness affect recall of structured (categorized) word lists? On one theory, enhanced item-specific information (e.g., more distinct encoding) in concert with robust relational information (e.g., categorical information) optimally supports free recall. This predicts that for categorically structured lists,…

  18. Neurobehavioral Perspectives on the Distinction between Fear and Anxiety

    ERIC Educational Resources Information Center

    Perusini, Jennifer N.; Fanselow, Michael S.

    2015-01-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the…

  19. Neurobehavioral Perspectives on the Distinction between Fear and Anxiety

    ERIC Educational Resources Information Center

    Perusini, Jennifer N.; Fanselow, Michael S.

    2015-01-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the…

  20. Explicit-Implicit Distinction: A Review of Related Literature

    ERIC Educational Resources Information Center

    Jarrah, Marwan A.

    2016-01-01

    This paper sketches out the main views of the major pragmatic approaches (i.e., Grice's theory of conversation, Relevance Theory, and Neo-Gricean pragmatic theory) on explicit-implicit distinction. It makes clear how this distinction has been differently drawn for utterance interpretation. Additionally, it highlights several corresponding problems…

  1. Creating Distinctiveness: Lessons from Uncommon Colleges and Universities. ERIC Digest.

    ERIC Educational Resources Information Center

    Townsend, Barbara K.; And Others

    This brief report summarizes a longer document with the same title. Distinctive colleges and universities possess a unifying theme or vision that is expressed in all their activities. They also usually respond to newly emerging societal or community needs unmet by existing schools of higher education. Distinctiveness, however, can limit the…

  2. 34 CFR 110.24 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As...

  3. 34 CFR 110.24 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As...

  4. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with...

  5. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with...

  6. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with...

  7. 34 CFR 110.24 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As...

  8. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with...

  9. 14 CFR § 1252.411 - Age distinctions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Age distinctions. § 1252.411 Section Â... BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Investigation, Conciliation, and Enforcement Procedures § 1252.411 Age distinctions. There are no Federal statutes...

  10. 34 CFR 110.24 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Recipient assessment of age distinctions. 110.24..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Duties of ED Recipients § 110.24 Recipient assessment of age distinctions. (a) As...

  11. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with...

  12. Generations of interdisciplinarity in bioinformatics

    PubMed Central

    Bartlett, Andrew; Lewis, Jamie; Williams, Matthew L.

    2016-01-01

    Bioinformatics, a specialism propelled into relevance by the Human Genome Project and the subsequent -omic turn in the life science, is an interdisciplinary field of research. Qualitative work on the disciplinary identities of bioinformaticians has revealed the tensions involved in work in this “borderland.” As part of our ongoing work on the emergence of bioinformatics, between 2010 and 2011, we conducted a survey of United Kingdom-based academic bioinformaticians. Building on insights drawn from our fieldwork over the past decade, we present results from this survey relevant to a discussion of disciplinary generation and stabilization. Not only is there evidence of an attitudinal divide between the different disciplinary cultures that make up bioinformatics, but there are distinctions between the forerunners, founders and the followers; as inter/disciplines mature, they face challenges that are both inter-disciplinary and inter-generational in nature. PMID:27453689

  13. Generations of interdisciplinarity in bioinformatics.

    PubMed

    Bartlett, Andrew; Lewis, Jamie; Williams, Matthew L

    2016-04-02

    Bioinformatics, a specialism propelled into relevance by the Human Genome Project and the subsequent -omic turn in the life science, is an interdisciplinary field of research. Qualitative work on the disciplinary identities of bioinformaticians has revealed the tensions involved in work in this "borderland." As part of our ongoing work on the emergence of bioinformatics, between 2010 and 2011, we conducted a survey of United Kingdom-based academic bioinformaticians. Building on insights drawn from our fieldwork over the past decade, we present results from this survey relevant to a discussion of disciplinary generation and stabilization. Not only is there evidence of an attitudinal divide between the different disciplinary cultures that make up bioinformatics, but there are distinctions between the forerunners, founders and the followers; as inter/disciplines mature, they face challenges that are both inter-disciplinary and inter-generational in nature.

  14. Dynamic melody recognition: distinctiveness and the role of musical expertise.

    PubMed

    Bailes, Freya

    2010-07-01

    The hypothesis that melodies are recognized at moments when they exhibit a distinctive musical pattern was tested. In a melody recognition experiment, point-of-recognition (POR) data were gathered from 32 listeners (16 musicians and 16 nonmusicians) judging 120 melodies. A series of models of melody recognition were developed, resulting from a stepwise multiple regression of two classes of information relating to melodic familiarity and melodic distinctiveness. Melodic distinctiveness measures were assembled through statistical analyses of over 15,000 Western themes and melodies. A significant model, explaining 85% of the variance, entered measures primarily of timing distinctiveness and pitch distinctiveness, but excluding familiarity, as predictors of POR. Differences between nonmusician and musician models suggest a processing shift from momentary to accumulated information with increased exposure to music. Supplemental materials for this article may be downloaded from http://mc.psychonomic-journals.org/content/supplemental.

  15. Positive and negative reinforcement: Should the distinction be preserved?

    PubMed Central

    Baron, Alan; Galizio, Mark

    2005-01-01

    Michael (1975) reviewed efforts to classify reinforcing events in terms of whether stimuli are added (positive reinforcement) or removed (negative reinforcement). He concluded that distinctions in these terms are confusing and ambiguous. Of necessity, adding a stimulus requires its previous absence and removing a stimulus its previous presence. Moreover, there is no good basis, either behavioral or physiological, that indicates the involvement of distinctly different processes, and on these grounds he proposed that the distinction be abandoned. Despite the cogency of Michael's analysis, the distinction between positive and negative reinforcement is still being taught. In this paper, we reconsider the issue from the perspective of 30 years. However, we could not find new evidence in contemporary research and theory that allows reliable classification of an event as a positive rather than a negative reinforcer. We conclude by reiterating Michael's admonitions about the conceptual confusion created by such a distinction. PMID:22478443

  16. Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells

    PubMed Central

    Ramos, Lavoisier S.; Zippin, Jonathan Hale; Kamenetsky, Margarita; Buck, Jochen; Levin, Lonny R.

    2008-01-01

    In β cells, both glucose and hormones, such as GLP-1, stimulate production of the second messenger cAMP, but glucose and GLP-1 elicit distinct cellular responses. We now show in INS-1E insulinoma cells that glucose and GLP-1 produce cAMP with distinct kinetics via different adenylyl cyclases. GLP-1 induces a rapid cAMP signal mediated by G protein–responsive transmembrane adenylyl cyclases (tmAC). In contrast, glucose elicits a delayed cAMP rise mediated by bicarbonate, calcium, and ATP-sensitive soluble adenylyl cyclase (sAC). This glucose-induced, sAC-dependent cAMP rise is dependent upon calcium influx and is responsible for the glucose-induced activation of the mitogen-activated protein kinase (ERK1/2) pathway. These results demonstrate that sAC-generated and tmAC-generated cAMP define distinct signaling cascades. PMID:18695009

  17. ELK1 uses different DNA binding modes to regulate functionally distinct classes of target genes.

    PubMed

    Odrowaz, Zaneta; Sharrocks, Andrew D

    2012-01-01

    Eukaryotic transcription factors are grouped into families and, due to their similar DNA binding domains, often have the potential to bind to the same genomic regions. This can lead to redundancy at the level of DNA binding, and mechanisms are required to generate specific functional outcomes that enable distinct gene expression programmes to be controlled by a particular transcription factor. Here we used ChIP-seq to uncover two distinct binding modes for the ETS transcription factor ELK1. In one mode, other ETS transcription factors can bind regulatory regions in a redundant fashion; in the second, ELK1 binds in a unique fashion to another set of genomic targets. Each binding mode is associated with different binding site features and also distinct regulatory outcomes. Furthermore, the type of binding mode also determines the control of functionally distinct subclasses of genes and hence the phenotypic response elicited. This is demonstrated for the unique binding mode where a novel role for ELK1 in controlling cell migration is revealed. We have therefore uncovered an unexpected link between the type of binding mode employed by a transcription factor, the subsequent gene regulatory mechanisms used, and the functional categories of target genes controlled.

  18. TWO DISTINCT RED GIANT BRANCHES IN THE GLOBULAR CLUSTER NGC 288

    SciTech Connect

    Roh, Dong-Goo; Lee, Young-Wook; Joo, Seok-Joo; Han, Sang-Il; Sohn, Young-Jong; Lee, Jae-Woo

    2011-06-01

    We report the presence of two distinct red giant branches (RGBs) in the globular cluster NGC 288 from the narrowband calcium and Stroemgren b and y photometry obtained at the CTIO 4 m Blanco telescope. The RGB of NGC 288 is clearly split into two in the hk [=(Ca - b) - (b - y)] index, while the split is not shown in the b - y color. Unlike other globular clusters with multiple populations reported thus far, the horizontal branch of NGC 288 is only mildly extended. Our stellar population models show that this and the presence of two distinct RGBs in NGC 288 can be reproduced if slightly metal-rich ({Delta}[m/H] {approx} 0.16) second generation stars are also enhanced in helium by small amount ({Delta}Y {approx} 0.03) and younger by {approx}1.5 Gyr. The RGB split in the hk index is most likely indicating that the second generation stars were affected by supernovae enrichment, together with the pollution of lighter elements by intermediate-mass asymptotic giant branch stars or fast-rotating massive stars. In order to confirm this, however, spectroscopy of stars in the two distinct RGB groups is urgently required.

  19. Net Generation's Learning Styles in Nursing Education.

    PubMed

    Christodoulou, Eleni; Kalokairinou, Athina

    2015-01-01

    Numerous surveys have confirmed that emerging technologies and Web 2.0 tools have been a defining feature in the lives of current students, estimating that there is a fundamental shift in the way young people communicate, socialize and learn. Nursing students in higher education are characterized as digital literate with distinct traits which influence their learning styles. Millennials exhibit distinct learning preferences such as teamwork, experiential activities, structure, instant feedback and technology integration. Higher education institutions should be aware of the implications of the Net Generation coming to university and be prepared to meet their expectations and learning needs.

  20. Aposematic signals and the relationship between conspicuousness and distinctiveness.

    PubMed

    Merilaita, Sami; Ruxton, Graeme D

    2007-03-21

    It has long been recognized that prey that invest in toxic or other defenses often advertise these defenses by means of conspicuously coloured signals. One question that remains unanswered is why conspicuousness is such a universal trait of aposematic signals. Conspicuousness may allow more rapid avoidance learning by predators or improved retention of such learning. An alternative or complementary explanation is that defended species should adopt a conspicuous signal of their defence to make them visually distinct from inconspicuous undefended prey. Here, we use a neural network model of prey detection and attack decision making by a predator in combination with evolving, virtual prey to shed light on the relative importance of conspicuousness against the background and distinctiveness from other species as mechanisms underlying aposematic signalling. Our model suggests that prey conspicuousness may result from selection for distinctiveness, but that selection for distinctiveness does not result in maximization of conspicuousness. On the other hand, our model does not justify the exclusion of the possibility that conspicuousness as such may be a beneficial attribute of warning coloration. It is likely that the relative importance of the two selective forces (for conspicuousness and for distinctiveness) will differ on a case-by-case basis, however there is no empirical or logical reason for the current neglect of evolutionary pressure for distinctiveness. Thus, we suggest that description of aposematism as the teaming of a secondary defence with a conspicuous signal may be overly simplistic; we would rather that the signal were described as conspicuous and/or distinctive.

  1. Compositionally distinct nuclear pore complexes of functionally distinct dimorphic nuclei in the ciliate Tetrahymena

    PubMed Central

    Iwamoto, Masaaki; Osakada, Hiroko; Mori, Chie; Fukuda, Yasuhiro; Nagao, Koji; Obuse, Chikashi

    2017-01-01

    ABSTRACT The nuclear pore complex (NPC), a gateway for nucleocytoplasmic trafficking, is composed of ∼30 different proteins called nucleoporins. It remains unknown whether the NPCs within a species are homogeneous or vary depending on the cell type or physiological condition. Here, we present evidence for compositionally distinct NPCs that form within a single cell in a binucleated ciliate. In Tetrahymena thermophila, each cell contains both a transcriptionally active macronucleus (MAC) and a germline micronucleus (MIC). By combining in silico analysis, mass spectrometry analysis for immuno-isolated proteins and subcellular localization analysis of GFP-fused proteins, we identified numerous novel components of MAC and MIC NPCs. Core members of the Nup107–Nup160 scaffold complex were enriched in MIC NPCs. Strikingly, two paralogs of Nup214 and of Nup153 localized exclusively to either the MAC or MIC NPCs. Furthermore, the transmembrane components Pom121 and Pom82 localize exclusively to MAC and MIC NPCs, respectively. Our results argue that functional nuclear dimorphism in ciliates is likely to depend on the compositional and structural specificity of NPCs. PMID:28386019

  2. Compositionally distinct nuclear pore complexes of functionally distinct dimorphic nuclei in ciliate Tetrahymena.

    PubMed

    Iwamoto, Masaaki; Osakada, Hiroko; Mori, Chie; Fukuda, Yasuhiro; Nagao, Koji; Obuse, Chikashi; Hiraoka, Yasushi; Haraguchi, Tokuko

    2017-04-06

    The nuclear pore complex (NPC), a gateway for nucleocytoplasmic trafficking, is composed of about 30 different proteins called nucleoporins. It remains unknown whether the NPCs within a species are homogeneous or vary depending on the cell type, or physiological condition. Here, we present evidence for compositionally distinct NPCs that form within a single cell in a binucleated ciliate. In Tetrahymena thermophila, each cell contains both a transcriptionally-active macronucleus (MAC) and a germline micronucleus (MIC). By combining in silico analysis, mass spectrometry analysis for immuno-isolated proteins, and subcellular localization analysis of GFP fused proteins, we identified numerous novel components of MAC and MIC NPCs. Core members of the Nup107-160 scaffold complex were enriched in MIC NPCs. Strikingly, two paralogs of Nup214 and of Nup153 localized exclusively to either MAC or MIC NPCs. Furthermore, the transmembrane components Pom121 and Pom82 localize exclusively to MAC and MIC NPCs, respectively. Our results argue that functional nuclear dimorphism in ciliates is likely to depend on compositional and structural specificity of NPCs.

  3. Distinct steps in yeast spore morphogenesis require distinct SMK1 MAP kinase thresholds.

    PubMed Central

    Wagner, M; Briza, P; Pierce, M; Winter, E

    1999-01-01

    The SMK1 mitogen-activated protein kinase is required for spore morphogenesis in Saccharomyces cerevisiae. In contrast to the multiple aberrant spore wall assembly patterns seen even within a single smk1 null ascus, different smk1 missense mutants block in a coordinated fashion at intermediate stages. One smk1 mutant forms asci in which the four spores are surrounded only by prospore wall-like structures, while another smk1 mutant forms asci in which the spores are surrounded by inner but not outer spore wall layers. Stepwise increases in gene dosage of a hypomorphic smk1 allele allow for the completion of progressively later morphological and biochemical events and for the acquisition of distinct spore-resistance phenotypes. Furthermore, smk1 allelic spore phenotypes can be recapitulated by reducing wild-type SMK1 expression. The data demonstrate that SMK1 is required for the execution of multiple steps in spore morphogenesis that require increasing thresholds of SMK1 activity. These results suggest that quantitative changes in mitogen-activated protein kinase signaling play a role in coordinating multiple events of a single cellular differentiation program. PMID:10101160

  4. Evaluation of Spatial Agreement of Distinct Landslide Prediction Models

    NASA Astrophysics Data System (ADS)

    Sterlacchini, Simone; Bordogna, Gloria; Frigerio, Ivan

    2013-04-01

    The aim of the study was to assess the degree of spatial agreement of different predicted patterns in a majority of coherent landslide prediction maps with almost similar success and prediction rate curves. If two or more models have a similar performance, the choice of the best one is not a trivial operation and cannot be based on success and prediction rate curves only. In fact, it may happen that two or more prediction maps with similar accuracy and predictive power do not have the same degree of agreement in terms of spatial predicted patterns. The selected study area is the high Valtellina valley, in North of Italy, covering a surface of about 450 km2 where mapping of historical landslides is available. In order to assess landslide susceptibility, we applied the Weights of Evidence (WofE) modeling technique implemented by USGS by means of ARC-SDM tool. WofE efficiently investigate the spatial relationships among past events and multiple predisposing factors, providing useful information to identify the most probable location of future landslide occurrences. We have carried out 13 distinct experiments by changing the number of morphometric and geo-environmental explanatory variables in each experiment with the same training set and thus generating distinct models of landslide prediction, computing probability degrees of occurrence of landslides in each pixel. Expert knowledge and previous results from indirect statistically-based methods suggested slope, land use, and geology the best "driving controlling factors". The Success Rate Curve (SRC) was used to estimate how much the results of each model fit the occurrence of landslides used for the training of the models. The Prediction Rate Curve (PRC) was used to estimate how much the model predict the occurrence of landslides in the validation set. We found that the performances were very similar for different models. Also the dendrogram of the Cohen's kappa statistic and Principal Component Analysis (PCA) were

  5. Generations at School: Building an Age-Friendly Learning Community

    ERIC Educational Resources Information Center

    Lovely, Suzette; Buffum, Austin G.; Barth, Roland S.

    2007-01-01

    Today's workforce comprises distinct generational cohorts-Veterans, Baby Boomers, Gen-Xers, and Millennials. "Generations at School" provides educators with the knowledge and tools to create and sustain true collaboration, teamwork, and consensus. Suzette Lovely and Austin G. Buffum introduce the traits and tipping points of these diverse age…

  6. Generations at School: Building an Age-Friendly Learning Community

    ERIC Educational Resources Information Center

    Lovely, Suzette; Buffum, Austin G.; Barth, Roland S.

    2007-01-01

    Today's workforce comprises distinct generational cohorts-Veterans, Baby Boomers, Gen-Xers, and Millennials. "Generations at School" provides educators with the knowledge and tools to create and sustain true collaboration, teamwork, and consensus. Suzette Lovely and Austin G. Buffum introduce the traits and tipping points of these diverse age…

  7. The Millennial Generation: Common Experience Guiding Them into Adulthood

    ERIC Educational Resources Information Center

    Cecere, Donna-Marie

    2017-01-01

    The Millennial Generation, those born from 1980-2000, see the world from a different viewpoint. This distinctive cohort has structured their lives in a different manner than preceding generations. The introduction and influence of social, political, and technological changes over the past few decades have structured Millennials' unique and…

  8. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development.

    PubMed

    Mizoguchi, Toshihide; Pinho, Sandra; Ahmed, Jalal; Kunisaki, Yuya; Hanoun, Maher; Mendelson, Avital; Ono, Noriaki; Kronenberg, Henry M; Frenette, Paul S

    2014-05-12

    Mesenchymal stem and progenitor cells (MSPCs) contribute to bone marrow (BM) homeostasis by generating multiple types of stromal cells. MSPCs can be labeled in the adult BM by Nestin-GFP, whereas committed osteoblast progenitors are marked by Osterix expression. However, the developmental origin and hierarchical relationship of stromal cells remain largely unknown. Here, by using a lineage-tracing system, we describe three distinct waves of contributions of Osterix(+) cells in the BM. First, Osterix(+) progenitors in the fetal BM contribute to nascent bone tissues and transient stromal cells that are replaced in the adult marrow. Second, Osterix-expressing cells perinatally contribute to osteolineages and long-lived BM stroma, which have characteristics of Nestin-GFP(+) MSPCs. Third, Osterix labeling in the adult marrow is osteolineage-restricted, devoid of stromal contribution. These results uncover a broad expression profile of Osterix and raise the intriguing possibility that distinct waves of stromal cells, primitive and definitive, may organize the developing BM.

  9. Damped propagation of cell polarization explains distinct PCP phenotypes of epithelial patterning

    PubMed Central

    Zhu, Hao; Owen, Markus R.

    2013-01-01

    During epithelial patterning in metazoans cells are polarized in the plane of a tissue, a process referred to as planar cell polarity (PCP). Interactions between a few molecules produce distinct phenotypes in diverse tissues in animals from flies to humans and make PCP tightly associated with tissue and organ growth control. An interesting question is whether these phenotypes share common traits. Previous computational models revealed how PCP signalling determines cell polarization in some specific contexts. We have developed a computational model, examined PCP signalling in varied molecular contexts, and revealed how details of molecular interactions and differences in molecular contexts affect the direction, speed, and propagation of cell polarization. The main finding is that damped propagation of cell polarization can generate rich variances in phenotypes of domineering non-autonomy and error correction in different contexts. These results impressively demonstrate how simple molecular interactions cause distinct, yet inherently analogous, developmental patterning. PMID:23995897

  10. Reassortment and distinct evolutionary dynamics of Rift Valley Fever virus genomic segments.

    PubMed

    Freire, Caio C M; Iamarino, Atila; Soumaré, Peinda O Ly; Faye, Ousmane; Sall, Amadou A; Zanotto, Paolo M A

    2015-06-23

    Rift Valley Fever virus (RVFV) is a member of Bunyaviridae family that causes a febrile disease affecting mainly ruminants and occasionally humans in Africa, with symptoms that range from mid to severe. RVFV has a tri-segmented ssRNA genome that permits reassortment and could generate more virulent strains. In this study, we reveal the importance of reassortment for RVFV evolution using viral gene genealogy inference and phylodynamics. We uncovered seven events of reassortment that originated RVFV lineages with discordant origins among segments. Moreover, we also found that despite similar selection regimens, the three segments have distinct evolutionary dynamics; the longer segment L evolves at a significant lower rate. Episodes of discordance between population size estimates per segment also coincided with reassortment dating. Our results show that RVFV segments are decoupled enough to have distinct demographic histories and to evolve under different molecular rates.

  11. Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes.

    PubMed

    Winnard, Paul T; Zhang, Chi; Vesuna, Farhad; Kang, Jeon Woong; Garry, Jonah; Dasari, Ramachandra Rao; Barman, Ishan; Raman, Venu

    2017-03-21

    Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker. Decision algorithms derived from the Raman spectra unambiguously identified these isogenic cell lines as unique biological entities - a finding reinforced through metabolomic analyses that indicated tissue of origin metabolite distinctions between the cell lines. Notably, complementarity of the metabolomics and Raman datasets was found. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, which can be differentiated with Raman spectroscopy.

  12. Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes

    PubMed Central

    Winnard, Paul T.; Zhang, Chi; Vesuna, Farhad; Kang, Jeon Woong; Garry, Jonah; Dasari, Ramachandra Rao; Barman, Ishan; Raman, Venu

    2017-01-01

    Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker. Decision algorithms derived from the Raman spectra unambiguously identified these isogenic cell lines as unique biological entities – a finding reinforced through metabolomic analyses that indicated tissue of origin metabolite distinctions between the cell lines. Notably, complementarity of the metabolomics and Raman datasets was found. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, which can be differentiated with Raman spectroscopy. PMID:28145887

  13. Central pattern generator for vocalization: Is there a vertebrate morphotype?

    PubMed Central

    Bass, Andrew H.

    2014-01-01

    Animals that generate acoustic signals for social communication are faced with two essential tasks: generate a temporally precise signal and inform the auditory system about the occurrence of one’s own sonic signal. Recent studies of sound producing fishes delineate a hindbrain network comprised of anatomically distinct compartments coding equally distinct neurophysiological properties that allow an organism to meet these behavioral demands. A set of neural characters comprising a vocal-sonic central pattern generator (CPG) morphotype is proposed for fishes and tetrapods that shares evolutionary developmental origins with pectoral appendage motor systems. PMID:25050813

  14. Central pattern generator for vocalization: is there a vertebrate morphotype?

    PubMed

    Bass, Andrew H

    2014-10-01

    Animals that generate acoustic signals for social communication are faced with two essential tasks: generate a temporally precise signal and inform the auditory system about the occurrence of one's own sonic signal. Recent studies of sound producing fishes delineate a hindbrain network comprised of anatomically distinct compartments coding equally distinct neurophysiological properties that allow an organism to meet these behavioral demands. A set of neural characters comprising a vocal-sonic central pattern generator (CPG) morphotype is proposed for fishes and tetrapods that shares evolutionary developmental origins with pectoral appendage motor systems.

  15. Distinctions in Breast Tumor Recurrence Patterns Post-Therapy among Racially Distinct Populations

    PubMed Central

    Cantuaria, Guilherme; Klimov, Sergey; Jones, Mildred; Neema, Pranay; Il’yasova, Dora; Krishnamurti, Uma; Li, Xiaoxian; Reid, Michelle D.; Gupta, Meenakshi; Rida, Padmashree C. G.; Osan, Remus; Aneja, Ritu

    2017-01-01

    Background Clinical studies have revealed a higher risk of breast tumor recurrence in African-American (AA) patients compared to European-American (EA) patients, contributing to the alarming inequality in clinical outcomes among the ethnic groups. However, distinctions in recurrence patterns upon receiving hormone, radiation, and/or chemotherapy between the races remain poorly characterized. Methods We compared patterns and rates (per 1000 cancer patients per 1 year) of recurrence following each form of treatment between AA (n = 1850) and EA breast cancer patients (n = 7931) from a cohort of patients (n = 10504) treated between 2005–2015 at Northside Hospital in Atlanta, GA. Results Among patients who received any combination of adjuvant therapy, AA displayed higher overall rates of recurrence than EA (p = 0.015; HR: 1.699; CI: 1.108–2.606). Furthermore, recurrence rates were higher in AA than EA among stage I (p = 0.031; HR: 1.736; CI: 1.052–2.864) and T1 classified patients (p = 0.003; HR: 2.009; CI: 1.263–3.197). Interestingly, among patients who received neoadjuvant chemotherapy, AA displayed higher rates of local recurrence than EA (p = 0.024; HR: 7.134; CI: 1.295–39.313). Conclusion Our analysis revealed higher incidence rates of recurrence in AA compared to EA among patients that received any combination of adjuvant therapy. Moreover, our data demonstrates an increased risk of tumor recurrence in AA than EA among patients diagnosed with minimally invasive disease. This is the first clinical study to suggest that neoadjuvant chemotherapy improves breast cancer recurrence rates and patterns in AA. PMID:28085947

  16. CONSIDERATION OF CHILDREN'S DISTINCTIVE SUSCEPTIBILITY IN ENVIRONMENTAL HEALTH STUDIES

    EPA Science Inventory

    Consideration of children's distinctive susceptibility in environmental health studies.
    Pauline Mendola (US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711)

    Children are a particularly susceptible subpopulation with ...

  17. Increasing Intergroup Distinctiveness: The Benefits of Third Party Helping.

    PubMed

    van Leeuwen, Esther; Harinck, Fieke

    2016-10-01

    Discrimination is often used to increase public perceptions of group distinctiveness. The current research studied the effectiveness of third party helping as an alternative, more benign strategy to this end. Across four studies, we examined whether helping a third party can position the helping group as more distinct from, or more similar to, a comparison group, depending on the nature of the comparison group's relationship with the third party. Results from three studies showed that third party helping was as effective as discrimination of the comparison group, but third party helping elicited a more positive public image of the group compared with discrimination. Study 4 provided evidence for the spontaneous use of third party helping in response to distinctiveness threat. These findings extend insights from classic balance theories and research on strategic intergroup helping to the domain of intergroup differentiation, and highlight a benign strategy to achieve positive group distinctiveness. © 2016 by the Society for Personality and Social Psychology, Inc.

  18. Education and Training: Is There Any Longer a Useful Distinction?

    ERIC Educational Resources Information Center

    Hager, Paul; Laurent, John

    1990-01-01

    Although education and training were distinct concepts when Taylorism dominated the workplace, it is no longer appropriate to separate them. Today's highly competitive environment requires the education of a flexible, multiskilled workforce, not training for narrowly defined employment tasks. (SK)

  19. Education and Training: Is There Any Longer a Useful Distinction?

    ERIC Educational Resources Information Center

    Hager, Paul; Laurent, John

    1990-01-01

    Although education and training were distinct concepts when Taylorism dominated the workplace, it is no longer appropriate to separate them. Today's highly competitive environment requires the education of a flexible, multiskilled workforce, not training for narrowly defined employment tasks. (SK)

  20. CONSIDERATION OF CHILDREN'S DISTINCTIVE SUSCEPTIBILITY IN ENVIRONMENTAL HEALTH STUDIES

    EPA Science Inventory

    Consideration of children's distinctive susceptibility in environmental health studies.
    Pauline Mendola (US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711)

    Children are a particularly susceptible subpopulation with ...

  1. 4. West side of pier showing distinct piling configuration. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. West side of pier showing distinct piling configuration. - Charlestown Navy Yard, Pier 10, Between Piers 9 & 11 along Mystic River on Charlestown Waterfront at eastern edge of Charlestown Navy Yard, Boston, Suffolk County, MA

  2. Does social distinction contribute to socioeconomic inequalities in diet: the case of 'superfoods' consumption.

    PubMed

    Oude Groeniger, Joost; van Lenthe, Frank J; Beenackers, Mariëlle A; Kamphuis, Carlijn B M

    2017-03-27

    The key mechanisms underlying socioeconomic inequalities in dietary intake are still poorly understood, hampering the development of interventions. An important, but sparsely mentioned mechanism is that of 'social distinction', whereby those in a higher socioeconomic position adopt dietary patterns by which they can distinguish themselves from lower socioeconomic groups. We investigated the importance of distinction as a mechanism, by testing the socioeconomic gradient in the consumption of so-called 'superfoods' and the contribution of a well-established indicator of distinction, cultural participation. Data from participants (25-75 years) of the 2014 survey of the Dutch population-based GLOBE study were used (N = 2812). Multivariable regression models were used to analyse the association between education, income and cultural participation (e.g. visits to museums, opera, theatre, concerts) and the consumption of superfoods (spelt, quinoa and goji berries, chia seeds or wheatgrass). The consumption of superfoods is far more prevalent among higher socioeconomic groups. Adjusting for cultural participation strongly attenuated the educational and income gradient in superfoods consumption, whereas cultural participation remained strongly associated with superfoods consumption. Those in the highest quintile of cultural participation reported the highest consumption of spelt products (OR = 2.97, 95% CI = 2.10;4.18), quinoa (OR = 3.50, 95% CI = 2.12;5.79) and goji berries, chia seeds or wheatgrass (OR = 2.69, 95% CI = 1.73;4.17). The associations between socioeconomic position and the consumption of 'superfoods' seem to be partially driven by a process of social distinction. These findings suggest that distinction may be an important, but currently neglected mechanism in generating socioeconomic inequalities in dietary intake. It deserves a more prominent role in interventions to reduce these inequalities.

  3. Different AMPA receptor subtypes mediate the distinct kinetic components of a biphasic EPSC in hippocampal interneurons

    PubMed Central

    Stincic, Todd L.; Frerking, Matthew E.

    2015-01-01

    CA1 hippocampal interneurons at the border between stratum radiatum (SR) and stratum lacunosum-moleculare (SLM) have AMPA receptor (AMPAR)-mediated excitatory postsynaptic currents (EPSCs) that consist of two distinct phases: a typical fast component (FC), and a highly unusual slow component (SC) that persists for hundreds of milliseconds. To determine whether these kinetically distinct components of the EPSC are mediated by distinct AMPAR subpopulations, we examined the relative contributions of GluA2-containing and—lacking AMPARs to the SC. GluA2-containing AMPARs mediated the majority of the FC whereas GluA2-lacking AMPARs preferentially generated the SC. When glutamate uptake through the glial glutamate transporter excitatory amino acid transporter (EAAT1) was inhibited, spill over-mediated AMPAR activation recruited an even slower third kinetic component that persisted for several seconds; however, this spillover-mediated current was mediated predominantly by GluA2-containing AMPARs and therefore was clearly distinct from the SC when uptake is intact. Thus, different AMPAR subpopulations that vary in GluA2 content mediate the distinct components of the AMPAR EPSC. The SC is developmentally downregulated in mice, declining after the second postnatal week. This downregulation affects both GluA2-containing and GluA2-lacking AMPARs mediating the SC, and is not accompanied by developmental changes in the GluA2 content of AMPARs underlying the FC. Thus, the downregulation of the SC appears to be independent of synaptic GluA2 expression, suggesting the involvement of another AMPAR subunit or an auxiliary protein. Our results therefore identify GluA2-dependent and GluA2-independent determinants of the SC: GluA2-lacking AMPARs preferentially contribute to the SC, while the developmental downregulation of the SC is independent of GluA2 content. PMID:26042027

  4. Distinct contributions by frontal and parietal cortices support working memory.

    PubMed

    Mackey, Wayne E; Curtis, Clayton E

    2017-07-21

    Although subregions of frontal and parietal cortex both contribute and coordinate to support working memory (WM) functions, their distinct contributions remain elusive. Here, we demonstrate that perturbations to topographically organized human frontal and parietal cortex during WM maintenance cause distinct but systematic distortions in WM. The nature of these distortions supports theories positing that parietal cortex mainly codes for retrospective sensory information, while frontal cortex codes for prospective action.

  5. 29 CFR 549.3 - Distinction between plan and trust.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Distinction between plan and trust. 549.3 Section 549.3... REQUIREMENTS OF A âBONA FIDE PROFIT-SHARING PLAN OR TRUSTâ § 549.3 Distinction between plan and trust. As used... profits; (b) Profit-sharing trust means any such program or arrangement as qualifies under this part...

  6. Electrical power generating system. [for windpowered generation

    NASA Technical Reports Server (NTRS)

    Nola, F. J. (Inventor)

    1981-01-01

    An alternating current power generation system adopted to inject power in an already powered power line is discussed. The power generating system solves to adjustably coup an induction motor, as a generator, to an ac power line wherein the motor and power line are connected through a triac. The triac is regulated to normally turn on at a relatively late point in each half cycle of its operation, whereby at less than operating speed, and thus when the induction motor functions as a motor rather than as a generator, power consumption from the line is substantially reduced. The principal application will be for windmill powered generation.

  7. Distinctive voices enhance the visual recognition of unfamiliar faces.

    PubMed

    Bülthoff, I; Newell, F N

    2015-04-01

    Several studies have provided evidence in favour of a norm-based representation of faces in memory. However, such models have hitherto failed to take account of how other person-relevant information affects face recognition performance. Here we investigated whether distinctive or typical auditory stimuli affect the subsequent recognition of previously unfamiliar faces and whether the type of auditory stimulus matters. In this study participants learned to associate either unfamiliar distinctive and typical voices or unfamiliar distinctive and typical sounds to unfamiliar faces. The results indicated that recognition performance was better to faces previously paired with distinctive than with typical voices but we failed to find any benefit on face recognition when the faces were previously associated with distinctive sounds. These findings possibly point to an expertise effect, as faces are usually associated to voices. More importantly, it suggests that the memory for visual faces can be modified by the perceptual quality of related vocal information and more specifically that facial distinctiveness can be of a multi-sensory nature. These results have important implications for our understanding of the structure of memory for person identification. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Distinct temperature sensitivity among taiga and tundra shrubs in Alaska

    NASA Astrophysics Data System (ADS)

    Andreu-Hayles, L.; Anchukaitis, K. J.; D'Arrigo, R.

    2014-12-01

    Shrub expansion into Arctic and alpine tundra ecosystems is well documented, mostly over the last 50 years, based on remote sensing data, aerial photography, and in-situ observations. Warming temperatures are considered the main driver of the observed change in shrub vegetation patterns. Here, we assess the relationship between temperatures and shrub growth from five populations of Salix spp. (willow) and Alnus spp. (alder) in Alaska growing within the tundra and the boreal forest (~taiga) using dendrochronological techniques. The three tundra shrub sites are located on the Dalton Highway north from Toolik Lake (~69ºN 148ºW), whereas the two taiga shrub sites are located closer to Fairbanks at the Twelve Mile Summit site (~65ºN 146ºW). Because shrub ages vary among the studied populations lead to different time spans for the ring-width chronologies generated, a common period with available satellite data spanning from 1982 to 2010 was selected for this study. All tundra shrub chronologies shared a strong positive response to summer temperatures despite growing in heterogeneous site conditions and belonging to different species. In contrast, in the taiga, summer temperatures enhance willow growth, whereas alder growth appears almost insensitive to temperature over the interval studied. Extending the analyses back in time, a very strong positive relationship was found between alder ring-width and June temperatures prior to 1970. This phenomenon, a weakening of the previously existing relationship between growth and temperatures, was also detected in white spruce (Picea glauca) growing at the same site, and it is known in the literature as the 'divergence problem'. Thus, at this taiga location, alder shrubs and trees seem to have similar growth patterns. Summer temperatures no longer seem to enhance taiga alder growth. Shrubs of different species exposed to the same climatic conditions can exhibit varied growth responses. The distinct temperature sensitivities

  9. Distinct Element modeling of geophysical signatures during sinkhole collapse

    NASA Astrophysics Data System (ADS)

    Al-Halbouni, Djamil; Holohan, Eoghan P.; Taheri, Abbas; Dahm, Torsten

    2017-04-01

    A sinkhole forms due to the collapse of rocks or soil near the Earth's surface into an underground cavity. Such cavities represent large secondary pore spaces derived by dissolution and subrosion in the underground. By changing the stress field in the surrounding material, the growth of cavities can lead to a positive feedback, in which expansion and mechanical instability in the surrounding material increases or generates new secondary pore space (e.g. by fracturing), which in turn increases the cavity size, etc. A sinkhole forms due to the eventual subsidence or collapse of the overburden that becomes destabilized and fails all the way to the Earth's surface. Both natural processes like (sub)surface water movement and earthquakes, and human activities, such as mining, construction and groundwater extraction, intensify such feedbacks. The development of models for the mechanical interaction of a growing cavity and fracturing of its surrounding material, thus capturing related precursory geophysical signatures, has been limited, however. Here we report on the advances of a general, simplified approach to simulating cavity growth and sinkhole formation by using 2D Distinct Element Modeling (DEM) PFC5.0 software and thereby constraining pre-, syn- and post-collapse geophysical and geodetic signatures. This physically realistic approach allows for spontaneous cavity development and dislocation of rock mass to be simulated by bonded particle formulation of DEM. First, we present calibration and validation of our model. Surface subsidence above an instantaneously excavated circular cavity is tracked and compared with an incrementally increasing dissolution zone both for purely elastic and non-elastic material.This validation is important for the optimal choice of model dimensions and particles size with respect to simulation time. Second, a cavity growth approach is presented and compared to a well-documented case study, the deliberately intensified sinkhole collapse at

  10. A distinct epigenetic signature at targets of a leukemia protein

    PubMed Central

    Rossetti, Stefano; Hoogeveen, André T; Liang, Ping; Stanciu, Cornel; van der Spek, Peter; Sacchi, Nicoletta

    2007-01-01

    Background Human myelogenous leukemia characterized by either the non random t(8; 21)(q22; q22) or t(16; 21)(q24; q22) chromosome translocations differ for both their biological and clinical features. Some of these features could be consequent to differential epigenetic transcriptional deregulation at AML1 targets imposed by AML1-MTG8 and AML1-MTG16, the fusion proteins deriving from the two translocations. Preliminary findings showing that these fusion proteins lead to transcriptional downregulation of AML1 targets, marked by repressive chromatin changes, would support this hypothesis. Here we show that combining conventional global gene expression arrays with the power of bioinformatic genomic survey of AML1-consensus sequences is an effective strategy to identify AML1 targets whose transcription is epigenetically downregulated by the leukemia-associated AML1-MTG16 protein. Results We interrogated mouse gene expression microarrays with probes generated either from 32D cells infected with a retroviral vector carrying AML1-MTG16 and unable of granulocyte differentiation and proliferation in response to the granulocyte colony stimulating factor (G-CSF), or from 32D cells infected with the cognate empty vector. From the analysis of differential gene expression alone (using as criteria a p value < 0.01 and an absolute fold change > 3), we were unable to conclude which of the 37 genes downregulated by AML1-MTG16 were, or not, direct AML1 targets. However, when we applied a bioinformatic approach to search for AML1-consensus sequences in the 10 Kb around the gene transcription start sites, we closed on 17 potential direct AML1 targets. By focusing on the most significantly downregulated genes, we found that both the AML1-consensus and the transcription start site chromatin regions were significantly marked by aberrant repressive histone tail changes. Further, the promoter of one of these genes, containing a CpG island, was aberrantly methylated. Conclusion This study

  11. D-D neutron generator development at LBNL.

    PubMed

    Reijonen, J; Gicquel, F; Hahto, S K; King, M; Lou, T-P; Leung, K-N

    2005-01-01

    The plasma and ion source technology group in Lawrence Berkeley National Laboratory is developing advanced, next generation D-D neutron generators. There are three distinctive developments, which are discussed in this presentation, namely, multi-stage, accelerator-based axial neutron generator, high-output co-axial neutron generator and point source neutron generator. These generators employ RF-induction discharge to produce deuterium ions. The distinctive feature of RF-discharge is its capability to generate high atomic hydrogen species, high current densities and stable and long-life operation. The axial neutron generator is designed for applications that require fast pulsing together with medium to high D-D neutron output. The co-axial neutron generator is aimed for high neutron output with cw or pulsed operation, using either the D-D or D-T fusion reaction. The point source neutron generator is a new concept, utilizing a toroidal-shaped plasma generator. The beam is extracted from multiple apertures and focus to the target tube, which is located at the middle of the generator. This will generate a point source of D-D, T-T or D-T neutrons with high output flux. The latest development together with measured data will be discussed in this article.

  12. Distinctive Feature Extraction for Indian Sign Language (ISL) Gesture using Scale Invariant Feature Transform (SIFT)

    NASA Astrophysics Data System (ADS)

    Patil, Sandeep Baburao; Sinha, G. R.

    2017-02-01

    India, having less awareness towards the deaf and dumb peoples leads to increase the communication gap between deaf and hard hearing community. Sign language is commonly developed for deaf and hard hearing peoples to convey their message by generating the different sign pattern. The scale invariant feature transform was introduced by David Lowe to perform reliable matching between different images of the same object. This paper implements the various phases of scale invariant feature transform to extract the distinctive features from Indian sign language gestures. The experimental result shows the time constraint for each phase and the number of features extracted for 26 ISL gestures.

  13. Distinctive Feature Extraction for Indian Sign Language (ISL) Gesture using Scale Invariant Feature Transform (SIFT)

    NASA Astrophysics Data System (ADS)

    Patil, Sandeep Baburao; Sinha, G. R.

    2016-07-01

    India, having less awareness towards the deaf and dumb peoples leads to increase the communication gap between deaf and hard hearing community. Sign language is commonly developed for deaf and hard hearing peoples to convey their message by generating the different sign pattern. The scale invariant feature transform was introduced by David Lowe to perform reliable matching between different images of the same object. This paper implements the various phases of scale invariant feature transform to extract the distinctive features from Indian sign language gestures. The experimental result shows the time constraint for each phase and the number of features extracted for 26 ISL gestures.

  14. Characterization of two distinct, simultaneous hot electron beams in intense laser-solid interactions.

    PubMed

    Cho, B I; Osterholz, J; Bernstein, A C; Dyer, G M; Karmakar, A; Pukhov, A; Ditmire, T

    2009-11-01

    The transport of energetic electron beams generated from aluminum foils irradiated by ultraintense laser pulses has been studied by imaging coherent transition radiation from the rear side of the target. Two distinct beams of MeV electrons are emitted from the target rear side at the same time. This measurement indicates that two different mechanisms, namely resonance absorption and jxB heating, accelerate the electrons at the targets front side and drive them to different directions, with different temperatures. This interpretation is consistent with 3D-particle-in-cell simulations.

  15. MHD Power Generation

    ERIC Educational Resources Information Center

    Kantrowitz, Arthur; Rosa, Richard J.

    1975-01-01

    Explains the operation of the Magnetohydrodynamic (MHD) generator and advantages of the system over coal, oil or nuclear powered generators. Details the development of MHD generators in the United States and Soviet Union. (CP)

  16. MHD Power Generation

    ERIC Educational Resources Information Center

    Kantrowitz, Arthur; Rosa, Richard J.

    1975-01-01

    Explains the operation of the Magnetohydrodynamic (MHD) generator and advantages of the system over coal, oil or nuclear powered generators. Details the development of MHD generators in the United States and Soviet Union. (CP)

  17. Power Generation for River and Tidal Generators

    SciTech Connect

    Muljadi, Eduard; Wright, Alan; Gevorgian, Vahan; Donegan, James; Marnagh, Cian; McEntee, Jarlath

    2016-06-01

    Renewable energy sources are the second largest contributor to global electricity production, after fossil fuels. The integration of renewable energy continued to grow in 2014 against a backdrop of increasing global energy consumption and a dramatic decline in oil prices during the second half of the year. As renewable generation has become less expensive during recent decades, and it becomes more accepted by the global population, the focus on renewable generation has expanded from primarily wind and solar to include new types with promising future applications, such as hydropower generation, including river and tidal generation. Today, hydropower is considered one of the most important renewable energy sources. In river and tidal generation, the input resource flow is slower but also steadier than it is in wind or solar generation, yet the level of water turbulent flow may vary from one place to another. This report focuses on hydrokinetic power conversion.

  18. ELECTROSTATIC POWER GENERATOR.

    DTIC Science & Technology

    ELECTROSTATIC GENERATORS , POWER EQUIPMENT, ELECTRIC GOVERNORS, CIRCUITS, VACUUM SEALS, ELECTRICAL INSULATION, VACUUM, ELECTRODES, FINISHES, SURFACE...FINISHING, SURFACE PROPERTIES, HARDNESS, PULSE GENERATORS , TRANSFORMERS, FIELD EMISSION.

  19. ELECTROSTATIC POWER GENERATOR.

    DTIC Science & Technology

    ELECTROSTATIC GENERATORS , POWER EQUIPMENT, ELECTRICAL INSULATION, FIELD EMISSION, ELECTRODES, VACUUM, SURFACE PROPERTIES, ANODES, CATHODES, POLISHES...DIELECTRICS, COATINGS, PRESSURE, HARDNESS, PULSE GENERATORS , TRANSFORMERS, VACUUM SEALS, EQUATIONS.

  20. Distinct circuit-dependent functions of presynaptic neurexin-3 at GABAergic and glutamatergic synapses

    PubMed Central

    Aoto, Jason; Földy, Csaba; Ilcus, Silviana Maria Ciurea; Tabuchi, Katsuhiko; Südhof, Thomas C.

    2015-01-01

    α- and β-neurexins are presynaptic cell-adhesion molecules whose general importance for synaptic transmission is well documented. The specific functions of neurexins, however, remain largely unknown because no conditional neurexin knockouts are available, and because targeting all α- and β-neurexins produced by a particular gene is challenging. Using newly-generated constitutive and conditional knockout mice that target all neurexin-3α and -3β isoforms, we here show that neurexin-3 is differentially required for distinct synaptic functions in different brain regions. Specifically, we find that in cultured neurons and acute slices of the hippocampus, presynaptic neurexin-3 mediates trans-synaptic regulation of postsynaptic AMPA-receptors via its extracellular sequences. In cultured neurons and acute slices of the olfactory bulb, however, presynaptic neurexin-3 is selectively required for GABA release by a mechanism involving its intracellular sequences. Thus, our data demonstrate that neurexin-3 performs distinct essential pre- or postsynaptic functions in different brain regions by distinct mechanisms. PMID:26030848

  1. Use of optical mapping to sort uropathogenic Escherichia coli strains into distinct subgroups

    PubMed Central

    Schwan, William R.; Briska, Adam; Stahl, Buffy; Wagner, Trevor K.; Zentz, Emily; Henkhaus, John; Lovrich, Steven D.; Agger, William A.; Callister, Steven M.; DuChateau, Brian; Dykes, Colin W.

    2010-01-01

    Optical maps were generated for 33 uropathogenic Escherichia coli (UPEC) isolates. For individual genomes, the NcoI restriction fragments aligned into a unique chromosome map for each individual isolate, which was then compared with the in silico restriction maps of all of the sequenced E. coli and Shigella strains. All of the UPEC isolates clustered separately from the Shigella strains as well as the laboratory and enterohaemorrhagic E. coli strains. Moreover, the individual strains appeared to cluster into distinct subgroups based on the dendrogram analyses. Phylogenetic grouping of these 33 strains showed that 32/33 were the B2 subgroup and 1/33 was subgroup A. To further characterize the similarities and differences among the 33 isolates, pathogenicity island (PAI), haemolysin and virulence gene comparisons were performed. A strong correlation was observed between individual subgroups and virulence factor genes as well as haemolysis activity. Furthermore, there was considerable conservation of sequenced-strain PAIs in the specific subgroups. Strains with different antibiotic-resistance patterns also appeared to sort into separate subgroups. Thus, the optical maps distinguished the UPEC strains from other E. coli strains and further subdivided the strains into distinct subgroups. This optical mapping procedure holds promise as an alternative way to subgroup all E. coli strains, including those involved in infections outside of the intestinal tract and epidemic strains with distinct patterns of antibiotic resistance. PMID:20378655

  2. Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems.

    PubMed

    Schuyler, Ronald P; Merkel, Angelika; Raineri, Emanuele; Altucci, Lucia; Vellenga, Edo; Martens, Joost H A; Pourfarzad, Farzin; Kuijpers, Taco W; Burden, Frances; Farrow, Samantha; Downes, Kate; Ouwehand, Willem H; Clarke, Laura; Datta, Avik; Lowy, Ernesto; Flicek, Paul; Frontini, Mattia; Stunnenberg, Hendrik G; Martín-Subero, José I; Gut, Ivo; Heath, Simon

    2016-11-15

    DNA methylation and the localization and post-translational modification of nucleosomes are interdependent factors that contribute to the generation of distinct phenotypes from genetically identical cells. With 112 whole-genome bisulfite sequencing datasets from the BLUEPRINT Epigenome Project, we analyzed the global development of DNA methylation patterns during lineage commitment and maturation of a range of immune system effector cells and the cancers that arise from them. We show clear trends in methylation patterns that are distinct in the innate and adaptive arms of the human immune system, both globally and in relation to consistently positioned nucleosomes. Most notable are a progressive loss of methylation in developing lymphocytes and the consistent occurrence of non-CG methylation in specific cell types. Cancer samples from the two lineages are further polarized, suggesting the involvement of distinct lineage-specific epigenetic mechanisms. We anticipate broad utility for this resource as a basis for further comparative epigenetic analyses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

    PubMed Central

    Thapa, Dharendra; Shepherd, Danielle L.

    2014-01-01

    Cardiac tissue contains discrete pools of mitochondria that are characterized by their subcellular spatial arrangement. Subsarcolemmal mitochondria (SSM) exist below the cell membrane, interfibrillar mitochondria (IFM) reside in rows between the myofibrils, and perinuclear mitochondria are situated at the nuclear poles. Microstructural imaging of heart tissue coupled with the development of differential isolation techniques designed to sequentially separate spatially distinct mitochondrial subpopulations have revealed differences in morphological features including shape, absolute size, and internal cristae arrangement. These findings have been complemented by functional studies indicating differences in biochemical parameters and, potentially, functional roles for the ATP generated, based upon subcellular location. Consequently, mitochondrial subpopulations appear to be influenced differently during cardiac pathologies including ischemia/reperfusion, heart failure, aging, exercise, and diabetes mellitus. These influences may be the result of specific structural and functional disparities between mitochondrial subpopulations such that the stress elicited by a given cardiac insult differentially impacts subcellular locales and the mitochondria contained within. The goal of this review is to highlight some of the inherent structural and functional differences that exist between spatially distinct cardiac mitochondrial subpopulations as well as provide an overview of the differential impact of various cardiac pathologies on spatially distinct mitochondrial subpopulations. As an outcome, we will instill a basis for incorporating subcellular spatial location when evaluating the impact of cardiac pathologies on the mitochondrion. Incorporation of subcellular spatial location may offer the greatest potential for delineating the influence of cardiac pathology on this critical organelle. PMID:24778166

  4. Maintaining a Distinction Between Possible and Impossible Topics of Conversation in the Outpatient Respiratory Medical Clinic.

    PubMed

    Jensen, Lone Birgitte Skov; Larsen, Kristian; Konradsen, Hanne

    2016-01-01

    The aim of this study is to generate a grounded theory explaining patterns of behavior among health care professionals (HCPs) during interactions with patients in outpatient respiratory medical clinics. The findings suggest that the HCPs managed contradictory expectations to the interaction by maintaining a distinction between possible and impossible topics to counseling. Three subcategories explaining the effort that maintain the impossible and possible topics separated were identified: (a) an effort to maintain the diseased lungs as the main task in counseling, (b) navigating interactions to avoid strong emotions of suffering in patients to reveal, (c) avoiding the appearance of the non-alterable life circumstances of the patients. The HCPs' attitudes toward what patients could be offered generated a distance and a difficulty during counseling and created further suffering in the patients but likewise a discomfort and frustration among the HCPs.

  5. Separate microcircuit modules of distinct v2a interneurons and motoneurons control the speed of locomotion.

    PubMed

    Ampatzis, Konstantinos; Song, Jianren; Ausborn, Jessica; El Manira, Abdeljabbar

    2014-08-20

    Spinal circuits generate locomotion with variable speed as circumstances demand. These circuits have been assumed to convey equal and uniform excitation to all motoneurons whose input resistance dictates their activation sequence. However, the precise connectivity pattern between excitatory premotor circuits and the different motoneuron types has remained unclear. Here, we generate a connectivity map in adult zebrafish between the V2a excitatory interneurons and slow, intermediate, and fast motoneurons. We show that the locomotor network does not consist of a uniform circuit as previously assumed. Instead, it can be deconstructed into three separate microcircuit modules with distinct V2a interneuron subclasses driving slow, intermediate, or fast motoneurons. This modular design enables the increase of locomotor speed by sequentially adding microcircuit layers from slow to intermediate and fast. Thus, this principle of organization of vertebrate spinal circuits represents an intrinsic mechanism to increase the locomotor speed by incrementally engaging different motor units. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Maintaining a Distinction Between Possible and Impossible Topics of Conversation in the Outpatient Respiratory Medical Clinic

    PubMed Central

    Jensen, Lone Birgitte Skov; Larsen, Kristian; Konradsen, Hanne

    2016-01-01

    The aim of this study is to generate a grounded theory explaining patterns of behavior among health care professionals (HCPs) during interactions with patients in outpatient respiratory medical clinics. The findings suggest that the HCPs managed contradictory expectations to the interaction by maintaining a distinction between possible and impossible topics to counseling. Three subcategories explaining the effort that maintain the impossible and possible topics separated were identified: (a) an effort to maintain the diseased lungs as the main task in counseling, (b) navigating interactions to avoid strong emotions of suffering in patients to reveal, (c) avoiding the appearance of the non-alterable life circumstances of the patients. The HCPs’ attitudes toward what patients could be offered generated a distance and a difficulty during counseling and created further suffering in the patients but likewise a discomfort and frustration among the HCPs. PMID:28462333

  7. Liquidity Spillover in International Stock Markets through Distinct Time Scales

    PubMed Central

    Righi, Marcelo Brutti; Vieira, Kelmara Mendes

    2014-01-01

    This paper identifies liquidity spillovers through different time scales based on a wavelet multiscaling method. We decompose daily data from U.S., British, Brazilian and Hong Kong stock markets indices in order to calculate the scale correlation between their illiquidities. The sample is divided in order to consider non-crisis, sub-prime crisis and Eurozone crisis. We find that there are changes in correlations of distinct scales and different periods. Association in finest scales is smaller than in coarse scales. There is a rise on associations in periods of crisis. In frequencies, there is predominance for significant distinctions involving the coarsest scale, while for crises periods there is predominance for distinctions on the finest scale. PMID:24465918

  8. Liquidity spillover in international stock markets through distinct time scales.

    PubMed

    Righi, Marcelo Brutti; Vieira, Kelmara Mendes

    2014-01-01

    This paper identifies liquidity spillovers through different time scales based on a wavelet multiscaling method. We decompose daily data from U.S., British, Brazilian and Hong Kong stock markets indices in order to calculate the scale correlation between their illiquidities. The sample is divided in order to consider non-crisis, sub-prime crisis and Eurozone crisis. We find that there are changes in correlations of distinct scales and different periods. Association in finest scales is smaller than in coarse scales. There is a rise on associations in periods of crisis. In frequencies, there is predominance for significant distinctions involving the coarsest scale, while for crises periods there is predominance for distinctions on the finest scale.

  9. Central and Peripheral Retina Arise through Distinct Developmental Paths

    PubMed Central

    Venters, Sara J.; Mikawa, Takashi; Hyer, Jeanette

    2013-01-01

    In the mature eye, three distinct tissue fates, retina, ciliary body, and iris, arrange with a strict linear organization along the central (back) to peripheral (front) axis. The establishment of this topographical relationship within the optic vesicle is not well understood. We use a targeted vital labeling strategy to test the derivation of mature eye tissues from the optic vesicle of the chick embryo. Fate mapping uncovers two distinct origins of the neural retina. Contrary to expectations, the central neural retina has a discrete origin within the posterior optic vesicle. The peripheral retina derives from the distal optic vesicle, sharing a common origin with more peripheral tissue fates. This study identifies for the first time two distinct retinal sub-domains, central and peripheral, which arise during embryogenesis. Identification of these discrete retinal compartments provides a framework for understanding functional and disease processes throughout retinal tissue. PMID:23613848

  10. Work Values across Generations

    ERIC Educational Resources Information Center

    Hansen, Jo-Ida C.; Leuty, Melanie E.

    2012-01-01

    Mainstream publication discussions of differences in generational cohorts in the workplace suggest that individuals of more recent generations, such as Generation X and Y, have different work values than do individuals of the Silent and Baby Boom generations. Although extant research suggests that age may influence work values, few of the…

  11. Work Values across Generations

    ERIC Educational Resources Information Center

    Hansen, Jo-Ida C.; Leuty, Melanie E.

    2012-01-01

    Mainstream publication discussions of differences in generational cohorts in the workplace suggest that individuals of more recent generations, such as Generation X and Y, have different work values than do individuals of the Silent and Baby Boom generations. Although extant research suggests that age may influence work values, few of the…

  12. Talkin' 'bout My Generation

    ERIC Educational Resources Information Center

    Rickes, Persis C.

    2010-01-01

    The monikers are many: (1) "Generation Y"; (2) "Echo Boomers"; (3) "GenMe"; (4) the "Net Generation"; (5) "RenGen"; and (6) "Generation Next". One name that appears to be gaining currency is "Millennials," perhaps as a way to better differentiate the current generation from its…

  13. Talkin' 'bout My Generation

    ERIC Educational Resources Information Center

    Rickes, Persis C.

    2010-01-01

    The monikers are many: (1) "Generation Y"; (2) "Echo Boomers"; (3) "GenMe"; (4) the "Net Generation"; (5) "RenGen"; and (6) "Generation Next". One name that appears to be gaining currency is "Millennials," perhaps as a way to better differentiate the current generation from its…

  14. Minding the Generation Gap

    ERIC Educational Resources Information Center

    Field, John

    2011-01-01

    Generational conflict is back. After years of relative silence, and mutual ignorance, the young and old are once more at war. With youth unemployment high on the political agenda, the fortunes of the "jobless generation" are being contrasted with those of the "golden generation" of baby boomers, but is one generation really…

  15. Aggregates and Superaggregates of Soot with Four Distinct Fractal Morphologies

    NASA Technical Reports Server (NTRS)

    Sorensen, C. M.; Kim, W.; Fry, D.; Chakrabarti, A.

    2004-01-01

    Soot formed in laminar diffusion flames of heavily sooting fuels evolves through four distinct growth stages which give rise to four distinct aggregate fractal morphologies. These results were inferred from large and small angle static light scattering from the flames, microphotography of the flames, and analysis of soot sampled from the flames. The growth stages occur approximately over four successive orders of magnitude in aggregate size. Comparison to computer simulations suggests that these four growth stages involve either diffusion limited cluster aggregation or percolation in either three or two dimensions.

  16. Radical behaviorism and the subjective—objective distinction

    PubMed Central

    Moore, Jay

    1995-01-01

    The distinction between subjective and objective domains is central to traditional psychology, including the various forms of mediational stimulus—organism—response neobehaviorism that treat the elements of a subjective domain as hypothetical constructs. Radical behaviorism has its own unique perspective on the subjective—objective distinction. For radical behaviorism, dichotomies between subjective and objective, knower and known, or observer and agent imply at most unique access to a part of the world, rather than dichotomous ontologies. This perspective leads to unique treatments of such important philosophical matters as (a) dispositions and (b) the difference between first- and third-person psychological sentences. PMID:22478203

  17. Radical behaviorism and the subjective-objective distinction.

    PubMed

    Moore, J

    1995-01-01

    The distinction between subjective and objective domains is central to traditional psychology, including the various forms of mediational stimulus-organism-response neobehaviorism that treat the elements of a subjective domain as hypothetical constructs. Radical behaviorism has its own unique perspective on the subjective-objective distinction. For radical behaviorism, dichotomies between subjective and objective, knower and known, or observer and agent imply at most unique access to a part of the world, rather than dichotomous ontologies. This perspective leads to unique treatments of such important philosophical matters as (a) dispositions and (b) the difference between first- and third-person psychological sentences.

  18. Mapping Phylogenetic Trees to Reveal Distinct Patterns of Evolution

    PubMed Central

    Kendall, Michelle; Colijn, Caroline

    2016-01-01

    Evolutionary relationships are frequently described by phylogenetic trees, but a central barrier in many fields is the difficulty of interpreting data containing conflicting phylogenetic signals. We present a metric-based method for comparing trees which extracts distinct alternative evolutionary relationships embedded in data. We demonstrate detection and resolution of phylogenetic uncertainty in a recent study of anole lizards, leading to alternate hypotheses about their evolutionary relationships. We use our approach to compare trees derived from different genes of Ebolavirus and find that the VP30 gene has a distinct phylogenetic signature composed of three alternatives that differ in the deep branching structure. Key words: phylogenetics, evolution, tree metrics, genetics, sequencing. PMID:27343287

  19. Number of distinct sites visited by a subdiffusive random walker.

    PubMed

    Yuste, Santos Bravo; Klafter, J; Lindenberg, Katja

    2008-03-01

    The asymptotic mean number of distinct sites visited by a subdiffusive continuous-time random walker in two dimensions seems not to have been explicitly calculated anywhere in the literature. This number has been calculated for other dimensions for only one specific asymptotic behavior of the waiting time distribution between steps. We present an explicit derivation for two cases in all integer dimensions so as to formally complete a tableau of results. In this tableau we include the dominant as well as subdominant contributions in all integer dimensions. Other quantities that can be calculated from the mean number of distinct sites visited are also discussed.

  20. Genome-Wide Association Identifies Regulatory Loci Associated with Distinct Local Histogram Emphysema Patterns

    PubMed Central

    Cho, Michael H.; San José Estépar, Raúl; McDonald, Merry-Lynn N.; Laird, Nan; Beaty, Terri H.; Washko, George; Crapo, James D.; Silverman, Edwin K.

    2014-01-01

    Rationale: Emphysema is a heritable trait that occurs in smokers with and without chronic obstructive pulmonary disease. Emphysema occurs in distinct pathologic patterns, but the genetic determinants of these patterns are unknown. Objectives: To identify genetic loci associated with distinct patterns of emphysema in smokers and investigate the regulatory function of these loci. Methods: Quantitative measures of distinct emphysema patterns were generated from computed tomography scans from smokers in the COPDGene Study using the local histogram emphysema quantification method. Genome-wide association studies (GWAS) were performed in 9,614 subjects for five emphysema patterns, and the results were referenced against enhancer and DNase I hypersensitive regions from ENCODE and Roadmap Epigenomics cell lines. Measurements and Main Results: Genome-wide significant associations were identified for seven loci. Two are novel associations (top single-nucleotide polymorphism rs379123 in MYO1D and rs9590614 in VMA8) located within genes that function in cell-cell signaling and cell migration, and five are in loci previously associated with chronic obstructive pulmonary disease susceptibility (HHIP, IREB2/CHRNA3, CYP2A6/ADCK, TGFB2, and MMP12). Five of these seven loci lay within enhancer or DNase I hypersensitivity regions in lung fibroblasts or small airway epithelial cells, respectively. Enhancer enrichment analysis for top GWAS associations (single-nucleotide polymorphisms associated at P < 5 × 10−6) identified multiple cell lines with significant enhancer enrichment among top GWAS loci, including lung fibroblasts. Conclusions: This study demonstrates for the first time genetic associations with distinct patterns of pulmonary emphysema quantified by computed tomography scan. Enhancer regions are significantly enriched among these GWAS results, with pulmonary fibroblasts among the cell types showing the strongest enrichment. PMID:25006744

  1. Distinct populations of innate CD8+ T cells revealed in a CXCR3 reporter mouse.

    PubMed

    Oghumu, Steve; Dong, Ran; Varikuti, Sanjay; Shawler, Todd; Kampfrath, Thomas; Terrazas, Cesar A; Lezama-Davila, Claudio; Ahmer, Brian M M; Whitacre, Caroline C; Rajagopalan, Sanjay; Locksley, Richard; Sharpe, Arlene H; Satoskar, Abhay R

    2013-03-01

    CXCR3, expressed mainly on activated T and NK cells, is implicated in a host of immunological conditions and can contribute either to disease resolution or pathology. We report the generation and characterization of a novel CXCR3 internal ribosome entry site bicistronic enhanced GFP reporter (CIBER) mouse in which enhanced GFP expression correlates with surface levels of CXCR3. Using CIBER mice, we identified two distinct populations of innate CD8(+) T cells based on constitutive expression of CXCR3. We demonstrate that CXCR3(+) innate CD8(+) T cells preferentially express higher levels of Ly6C and CD122, but lower levels of CCR9 compared with CXCR3(-) innate CD8(+) T cells. Furthermore, we show that CXCR3(+) innate CD8(+) T cells express higher transcript levels of antiapoptotic but lower levels of proapoptotic factors, respond more robustly to IL-2 and IL-15, and produce significantly more IFN-γ and granzyme B. Interestingly, CXCR3(+) innate CD8(+) T cells do not respond to IL-12 or IL-18 alone, but produce significant amounts of IFN-γ on stimulation with a combination of these cytokines. Taken together, these findings demonstrate that CXCR3(+) and CXCR3(-) innate CD8(+) T cells are phenotypically and functionally distinct. These newly generated CIBER mice provide a novel tool for studying the role of CXCR3 and CXCR3-expressing cells in vivo.

  2. Distinctive Feature of Microbial Communities and Bacterial Functional Profiles in Tricholoma matsutake Dominant Soil

    PubMed Central

    Oh, Seung-Yoon; Fong, Jonathan J.; Park, Myung Soo; Lim, Young Woon

    2016-01-01

    Tricholoma matsutake, the pine mushroom, is a valuable forest product with high economic value in Asia, and plays an important ecological role as an ectomycorrhizal fungus. Around the host tree, T. matsutake hyphae generate a distinctive soil aggregating environment called a fairy ring, where fruiting bodies form. Because T. matsutake hyphae dominate the soil near the fairy ring, this species has the potential to influence the microbial community. To explore the influence of T. matsutake on the microbial communities, we compared the microbial community and predicted bacterial function between two different soil types—T. matsutake dominant and T. matsutake minor. DNA sequence analyses showed that fungal and bacterial diversity were lower in the T. matsutake dominant soil compared to T. matsutake minor soil. Some microbial taxa were significantly more common in the T. matsutake dominant soil across geographic locations, many of which were previously identified as mycophillic or mycorrhiza helper bacteria. Between the two soil types, the predicted bacterial functional profiles (using PICRUSt) had significantly distinct KEGG modules. Modules for amino acid uptake, carbohydrate metabolism, and the type III secretion system were higher in the T. matsutake dominant soil than in the T. matsutake minor soil. Overall, similar microbial diversity, community structure, and bacterial functional profiles of the T. matsutake dominant soil across geographic locations suggest that T. matsutake may generate a dominance effect. PMID:27977803

  3. Distinct actions of Rab3 and Rab27 GTPases on late stages of exocytosis of insulin.

    PubMed

    Cazares, Victor A; Subramani, Arasakumar; Saldate, Johnny J; Hoerauf, Widmann; Stuenkel, Edward L

    2014-09-01

    Rab GTPases associated with insulin-containing secretory granules (SGs) are key in targeting, docking and assembly of molecular complexes governing pancreatic β-cell exocytosis. Four Rab3 isoforms along with Rab27A are associated with insulin granules, yet elucidation of the distinct roles of these Rab families on exocytosis remains unclear. To define specific actions of these Rab families we employ Rab3GAP and/or EPI64A GTPase-activating protein overexpression in β-cells from wild-type or Ashen mice to selectively transit the entire Rab3 family or Rab27A to a GDP-bound state. Ashen mice carry a spontaneous mutation that eliminates Rab27A expression. Using membrane capacitance measurements we find that GTP/GDP nucleotide cycling of Rab27A is essential for generation of the functionally defined immediately releasable pool (IRP) and central to regulating the size of the readily releasable pool (RRP). By comparison, nucleotide cycling of Rab3 GTPases, but not of Rab27A, is essential for a kinetically rapid filling of the RRP with SGs. Aside from these distinct functions, Rab3 and Rab27A GTPases demonstrate considerable functional overlap in building the readily releasable granule pool. Hence, while Rab3 and Rab27A cooperate to generate release-ready SGs in β-cells, they also direct unique kinetic and functional properties of the exocytotic pathway.

  4. Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus

    PubMed Central

    Throckmorton, Kurt; Lim, Fang Yun; Kontoyiannis, Dimitrios P.; Zheng, Weifa; Keller, Nancy P.

    2016-01-01

    Summary Filamentous fungi are renowned for the production of bioactive secondary metabolites. Typically, one distinct metabolite is generated from a specific secondary metabolite cluster. Here, we characterize the newly described trypacidin (tpc) cluster in the opportunistic human pathogen Aspergillus fumigatus. We find that this cluster as well as the previously characterized endocrocin (enc) cluster both contribute to the production of the spore metabolite endocrocin. Whereas trypacidin is eliminated when only tpc cluster genes are deleted, endocrocin production is only eliminated when both the tpc and enc non-reducing polyketide synthase-encoding genes, tpcC and encA, respectively, are deleted. EncC, an anthrone oxidase, converts the product released from EncA to endocrocin as a final product. In contrast, endocrocin synthesis by the tpc cluster likely results from incomplete catalysis by TpcK (a putative decarboxylase), as its deletion results in a nearly 10-fold increase in endocrocin production. We suggest endocrocin is likely a shunt product in all related non-reducing polyketide synthase clusters containing homologues of TpcK and TpcL (a putative anthrone oxidase), e.g. geodin and monodictyphenone. This finding represents an unusual example of two physically discrete secondary metabolite clusters generating the same natural product in one fungal species by distinct routes. PMID:26242966

  5. Durable and scalable icephobic surfaces: similarities and distinctions from superhydrophobic surfaces.

    PubMed

    Sojoudi, H; Wang, M; Boscher, N D; McKinley, G H; Gleason, K K

    2016-02-21

    Formation, adhesion, and accumulation of ice, snow, frost, glaze, rime, or their mixtures can cause severe problems for solar panels, wind turbines, aircrafts, heat pumps, power lines, telecommunication equipment, and submarines. These problems can decrease efficiency in power generation, increase energy consumption, result in mechanical and/or electrical failure, and generate safety hazards. To address these issues, the fundamentals of interfaces between liquids and surfaces at low temperatures have been extensively studied. This has lead to development of so called "icephobic" surfaces, which possess a number of overlapping, yet distinctive, characteristics from superhydrophobic surfaces. Less attention has been given to distinguishing differences between formation and adhesion of ice, snow, glaze, rime, and frost or to developing a clear definition for icephobic, or more correctly pagophobic, surfaces. In this review, we strive to clarify these differences and distinctions, while providing a comprehensive definition of icephobicity. We classify different canonical families of icephobic (pagophobic) surfaces providing a review of those with potential for scalable and robust development.

  6. Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements.

    PubMed

    Zieger, Martin; Mayer, Andreas

    2012-09-01

    Yeast vacuoles fragment and fuse in response to environmental conditions, such as changes in osmotic conditions or nutrient availability. Here we analyze osmotically induced vacuole fragmentation by time-lapse microscopy. Small fragmentation products originate directly from the large central vacuole. This happens by asymmetrical scission rather than by consecutive equal divisions. Fragmentation occurs in two distinct phases. Initially, vacuoles shrink and generate deep invaginations that leave behind tubular structures in their vicinity. Already this invagination requires the dynamin-like GTPase Vps1p and the vacuolar proton gradient. Invaginations are stabilized by phosphatidylinositol 3-phosphate (PI(3)P) produced by the phosphoinositide 3-kinase complex II. Subsequently, vesicles pinch off from the tips of the tubular structures in a polarized manner, directly generating fragmentation products of the final size. This phase depends on the production of phosphatidylinositol-3,5-bisphosphate and the Fab1 complex. It is accelerated by the PI(3)P- and phosphatidylinositol 3,5-bisphosphate-binding protein Atg18p. Thus vacuoles fragment in two steps with distinct protein and lipid requirements.

  7. Gamma ray generator

    SciTech Connect

    Firestone, Richard B; Reijonen, Jani

    2014-05-27

    An embodiment of a gamma ray generator includes a neutron generator and a moderator. The moderator is coupled to the neutron generator. The moderator includes a neutron capture material. In operation, the neutron generator produces neutrons and the neutron capture material captures at least some of the neutrons to produces gamma rays. An application of the gamma ray generator is as a source of gamma rays for calibration of gamma ray detectors.

  8. Distinct mechanisms are utilized to induce stress sensor gadd45b by different stress stimuli.

    PubMed

    Zumbrun, Steven D; Hoffman, Barbara; Liebermann, Dan A

    2009-12-01

    The GADD45 family of proteins consists of three small proteins, GADD45A, GADD45B, and GADD45G, implicated in modulating the cellular response to genotoxic/physiological stressors. Despite similarities in sequence, structure and function, each gadd45 gene is induced differentially by different stress stimuli. Studies on stress-mediated induction of the gadd45 genes have predominantly focused on gadd45a, with knowledge of gadd45b and gadd45g regulation lacking. To generate a more complete understanding of the regulation of gadd45 genes, a comprehensive analysis of stress-mediated induction of human gadd45b has been carried out using human RKO colorectal carcinoma cells as a model system. Novel data indicate that gadd45b induction in RKO cells is regulated by distinct mechanisms in a stress-specific manner. Methylmethane sulfonate (MMS), a DNA alkylating agent, induces gadd45b transcription through a cohort of both constitutive and inducible bound factors, including NFY, Sp1 and Egr1. In contrast, in a hyperosmotic environment generated with sorbitol, gadd45b mRNA is induced exclusively by mRNA stabilization. These findings indicate that the stress-mediated induction of gadd45b is largely distinct from gadd45a. Furthermore, data obtained provide a novel paradigm for stress-response gene induction, indicating that gadd45b induction by distinct stressors, in the same cell type and under the same experimental settings, is differentially regulated at the level of mRNA transcription or mRNA stability. Importantly, this study also provides the groundwork to further examine the regulation of gadd45b expression in in vivo settings using animal models and tissues obtained from normal individuals and cancer patients prior to and after chemotherapeutic intervention.

  9. Coordination of distinct motor structures through remote axonal coupling of projection interneurons

    PubMed Central

    Jing, Jian; Sasaki, Kosei; Perkins, Matthew H; Siniscalchi, Michael J; Ludwar, Bjoern C; Cropper, Elizabeth C; Weiss, Klaudiusz R

    2011-01-01

    Complex behaviors often require coordinated movements of dissimilar motor structures. The underlying neural mechanisms are poorly understood. We investigated cycle-by-cycle coordination of two dissimilar feeding structures in Aplysia californica: the external lips and the internal radula. During feeding, the lips open while the radula protracts. Lip and radula motoneurons are located in the cerebral and buccal ganglia respectively, and radula motoneurons are controlled by a well-characterized buccal central pattern generator (CPG). Here, we examined whether the three electrically-coupled lip motoneurons C15/16/17 are controlled by the buccal CPG or by a previously-postulated cerebral CPG. Two buccal-cerebral projection interneurons, B34 and B63, which are part of the buccal CPG and mediate radula protraction, monosynaptically excite C15/16/17. Recordings from the B34 axon in the cerebral ganglion demonstrate its direct electrical coupling with C15/16/17, eliminating the need for a cerebral CPG. Moreover, when the multifunctional buccal CPG generates multiple forms of motor programs due to the activation of two inputs: the command-like neuron CBI-2 and the esophageal nerve (EN), C15/16 exhibit activity patterns that are distinct from C17. These distinct activity patterns result from combined activity of B34 and B63 and their differential excitation of C15/16 vs. C17. In more general terms, we identified neuronal mechanisms that allow a single CPG to coordinate the phasing and activity of remotely-located motoneurons innervating distinct structures that participate in the production of different motor outputs. We also demonstrated that axo-dendritic electrical coupling by projection interneurons plays a pivotal role in coordinating activity of these remotely-located neurons. PMID:22031890

  10. Getting at the source of distinctive encoding effects in the DRM paradigm: evidence from signal-detection measures and source judgments.

    PubMed

    Bodner, Glen E; Huff, Mark J; Lamontagne, Raymond W; Azad, Tanjeem

    2017-05-01

    Studying Deese-Roediger-McDermott (DRM) lists using a distinctive encoding task can reduce the DRM false memory illusion. Reductions for both distinctively encoded lists and non-distinctively encoded lists in a within-group design have been ascribed to use of a distinctiveness heuristic by which participants monitor their memories at test for distinctive-task details. Alternatively, participants might simply set a more conservative response criterion, which would be exceeded by distinctive list items more often than all other test items, including the critical non-studied items. To evaluate these alternatives, we compared a within-group who studied 5 lists by reading, 5 by anagram generation, and 5 by imagery, relative to a control group who studied all 15 lists by reading. Generation and imagery improved recognition accuracy by impairing relational encoding, but the within group did not show greater memory monitoring at test relative to the read control group. Critically, the within group's pattern of list-based source judgments provided new evidence that participants successfully monitored for distinctive-task details at test. Thus, source judgments revealed evidence of qualitative, recollection-based monitoring in the within group, to which our quantitative signal-detection measure of monitoring was blind.

  11. Preschoolers' Fantasy-Reality Distinctions of Emotional Events

    ERIC Educational Resources Information Center

    Carrick, Nathalie; Ramirez, Madisenne

    2012-01-01

    Research suggests that emotions influence children's ability to discern fantasy from reality; however, reasons for this association remain unknown. The current research sought to better understand the mechanisms underlying children's distinctions by examining the roles discrete emotions and context have in 3- to 5-year-olds' evaluations of fantasy…

  12. Reasoning across Ontologically Distinct Levels: Students' Understandings of Molecular Genetics

    ERIC Educational Resources Information Center

    Duncan, Ravit Golan; Reiser, Brian J.

    2007-01-01

    In this article we apply a novel analytical framework to explore students' difficulties in understanding molecular genetics--a domain that is particularly challenging to learn. Our analytical framework posits that reasoning in molecular genetics entails mapping across ontologically distinct levels--an information level containing the genetic…

  13. Differential Recruitment of Distinct Amygdalar Nuclei across Appetitive Associative Learning

    ERIC Educational Resources Information Center

    Cole, Sindy; Powell, Daniel J.; Petrovich, Gorica D.

    2013-01-01

    The amygdala is important for reward-associated learning, but how distinct cell groups within this heterogeneous structure are recruited during appetitive learning is unclear. Here we used Fos induction to map the functional amygdalar circuitry recruited during early and late training sessions of Pavlovian appetitive conditioning. We found that a…

  14. 34 CFR 110.24 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Recipient assessment of age distinctions. 110.24 Section 110.24 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL...

  15. Writers on Writers: Literary Biography, A Distinctive Genre.

    ERIC Educational Resources Information Center

    Bloom, Lynn Z.

    This essay identifies and illustrates a number of significant features that, in combination, make literary biography a distinct and recognizable genre. Among these are considerations of the various aspects of the composition of literary works, such as sources of inspiration, authors' motives and methods in transforming life into art, and…

  16. Differential Recruitment of Distinct Amygdalar Nuclei across Appetitive Associative Learning

    ERIC Educational Resources Information Center

    Cole, Sindy; Powell, Daniel J.; Petrovich, Gorica D.

    2013-01-01

    The amygdala is important for reward-associated learning, but how distinct cell groups within this heterogeneous structure are recruited during appetitive learning is unclear. Here we used Fos induction to map the functional amygdalar circuitry recruited during early and late training sessions of Pavlovian appetitive conditioning. We found that a…

  17. Individual Distinctiveness in Call Types of Wild Western Female Gorillas

    PubMed Central

    Salmi, Roberta; Hammerschmidt, Kurt; Doran-Sheehy, Diane M.

    2014-01-01

    Individually distinct vocalizations play an important role in animal communication, allowing call recipients to respond differentially based on caller identity. However, which of the many calls in a species' repertoire should have more acoustic variability and be more recognizable is less apparent. One proposed hypothesis is that calls used over long distances should be more distinct because visual cues are not available to identify the caller. An alternative hypothesis proposes that close calls should be more recognizable because of their importance in social interactions. To examine which hypothesis garners more support, the acoustic variation and individual distinctiveness of eight call types of six wild western gorilla (Gorilla gorilla) females were investigated. Acoustic recordings of gorilla calls were collected at the Mondika Research Center (Republic of Congo). Acoustic variability was high in all gorilla calls. Similar high inter-individual variation and potential for identity coding (PIC) was found for all call types. Discriminant function analyses confirmed that all call types were individually distinct (although for call types with lowest sample size - hum, grumble and scream - this result cannot be generalized), suggesting that neither the distance at which communication occurs nor the call social function alone can explain the evolution of identity signaling in western gorilla communication. PMID:25029238

  18. The Development of Distinct Speaking Styles in Preschool Children

    ERIC Educational Resources Information Center

    Redford, Melissa A.; Gildersleeve-Neumann, Christina E.

    2009-01-01

    Purpose: To examine when and how socially conditioned distinct speaking styles emerge in typically developing preschool children's speech. Method: Thirty preschool children, ages 3, 4, and 5 years old, produced target monosyllabic words with monophthongal vowels in different social-functional contexts designed to elicit clear and casual speaking…

  19. Are Specific Language Impairment and Dyslexia Distinct Disorders?

    ERIC Educational Resources Information Center

    Catts, Hugh W.; Adlof, Suzanne M.; Hogan, Tiffany P.; Weismer, Susan Ellis

    2005-01-01

    Purpose: The purpose of this study was to determine whether specific language impairment (SLI) and dyslexia are distinct developmental disorders. Method: Study 1 investigated the overlap between SLI identified in kindergarten and dyslexia identified in 2nd, 4th, or 8th grades in a representative sample of 527 children. Study 2 examined…

  20. On the Distinction between Positive and Negative Reinforcement

    ERIC Educational Resources Information Center

    Iwata, Brian A.

    2006-01-01

    In this article, the author presents his views on Michael's (1975) and Baron and Galizio's (2005) arguments on eliminating the distinction between positive and negative reinforcement. He first discusses Michael's concept of these two types of operations and contrasts it with the notions of Baron and Galizio. The author provides the readers his own…

  1. Neural correlates of the food/non-food visual distinction.

    PubMed

    Tsourides, Kleovoulos; Shariat, Shahriar; Nejati, Hossein; Gandhi, Tapan K; Cardinaux, Annie; Simons, Christopher T; Cheung, Ngai-Man; Pavlovic, Vladimir; Sinha, Pawan

    2016-03-01

    An evolutionarily ancient skill we possess is the ability to distinguish between food and non-food. Our goal here is to identify the neural correlates of visually driven 'edible-inedible' perceptual distinction. We also investigate correlates of the finer-grained likability assessment. Our stimuli depicted food or non-food items with sub-classes of appealing or unappealing exemplars. Using data-classification techniques drawn from machine-learning, as well as evoked-response analyses, we sought to determine whether these four classes of stimuli could be distinguished based on the patterns of brain activity they elicited. Subjects viewed 200 images while in a MEG scanner. Our analyses yielded two successes and a surprising failure. The food/non-food distinction had a robust neural counterpart and emerged as early as 85 ms post-stimulus onset. The likable/non-likable distinction too was evident in the neural signals when food and non-food stimuli were grouped together, or when only the non-food stimuli were included in the analyses. However, we were unable to identify any neural correlates of this distinction when limiting the analyses only to food stimuli. Taken together, these positive and negative results further our understanding of the substrates of a set of ecologically important judgments and have clinical implications for conditions like eating-disorders and anhedonia.

  2. The Emergence of Three Distinct Worldviews among American College Students

    ERIC Educational Resources Information Center

    Keysar, Ariela

    2013-01-01

    American college students' worldviews affect what they value, the way they behave and potentially how they learn. The study described in this article finds that today's students are divided not dichotomously, between religious and secular, but rather among three distinct worldviews: religious, secular, and spiritual. The author asserts that…

  3. Distinctive Pattern of Behavioral Functioning in Angelman Syndrome.

    ERIC Educational Resources Information Center

    Summers, Jane A.; Feldman, Maurice A.

    1999-01-01

    A study compared 27 participants with Angelman syndrome to clinical and community participants (n=948) with developmental disabilities of mixed etiology to determine whether Angelman syndrome is associated with a distinctive patterns of behavioral functioning. Those with Angelman syndrome had significantly lower scores on measures of irritability…

  4. When Does the Factor-Mixture Distinction Matter?

    ERIC Educational Resources Information Center

    Loken, Eric

    2012-01-01

    Von Davier, Naemi, and Roberts (this issue) present a nice summary of the statistical ambiguity often encountered in making distinctions between qualitative and quantitative constructs. In this commentary, the author begins with two broad points. The first is that the mixture/factor arguments are most intriguing when firmly embedded in a…

  5. Positive and Negative Reinforcement: Should the Distinction Be Preserved?

    ERIC Educational Resources Information Center

    Baron, Alan; Galizio, Mark

    2005-01-01

    Michael (1975) reviewed efforts to classify reinforcing events in terms of whether stimuli are added (positive reinforcement) or removed (negative reinforcement). He concluded that distinctions in these terms are confusing and ambiguous. Of necessity, adding a stimulus requires its previous absence and removing a stimulus its previous presence.…

  6. An Explanation of the Distinction between Developmental Factors and Mechanisms

    ERIC Educational Resources Information Center

    Laski, Elida V.

    2017-01-01

    This paper provides five clear, relatable examples that can help students understand the distinction between the term "factors" and "mechanisms" in Developmental Psychology. The examples emphasize the idea that factors are related to changes in ways that moderate development, but are not causal. On the other hand, the term…

  7. Distinctive aspects of the evolution of galactic magnetic fields

    SciTech Connect

    Yar-Mukhamedov, D.

    2016-11-15

    We perform an in-depth analysis of the evolution of galactic magnetic fields within a semi-analytic galaxy formation and evolution framework, determine various distinctive aspects of the evolution process, and obtain analytic solutions for a wide range of possible evolution scenarios.

  8. The Distinction between Positive and Negative Reinforcement: Use with Care

    ERIC Educational Resources Information Center

    Baron, A.; Galizio, M.

    2006-01-01

    It is customary in behavior analysis to distinguish between positive and negative reinforcement in terms of whether the reinforcing event involves onset or offset of a stimulus. In a previous article (Baron & Galizio, 2005), we concluded that a distinction of these terms is not only ambiguous but has little if any functional significance. Here, we…

  9. Verb class distinctions and AAC language-encoding limitations.

    PubMed

    Sutton, A E; Gallagher, T M

    1993-12-01

    This study explored the status of an English grammatical distinction in the language of individuals who have never been able to encode that distinction previously. English past tense marking was used as a context to examine regular and irregular verb class distinctions in the language of two adults with severe congenital physical impairments who rely on augmentative and alternative communication (AAC) systems to communicate. In the subjects' lexically based AAC systems, past tense was marked on regular verbs and irregular verbs using the same strategy. The subjects accessed their AAC displays using four-digit eye gaze number codes. They were shown a novel affixation strategy through manipulation of the four-digit codes that allowed them to mark past tense on regular verbs via an affixation process. Their semantic strategy for marking past tense on irregular verbs was not changed. The subjects' patterns of use of the two strategies on exemplars of each verb class revealed limited evidence of distinctive use of the two strategies based on verb class membership. Theoretical and clinical implications are discussed.

  10. Aspiring for Distinction: Gendered Educational Choices in an Indian Village

    ERIC Educational Resources Information Center

    Rao, Nitya

    2010-01-01

    Schooling is not a benign process, rather the choice of schooling is often an opportunity for marginalised groups to creatively express particular sets of values in an attempt to gain distinction. Educational attainments carry the potential to open up a range of employment opportunities, but even if these options fail due to structural…

  11. MAGDM linear-programming models with distinct uncertain preference structures.

    PubMed

    Xu, Zeshui S; Chen, Jian

    2008-10-01

    Group decision making with preference information on alternatives is an interesting and important research topic which has been receiving more and more attention in recent years. The purpose of this paper is to investigate multiple-attribute group decision-making (MAGDM) problems with distinct uncertain preference structures. We develop some linear-programming models for dealing with the MAGDM problems, where the information about attribute weights is incomplete, and the decision makers have their preferences on alternatives. The provided preference information can be represented in the following three distinct uncertain preference structures: 1) interval utility values; 2) interval fuzzy preference relations; and 3) interval multiplicative preference relations. We first establish some linear-programming models based on decision matrix and each of the distinct uncertain preference structures and, then, develop some linear-programming models to integrate all three structures of subjective uncertain preference information provided by the decision makers and the objective information depicted in the decision matrix. Furthermore, we propose a simple and straightforward approach in ranking and selecting the given alternatives. It is worth pointing out that the developed models can also be used to deal with the situations where the three distinct uncertain preference structures are reduced to the traditional ones, i.e., utility values, fuzzy preference relations, and multiplicative preference relations. Finally, we use a practical example to illustrate in detail the calculation process of the developed approach.

  12. The identification of distinct patterns in California temperature trends

    USDA-ARS?s Scientific Manuscript database

    Regional changes in California surface temperatures over the last 80 years are analyzed using station data from the US Historical Climate Network and the National Weather Service Cooperative Network. Statistical analyses using annual and seasonal temperature data over the last 80 years show distinct...

  13. Forgetting in Immediate Serial Recall: Decay, Temporal Distinctiveness, or Interference?

    ERIC Educational Resources Information Center

    Oberauer, Klaus; Lewandowsky, Stephan

    2008-01-01

    Three hypotheses of forgetting from immediate memory were tested: time-based decay, decreasing temporal distinctiveness, and interference. The hypotheses were represented by 3 models of serial recall: the primacy model, the SIMPLE (scale-independent memory, perception, and learning) model, and the SOB (serial order in a box) model, respectively.…

  14. Genetic Determinism and the Innate-Acquired Distinction in Medicine

    PubMed Central

    2009-01-01

    This article illustrates in which sense genetic determinism is still part of the contemporary interactionist consensus in medicine. Three dimensions of this consensus are discussed: kinds of causes, a continuum of traits ranging from monogenetic diseases to car accidents, and different kinds of determination due to different norms of reaction. On this basis, this article explicates in which sense the interactionist consensus presupposes the innate–acquired distinction. After a descriptive Part 1, Part 2 reviews why the innate–acquired distinction is under attack in contemporary philosophy of biology. Three arguments are then presented to provide a limited and pragmatic defense of the distinction: an epistemic, a conceptual, and a historical argument. If interpreted in a certain manner, and if the pragmatic goals of prevention and treatment (ideally specifying what medicine and health care is all about) are taken into account, then the innate–acquired distinction can be a useful epistemic tool. It can help, first, to understand that genetic determination does not mean fatalism, and, second, to maintain a system of checks and balances in the continuing nature–nurture debates. PMID:20234831

  15. Different activation signals induce distinct mast cell degranulation strategies

    PubMed Central

    Sibilano, Riccardo; Marichal, Thomas; Reber, Laurent L.; Cenac, Nicolas; McNeil, Benjamin D.; Dong, Xinzhong; Hernandez, Joseph D.; Sagi-Eisenberg, Ronit; Hammel, Ilan; Roers, Axel; Valitutti, Salvatore; Tsai, Mindy

    2016-01-01

    Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P–dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation. PMID:27643442

  16. Genetic Determinism and the Innate-Acquired Distinction in Medicine.

    PubMed

    Kronfeldner, Maria E

    2009-06-01

    This article illustrates in which sense genetic determinism is still part of the contemporary interactionist consensus in medicine. Three dimensions of this consensus are discussed: kinds of causes, a continuum of traits ranging from monogenetic diseases to car accidents, and different kinds of determination due to different norms of reaction. On this basis, this article explicates in which sense the interactionist consensus presupposes the innate-acquired distinction. After a descriptive Part 1, Part 2 reviews why the innate-acquired distinction is under attack in contemporary philosophy of biology. Three arguments are then presented to provide a limited and pragmatic defense of the distinction: an epistemic, a conceptual, and a historical argument. If interpreted in a certain manner, and if the pragmatic goals of prevention and treatment (ideally specifying what medicine and health care is all about) are taken into account, then the innate-acquired distinction can be a useful epistemic tool. It can help, first, to understand that genetic determination does not mean fatalism, and, second, to maintain a system of checks and balances in the continuing nature-nurture debates.

  17. Preschoolers' Fantasy-Reality Distinctions of Emotional Events

    ERIC Educational Resources Information Center

    Carrick, Nathalie; Ramirez, Madisenne

    2012-01-01

    Research suggests that emotions influence children's ability to discern fantasy from reality; however, reasons for this association remain unknown. The current research sought to better understand the mechanisms underlying children's distinctions by examining the roles discrete emotions and context have in 3- to 5-year-olds' evaluations of fantasy…

  18. Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity.

    PubMed

    Simeonov, Dimitre R; Kenny, Katelyn; Seo, Lan; Moyer, Amanda; Allen, Jessica; Paluh, Janet L

    2009-11-01

    Kinesin-like proteins are integral to formation and function of a conserved mitotic spindle apparatus that directs chromosome segregation and precedes cell division. Ubiquitous to the mechanism of spindle assembly and stability are balanced Kinesin-5 promoting and Kinesin-14 opposing forces. Distinct Kinesin-14 roles in bipolarity in eukaryotes have not been shown, but are suggested by gamma-tubulin-based pole interactions that affect establishment and by microtubule cross-linking and sliding that maintain bipolarity and spindle length. Distinct roles also imply specialized functional domains. By cross-species analysis of compatible mechanisms in establishing mitotic bipolarity we demonstrate that Kinesin-14 human HSET (HsHSET) functionally replaces Schizosaccharomyces pombe Pkl1 and its action is similarly blocked by mutation in a Kinesin-14 binding site on gamma-tubulin. Drosophila DmNcd localizes preferentially to bundled interpolar microtubules in fission yeast and does not replace SpPkl1. Analysis of twenty-six Kinesin-14 derivatives, including Tail, Stalk or Neck-Motor chimeras, for spindle localization, spindle assembly and mitotic progression defined critical domains. The Tail of SpPkl1 contains functional elements enabling its role in spindle assembly that are distinct from but transferable to DmNcd, whereas HsHSET function utilizes both Tail and Stalk features. Our analysis is the first to demonstrate distinct mechanisms between SpPkl1 and DmNcd, and reveal that HsHSET shares functional overlap in spindle pole mechanisms.

  19. Recursion and the Competence/Performance Distinction in AGL Tasks

    ERIC Educational Resources Information Center

    Lobina, David J.

    2011-01-01

    The term "recursion" is used in at least four distinct theoretical senses within cognitive science. Some of these senses in turn relate to the different levels of analysis described by David Marr some 20 years ago; namely, the underlying competence capacity (the "computational" level), the performance operations used in real-time processing (the…

  20. [Further Distinctions between Magic, Reality, Religion, and Fiction. Commentaries.

    ERIC Educational Resources Information Center

    Boyer, Pascal; Taylor, Marjorie; Harris, Paul L.; Chandler, Michael; Johnson, Carl N.

    1997-01-01

    Contains the following commentaries: "Further Distinctions between Magic, Reality, Religion, and Fiction"; "The Role of Creative Control and Culture in Children's Fantasy/Reality Judgments"; "The Last of the Magicians? Children, Scientists, and the Invocation of Hidden Causal Powers"; "Rescuing Magical Thinking…

  1. The Emergence of Three Distinct Worldviews among American College Students

    ERIC Educational Resources Information Center

    Keysar, Ariela

    2013-01-01

    American college students' worldviews affect what they value, the way they behave and potentially how they learn. The study described in this article finds that today's students are divided not dichotomously, between religious and secular, but rather among three distinct worldviews: religious, secular, and spiritual. The author asserts that…

  2. 28 CFR 42.722 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Recipient assessment of age distinctions... EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Nondiscrimination on the Basis of Age in Federally Assisted Programs or Activities; Implementation of the Age Discrimination Act of 1975 Duties of Recipients §...

  3. 29 CFR 35.17 - Age distinctions in DOL regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Age distinctions in DOL regulations. 35.17 Section 35.17 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM THE DEPARTMENT OF LABOR Standards for Determining...

  4. 28 CFR 42.722 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Recipient assessment of age distinctions... EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Nondiscrimination on the Basis of Age in Federally Assisted Programs or Activities; Implementation of the Age Discrimination Act of 1975 Duties of Recipients §...

  5. 28 CFR 42.722 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Recipient assessment of age distinctions... EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Nondiscrimination on the Basis of Age in Federally Assisted Programs or Activities; Implementation of the Age Discrimination Act of 1975 Duties of Recipients §...

  6. 28 CFR 42.722 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Recipient assessment of age distinctions... EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Nondiscrimination on the Basis of Age in Federally Assisted Programs or Activities; Implementation of the Age Discrimination Act of 1975 Duties of Recipients §...

  7. 29 CFR 35.17 - Age distinctions in DOL regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Age distinctions in DOL regulations. 35.17 Section 35.17 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM THE DEPARTMENT OF LABOR Standards for Determining...

  8. 29 CFR 35.17 - Age distinctions in DOL regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false Age distinctions in DOL regulations. 35.17 Section 35.17 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM THE DEPARTMENT OF LABOR Standards for Determining...

  9. 29 CFR 35.17 - Age distinctions in DOL regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false Age distinctions in DOL regulations. 35.17 Section 35.17 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM THE DEPARTMENT OF LABOR Standards for Determining...

  10. Visual Distinctiveness and the Development of Children's False Memories

    ERIC Educational Resources Information Center

    Howe, Mark L.

    2008-01-01

    Distinctiveness effects in children's (5-, 7-, and 11-year-olds) false memory illusions were examined using visual materials. In Experiment 1, developmental trends (increasing false memories with age) were obtained using Deese-Roediger-McDermott lists presented as words and color photographs but not line drawings. In Experiment 2, when items were…

  11. 29 CFR 35.17 - Age distinctions in DOL regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Age distinctions in DOL regulations. 35.17 Section 35.17 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM THE DEPARTMENT OF LABOR Standards for Determining...

  12. 28 CFR 42.722 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Recipient assessment of age distinctions... EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Nondiscrimination on the Basis of Age in Federally Assisted Programs or Activities; Implementation of the Age Discrimination Act of 1975 Duties of Recipients §...

  13. Sector Distinctions and the Privatization of Public Education Policymaking

    ERIC Educational Resources Information Center

    Lubienski, Christopher

    2016-01-01

    Current trends indicate declining distinctions between "public" and "private" sectors in education. Reformers see sector barriers as unnecessary impediments to innovation, distracting attention and effort from "what works". This analysis questions whether trends in education policy are simply a natural evolution away…

  14. Distinctive Feature Scoring of the California Consonant Test.

    ERIC Educational Resources Information Center

    Feeney, M. Patrick

    1990-01-01

    The study evaluated a distinctive feature scoring technique for List 1 of the California Consonant Test for the purpose of improving test reliability in this test used to identify errors in speech recognition made by adult listeners (N=50) with high frequency sensorineural hearing loss. (DB)

  15. Distinct cellular states determine calcium signaling response.

    PubMed

    Yao, Jason; Pilko, Anna; Wollman, Roy

    2016-12-15

    The heterogeneity in mammalian cells signaling response is largely a result of pre-existing cell-to-cell variability. It is unknown whether cell-to-cell variability rises from biochemical stochastic fluctuations or distinct cellular states. Here, we utilize calcium response to adenosine trisphosphate as a model for investigating the structure of heterogeneity within a population of cells and analyze whether distinct cellular response states coexist. We use a functional definition of cellular state that is based on a mechanistic dynamical systems model of calcium signaling. Using Bayesian parameter inference, we obtain high confidence parameter value distributions for several hundred cells, each fitted individually. Clustering the inferred parameter distributions revealed three major distinct cellular states within the population. The existence of distinct cellular states raises the possibility that the observed variability in response is a result of structured heterogeneity between cells. The inferred parameter distribution predicts, and experiments confirm that variability in IP3R response explains the majority of calcium heterogeneity. Our work shows how mechanistic models and single-cell parameter fitting can uncover hidden population structure and demonstrate the need for parameter inference at the single-cell level. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  16. The Distinction between Positive and Negative Reinforcement: Some Additional Considerations

    ERIC Educational Resources Information Center

    Sidman, Murray

    2006-01-01

    In this article, the author discusses the distinction between positive and negative reinforcement and some additional considerations. He states that the concept of negative reinforcement has caused confusion, and he believes that the difficulty stems from conventions of ordinary speech, in which the term "negative" usually denotes the opposite of…

  17. Repeated cocaine treatments induce distinct locomotor effects in crayfish.

    PubMed

    Nathaniel, Thomas I; Huber, Robert; Panksepp, Jaak

    2012-02-10

    A repeated injection of cocaine regime is known to induce complex locomotion alterations in both vertebrate and invertebrate models of drug addiction. However, the specific effect of cocaine on behaviorally distinct locomotion and non locomotion parameters is not well known. The present experiments determined whether cocaine has distinct effect on multifarious locomotor activity of crayfish (Orconectes rusticus). Following repeated injections of 2.5 μg/g or 10.0 μg/g dose of cocaine for three days, videotaped recordings of locomotion were analyzed to determine whether repeated injections of cocaine produced distinct effect on multifarious locomotor activity of crayfish. Cocaine decreased immobility in day 1 when compared with saline. Thereafter, cocaine increased immobility in days 2 and 3. Repeated injections of cocaine increased distance traveled, average speed, mobility and decreased lingering episodes. These findings indicate that cocaine has distinct action on movement and non-movement behavioral activities, suggesting that locomotion as a unitary phenomenon comprised of assemblage of multifarious components, which can be manipulated and separated by cocaine in crayfish. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Visual Distinctiveness and the Development of Children's False Memories

    ERIC Educational Resources Information Center

    Howe, Mark L.

    2008-01-01

    Distinctiveness effects in children's (5-, 7-, and 11-year-olds) false memory illusions were examined using visual materials. In Experiment 1, developmental trends (increasing false memories with age) were obtained using Deese-Roediger-McDermott lists presented as words and color photographs but not line drawings. In Experiment 2, when items were…

  19. Reasoning across Ontologically Distinct Levels: Students' Understandings of Molecular Genetics

    ERIC Educational Resources Information Center

    Duncan, Ravit Golan; Reiser, Brian J.

    2007-01-01

    In this article we apply a novel analytical framework to explore students' difficulties in understanding molecular genetics--a domain that is particularly challenging to learn. Our analytical framework posits that reasoning in molecular genetics entails mapping across ontologically distinct levels--an information level containing the genetic…

  20. Sector Distinctions and the Privatization of Public Education Policymaking

    ERIC Educational Resources Information Center

    Lubienski, Christopher

    2016-01-01

    Current trends indicate declining distinctions between "public" and "private" sectors in education. Reformers see sector barriers as unnecessary impediments to innovation, distracting attention and effort from "what works". This analysis questions whether trends in education policy are simply a natural evolution away…